Han d book of Neu rosu rger y
Mark S. Green berg, MD
Associate Professor
Depart m en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida
Tam pa, Florida
Eigh th Edition
179 illust ration s
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Libra r y of Congress Ca ta loging-in-Publica tion Da ta
Nam es: Green berg, Mark S., M.D., auth or.
Title: Handbook of neurosurgery / Mark S. Greenberg.
Description : Eigh th edition . | New York : Th iem e,
[2016] | Preceded by Han dbook of n eurosurger y /
editor, Mark S. Green berg. 7th ed. 2010. | In cludes
bibliograph ical referen ces an d in dex.
Iden tifiers: LCCN 2015051094| ISBN
9781626232419 | ISBN 9781626232426 (e-book)
Subjects: | MESH: Ner vous System Diseases–surgery | Neurosurgical Procedures | Handbooks
Classification : LCC RD593 | NLM W L 39 | DDC
617.4/8–dc23 LC record available at h tt p://lccn .loc.
gov/2015051094
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5
Dedicat ion
The eighth edit ion of the Han dbook of Neurosurger y is dedica ted to my wonderful w ife, Debbie. She
inspires me to be the best I ca n be.
This book is a lso dedica ted to “Duke” (August Henr y Wagner III), beloved uncle of contr ibutor Ja yson
Sa ck, who su ered a fa ta l a neur ysma l suba ra chnoid hemorrha ge a s this book wa s going to press. His
selfless life wa s a n inspira t ion to Ja yson a nd his fa mily. He w ill be missed a nd never forgotten.
6
Cont ribut ors
Naom i A. Abel, MD
Assistan t Professor
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Fa ilure of ca r pa l tunnel a nd ulna r ner ve surger y
Electrodia gnost ics (EDX)
Siviero Agazzi, MD, MBA
Associate Professor
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Vest ibula r schwa nnoma s
Am ir Ah m ad ian , MD
Atten ding physician
Neurosurgery of West Florida
Hudson , Florida
Adult spina l deformit y
Ca vernous ma lforma tions*
Norber t o An d alu z, MD
Associate Professor
Departm en t of Neurosurger y
Un iversit y of Cin cin n ati College of Medicin e
Cin cin n at i VA Medical Cen ter
Cin cin n at i, Oh io
Ca rotid stenosis a nd enda rterectomy*
Emergency ca rotid enda r terectomy*
Tota lly occluded ca rotid a rter y*
Ram sey Ash ou r, MD
Com plex cran ial fellow
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Dura l a rter iovenous fistula e
Ali A. Baaj, MD
Assistan t Professor
Departm en t of Neurological Surger y
Weill Corn ell Medical College
New York Presbyterian Hospital
New York, New York
Moya moya disea se*
Kon rad Bach , MD
Research Associate
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Ankylosing spondylit is
Clayt on Bau er, MD, Ph D
Residen t physician
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Sta tus epilepticus
Josh u a M. Beckm an , MD
Residen t physician
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Concussion (mTBI)
Ad arsh Bh im raj, MD
Atten ding physician
Sect ion Head, Neuroin fect ion s
Clevelan d Clin ic
Clevelan d, Oh io
EVD-rela ted infections
Elias Dak w ar, MD
Assistan t Professor
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
CSF Fist ula s
An gela Dow n es, MD
Fellow, Neurocritical Care
Departm en t of Neurosurger y
Un iversit y of Colorado
Denver, Colorado
Stereota ctic ra diosurger y
Sponta neous subdura l hema toma *
Melissa Giarrat an o, Ph ar m D, BCPS
Clin ical Pharm acist – Neuroscien ces
Tam pa Gen eral Hospital
Tam pa, Florida
Antibiot ics
Alexan d er Haas, MD
Residen t physician
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Colloid cysts
Gh ait h Habbou b, MD
Residen t physician
Neurological In stit ute
Clevelan d Clin ic
Clevelan d, Oh io
EVD-rela ted infections
Cont ributors
Sh an n on Han n , MD
Residen t physician
Departm en t of Neurological Surger y
Th om as Je erson Un iversit y
Ph iladelph ia, Pen n sylvan ia
Neurocuta neous mela nosis*
Tim ot h y D. Miller Jr., MD
Residen t physician
Division of Neurosurgery
Duke Un iversit y Sch ool of Medicin e
Durham , North Carolin a
Cerebra l va sospa sm
Sh ah -Naz H. Kh an , MD, FRCS(C), FAANS
Ch air an d Director
In stit ute of Gen eral an d En dovascular Neurosurger y
Clin ical Assistan t Professor
Departm en t of Surger y
Mich igan State Un iversit y
Flin t, Mich igan
Endova scula r neurosurger y
Jose Mon t er o, MD
Associate Professor
Depar tm en t of In tern al Medicin e
Un iversity of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Antibiotics
Tsz Y. Lau , MD
Assistan t Professor
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Suba ra chnoid hemor rha ge
Sh ih -Sin g Liu , MD
Assistan t Professor
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Jugula r fora men
Anticoa gula tion & a nt ipla telet thera py
Wai-m an Liu , MBBS, FRCS, FHKAM
Ch ief of Ser vice, Hon orar y Associate Professor
Division of Neurosurgery, Departm en t of Surger y
Li Ka Sh ing Facult y of Medicin e
Th e Un iversit y of Hon g Kon g
Pokfulam , Hon g Kon g
Astrocytoma
Jot h am Man w arin g, MD
Atten ding physician
South ern Utah Neuroscien ces In stit ute
St . George, Utah
Third ventr iculostomy (ETV)
X-linked hydrocepha lus*
Car los R. Mar t in ez, MD, FACR
Professor of Radiology
USF College of Medicin e
Assistan t Ch ief of Radiology
Bay Pin es VA Hospital
Tam pa, Florida
Int ra cra nia l hypotension
Melein e Mar t in ez-Sosa, MD
Residen t physician
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Int ra cra nia l hypotension
Jason Palu zzi, MD
Residen t physician
Depar tm en t of Neurosurger y an d Brain Repair
Un iversity of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Wilbra nd’s knee
Mich ael S. Park, MD
Residen t physician
Depar tm en t of Neurosurger y an d Brain Repair
Un iversity of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Ca rot id enda rterectomy vs. stenting
Glen A. Pollock, MD
Atten ding physician
Raleigh Neurosurgical Clin ic
Raleigh , North Carolin a
PRES*
Kan -su en Jen n y Pu , BSC, MBBS, FHKAM,
FRCSHK, FRCS (Su rgical Neu rology)
Division of Neurosurgery, Depart m en t of Surgery
Li Ka Sh ing Facult y of Medicin e
Th e Un iversit y of Hon g Kon g
Pokfulam , Hon g Kon g
Astrocytoma
Ed w in Ram os, MD
Assistan t Professor
Depar tm en t of Surger y
Th e Un iversit y of Ch icago Medicin e
Ch icago, Illin ois
Hypotha la mic ha ma rtoma s*
Step h en Rein t jes, MD
Residen t physician
Depar tm en t of Neurosurger y an d Brain Repair
Un iversity of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Anticoa gula t ion & a nt ipla telet thera py
7
8
Cont ributors
Jayson Sack, MD
Residen t physician
Division of Neurosurgery
Un iversit y of Californ ia, San Diego
San Diego, Californ ia
Suba ra chnoid hemor rha ge
Step h en San d w ell, MD
Residen t physician
Departm en t of Neurosurger y
Un iversit y of Roch ester
Roch ester, New York
Centra l neurocytoma
Josep h Serron e, MD
Atten ding physician
Virgin ia Mason Hospital an d Seattle Medical
Cen ter
Seattle, Wash in gton
Pleomor phic xa nthoa strocytoma s*
San an t h an Sivakan t h an
Medical st uden t
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Jugula r fora men
L. Bran n on Th om as, MD, Ph D
Atten ding physician
Jam es A. Haley Veteran s Adm in istration Hospital
Un iversit y Com m un ity Hospital
Tam pa, Florida
Neuropa thology
Fern an d o L. Vale, MD
Professor an d Vice-Ch airm an
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Seizure surger y
Jam ie J. Van Gom p el, MD
Assistan t Professor
Departm en t of Neurosurger y
Mayo Clin ic
Roch ester, Min n esota
Esthesioneurobla stoma s
Ju an S. Uribe, MD
Associate Professor
Director, Spin e Sect ion
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Tra nspsoa s a pproa ch
Lher mitte-Duclos disea se*
Bone gra ft ma teria ls*
New spine fusion techniques*
Roh it Vasan , MD
Atten ding physician
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Syncope*
Ch ar les E. Wr igh t , MD
Medical Director
LifeLin k of Florida
Tam pa, Florida
Bra in dea th & orga n dona t ion
Ch u n -Po Yen , MD
Fellow
Departm en t of Neurosurger y an d Brain Repair
Un iversit y of South Florida Morsan i College of
Medicin e
Tam pa, Florida
Tra nspsoa s a pproa ch
Stereota ctic ra diosurger y
Ash raf Sam y You ssef, MD, Ph D
Visitin g Associate Professor
Director of Skull Base Surger y
Departm en t of Neurosurger y
Un iversit y of Colorado Sch ool of Medicin e
Denver, Colorado
Ma nagement of pinea l region t umors*
*Or igin a lly cont r ibu ted to the Ha ndbook of
Neurosu rger y, seventh edit ion
9
Preface
Sh ortly after fin ish in g m y residen cy t rain ing in 1989, in a tim e lon g before th e in tern et, I w rote th e
first edition of th e Ha ndbook of Neurosurger y w ith th e in ten t to m ake pract ical, act ion able n eurosurgical in form at ion accessible at th e fin gert ips of th e pract it ion er.
Over th e years, I used desktop publish ing tech n ology to expan d th e scope of th e book, an d to
in corporate diagram s an d literature referen ces. I always w an ted to m ake th e book “academ ic” by
presen tin g data th at backed up th e assert ion s. My goal w as to n ever publish a cookbook.
W ith out advert isin g, I relied solely on w ord-of-m outh to prom ote th e book. I believed in th e sam e
th in g th at Edw in Lan d m ust h ave w h en h e said, “Marketin g is w h at you do w h en your product is n o
good.” I h ad a test run of 600 copies of th e book prin ted at a sm all van it y press in An n Arbor, an d sold
copies to in dividuals by m ail. My big break cam e w h en th e m edical bookstore at th e State Un iversity
of New York in Syracuse purch ased 6 copies to put on th eir sh elves. After th at, I regularly packaged 5
or 6 books in a box dest in ed for various bookstores an d dropped th em o at th e loading dock on m y
w ay to th e O.R. in th e m orn in g. After a tim e, th e m ajor m edical book distributors in th e coun tr y
began orderin g cases of books an d m y garage becam e a sh ipping depart m en t. (I st ill h ave th e pallet
jack th at I used to un load th e deliver y trucks.) Th en , som eh ow, in tern at ion al orders began to arrive.
I w as fin ally able to get out of th e packing an d t ran sport in g busin ess w h en I partn ered w ith
Th iem e Medical Publish ers in 2001. At th at tim e th e in tern et w as just becom ing “a th in g,” an d w h ile
it w as a great w ay to m ake con n ect ion s, th e in form ation explosion w as still to com e. Th e goal of th e
book regardless w as still th e sam e—to m ake useful in form ation readily available.
By th e tim e th e 6 th edition w as publish ed in 2006, th e process I used to produce th e book w as
becom ing m ore di cult. Th e page layout soft w are th at h ad been m y w orkh orse for over 10 years
w as n o lon ger supported, an d th e developers of th e referen ce m an ager I ut ilized h ad ch anged th eir
focus an d th e product w as n ow com pat ible prim arily w ith w ord processors (w h ich w ere poorly
suited for com plex m ulti-ch apter books like th is on e). As a result , I w as forced to use an obsolete
Pow erPC com puter an d h ad to h ack th e ch apter files in order to trick th e referen ce m an ager to w ork
w ith th em ! After th e 7 th edition w as com pleted, I could see n o w ay forw ard w ith th is approach . I
n ever im agin ed th at desktop publish ing w as going to atrophy an d fall vict im to th e sam e fate th at
w ould later com e to claim prin t n ew spapers. W ith th e availabilit y of th e w orld w ide w eb, th e in tern et w as quickly becom in g th e ch ief m ean s of accessin g in form ation on dem an d.
Th e birth of th is 8 th edition of th e h an dbook th at you are n ow reading w as a particularly di cult
on e. Th an ks to th e people at Th iem e, th e m aterial w as pain stakin gly converted from th e defun ct
soft w are platform to a con tem porar y form at th at w ill facilitate con tin ued updates an d availabilit y in
digital m edia. Th is tim e-con sum ing an d labor-in ten sive process in cluded port in g th ousan ds of cross
referen ces, in dex en tr ies, an d literature citation s.
In terestin gly, th e objectives of th e h an dbook h ave also gon e th rough a t ran sform ation . It is ch allen gin g to distill w h at all of th ose objectives are, but I believe th at it is im por tan t to present m aterial
in a fram ework th at can ser ve as a foun dation for st udying th e field of n eurosurger y. Th is book is
in ten ded to be a place th at brin gs togeth er th e im por tan t in form ation th at is in creasingly scattered
across th e literature and th e w eb (for in stan ce, pract ice guidelin es for disparate subjects like spin al
cord injur y, st roke, an eur ysm s…) th at m igh t n ot n ecessarily be en countered un less on e is actively
seeking it out.
My goal w ith th e book h as alw ays been to presen t in form at ion succin ctly an d clearly. To th at en d,
th is edition is a com pletely restruct ured version of th e Ha ndbook of Neurosurger y, presen tin g th e
en tire con ten t in a collection of m ore th an 100 w ell-ordered ch apters of com parable len gth an d form at w h ile retain ing th e w ealth of crosslin ks an d referen ces th e book is kn ow n for. Th is n ew organ ization was design ed to m ake th e con ten t m ore easily digestible an d accessible – for both brow sing
th e prin t book an d n avigatin g any elect ron ic version .
W ith its n ew struct ure an d form at, as w ell as revised an d updated con ten t, I h ope I h ave provided
readers w ith an even m ore valuable resource in th is 8 th edit ion of th e Ha ndbook of Neurosurger y.
10
Acknow ledgm ent s
I w ould like to th an k all of th ose w h o par ticipated in th e preparation of th is edition . Th an ks to th e
m any con tributors w h o h elped w ith th e m aterial, an d th e people kn ow n an d n ot kn ow n to m e at
Th iem e Medical Publish ers. To Brian Scan lan , Presiden t of Th iem e Medical Publish ers, for m akin g
th e resources available to save th e book from disappearin g en tirely. To Sarah Lan dis an d Torsten
Scheih agen for th eir editorial h elp. An d th e deepest debt of gratitude to Dr. Mich ael Wach in ger,
Th iem e’s Director of Clin ical Solution s, w h o person ally spen t coun tless h ours an d a n um ber of tran satlan tic trips, guiding th e restructur ing of th e in form ation in to a m ore accessible an d logical fram ew ork, an d en surin g th at th e con ten t w as preser ved in th e soft ware tran sfer.
Th an ks also to m y colleagues an d th e residen ts in th e n eurosurger y program at th e Un iversit y of
South Florida from w h om I learn ever y day. Special th an ks to our ch airm an , Dr. Harr y van Loveren ,
for h is advice, calm leadersh ip an d for in spirin g excellen ce in n eurosurger y.
11
Abbreviat ions and Sym bols
Abbreviation s used on ly locally are defin ed in th at sect ion usin g boldface t ype. Num bers follow in g
en tries below in dicate th e page n um ber for th e relevan t sect ion .
Abbreviations
a.
artery (aa. = arteries)
AA
anaplastic astrocytoma (p. 616)
ABC
aneurysm al bone cyst (p. 784)
Abx.
antibiotics
AC
arachnoid cyst (p. 248)
ACA
anterior cerebral artery
ACAS
asymptomatic carotid artery stenosis (p. 1275) or Asymptomatic Carotid Atherosclerosis Study
(p. 1276)
ACDF
anterior cervical discectomy & fusion (p. 1072)
ACE
angiotensin-converting enzyme
ACh
acet ylcholine (neurotransm it ter)
AChA
anterior choroidal artery
ACoA
anterior com municating artery
ACTH
adrenocorticotropic horm one (corticotropin) (p. 151)
AD
autosomal dominant
ADH
antidiuretic horm one (p. 151)
ADI
atlantodental interval (p. 213)
ADPKD
autosomal dominant polycystic kidney disease (p. 1193)
ADQ
abductor digiti quinti (or m inim i)
AED
anti-epileptic drug (anticonvulsant) (p. 443)
AFP
alpha-fetoprotein (p. 600)
Ag
antigen
AHCPR
Agency for Health Care Policy and Research (of the U. S. Public Health Service)
AICA
anterior inferior cerebellar artery (p. 83)
AIDP
acute inflam m atory demyelinating polyradiculoneuropathy (p. 185)
AIDS
acquired im munodeficiency syndrom e (p. 329)
AIN
anterior interosseous neuropathy (p. 518)
AD
autosomal dominant (inheritance)
AFO
ankle-foot-orthosis (p. 537)
AKA
also known as
ALIF
anterior lum bar interbody fusion (p. 1493)
ALARA
As Low As Reasonably Achievable (p. 224)
12
Abbreviations and Sym bols
A-line
arterial line
ALL
anterior longitudinal ligam ent
ALS
amyotrophic lateral sclerosis (p. 1086)
AMS
acute m ountain sickness (p. 848)
AN
acoustic neurom a (p. 670)
ANA
antinuclear antibodies
AOD
atlantooccipital dislocation (p. 963)
AOI
atlantooccipital interval (p. 964)
AP
antero-posterior
APAG
antipseudom onal am inoglycoside
APAP
acetam inophen (p. 137)
APD
afferent pupillary defect (p. 562)
APTT
(or PTT) activated partial throm boplastin time
ARDS
adult respiratory distress syndrom e
ASA
Am erican Societ y of Anesthesiologist s or aspirin (acet ylsalicylic acid)
ASAP
as soon as possible
ASD
antisiphon device
AT
anterior tibialis (tibialis anterior)
AT/RT
at ypical teratoid/rhabdoid tumor (p. 666)
ASHD
atherosclerotic heart disease
AVM
arteriovenous malform ation (p. 1238)
AVP
arginine vasopressin (p. 151)
β-hCG
beta-human chorionic gonadotropin (p. 600)
BA
basilar artery
BBB
blood-brain barrier (p. 90)
BC
basal cisterns (p. 921)
BCP
birth control pills (oral contraceptives)
BCVI
blunt cerebrovascular injury (p. 849)
BG
basal ganglia
BI
basilar impression/invagination (p. 217)
BMD
bone mineral densit y (p. 1009)
BMP
bone morphogenic protein (p. 1439)
BOB
benign osteoblastoma (p. 792)
BP
blood pressure
BR
bed rest (activit y restriction)
BSF
basal skull fracture (p. 884)
Abbreviat ions and Sym bols
BSG
brainstem gliom a (p. 633)
Ca
cancer
CA
cavernous angioma (p. 1247)
CAA
cerebral am yloid angiopathy (p. 1334)
CABG
coronary artery bypass graft
CAD
coronary artery disease
CAT
(or CT) com puterized (axial) tomography
CBF
cerebral blood flow (p. 1264)
CBV
cerebral blood volum e
CBZ
carbamazepine (p. 449)
CCB
calcium-channel blocker
CCF
carotid-cavernous (sinus) fistula (p. 1256)
CCHD
congenital cyanotic heart disease
CD
Cushing’s disease (p. 723)
CEA
carotid endarterectomy (p. 1290) or carcinoem bryonic antigen (p. 601)
CECT
contrast enhanced CT
cf
(Latin: confer) compare
cGy
centi-Gray (1cGy = 1 rad)
CHF
congestive heart failure
CI
confidence interval (statistics)
CIDP
chronic inflamm atory demyelinating polyradiculoneuropathy (p. 186)
CIP
critical illness polyneuropathy (p. 542)
CJD
Creutzfeldt-Jakob disease (p. 367)
CM
cavernous malform ation (p. 1247)
CMAP
compound m otor action potential (EMG)
CMRO2
cerebral metabolic rate of oxygen consumption (p. 1265)
CMT
Charcot-Marie-Tooth (p. 541)
CMV
cytomegalovirus
CNL
chemonucleolysis
CNS
central nervous system
cCO
continuous cardiac output
CO
cardiac output or carbon monoxide (p. 208)
CPA
cerebellopontine angle
CPM
central pontine m yelinolysis (p. 115)
CPN
common peroneal nerve (p. 535)
CPP
cerebral perfusion pressure (p. 856)
13
14
Abbreviations and Sym bols
Cr. N.
cranial nerve(s)
CRH
corticotropin-releasing horm one (p. 151)
CRP
C-reactive protein
CRPS
com plex regional pain syndrome (p. 497)
CSM
cervical spondylotic m yelopathy (p. 1084)
CSO
craniosynostosis (p. 252)
CSW
cerebral salt wasting (p. 118)
CTA
CT angiogram (p. 227)
CTP
CT perfusion (p. 228)
CTS
carpal tunnel syndrom e (p. 519)
CVA
cerebrovascular accident (stroke) (p. 1264)
CVP
central venous pressure
CVVT
cerebrovascular venous throm bosis (p. 1308)
CVR
cerebrovascular resistance (p. 1264)
CVS
cerebral vasospasm (p. 1178)
CXR
chest x-ray
DACA
distal anterior cerebral artery
DAI
diffuse axonal injury (p. 848)
DBM
dem ineralized bone m atrix (p. 1439)
D/C
discontinue
DDAVP
1-deam ino-8-D-arginine vasopressin (desmopressin) (p. 125)
DDx
differential diagnosis (p. 1395)
DBS
deep brain stimulation (p. 1524)
DI
diabetes insipidus (p. 120)
DIND
delayed ischem ic neurologic deficit (p. 1179)
DIG
desmoplastic infantile astrocytom a and gangliogliom a (p. 645)
DISH
diffuse idiopathic skeletal hyperostosis (p. 1129)
DKA
diabetic keto-acidosis
DLC
disco-ligam entous com plex (p. 986)
DLIF
direct lateral lum bar interbody fusion (p. 1498)
DOC
drug of choice
DM
diabetes m ellitus
DMZ
dexam ethasone
DNT
(or DNET) dysembryoplastic neuroepithelial tum ors (p. 646)
DOE
dyspnea on exertion
DOMS
delayed onset m uscle soreness (p. 1101)
Abbreviat ions and Sym bols
DPL
diagnostic peritoneal lavage
DREZ
dorsal root entry zone lesion (p. 1550)
DSA
digital subtraction angiogram
DSD
degenerative spine disease (p. 1096)
DST
dural sinus throm bosis (p. 1308)
DTs
delirium trem ens (p. 206)
DTT
diffusion tensor tractography MRI (p. 234)
DVT
deep-vein thrombosis (p. 167)
DWI
(or DWMRI) diffusion-weighted imaging (MRI) (p. 232)
EAC
external auditory canal
EAM
external auditory m eatus
EAST
Eastern Association for the Surgery of Trauma
EBRT
external beam radiation therapy
EBV
Epstein-Barr Virus
ECM
erythem a chronicum m igrans (p. 334)
EDC
electrolytically detachable coils
EDH
epidural hem atoma (p. 892)
EHL
extensor hallicus longus
ELISA
enzym e-linked im munosorbent assay
ELST
endolym phatic sac tum ors (p. 705)
EM
electron m icroscope (m icroscopy)
ENG
electronystagmography (p. 674)
ENT
ear, nose and throat (otolaryngology)
EOM
extra-ocular muscles (p. 565)
EOO
external oculom otor ophthalmoplegia
ESR
erythrocyte sedimentation rate
EST
endoderm al sinus tumor (p. 660)
EtOH
ethyl alcohol (ethanol)
ET tube
endotracheal tube
ETV
endoscopic third ventriculostomy (p. 415)
EVD
external ventricular drain (ventriculostomy)
FCU
flexor carpi ulnaris
FDP
flexor digitorum profundus
FIM
Functional Independence Measure (p. 1362)
FLAIR
fluid-attenuated inversion recovery (on MRI) (p. 229)
FM
face m ask
15
16
Abbreviations and Sym bols
FMD
fibrom uscular dysplasia (p. 200)
FSH
follicle stimulating horm one (p. 151)
F/ U
follow-up
FUO
fever of unknown origin
GABA
gamm a-am inobut yric acid
GBM
glioblastoma (m ultiforme) (p. 616)
GBS
Guillain-Barré syndrom e (p. 184)
GCA
giant cell arteritis (p. 195)
GCS
Glasgow coma scale (p. 296)
GCT
granular cell tum or (p. 727) or germ cell tum or (p. 659)
GD
Graves’ disease
GFAP
glial fibrillary acidic protein (p. 598)
GGT
gamm a glutam yl transpeptidase
GH
growth hormone (p. 151)
GH-RH
growth hormone releasing horm one (p. 151)
GMH
germ inal m atrix hem orrhage (p. 1346)
GNR
gram negative rods
GnRH
gonadotropin-releasing horm one (p. 151)
GSW
gunshot wound
GTC
generalized tonic-clonic (seizure)
H/A
headache (p. 174)
H&H
Hunt and Hess (SAH grade) (p. 1162)
H&P
history and physical exam
HBsAg
hepatitis B surface antigen
HCD
herniated cervical disc (p. 1069)
hCG
hum an chorionic gonadotropin (p. 600)
HCP
hydrocephalus (p. 394)
HDT
hyperdynamic therapy (p. 1186)
HGB
hem angioblastoma (p. 701)
Hgb-A1C
hem oglobin A1C
hGH
hum an growth horm one
HH
hypothalam ic ham artomas (p. 261) or hom onymous hem ianopsia
HHT
hereditary hemorrhagic telangiectasia (p. 1246)
HIV
hum an imm unodeficiency virus
HLD
herniated lumbar disc (p. 1046)
HLA
hum an leukocyte antigen
Abbreviat ions and Sym bols
H.O.
house officer
HNP
herniated nucleus pulposus (herniated disc) (p. 1046)
HNPP
hereditary neuropathy with liability to pressure palsies (p. 541)
HOB
head of bed
HPA
hypothalam ic-pituitary-adrenal axis
HSE
herpes sim plex encephalitis (p. 364)
HTN
hypertension
IAC
internal auditory canal
IASDH
infantile acute subdural hem atom a (p. 898)
ICA
internal carotid artery
ICG
indocyanine green
ICH
intracerebral hemorrhage (p. 1330)
IC-HTN
intracranial hypertension (increased ICP)
ICP
intracranial pressure (p. 856)
ICU
intensive care unit
IDDM
insulin-dependent diabetes m ellitus
IDET
intradiscal endotherm al therapy (p. 1053)
IEP
im mune electrophoresis
IG
im age guidance (intra-operative)
IGF-1
insulin-like growth factor-1 (AKA som atom edin-C) (p. 151)
IIH
idiopathic intracranial hypertension (pseudotumor cerebri) (p. 766)
IIHWOP
idiopathic intracranial hypertension without papilledem a (p. 768)
IJV
internal jugular vein
IMRT
intensit y m odulated radiation therapy
INO
internuclear ophthalm oplegia (p. 565)
INR
international norm alized ratio (p. 164)
IPS
inferior petrosal sinus
IPA
idiopathic paralysis agitans (Parkinson’s disease) (p. 176)
ISAT
International Subarachnoid Hemorrhage Aneurysm Trial (p. 1195)
IT
intrathecal
ITB
intrathecal baclofen (p. 1531)
IVC
intraventricular catheter or inferior vena cava
IVH
intraventricular hemorrhage (p. 1386)
IVP
intravenous push (m edication route) or intravenous pyelogram (x-ray study)
JPS
joint position sense
LBP
low back pain (p. 1024)
17
18
Abbreviations and Sym bols
LDD
Lherm itte-Duclos disease (p. 647)
LE
lower extrem it y
LFTs
liver function tests
LGG
low-grade glioma
LH
luteinizing horm one (p. 151)
LH-RH
luteinizing horm one releasing hormone (p. 151)
LMD
low m olecular weight dextran
LMN
lower m otor neuron (p. 504)
LMW
low-m olecular-weight (e.g. heparins)
LOC
loss of consciousness
LOH
loss of heterozygosity
LP
lum bar puncture (p. 1504)
LSO
lum bo-sacral orthosis
MAC
m ycobacterium avian com plex (p. 354)
MAOI
m onoam ine oxidase inhibitor
MAP
m ean arterial pressure
MAST®
m ilitary anti-shock trousers
MB
m edulloblastom a (p. 664)
MBEN
m edulloblastom a with extensive nodularit y (p. 665)
MBI
m odified Barthel index ( Table 88.6)
MBS
m edulloblastom a (p. 664)
MCA
m iddle cerebral artery
m cg
(or µg) microgram
MCP
mean carotid pressure or m etacarpal phalangeal
MDCTA
multidetector CT angiography
MDMA
methylenedioxym ethamphetam ine (p. 177)
mg
milligram
MI
myocardial infarction
MIB-1
monoclonal anti-Ki-67 antibody (p. 599)
MIC
minim um inhibitory concentration (for antibiotics)
MID
multi-infarct dementia
MISS
minim ally invasive spine surgery
m JOA
modified Japanese Orthopedic Association scale (p. 1086)
MLF
medial longitudinal fasciculus
MLS
midline shift (p. 921)
MM
myelomeningocele (p. 265) or multiple m yelom a (p. 714)
Abbreviat ions and Sym bols
MMD
moyamoya disease (p. 1313)
MMN
multifocal motor neuropathy (p. 1410)
MMPI
Minnesota Multiphasic Personalit y Inventory
m os
months
MPTP
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (p. 177)
MRA
MRI angiogram (p. 232)
MRS
MRI spectroscopy (p. 233)
MRSA
methicillin resistant staphylococcus aureus
MS
microsurgery or multiple sclerosis (p. 179)
MSO4
morphine sulfate
MTP
metatarsal phalangeal
MTT
meant transit tim e (on CT perfusion) (p. 228)
MUAP
motor unit action potential (p. 243)
MVA
motor vehicle accident
MVD
microvascular decompression (p. 488)
MW
molecular weight
n.
nerve (nn. = nerves)
Na
(or Na +) sodium
N2 O
nitrous oxide (p. 105)
NAA
N-acetyl aspartate (p. 233)
NAP
nerve action potential (p. 509)
NASCET
North Am erican Symptom atic Carotid Endarterectomy Trial (p. 1290)
NB
(Latin: nota bene) note well
NC
nasal cannula
NCCN
National Comprehensive Cancer Network
NCD
neurocutaneous disorders (p. 603)
NCV
nerve conduction velocit y
NEC
neurenteric cyst (p. 290) or necrotizing enterocolitis
NEXUS
National Em ergency X-Radiography Utilization Study (p. 953)
NF
(or NFT) neurofibromatosis (p. 603)
NF1
neurofibrom atosis t ype 1 (p. 604)
NF2
neurofibrom atosis t ype 2 (p. 605)
NG tube
nasogastric tube
NGGCT
non-germ inom atous germ cell tum ors (p. 659)
NIHSS
NIH Stroke Scale (p. 1282)
NMBA
neuromuscular blocking agent (p. 134)
19
20
Abbreviat ions and Sym bols
NMO
neurom yelitis optica (Devic disease) (p. 1409)
NPH
norm al pressure hydrocephalus (p. 403)
NPS
neuropathic pain syndrome (p. 476)
NS
norm al saline
NSAID
non-steroidal anti-inflam m atory drug (p. 137)
NSCLC
non-sm all-cell cancer of the lung (p. 803)
NSF
nephrogenic system ic fibrosis (p. 231)
NSM
neurogenic stunned myocardium (p. 1177)
N/V
nausea and vom iting
NVB
neurovascular bundle
OAD
occipital atlantal dislocation, see atlantooccipital dislocation (p. 963)
OALL
ossification of the anterior longitudinal ligam ent (p. 1129)
OC
occipital condyle
OCB
oligoclonal bands (in CSF) (p. 181)
OCF
occipital condyle fracture (p. 885)
ODG
oligodendrogliom a (p. 638)
OEF
oxygen extraction fraction
OFC
occipital-frontal (head) circumference
OGST
oral glucose suppression test (for growth horm one) (p. 736)
OMO
open-m outh odontoid (C-spine x-ray view)
OMP
oculom otor (third nerve) palsy
ONSF
optic nerve sheath fenestration (p. 772)
OP
opening pressure (on LP) (p. 1505)
OPLL
ossification of the posterior longitudinal ligam ent (p. 1127)
ORIF
open reduction/internal fixation
OS
overall survival
OTC
over the counter (i.e. without prescription)
PACU
post-anesthesia care unit (AKA recovery room , PAR)
PADI
posterior atlantodental interval (p. 213)
PAN
poly- (or peri-) arteritis nodosa (p. 199)
PBPP
perinatal brachial plexus palsy (p. 552)
p Bt O2
brain tissue oxygen tension (p. 865)
PC
pineal cyst (p. 658)
PCA
pilocytic astrocytoma (p. 629) or posterior cerebral artery
PCB
pneum atic com pression boot
PCC
prothrom bin complex concentrate (p. 166)
Abbreviat ions and Sym bols
PCI
prophylactic cranial irradiation
PCN
penicillin
PCNSL
prim ary CNS lym phom a (p. 710)
P-com m
posterior comm unicating artery
PCV
procarbazine, CCNU, & vincristine (chem otherapy)
PCWP
pulm onary capillary wedge pressure
PDA
patent ductus arteriosus
PDN
painful diabetic neuropathy (p. 476)
PDR
Physicians Desk Reference®
peds
pediatrics (infants & children)
PEEK
poly-ether-ether-ketone (graft material)
PET
positron em ission tomography (scan)
p-fossa
posterior fossa
PFS
progression-free survival
PFT
pulm onary function test
PHN
postherpetic neuralgia (p. 493)
PHT
phenytoin (Dilantin®) (p. 446)
PICA
posterior inferior cerebellar artery (p. 82)
PIF
prolactin release inhibitory factor (p. 151)
PIN
posterior interosseous neuropathy (p. 532)
PION
posterior ischem ic optic neuropathy (p. 1056)
PIVH
periventricular-intraventricular hemorrhage (p. 1346)
PLAP
placental alkaline phosphatase (p. 660)
PLEDs
periodic lateralizing epileptiform discharges
PLIF
posterior lum bar interbody fusion
PM
pars m arginalis (p. 60)
PMA
progressive m uscular atrophy (p. 183) or pilomyxoid astrocytoma (p. 632)
PMH
pure m otor hem iparesis
PML
progressive m ultifocal leukoencephalopathy (p. 329)
PMMA
polym ethylm ethacrylate (methylm ethacrylate)
PMR
polymyalgia rheumatica (p. 198)
PMV
pontom esencephalic vein
PNET
prim itive neuroectoderm al tum or (p. 663)
POD
post-operative day
PPV
positive predictive value: in unselected patients who test positive, PPV is the probabilit y that
the patient has the disease
PR
per rectum
21
22
Abbreviations and Sym bols
PRES
posterior reversible encephalopathy syndrom e (p. 194)
PRF
prolactin releasing factor (p. 151)
PRIF
prolactin (releasing) inhibitory factor (p. 151)
PRN
as needed
PRSP
penicillinase resistant synthetic PCN
PSNP
progressive supra-nuclear palsy (p. 178)
PSR
percutaneous stereotactic rhizotom y (for trigem inal neuralgia) (p. 483)
PSW
positive sharp waves (on EMG) (p. 242)
pt
patient
PT
physical therapy or prothrom bin tim e
PTC
pituicytom a (p. 728)
PTR
percutaneous trigem inal rhizotomy
PTT
(or APTT) partial thromboplastin tim e
PUD
peptic ulcer disease
PVP
percutaneous vertebroplast y (p. 1011)
PWI
perfusion-weighted im aging (MRI) (p. 233)
PXA
pleomorphic xanthoastrocytom a (p. 635)
q
(Latin: quaque) every (medication dosing)
RA
rheum atoid arthritis
RAPD
relative afferent pupillary defect (p. 562)
RASS
Richmond agitation-sedation scale (p. 132)
RCVS
reversible cerebral vasoconstrictive syndrom e (p. 1158)
rem
roentgen-equivalent man
REZ
root entry zone
RFR
radiofrequency rhizotom y (p. 483)
rFVIIa
recombinant (activated) factor VII
RH
recurrent artery of Heubner
rhBMP
recombinant human BMP (p. 1439)
R/O
rule out
ROM
range of m otion
RPA
recursive partitioning analysis
RPDB
randomized prospective double-blind
RPLS
reversible posterior leukoencephalopathy syndrom e; see posterior reversible encephalopathy
syndrome (p. 194)
RPNB
randomized prospective non-blinded
RTOG
Radiation Therapy Oncology Group
RTP
return to play (sports)
Abbreviat ions and Sym bols
rt-PA
recombinant tissue plasminogen activator (AKA tissue plasminogen activator)
RTX
(or XRT) radiation therapy (p. 1560)
S/S
signs and symptom s
SAH
subarachnoid hem orrhage (p. 1191)
SBE
subacute bacterial endocarditis
SBO
spina bifida occulta (p. 265)
SBP
systolic blood pressure
SCA
superior cerebellar artery
SCLC
sm all-cell lung cancer (p. 802)
SCD
sequential com pression device
SCI
spinal cord injury (p. 943)
SCM
sternocleidom astoid (m uscle)
SD
standard deviation
SDE
subdural em pyem a (p. 327)
SDH
subdural hem atoma (p. 895)
SE
status epilepticus (for seizures) (p. 468)
SEA
spinal epidural abscess (p. 349)
SEP
(or SSEP) somatosensory evoked potential
SG
specific gravit y
SIAD
syndrom e of inappropriate antidiuresis (p. 112)
SIADH
syndrom e of inappropriate antidiuretic hormone (ADH) secretion (p. 114)
SIDS
sudden infant death syndrom e
SIH
spontaneous intracranial hypotension (p. 389)
SIRS
septic inflam m atory response syndrom e
SjVO2
jugular venous oxygen saturation (p. 865)
SLAD
surgical laser aim ing device
SLE
system ic lupus erythematosus
SLIC
subaxial injury classification (p. 986)
SMC
spinal m eningeal cyst (p. 1142)
SMT
spinal m anipulation therapy (p. 1034)
SNAP
sensory nerve act ion potential (EMG) (p. 243)
SNUC
sinonasal undifferentiated carcinom a (p. 1387)
SOMI
sternal-occipital-m andibular im mobilizer (p. 935)
SON
supraorbital neuralgia (p. 491)
S/P
status-post
SPAM
subacute progressive ascending m yelopathy (p. 1019)
23
24
Abbreviations and Sym bols
SPECT
single positron emission com puted tomography (scan)
SPEP
serum protein electrophoresis
sPNET
supratentorial prim itive neuroectoderm al tum or (p. 666)
SQ
subcutaneous injection
SRS
stereotactic radiosurgery (p. 1564)
SRT
stereotactic radiotherapy (p. 1564)
SSEP
(or SEP) som atosensory evoked potential
SSPE
subacute sclerosing panencephalitis (p. 238)
SSRI
selective serotonin reuptake inhibitors
SSS
superior sagittal sinus
STA
superficial tem poral artery
STICH
Surgical Trial in Intracerebral Haem orrhage (p. 1343)
STIR
short tau inversion recover (MRI image)
STN
subthalam ic nucleus
STSG
Spine Traum a Study Group
SUNCT
short-lasting unilateral neuralgiform H/A with conjunctival injection and tearing (p. 478)
SVC
superior vena cava
SVM
spinal vascular m alformations (p. 1140)
SVR
system ic venous resistance
SVT
supraventricular tachycardia
Sz.
seizure (p. 440)
T1WI
T1 weighted image (on MRI) (p. 228)
T2WI
T2 weighted image (on MRI) (p. 229)
TAL
transverse atlantal ligam ent (p. 70)
TBA
total bilateral adrenalectomy (p. 743)
TBI
traumatic brain injury
TCA
tricyclic antidepressants
TCD
transcranial doppler (p. 1182)
TDL
tum efactive dem yelinating lesions (p. 181)
TE
time to echo (on MRI) (p. 228)
TEE
transesophageal echocardiogram
TEN
toxic epiderm al necrolysis
TENS
transcutaneous electrical nerve stim ulation
TGN
trigem inal neuralgia (p. 479)
T-H lines
Taylor-Haughton lines (p. 61)
TIA
transient ischem ic attack (p. 1264)
Abbreviat ions and Sym bols
TICH
traumatic intracerebral hemorrhage (hem orrhagic contusion) (p. 891)
TIVA
total intravenous anesthesia
TLIF
transforaminal lum bar interbody fusion (p. 1497)
TLISS
thoracolumbar injury severity score (p. 1006)
TLJ
thoracolumbar junction
TLSO
thoracolumbar-sacral orthosis
TM
t ym panic m embrane
TMB
transient monocular blindness (am aurosis fugax) (p. 1271)
t-PA
tissue plasm inogen activator
TR
tim e to repetition (on MRI) (p. 228)
TRH
thyrotropin releasing horm one; AKA TSH-RH (p. 151)
TS
transverse sinus
TSC
tuberous sclerosis com plex (p. 606)
TSH
thyroid-stim ulating horm one (thyrotropin) (p. 151)
TSV
thalam ostriate vein
TTP
throm botic throm bocytopenic purpura
TVO
transient visual obscurations (p. 768)
Tx.
treatment
UBOs
unidentified bright objects (on MRI)
UE
upper extrem it y
UMN
upper m otor neuron (p. 504)
UTI
urinary tract infection
URI
upper respiratory tract infection
U/S
ultrasound
VA
vertebral artery or ventriculoatrial
VB
vertebral body
VBI
vertebrobasilar insufficiency (p. 1305)
VEMP
vestibular evoked m yogenic potential (p. 675)
VHL
von Hippel-Lindau (disease) (p. 703)
VMA
vanillylm andelic acid
VP
ventriculoperitoneal
VS
vestibular schwannoma (p. 670)
VZV
(herpes) varicella zoster virus
WBC
white blood cell (count)
WBXRT
whole brain radiation therapy (p. 810)
WFNS
World Federation of Neurosurgical Societies (grading SAH) (p. 1163)
25
26
Abbreviations and Sym bols
WHO
World Health Organization. For tum or grading, e.g. WHO II indicates WHO grade II
wks
weeks
WNL
within norm al lim its
w/o
without
WRS
word recognition score (p. 673)
W/U
work-up (evaluation)
XLIF
extrem e lateral lum bar interbody fusion (p. 1498)
XRT
(or RTX) radiation therapy (p. 1560)
Sym bols
prescribing information
→
causes or leads to
Δ
change
check (e.g. lab or exam item to check)
↑
increased
↓
decreased
≈
approxim ately
innervates (nerve distribution)
vascular supply
a branch of the preceding nerve
crucial point
caution; possible danger; negative factor…
Σ
summ ary
therefore
Instrum entation: the following shorthand allows rapid identification of m etrics for spinal instrum entation:
ENTRY
screw entry site
TRAJ
screw trajectory
TARGET
object to aim for
SCREWS
t ypical screw specifications
27
Conventions
Box t yp es. Th e Ha ndbook of Neurosurger y uses th e follow in g seven box t ypes:
Drug info
Drug description & dosage.
Key concept s
Foundational knowledge in brief.
Pract ice guideline
Evidence-based guidelines. See below (in this section) for definitions. For a listing of evidence-based
guidelines contained in this book, see the index under “Practice guideline.”
Booking t he case
These sections appear under certain specific operations to help when scheduling that surgery. Default
information appears below (in this section), for exam ple, a specific t ype of anesthesia will only be
mentioned if som ething other than general anesthesia is t ypically used. A list of operations addressed
by this m eans can be found in the index under “Booking the case.”
Σ
Summarizing or synthesizing information from the associated text.
Side inform at ion
E.g., Greenberg IMHO.
Signs / sym pt om s
A description of signs and symptoms.
Cr oss referen ces. Cross referen ces: th e term s “see below ” an d “see above” are n orm ally used
w h en th e referen ced item is on th e sam e page, or at m ost on th e follow in g (or precedin g) page.
W hen fur th er excursion s are n eeded, th e page n um ber w ill usually be in cluded.
Defau lt valu es. Th ese details are n ot repeated in each sect ion or “Booking th e case” box.
1. position : (depen ds on th e operation )
2. pre-op:
a) NPO after m idn igh t th e n igh t before except m eds w ith sips of w ater
b) an t ith rom botics: discon tin ue Coum adin ® ≥ 3 days prior to surger y, Plavix® 5–7 d pre-op,
aspirin 7–10 d pre-op, oth er NSAIDs 5 d pre-op
28
Convent ions
3.
4.
5.
6.
cardiology/m edical clearan ce as n eeded
an esth esia: default = gen eral an esth esia, un less oth erw ise specified
equipm en t: special devices such as ult rason ic aspirator, im age guidan ce…
in st rum en tation : stan dard surgical in st rum en t trays for a specific operation are assum ed. Special in strum en tat ion residen t in th e h ospital w ill be listed
7. im plan ts: th is usually requires sch edulin g w ith a ven dor (m an ufacturers represen tative/distributor) to provide
8. n eurom on itorin g w ill be listed if t ypically used
9. post-op: default care is on th e w ard (ICU is t ypically n eeded after cran iotom y)
10. blood availabilit y: specified if recom m en ded
11. con sen t (th ese item s use lay term s for th e patien t – n ot all-in clusive):
Disclaim ers: infor med consent for surger y requires disclosure of risks an d ben efits th at w ould
substan tively a ect a n orm al person’s decision to h ave th e operation . It can n ot an d sh ould n ot
attem pt to in clude ever y possibilit y. Th e item s listed in th is sect ion are in cluded as m em or y joggers for som e item s for various procedures, but are n ot m ean t to be all in clusive. Th e om ission
of in form ation from th is m em or y aid is n ot to be con strued as im plying th at th e om it ted item is
n ot im por tan t or sh ould n ot be m en tion ed.
a) procedure: th e t ypical operation an d som e possible com m on con tin gen cies
b) altern atives: n on -surgical (AKA “con servative”) t reatm en t is alm ost always an opt ion
c) com plicat ion s:
● risks of gen eral an esth esia in clude: h eart attack, stroke, pn eum on ia
● in fect ion : a risk w ith any invasive procedure
● usual cr an iotom y com plication s in clude: bleedin g in tra-op an d postop, seizure, st roke,
com a, death , hydroceph alus, m en in gitis, an d n eurologic deficit related to th e area of surger y in cludin g (for applicable location s): paralysis, lan guage or sen sor y dist urban ces, coordin ation im pairm en t…
● usual sp in e su rger y com plication s in clude: injur y to n er ve or spin al cord w ith possible
n um bn ess, w eakn ess or paralysis, failure of th e operation to ach ieve th e desired result,
dural open in g w h ich m ay cause a CSF leak w h ich occasion ally n eeds to be surgical repair.
Hardw are com plicat ion s (w h en used) in clude: breakage, pull-out, m alposition . Alth ough a
rare com plication , it is serious en ough th at it bears m en tion in g in cases position ed pron e
w ith possible sign ifican t blood loss (> 2 L): blin dn ess (due to PION (p. 1056) )
Evid en ce-Based Med icin e: Defin it ion s. Th ese defin ition s are referred to in th e “Pract ice guidelin e” boxes.
St rength of recom m endat ion
Descript ion
Level I, II, IIIa
Level A, B, C, Db
Level I
High degree of clinical certaint y
Level A
Based on consistent Class I evidence (well-designed,
prospective randomized controlled studies)
Level B
Single Class I study or consistent Class II evidence or
strong Class II evidence especially when circum stances
preclude randomized clinical trials
Level II
Moderate degree of clinical certainty
Level C
Usually derived from Class II evidence (one or m ore
well-designed comparative clinical studies or less welldesigned randomized studies) or a preponderance of
Class III evidence
Level III
Unclear clinical certaint y
Level D
Generally based on Class III evidence (case series,
historical controls, case report s and expert opinion).
Useful for educational purposes and to guide future
research
a as used in the Guidelines for the Managem ent of Severe Traum atic Brain Injury, 3rd edition (Brain Trauma
Foundation: Introduction. J Neurotraum a 24, Suppl 1: S1–2, 2007).
b as used in the Guidelines for the Surgical Managem ent of Cervical Degenerative Disease (Matz P G, et al.:
Introduction and m ethodology. J Neurosurg: Spine 11 (2): 101–3, 2009).
29
Cont ent s
Anat om y and Physiology
1
Gross Anat om y, Cranial and Spine . . . . . . . . . . . . . . . .
58
1.1
Cort ical surface anat om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
58
1.2
Cent ral sulcus on axial im aging . . . . . . . . . . . . . . . . . . . . . . . . . .
60
1.3
Surface anat om y of t he cranium . . . . . . . . . . . . . . . . . . . . . . . . .
61
1.4
Surface landm arks of spine levels . . . . . . . . . . . . . . . . . . . . . . . .
65
1.5
Cranial foram ina and t heir cont ent s . . . . . . . . . . . . . . . . . . . . . .
65
1.6
Int ernal capsule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
67
1.7
Cerebellopont ine angle anat om y . . . . . . . . . . . . . . . . . . . . . . . .
67
1.8
Occipit oat lant oaxial-com plex anat om y . . . . . . . . . . . . . . . . . .
68
1.9
Spinal cord anat om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
70
2
Vascular Anat om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
75
2.1
Cerebral vascular t errit ories . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
75
2.2
Cerebral art erial anat om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
75
2.3
Cerebral venous anat om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
85
2.4
Spinal cord vasculat ure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
87
3
Neurophysiology and Regional Brain Syndrom es
90
3.1
Neurophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
90
3.2
Regional brain syndrom es . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
96
3.3
Jugular foram en syndrom es . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
100
General and Neurology
4
Neuroanest hesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
104
4.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
104
4.2
Drugs used in neuroanest hesia . . . . . . . . . . . . . . . . . . . . . . . . . .
104
4.3
Anest het ic requirem ent s for int ra-operat ive evoked
pot ent ial m onit oring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
107
Malignant hypert herm ia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
108
4.4
30
Cont ent s
5
Sodium Hom eost asis and Osm olalit y . . . . . . . . . . . .
110
5.1
Serum osm olalit y and sodium concentrat ion . . . . . . . . . . . . .
110
5.2
Hyponat rem ia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
110
5.3
Hypernat rem ia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
119
6
General Neurocrit ical Care . . . . . . . . . . . . . . . . . . . . . . . . .
126
6.1
Parent eral agent s for hypert ension . . . . . . . . . . . . . . . . . . . . . .
126
6.2
Hypot ension (shock) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
127
6.3
Acid inhibit ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
129
7
Sedat ives, Paralyt ics, Analgesics . . . . . . . . . . . . . . . . . .
132
7.1
Sedat ives and paralyt ics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
132
7.2
Paralyt ics (neurom uscular blocking agent s) . . . . . . . . . . . . . .
134
7.3
Analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
136
8
Endocrinology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
144
8.1
Cort icost eroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
144
8.2
Hypot hyroidism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
148
8.3
Pit uit ary em bryology and neuroendocrinology . . . . . . . . . . .
149
9
Hem at ology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
153
9.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
153
9.2
Blood com ponent t herapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
153
9.3
Ext ram edullary hem at opoiesis . . . . . . . . . . . . . . . . . . . . . . . . . .
171
10
Neurology for Neurosurgeons . . . . . . . . . . . . . . . . . . . .
174
10.1
Dem ent ia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
174
10.2
Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
174
10.3
Parkinsonism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
176
10.4
Mult iple sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
179
10.5
Acut e dissem inat ed encephalom yelit is . . . . . . . . . . . . . . . . . . .
182
10.6
Mot or neuron diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
182
10.7
Guillain-Barré syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
184
Cont ents
10.8
Myelit is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
187
10.9
Neurosarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
189
11
Neurovascular Disorders and Neurot oxicology . .
194
11.1
Post erior reversible encephalopat hy syndrom e (PRES) . . . .
194
11.2
Crossed cerebellar diaschisis . . . . . . . . . . . . . . . . . . . . . . . . . . . .
194
11.3
Vasculit is and vasculopat hy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
195
11.4
Neurot oxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
204
Im aging and Diagnost ics
12
Plain Radiology and Cont rast Agent s . . . . . . . . . . . . .
212
12.1
C-Spine x-rays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
212
12.2
Lum bosacral (LS) spine x-rays . . . . . . . . . . . . . . . . . . . . . . . . . . .
216
12.3
Skull x-rays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
216
12.4
Cont rast agent s in neuroradiology . . . . . . . . . . . . . . . . . . . . . . .
219
12.5
Radiat ion safet y for neurosurgeons . . . . . . . . . . . . . . . . . . . . . .
223
13
Im aging and Angiography . . . . . . . . . . . . . . . . . . . . . . . . .
227
13.1
CATscan (AKA CTscan) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
227
13.2
Magnet ic resonance im aging (MRI) . . . . . . . . . . . . . . . . . . . . . .
228
13.3
Angiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
236
13.4
Myelography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
236
13.5
Radionuclide scanning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
236
14
Elect rodiagnost ics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
238
14.1
Elect roencephalogram (EEG) . . . . . . . . . . . . . . . . . . . . . . . . . . . .
238
14.2
Evoked pot ent ials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
238
14.3
NCS/EMG. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
242
Developm ent al Anom alies
15
Prim ary Int racranial Anom alies . . . . . . . . . . . . . . . . . . .
248
15.1
Arachnoid cyst s, int racranial . . . . . . . . . . . . . . . . . . . . . . . . . . . .
248
15.2
Craniofacial developm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
251
31
32
Cont ent s
15.3
Dandy Walker m alform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
256
15.4
Aqueduct al st enosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
258
15.5
Agenesis of t he corpus callosum . . . . . . . . . . . . . . . . . . . . . . . . .
259
15.6
Absence of t he sept um pellucidum . . . . . . . . . . . . . . . . . . . . . .
260
15.7
Int racranial lipom as . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
260
15.8
Hypot halam ic ham art om as . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
261
16
Prim ary Spinal Anom alies . . . . . . . . . . . . . . . . . . . . . . . . .
265
16.1
Spinal arachnoid cyst s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
265
16.2
Spinal dysraphism (spina bifida) . . . . . . . . . . . . . . . . . . . . . . . . .
265
16.3
Klippel-Feil syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
271
16.4
Tet hered cord syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
272
16.5
Split cord m alform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
274
16.6
Lum bosacral nerve root anom alies . . . . . . . . . . . . . . . . . . . . . .
275
17
Prim ary Craniospinal Anom alies . . . . . . . . . . . . . . . . . .
277
17.1
Chiari m alform at ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
277
17.2
Neural t ube defect s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
287
17.3
Neurent eric cyst s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
290
Com a and Brain Deat h
18
Com a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
296
18.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
296
18.2
Post uring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
297
18.3
Et iologies of com a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
297
18.4
Herniat ion syndrom es . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
302
18.5
Hypoxic com a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
305
19
Brain Deat h and Organ Donat ion . . . . . . . . . . . . . . . . .
307
19.1
Brain deat h in adult s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
307
19.2
Brain deat h crit eria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
307
19.3
Brain deat h in children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
312
19.4
Organ and t issue donat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
313
Cont ents
Infect ion
20
Bact erial Infect ions of t he Parenchym a and
Meninges and Com plex Infect ions . . . . . . . . . . . . . . . .
318
20.1
Meningit is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
318
20.2
Cerebral abscess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
320
20.3
Subdural em pyem a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
327
20.4
Neurologic involvem ent in HIV/AIDS . . . . . . . . . . . . . . . . . . . . .
329
20.5
Lym e disease – neurologic m anifest at ions . . . . . . . . . . . . . . . .
334
20.6
Nocardia brain abscess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
335
21
Skull, Spine, and Post -Surgical Infect ions . . . . . . . .
339
21.1
Shunt infect ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
339
21.2
Ext ernal vent ricular drain (EVD)-relat ed infect ion . . . . . . . . .
342
21.3
Wound infect ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
345
21.4
Ost eom yelit is of t he skull . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
348
21.5
Spine infect ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
349
22
Ot her Nonbact erial Infect ions . . . . . . . . . . . . . . . . . . . . .
364
22.1
Viral encephalit is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
364
22.2
Creut zfeldt -Jakob disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
367
22.3
Parasit ic infect ions of t he CNS . . . . . . . . . . . . . . . . . . . . . . . . . . .
371
22.4
Fungal infect ions of t he CNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
376
22.5
Am ebic infect ions of t he CNS . . . . . . . . . . . . . . . . . . . . . . . . . . . .
377
Hydrocephalus and Cerebrospinal Fluid (CSF)
23
Cerebrospinal Fluid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
382
23.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
382
23.2
Product ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
382
23.3
Absorpt ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
382
23.4
CSF const it uents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
382
23.5
Cranial CSF fist ula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
384
23.6
Spinal CSF fist ula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
386
23.7
Meningit is in CSF fist ula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
386
33
34
Cont ent s
23.8
Evaluat ion of t he pat ient w it h CSF fist ula . . . . . . . . . . . . . . . .
387
23.9
Treat m ent for CSF fist ula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
388
23.10
Int racranial hypot ension (spont aneous) . . . . . . . . . . . . . . . . . .
389
24
Hydrocephalus – General Aspect s . . . . . . . . . . . . . . . .
394
24.1
Basic definit ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
394
24.2
Epidem iology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
394
24.3
Et iologies of hydrocephalus . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
394
24.4
Signs and sym pt om s of HCP. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
395
24.5
CT/MRI crit eria of hydrocephalus . . . . . . . . . . . . . . . . . . . . . . . .
398
24.6
Di erent ial diagnosis of hydrocephalus . . . . . . . . . . . . . . . . . .
399
24.7
Chronic HCP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
400
24.8
Ext ernal hydrocephalus (AKA benign ext ernal hydrocephalus) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
400
24.9
X-linked hydrocephalus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
401
24.10
“Arrest ed hydrocephalus” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
402
24.11
Ent rapped fourt h vent ricle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
402
24.12
Norm al pressure hydrocephalus (NPH) . . . . . . . . . . . . . . . . . . .
403
24.13
Hydrocephalus and pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . .
410
25
Treat m ent of Hydrocephalus . . . . . . . . . . . . . . . . . . . . . .
414
25.1
Medical t reat m ent of hydrocephalus . . . . . . . . . . . . . . . . . . . .
414
25.2
Spinal t aps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
414
25.3
Surgical. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
414
25.4
Endoscopic t hird vent riculost om y . . . . . . . . . . . . . . . . . . . . . . .
415
25.5
Shunt s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
416
25.6
Shunt problem s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
419
25.7
Specific shunt syst em s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
427
25.8
Surgical insert ion t echniques . . . . . . . . . . . . . . . . . . . . . . . . . . .
435
25.9
Inst ruct ions t o pat ient s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
435
Cont ents
Seizures
26
Seizure Classificat ion and Ant i-Convulsant
Pharm acology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
440
26.1
Seizure classificat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
440
26.2
Ant iepilept ic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
443
27
Special Types of Seizures . . . . . . . . . . . . . . . . . . . . . . . . . . .
461
27.1
New onset seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
461
27.2
Post t raum at ic seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
462
27.3
Alcohol w it hdraw al seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
464
27.4
Nonepilept ic seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
464
27.5
Febrile seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
467
27.6
St at us epilept icus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
468
28
Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
476
28.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
476
28.2
Neuropat hic pain syndrom es . . . . . . . . . . . . . . . . . . . . . . . . . . . .
476
28.3
Craniofacial pain syndrom es . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
477
28.4
Post herpet ic neuralgia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
493
28.5
Com plex regional pain syndrom e (CRPS) . . . . . . . . . . . . . . . . .
497
Pain
Peripheral Nerves
29
Peripheral Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
504
29.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
504
29.2
Muscle innervat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
506
29.3
Peripheral nerve injury/surgery . . . . . . . . . . . . . . . . . . . . . . . . . .
509
30
Ent rapm ent Neuropat hies . . . . . . . . . . . . . . . . . . . . . . . . .
515
30.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
515
30.2
Mechanism of injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
515
30.3
Occipit al nerve ent rapm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
515
35
36
Cont ent s
30.4
Median nerve ent rapm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
517
30.5
Ulnar nerve ent rapm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
526
30.6
Radial nerve injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
532
30.7
Axillary nerve injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
533
30.8
Suprascapular nerve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
533
30.9
Meralgia parest het ica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
534
30.10
Obt urat or nerve ent rapm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . .
535
30.11
Fem oral nerve ent rapm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
535
30.12
Com m on peroneal nerve palsy . . . . . . . . . . . . . . . . . . . . . . . . . .
535
30.13
Tarsal t unnel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
538
31
Non-Ent rapm ent Peripheral Neuropat hies . . . . . . .
541
31.1
Definit ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
541
31.2
Et iologies of peripheral neuropat hy . . . . . . . . . . . . . . . . . . . . .
541
31.3
Classificat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
541
31.4
Clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
542
31.5
Syndrom es of peripheral neuropat hy . . . . . . . . . . . . . . . . . . . .
542
31.6
Peripheral nerve injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
550
31.7
Missile injuries of peripheral nerves . . . . . . . . . . . . . . . . . . . . .
553
31.8
Thoracic out let syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
554
Neuropht halm ology and Neurot ology
32
Neuropht halm ology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
558
32.1
Nyst agm us . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
558
32.2
Papilledem a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
558
32.3
Visual fields . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
559
32.4
Visual field deficit s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
559
32.5
Pupillary diam et er . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
560
32.6
Ext raocular m uscle (EOM) syst em . . . . . . . . . . . . . . . . . . . . . . .
565
32.7
Neuropht halm ologic syndrom es . . . . . . . . . . . . . . . . . . . . . . . .
569
32.8
Miscellaneous neuropht halm ologic signs . . . . . . . . . . . . . . . .
570
Cont ents
33
Neurot ology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
572
33.1
Dizziness and vert igo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
572
33.2
Meniere’s disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
573
33.3
Facial nerve palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
576
33.4
Hearing loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
580
Prim ary Tum ors of t he Nervous and Relat ed Syst em s:
Tum ors of Neuroepit helial Tissue
34
General Inform at ion, Classificat ion and Tum or
Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
584
34.1
Classificat ion of nervous syst em t um ors . . . . . . . . . . . . . . . . .
584
34.2
Brain t um ors – general clinical aspect s . . . . . . . . . . . . . . . . . . .
590
34.3
Pediat ric brain t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
593
34.4
Medicat ions for brain t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . .
594
34.5
Chem ot herapy for brain t um ors . . . . . . . . . . . . . . . . . . . . . . . . .
595
34.6
Int raoperat ive pat hology consult at ions (“frozen sect ion”) .
596
34.7
Select com m only ut ilized st ains in neuropat hology . . . . . . .
598
35
Syndrom es Involving Tum ors . . . . . . . . . . . . . . . . . . . . . .
603
35.1
Neurocut aneous disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
603
35.2
Fam ilial t um or syndrom es . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
610
36
Ast rocyt om as . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
612
36.1
Incidence, risk fact ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
612
36.2
Classificat ion and grading of ast rocyt ic t um ors . . . . . . . . . . .
612
36.3
Molecular genet ics and epigenet ics . . . . . . . . . . . . . . . . . . . . . .
616
36.4
Miscellaneous pat hological feat ures . . . . . . . . . . . . . . . . . . . . .
617
36.5
Neuroradiological grading and findings . . . . . . . . . . . . . . . . . .
617
36.6
Spread . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
618
36.7
Mult iple gliom as . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
619
36.8
Treat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
619
36.9
Out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
624
37
38
Cont ent s
37
Ot her Ast rocyt ic Tum ors . . . . . . . . . . . . . . . . . . . . . . . . . . .
629
37.1
Pilocyt ic ast rocyt om as . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
629
37.2
Pleom orphic xant hoast rocyt om a (PXA) . . . . . . . . . . . . . . . . . .
635
38
Oligodendroglial Tum ors and Tum ors of t he
Ependym a, Choroid Plexus, and Ot her
Neuroepit helial Tum ors . . . . . . . . . . . . . . . . . . . . . . . . . . . .
638
38.1
Oligodendroglial t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
638
38.2
Oligoast rocyt ic t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
641
38.3
Ependym al t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
642
38.4
Neuronal and m ixed glial t um ors . . . . . . . . . . . . . . . . . . . . . . . .
645
38.5
Choroid plexus t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
648
38.6
Ot her neuroepit helial t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . .
649
39
Neuronal and Mixed Neuronal-Glial Tum ors . . . . .
651
39.1
Gangliogliom a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
651
39.2
Paragangliom a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
652
39.3
Neuroblast om as . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
657
40
Pineal Region and Em bryonal Tum ors . . . . . . . . . . . .
658
40.1
Pineal region t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
658
40.2
Em bryonal t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
663
41
Tum ors of Cranial, Spinal and Peripheral Nerves
670
41.1
Vest ibular schw annom a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
670
41.2
Tum ors of peripheral nerves: Perineuriom a . . . . . . . . . . . . . .
687
42
Meningiom as . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
690
42.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
690
42.2
Epidem iology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
690
42.3
Com m on locat ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
690
42.4
Pat hology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
693
42.5
Present at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
695
42.6
Evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
695
Cont ents
42.7
Treat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
696
42.8
Out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
698
43
Ot her Tum ors Relat ed t o t he Meninges . . . . . . . . . .
701
43.1
Mesenchym al, non-m eningot helial t um ors . . . . . . . . . . . . . . .
701
43.2
Prim ary m elanocyt ic lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
701
43.3
Hem angioblast om a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
701
Tum ors Involving Non-Neural Origin: Met ast ases,
Lym phom as, Chordom as
44
Lym phom as and Hem at opoiet ic Neoplasm s . . . . .
710
44.1
CNS lym phom a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
710
44.2
Mult iple m yelom a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
714
44.3
Plasm acyt om a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
716
45
Pit uit ary Tum ors – General Inform at ion and
Classificat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
718
45.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
718
45.2
General t um or t ypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
718
45.3
Epidem iology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
718
45.4
Di erent ial diagnosis of pit uit ary t um ors . . . . . . . . . . . . . . . .
718
45.5
Clinical present at ion of pit uit ary t um ors . . . . . . . . . . . . . . . . .
719
45.6
Specific t ypes of pit uit ary t um ors . . . . . . . . . . . . . . . . . . . . . . . .
721
46
Pit uit ary Adenom as – Evaluat ion and
Nonsurgical Managem ent . . . . . . . . . . . . . . . . . . . . . . . . .
730
46.1
Evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
730
46.2
Managem ent /t reat m ent recom m endat ions . . . . . . . . . . . . . .
737
46.3
Radiat ion t herapy for pit uit ary adenom as . . . . . . . . . . . . . . . .
744
47
Pit uit ary Adenom as – Surgical Managem ent ,
Out com e, and Recurrence Managem ent . . . . . . . . .
747
47.1
Surgical t reat m ent for pit uit ary adenom as . . . . . . . . . . . . . . .
747
47.2
Out com e follow ing t ranssphenoidal surgery . . . . . . . . . . . . .
753
47.3
Managem ent of recurrent pit uit ary adenom as . . . . . . . . . . . .
755
39
40
Cont ent s
48
Cyst s and Tum or-Like Lesions . . . . . . . . . . . . . . . . . . . . .
756
48.1
Rat hke’s cleft cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
756
48.2
Colloid cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
756
48.3
Epiderm oid and derm oid t um ors . . . . . . . . . . . . . . . . . . . . . . . .
760
48.4
Craniopharyngiom a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
763
49
Pseudot um or Cerebri and Em pt y Sella
Syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
766
49.1
Pseudot um or cerebri . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
766
49.2
Em pt y sella syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
773
50
Tum ors and Tum or-Like Lesions of t he Skull . . . . .
775
50.1
Skull t um ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
775
50.2
Non-neoplast ic skull lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
779
51
Tum ors of t he Spine and Spinal Cord . . . . . . . . . . . . .
783
51.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
783
51.2
Com part m ent al locat ions of spinal t um ors . . . . . . . . . . . . . . .
783
51.3
Di erent ial diagnosis: spine and spinal cord t um ors . . . . . .
783
51.4
Int radural ext ram edullary spinal cord t um ors . . . . . . . . . . . .
785
51.5
Int ram edullary spinal cord t um ors . . . . . . . . . . . . . . . . . . . . . .
787
51.6
Prim ary bone t um ors of t he spine . . . . . . . . . . . . . . . . . . . . . . .
792
52
Cerebral Met ast ases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
800
52.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
800
52.2
Met ast ases t o t he brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
800
52.3
Met ast ases of prim ary CNS t um ors . . . . . . . . . . . . . . . . . . . . . .
800
52.4
Locat ion of cerebral m et s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
801
52.5
Prim ary cancers in pat ient s w it h cerebral m et ast ases . . . . .
801
52.6
Clinical present at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
805
52.7
Evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
806
52.8
Managem ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
806
52.9
Out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
810
52.10
Carcinom at ous m eningit is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
811
Cont ents
53
Spinal Epidural Met ast ases . . . . . . . . . . . . . . . . . . . . . . . .
814
53.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
814
53.2
Prim ary t um ors t hat m et ast asize t o t he spine . . . . . . . . . . . .
814
53.3
Present at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
814
53.4
Evaluat ion and m anagem ent of epidural spinal m et ast ases
815
Head Traum a
54
General Inform at ion, Grading, Init ial
Managem ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
824
54.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
824
54.2
Grading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
824
54.3
Transfer of t raum a pat ient s . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
825
54.4
Managem ent in E/R . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
826
54.5
Radiographic evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
832
54.6
Adm it t ing orders for m inor or m oderat e head injury . . . . . .
834
54.7
Pat ient s w it h associat ed severe syst em ic injuries . . . . . . . . .
834
54.8
Explorat ory burr holes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
836
55
Concussion, High-Alt it ude Cerebral Edem a,
Cerebrovascular Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . .
841
55.1
Concussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
841
55.2
Ot her TBI definit ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
848
55.3
High-alt it ude cerebral edem a . . . . . . . . . . . . . . . . . . . . . . . . . . .
848
55.4
Traum at ic cervical art ery dissect ions . . . . . . . . . . . . . . . . . . . . .
849
56
Neurom onit oring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
856
56.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
856
56.2
Int racranial pressure (ICP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
856
56.3
Adjunct s t o ICP m onit oring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
865
56.4
Treat m ent m easures for elevat ed ICP . . . . . . . . . . . . . . . . . . . .
866
57
Skull Fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
882
57.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
882
57.2
Linear skull fract ures over t he convexit y . . . . . . . . . . . . . . . . .
882
41
42
Cont ent s
57.3
Depressed skull fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
882
57.4
Basal skull fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
884
57.5
Craniofacial fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
886
57.6
Pneum ocephalus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
887
58
Traum at ic Hem orrhagic Condit ions . . . . . . . . . . . . . .
891
58.1
Post t raum at ic parenchym al injuries . . . . . . . . . . . . . . . . . . . . .
891
58.2
Hem orrhagic cont usion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
891
58.3
Epidural hem at om a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
892
58.4
Acut e subdural hem at om a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
895
58.5
Chronic subdural hem at om a . . . . . . . . . . . . . . . . . . . . . . . . . . . .
898
58.6
Spont aneous subdural hem at om a . . . . . . . . . . . . . . . . . . . . . . .
901
58.7
Traum at ic subdural hygrom a . . . . . . . . . . . . . . . . . . . . . . . . . . . .
902
58.8
Ext raaxial fluid collect ions in children . . . . . . . . . . . . . . . . . . . .
903
58.9
Traum at ic post erior fossa m ass lesions . . . . . . . . . . . . . . . . . .
905
59
Gunshot Wounds and Non-Missile Penet rat ing
Brain Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
908
59.1
Gunshot w ounds t o t he head . . . . . . . . . . . . . . . . . . . . . . . . . . . .
908
59.2
Non-m issile penet rat ing t raum a . . . . . . . . . . . . . . . . . . . . . . . . .
911
60
Pediat ric Head Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
913
60.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
913
60.2
Managem ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
913
60.3
Out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
914
60.4
Cephalhem at om a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
914
60.5
Skull fract ures in pediat ric pat ient s . . . . . . . . . . . . . . . . . . . . . .
914
60.6
Nonaccident al t raum a (NAT) . . . . . . . . . . . . . . . . . . . . . . . . . . . .
916
61
Head Injury: Long-Term Managem ent ,
Com plicat ions, Out com e . . . . . . . . . . . . . . . . . . . . . . . . . .
918
61.1
Airw ay m anagem ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
918
61.2
Deep -vein t hrom bosis (DVT) prophylaxis . . . . . . . . . . . . . . . .
918
61.3
Nut rit ion in t he head-injured pat ient . . . . . . . . . . . . . . . . . . . .
918
Cont ents
61.4
Post t raum at ic hydrocephalus . . . . . . . . . . . . . . . . . . . . . . . . . . .
920
61.5
Out com e from head t raum a . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
920
61.6
Lat e com plicat ions from t raum at ic brain injury . . . . . . . . . . .
923
Spine Traum a
62
General Inform at ion, Neurologic Assessm ent ,
Whiplash and Sport s-Relat ed Injuries, Pediat ric
Spine Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
930
62.1
Int roduct ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
930
62.2
Term inology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
930
62.3
Whiplash-associat ed disorders . . . . . . . . . . . . . . . . . . . . . . . . . .
931
62.4
Pediat ric spine injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
933
62.5
Cervical bracing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
935
62.6
Follow -up schedule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
935
62.7
Sport s-relat ed cervical spine injuries . . . . . . . . . . . . . . . . . . . . .
935
62.8
Neurological assessm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
939
62.9
Spinal cord injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
943
63
Managem ent of Spinal Cord Injury . . . . . . . . . . . . . . . .
949
63.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
949
63.2
Managem ent in t he field . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
949
63.3
Managem ent in t he hospit al. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
950
63.4
Radiographic evaluat ion and init ial C-spine im m obilizat ion
952
63.5
Tract ion/reduct ion of cervical spine injuries . . . . . . . . . . . . . .
957
63.6
Indicat ions for em ergency decom pressive surgery . . . . . . . .
960
64
Occipt oat lant oaxial Injuries (Occiput t o C2) . . . . .
963
64.1
At lant o -occipit al dislocat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
963
64.2
Occipit al condyle fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
966
64.3
At lant oaxial subluxat ion/dislocat ion . . . . . . . . . . . . . . . . . . . . .
968
64.4
At las (C1) fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
971
64.5
Axis (C2) fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
972
64.6
Com binat ion C1–2 injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
982
43
44
Cont ent s
65
Subaxial (C3 t hrough C7) Injuries / Fract ures . . . .
986
65.1
Classificat ion syst em s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
986
65.2
Clay shoveler’s fract ure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
988
65.3
Vert ical com pression injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . .
989
65.4
Flexion injuries of t he subaxial cervical spine . . . . . . . . . . . . .
989
65.5
Dist ract ion flexion injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
991
65.6
Ext ension injuries of t he subaxial cervical spine . . . . . . . . . .
994
65.7
Treat m ent of subaxial cervical spine fract ures . . . . . . . . . . . .
996
65.8
Spinal cord injury w it hout radiographic abnorm alit y
(SCIWORA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
999
66
Thoracic, Lum bar and Sacral Spine Fract ures . . . .
1002
66.1
Assessm ent and m anagem ent of t horacolum bar fract ures
1002
66.2
Surgical t reat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1007
66.3
Ost eoporot ic spine fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1008
66.4
Sacral fract ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1014
67
Penet rat ing Spine Injuries and Long Term
Managem ent / Com plicat ions . . . . . . . . . . . . . . . . . . . . .
1017
67.1
Gunshot w ounds t o t he spine . . . . . . . . . . . . . . . . . . . . . . . . . . .
1017
67.2
Penet rat ing t raum a t o t he neck . . . . . . . . . . . . . . . . . . . . . . . . .
1017
67.3
Delayed cervical inst abilit y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1019
67.4
Delayed det eriorat ion follow ing spinal cord injuries . . . . . .
1019
67.5
Chronic m anagem ent issues w it h spinal cord injuries . . . . .
1020
Spine and Spinal Cord
68
Low Back Pain and Radiculopat hy . . . . . . . . . . . . . . . .
1024
68.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1024
68.2
Int ervert ebral disc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1024
68.3
Nom enclat ure for disc pat hology . . . . . . . . . . . . . . . . . . . . . . . .
1024
68.4
Vert ebral body m arrow changes . . . . . . . . . . . . . . . . . . . . . . . .
1025
68.5
Clinical t erm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1025
68.6
Disabilit y, pain and out com e det erm inat ions . . . . . . . . . . . . .
1026
Cont ents
68.7
Di erent ial diagnosis of low back pain . . . . . . . . . . . . . . . . . . . 1026
68.8
Init ial assessm ent of t he pat ient w it h back pain . . . . . . . . . . 1026
68.9
Radiographic evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1029
68.10
Elect rodiagnost ics for low back problem s . . . . . . . . . . . . . . . . 1032
68.11
Bone scan for low back problem s . . . . . . . . . . . . . . . . . . . . . . . . 1032
68.12
Therm ography for low back problem s . . . . . . . . . . . . . . . . . . . 1033
68.13
Psychosocial fact ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1033
68.14
Treat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1033
68.15
Chronic low back pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1037
68.16
Coccydynia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1038
68.17
Failed back surgery syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . 1039
69
Lum bar and Thoracic Int ervert ebral Disk
Herniat ion / Radiculopat hy . . . . . . . . . . . . . . . . . . . . . . . .
1046
69.1
Lum bar disc herniat ion and lum bar radiculopat hy . . . . . . . . 1046
69.2
Thoracic disc herniat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1061
70
Cervical Disc Herniat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
70.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1069
70.2
Cervical nerve root syndrom es (cervical radiculopat hy) . . . 1069
70.3
Cervical m yelopat hy and SCI due t o cervical disc
herniat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1069
70.4
Di erent ial diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1070
70.5
Physical exam for cervical disc herniat ion . . . . . . . . . . . . . . . . 1070
70.6
Radiologic evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1070
70.7
Treat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1071
71
Degenerat ive Cervical Disc Disease and Cervical
Myelopat hy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1069
1083
71.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1083
71.2
Pat hophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1083
71.3
Clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1084
71.4
Di erent ial diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1086
71.5
Evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1088
71.6
Treat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1090
71.7
Coincident cervical and lum bar spinal st enosis . . . . . . . . . . . . 1093
45
46
Cont ent s
72
Thoracic and Lum bar Degenerat ive Disc Disease
1096
72.1
General inform at ion about degenerat ive disc disease
(DDD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1096
72.2
Anat om ic subst rat e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1096
72.3
Risk fact ors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1099
72.4
Associat ed condit ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1099
72.5
Clinical present at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1099
72.6
Di erent ial diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1101
72.7
Diagnost ic evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1101
72.8
Treat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1103
72.9
Out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1108
73
Adult Spinal Deform it y and Degenerat ive
Scoliosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1111
73.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1111
73.2
Epidem iology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1111
73.3
Clinical evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1111
73.4
Diagnost ic t est ing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1111
73.5
Pert inent spine m easurem ent s . . . . . . . . . . . . . . . . . . . . . . . . . .
1112
73.6
SRS-Schw ab classificat ion of adult spinal deform it y . . . . . . .
1112
73.7
Treat m ent /m anagem ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1113
74
Special Condit ions A ect ing t he Spine . . . . . . . . . . .
1120
74.1
Paget’s disease of t he spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1120
74.2
Ankylosing spondylit is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1123
74.3
Ossificat ion of t he post erior longit udinal ligam ent (OPLL) .
1127
74.4
Ossificat ion of t he ant erior longit udinal ligam ent (OALL) . .
1129
74.5
Di use idiopat hic skelet al hyperost osis (DISH) . . . . . . . . . . .
1129
74.6
Scheuerm ann’s kyphosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1130
74.7
Spinal epidural hem at om a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1131
74.8
Spinal subdural hem at om a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1131
Cont ents
75
Ot her Non-Spine Condit ions w it h Spine
Im plicat ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1134
75.1
Rheum at oid art hrit is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1134
75.2
Dow n syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1138
75.3
Morbid obesit y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139
76
Special Condit ions A ect ing t he Spinal Cord . . . .
76.1
Spinal vascular m alform at ions . . . . . . . . . . . . . . . . . . . . . . . . . . . 1140
76.2
Spinal m eningeal cyst s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1142
76.3
Juxt afacet cyst s of t he lum bar spine . . . . . . . . . . . . . . . . . . . . . 1143
76.4
Syringom yelia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1144
76.5
Post t raum at ic syringom yelia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1148
76.6
Spinal cord herniat ion (idiopat hic) . . . . . . . . . . . . . . . . . . . . . . . 1150
76.7
Spinal epidural lipom at osis (SEL) . . . . . . . . . . . . . . . . . . . . . . . . . 1150
76.8
Craniocervical junct ion and upper cervical spine
abnorm alit ies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1151
1140
SAH and Aneurysm s
77
Int roduct ion and General Inform at ion, Grading,
Medical Managem ent , Special Condit ions . . . . . . .
1156
77.1
Int roduct ion and overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1156
77.2
Et iologies of SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1156
77.3
Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1157
77.4
Risk fact ors for SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1157
77.5
Clinical feat ures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1157
77.6
Work-up of suspect ed SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1159
77.7
Grading SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1162
77.8
Init ial m anagem ent of SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1163
77.9
Rebleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1167
77.10
Pregnancy and int racranial hem orrhage . . . . . . . . . . . . . . . . . . 1169
77.11
Hydrocephalus aft er SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1170
47
48
Cont ent s
78
Crit ical Care of Aneurysm Pat ient s . . . . . . . . . . . . . . .
1177
78.1
Neurogenic st ress cardiom yopat hy (NSC) . . . . . . . . . . . . . . . .
1177
78.2
Neurogenic pulm onary edem a . . . . . . . . . . . . . . . . . . . . . . . . . .
1178
78.3
Vasospasm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1178
78.4
Post -op orders for aneurysm clipping . . . . . . . . . . . . . . . . . . . .
1186
79
SAH from Cerebral Aneurysm Rupt ure . . . . . . . . . . .
1191
79.1
Epidem iology of cerebral aneurysm s . . . . . . . . . . . . . . . . . . . .
1191
79.2
Et iology of cerebral aneuysm s . . . . . . . . . . . . . . . . . . . . . . . . . . .
1191
79.3
Locat ion of cerebral aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . .
1191
79.4
Present at ion of cerebral aneurysm s . . . . . . . . . . . . . . . . . . . . .
1191
79.5
Condit ions associat ed w it h aneurysm s . . . . . . . . . . . . . . . . . . .
1193
79.6
Treat m ent opt ions for aneurysm s . . . . . . . . . . . . . . . . . . . . . . .
1194
79.7
Tim ing of aneurysm surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1199
79.8
General t echnical considerat ions of aneurysm surgery . . . .
1200
80
Aneurysm Type by Locat ion . . . . . . . . . . . . . . . . . . . . . . .
1210
80.1
Ant erior com m unicat ing art ery aneurysm s . . . . . . . . . . . . . .
1210
80.2
Dist al ant erior cerebral art ery aneurysm s . . . . . . . . . . . . . . . .
1211
80.3
Post erior com m unicat ing art ery aneurysm s . . . . . . . . . . . . . .
1212
80.4
Carot id t erm inus (bifurcat ion) aneurysm s . . . . . . . . . . . . . . . .
1213
80.5
Middle cerebral art ery (MCA) aneurysm s . . . . . . . . . . . . . . . .
1213
80.6
Supraclinoid aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1214
80.7
Post erior circulat ion aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . .
1215
81
Special Aneurysm s and Non-Aneurysm al SAH . . .
1222
81.1
Unrupt ured aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1222
81.2
Mult iple aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1226
81.3
Fam ilial aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1226
81.4
Traum at ic aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1227
81.5
Mycot ic aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1228
81.6
Giant aneurysm s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1229
81.7
Cort ical subarachnoid hem orrhage . . . . . . . . . . . . . . . . . . . . . .
1230
81.8
SAH of unknow n et iology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1230
81.9
Pret runcal nonaneurysm al SAH (PNSAH) . . . . . . . . . . . . . . . . .
1231
Cont ents
Vascular Malform at ions
82
Vascular Malform at ions . . . . . . . . . . . . . . . . . . . . . . . . . . . .
82.1
General inform at ion and classificat ion . . . . . . . . . . . . . . . . . . . 1238
82.2
Art eriovenous m alform at ion (AVM) . . . . . . . . . . . . . . . . . . . . . . 1238
82.3
Venous angiom as . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1245
82.4
Angiographically occult vascular m alform at ions . . . . . . . . . . 1246
82.5
Osler-Weber-Rendu syndrom e . . . . . . . . . . . . . . . . . . . . . . . . . . . 1246
82.6
Cavernous m alform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1247
82.7
Dural art eriovenous fist ulae (DAVF) . . . . . . . . . . . . . . . . . . . . . . 1251
82.8
Vein of Galen m alform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1255
82.9
Carot id-cavernous fist ula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1256
82.10
Sigm oid sinus divert iculum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1258
1238
Stroke and Occlusive Cerebrovascular Disease
83
General Inform at ion and Stroke Physiology . . . . .
83.1
Definit ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1264
83.2
Cerebrovascular hem odynam ics . . . . . . . . . . . . . . . . . . . . . . . . . 1264
83.3
Collat eral circulat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1265
83.4
“Occlusion” syndrom es . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1265
83.5
St roke in young adult s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1269
83.6
At herosclerot ic carot id art ery disease . . . . . . . . . . . . . . . . . . . . 1271
84
Evaluat ion and Treat m ent for St roke . . . . . . . . . . . . .
84.1
Rat ionale for acut e st roke t reat m ent . . . . . . . . . . . . . . . . . . . . . 1280
84.2
Evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1280
84.3
Managem ent of TIA or st roke . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1282
84.4
Carot id endart erect om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1290
84.5
Carot id angioplast y/st ent ing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1297
85
Special Condit ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
85.1
Tot ally occluded int ernal carot id art ery . . . . . . . . . . . . . . . . . . 1301
85.2
Cerebellar infarct ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1302
85.3
Malignant m iddle cerebral art ery t errit ory infarct ion . . . . . 1303
1264
1280
1301
49
50
Cont ent s
85.4
Cardiogenic brain em bolism . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1304
85.5
Vert ebrobasilar insu ciency . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1305
85.6
Bow hunt er’s st roke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1307
85.7
Cerebrovascular venous t hrom bosis . . . . . . . . . . . . . . . . . . . . .
1308
85.8
Moyam oya disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1313
85.9
Ext racranial-int racranial (EC/IC) bypass . . . . . . . . . . . . . . . . . .
1317
86
Cerebral Art erial Dissect ions . . . . . . . . . . . . . . . . . . . . . .
1322
86.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1322
86.2
Nom enclat ure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1322
86.3
Pat hophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1322
86.4
Epidem iology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1323
86.5
Sit es of dissect ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1323
86.6
Clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1323
86.7
Evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1324
86.8
Overall out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1324
86.9
Vessel specific inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1324
Int racerebral Hem orrhage
87
Int racerebral Hem orrhage . . . . . . . . . . . . . . . . . . . . . . . . .
1330
87.1
General Inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1330
87.2
Int racerebral hem orrhage in adult s . . . . . . . . . . . . . . . . . . . . . .
1330
87.3
Epidem iology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1330
87.4
Locat ions of hem orrhage w it hin t he brain . . . . . . . . . . . . . . .
1331
87.5
Et iologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1332
87.6
Clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1336
87.7
Evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1338
87.8
Init ial m anagem ent of ICH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1339
87.9
Surgical t reat m ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1342
87.10
Out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1345
87.11
ICH in young adult s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1345
87.12
Int racerebral hem orrhage in t he new born . . . . . . . . . . . . . . .
1346
87.13
Ot her causes of int racerebral hem orrhage in t he new born
1352
Cont ents
Out com e Assessm ent
88
Out com e Assessm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
88.1
Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1358
88.2
Head injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1358
88.3
Cerebrovascular event s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1358
88.4
Spinal cord injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1362
1358
Di erent ial Diagnosis
89
Di erent ial Diagnosis by Locat ion or
Radiographic Finding – Int racranial . . . . . . . . . . . . . . .
1364
89.1
Diagnoses covered out side t his chapt er . . . . . . . . . . . . . . . . . . 1364
89.2
Post erior fossa lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1364
89.3
Mult iple int racranial lesions on CT or MRI . . . . . . . . . . . . . . . . 1368
89.4
Ring-enhancing lesions on CT/MRI . . . . . . . . . . . . . . . . . . . . . . . 1369
89.5
Whit e m at t er lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1371
89.6
Sellar, suprasellar and parasellar lesions . . . . . . . . . . . . . . . . . . 1371
89.7
Int racranial cyst s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1374
89.8
Orbit al lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1375
89.9
Cavernous sinus lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1376
89.10
Skull lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1376
89.11
Com bined int racranial/ext racranial lesions . . . . . . . . . . . . . . . 1380
89.12
Int racranial hyperdensit ies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1380
89.13
Int racranial calcificat ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1380
89.14
Int ravent ricular lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1381
89.15
Perivent ricular lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1384
89.16
Meningeal t hickening/enhancem ent . . . . . . . . . . . . . . . . . . . . . 1385
89.17
Ependym al and subependym al enhancem ent . . . . . . . . . . . . . 1385
89.18
Int ravent ricular hem orrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1386
89.19
Medial t em poral lobe lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1386
89.20
Basal ganglion abnorm alit ies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1386
89.21
Thalam ic lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1386
89.22
Int ranasal/int racranial lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . 1387
51
52
Cont ent s
90
Di erent ial Diagnosis by Locat ion or
Radiographic Finding – Spine . . . . . . . . . . . . . . . . . . . . .
1390
90.1
Diagnoses covered out side t his chapt er . . . . . . . . . . . . . . . . . .
1390
90.2
At lant oaxial subluxat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1390
90.3
Abnorm alit ies in vert ebral bodies . . . . . . . . . . . . . . . . . . . . . . .
1390
90.4
Axis (C2) vert ebra lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1391
90.5
Pat hologic fract ures of t he spine . . . . . . . . . . . . . . . . . . . . . . . .
1391
90.6
Spinal epidural m asses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1392
90.7
Dest ruct ive lesions of t he spine . . . . . . . . . . . . . . . . . . . . . . . . .
1392
90.8
Vert ebral hyperost osis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1393
90.9
Sacral lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1393
90.10
Enhancing nerve root s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1394
90.11
Nodular enhancing lesions in t he spinal canal . . . . . . . . . . . .
1394
90.12
Int raspinal cyst s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1394
90.13
Di use enhancem ent of nerve root s/cauda equina . . . . . . . .
1394
91
Di erent ial Diagnosis (DDx) by Signs and
Sym pt om s – Prim arily Int racranial . . . . . . . . . . . . . . .
1395
91.1
Diagnoses covered out side t his chapt er . . . . . . . . . . . . . . . . . .
1395
91.2
Encephalopat hy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1396
91.3
Syncope and apoplexy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1396
91.4
Transient neurologic deficit . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1398
91.5
At axia/balance di cult ies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1398
91.6
Diplopia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1399
91.7
Anosm ia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1399
91.8
Mult iple cranial nerve palsies (cranial neuropat hies) . . . . . .
1399
91.9
Binocular blindness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1401
91.10
Monocular blindness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1401
91.11
Exopht halm os . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1402
91.12
Pt osis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1403
91.13
Pat hologic lid ret ract ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1403
91.14
Macrocephaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1403
91.15
Tinnit us . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1404
91.16
Facial sensory changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1405
91.17
Language dist urbance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1406
Cont ents
92
Di erent ial Diagnosis (DDx) by Signs and
Sym pt om s – Prim arily Spine and Ot her . . . . . . . . . .
1407
92.1
Diagnoses covered out side t his chapt er . . . . . . . . . . . . . . . . . . 1407
92.2
Myelopat hy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1407
92.3
Sciat ica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1410
92.4
Acut e paraplegia or quadriplegia . . . . . . . . . . . . . . . . . . . . . . . . 1413
92.5
Hem iparesis or hem iplegia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1414
92.6
Low back pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1414
92.7
Foot drop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1416
92.8
Weakness/at rophy of t he hands/UEs . . . . . . . . . . . . . . . . . . . . . 1419
92.9
Radiculopat hy, upper ext rem it y (cervical) . . . . . . . . . . . . . . . . 1420
92.10
Neck pain (cervical pain) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1420
92.11
Burning hands/feet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1421
92.12
Muscle pain/t enderness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1421
92.13
Lherm it t e’s sign . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1421
92.14
Swallow ing di cult ies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1421
Procedures, Int ervent ions, Operat ions
93
General Inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
93.1
Int roduct ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1426
93.2
Int raoperat ive dyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1426
93.3
Operat ing room equipm ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1426
93.4
Surgical hem ost asis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1428
93.5
Craniot om y general inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . 1428
93.6
Int raoperat ive cort ical m apping (brain m apping) . . . . . . . . . 1432
93.7
Cranioplast y. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1436
93.8
Bone graft . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1437
93.9
St ereot act ic surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1441
94
Specific Craniot om ies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
94.1
Post erior fossa (suboccipit al) craniect om y . . . . . . . . . . . . . . . 1445
94.2
Pt erional craniot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1453
94.3
Tem poral craniot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1456
1426
1445
53
54
Cont ent s
94.4
Front al craniot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1459
94.5
Pet rosal craniot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1460
94.6
Approaches t o t he lat eral vent ricle . . . . . . . . . . . . . . . . . . . . . .
1461
94.7
Approaches t o t he t hird vent ricle . . . . . . . . . . . . . . . . . . . . . . . .
1461
94.8
Int erhem ispheric approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1466
94.9
Occipit al craniot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1466
94.10
Decom pressive craniect om y . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1467
95
Spine, Cervical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1472
95.1
Ant erior approaches t o t he cervical spine . . . . . . . . . . . . . . . .
1472
95.2
Transoral approach t o ant erior craniocervical junct ion . . . .
1472
95.3
Occipit ocervical fusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1474
95.4
Ant erior odont oid screw fixat ion . . . . . . . . . . . . . . . . . . . . . . . .
1476
95.5
At lant oaxial fusion (C1–2 art hrodesis) . . . . . . . . . . . . . . . . . . .
1479
95.6
C2 screw s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1483
95.7
Ant erior vert ebral body screw -plat e fixat ion . . . . . . . . . . . . .
1486
95.8
Zero profile int erbody devices . . . . . . . . . . . . . . . . . . . . . . . . . . .
1487
96
Spine, Thoracic and Lum bar . . . . . . . . . . . . . . . . . . . . . . .
1489
96.1
Ant erior access t o t he cervico-t horacic junct ion/upper
t horacic spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1489
96.2
Ant erior access t o m id and low er t horacic spine . . . . . . . . . .
1489
96.3
Thoracic pedicle screw s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1489
96.4
Ant erior access t o t horacolum bar junct ion . . . . . . . . . . . . . . .
1493
96.5
Ant erior access t o t he lum bar spine . . . . . . . . . . . . . . . . . . . . .
1493
96.6
Inst rum ent at ion/fusion pearls for t he lum bar and
lum bosacral spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1494
96.7
Lum bosacral pedicle screw s . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1494
96.8
Minim ally invasive lat eral ret roperit oneal t ranspsoas
int erbody fusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1498
96.9
Transfacet pedicle screw s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1501
96.10
Facet fusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1502
96.11
S2 screw s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1502
96.12
Iliac screw s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1502
96.13
Post -op clinic visits – lum bar and/or t horacic spine fusion .
1502
Cont ents
97
Miscellaneous Surgical Procedures . . . . . . . . . . . . . . .
97.1
Percut aneous vent ricular punct ure . . . . . . . . . . . . . . . . . . . . . . 1504
97.2
Percut aneous subdural t ap . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1504
97.3
Lum bar punct ure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1504
97.4
Lum bar cat het er CSF drainage . . . . . . . . . . . . . . . . . . . . . . . . . . . 1510
97.5
C1–2 punct ure and cist ernal t ap . . . . . . . . . . . . . . . . . . . . . . . . . 1511
97.6
CSF diversionary procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1512
97.7
Vent ricular access device . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1518
97.8
Sural nerve biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1520
97.9
Nerve blocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1521
98
Funct ional Neurosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . .
98.1
Deep brain st im ulat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1524
98.2
Typical t arget s used in funct ional brain surgery . . . . . . . . . . . 1524
98.3
Surgical t reat m ent of Parkinson’s disease . . . . . . . . . . . . . . . . 1524
98.4
Dyst onia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1528
98.5
Spast icit y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1528
98.6
Tort icollis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1533
98.7
Neurovascular com pression syndrom es . . . . . . . . . . . . . . . . . . 1534
98.8
Hyperhidrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1537
98.9
Trem or . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1537
98.10
Sym pat hect om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1537
99
Pain Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
99.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1541
99.2
Choice of pain procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1541
99.3
Types of pain procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1541
99.4
Cordot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1542
99.5
Com m issural m yelot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1544
99.6
Punct at e m idline m yelot om y . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1545
99.7
CNS narcot ic adm inist rat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1545
99.8
Spinal cord st im ulat ion (SCS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1547
99.9
Deep brain st im ulat ion (DBS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1550
99.10
Dorsal root ent ry zone (DREZ) lesions . . . . . . . . . . . . . . . . . . . . 1550
1504
1524
1541
55
56
Cont ent s
100
Seizure Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1553
100.1
General inform at ion, indicat ions . . . . . . . . . . . . . . . . . . . . . . . .
1553
100.2
Pre-surgical evaluat ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1553
100.3
Surgical t echniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1554
100.4
Surgical procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1555
100.5
Risks of seizure surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1557
100.6
MRI guided laser int erst it ial t herm al t herapy (MRGLITT) . .
1557
100.7
Post operat ive m anagem ent for seizure surgery (epilepsy
surgery) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1557
100.8
Out com e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1557
101
Radiat ion Therapy (XRT) . . . . . . . . . . . . . . . . . . . . . . . . . . .
1560
101.1
Int roduct ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1560
101.2
Convent ional ext ernal beam radiat ion . . . . . . . . . . . . . . . . . . .
1560
101.3
St ereot act ic radiosurgery and radiot herapy . . . . . . . . . . . . . .
1564
101.4
Int erst it ial brachyt herapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1571
102
Endovascular Neurosurgery . . . . . . . . . . . . . . . . . . . . . . .
1575
102.1
General inform at ion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1575
102.2
Pharm acologic agent s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1576
102.3
Neuroendovascular Procedure Basics . . . . . . . . . . . . . . . . . . . .
1582
102.4
Diagnost ic angiography for cerebral subarachnoid
hem orrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1583
Disease -specific int ervent ion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1584
102.5
Appendix
103
Quick Reference Tables and Figures . . . . . . . . . . . . . .
1604
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1633
Part I
1
Gross Anatom y,
Cranial and Spine
58
Anat om y and Physiology
2
Vascular Anatom y
75
3
Neurophysiology
and Regional Brain
Syndrom es
90
I
1 Gross Anat om y, Cranial and Spine
1.1 Cort ical surface anat om y
1.1.1 Lat eral cort ical surface
Fig. 1.1. For abbreviation s, see Table 1.1 an d Table 1.2. Th e m iddle fron tal gyrus (MFG) is usually m ore sin uous th an th e IFG or SFG, an d it often con n ects to th e pre-cen tral gyrus via a th in isth m us.1 Th e cen tral sulcus join s th e Sylvian fissure in on ly 2% of cases (i.e. in 98% of cases th ere is a
“subcen t ral” gyrus). Th e in traparietal sulcus (ips) separates th e superior an d in ferior parietal lobules.
Th e IPL is com posed prim arily of th e AG an d SMG. Th e Sylvian fissure term in ates in th e SMG (Brodm an n’s area 40). Th e superior tem poral sulcus term in ates in th e AG.
1.1.2 Brodm ann’s areas
Fig. 1.1 also iden tifies th e clin ically sign ifican t areas of Brodm an n’s (Br.) m ap of th e cytoarch itecton ic fields of th e h um an brain . Fun ction al sign ifican ce of th ese areas is as follow s:
1. Br. areas 3, 1, 2: prim ar y som atosen sor y cortex
2. Br. areas 41 & 42: prim ar y auditor y areas (tran sverse gyri of Hesch l)
3. Br. area 4: precen tral gyrus, prim ary m otor cortex (AKA “m otor strip”). Large con cen tration of
gian t pyram idal cells of Bet z
4. Br. area 6: prem otor area or supplem en tal m otor area. Im m ediately an terior to m otor strip, it
plays a role in con tralateral m otor program m in g
5. Br. area 44: (dom in an t h em isph ere) Broca’s area (m otor speech )
6. Br. area 17: prim ar y visual cortex
CENTRAL S ULCUS
(Rola ndic fis s ure )
Br. 4
Br. 6
Br. 8
s
Br. 3
Br. 1
Br. 2
POr
OG
LATERAL
S ULCUS
(Sylvian fissure)
c
o
p
SMG I
PL
SP
L
AG
f
po
s
to
sts
STG
lo
s
its
P
T
ips
s
Br. 40
Br. 39
p
O
P
IF
G
M
F
G
Po
st
C
G
P
re
C
G
c
pr
s
io
S
FG
Br. 44
ifs
1
Anat om y and Physiology
sf
s
58
MTG
ITG
pocn
Br. 42
Br. 41
Br. 17
Fig. 1.1 Left lateral cerebral cortical surface anatomy.
Br. = Brodmann’s area (shaded). See Table 1.1 and Table 1.2 for abbreviations (lowercase = sulci, UPPERCASE=
gyri).
Gross Anatom y, Cranial and Spine
Table 1.1 Cerebral sulci (abbreviations)
Abbreviat ion
Sulcus
cins
cingulate sulcus
cs
central sulcus
ips-ios
intraparietal-intraoccipital sulcus
los
lateral occipital sulcus
pM
pars marginalis
pocn
pre-occipital notch
pocs
post-central sulcus
pof
parieto-occipital fissure
pos
parieto-occipital sulcus
prcs
pre-central sulcus
sfs, ifs
superior, inferior frontal sulcus
sps
superior parietal sulcus
sts, its
superior, inferior tem poral sulcus
tos
trans occipital sulcus
Table 1.2 Cerebral gyri and lobules (abbreviations)
Abbreviat ion
Gyrus / lobule
AG
angular gyrus
CinG
cingulate gyrus
Cu
cuneus
LG
lingual gyrus
MFG, SFG
m iddle & superior frontal gyrus
OG
orbital gyrus
PCu
precuneous
PreCG, PostCG
pre- and post-central gyrus
PL
paracentral lobule (upper SFG and PreCG and PostCG)
IFG
● POp
● PT
● POr
inferior frontal gyrus
● pars opercularis
● pars triangularis
● pars orbitalis
STG, MTG, ITG
superior, middle & inferior temporal gyrus
SPL, IPL
superior & inferior parietal lobule
SMG
supramarginal gyrus
59
1
60
Anat om y and Physiology
1
CT
prcs
CENTRAL SULCUS
PL
SFG
cin s
rp
co
cins
CinG
u s ca llo su m
pM
sps
PCu
MRI
pos
Cu
LG
pons
Fig. 1.2 Medial aspect of the right hem isphere.
“CT” & “MRI” bars depict t ypical axial slice orientation for CT & MRI scans. See
abbreviations.
Table 1.1 and
Table 1.2 for
7. Wern icke’s area (lan guage): in th e dom in an t h em isphere, m ost of Br. area 40 an d a por tion of Br.
area 39 (m ay also in clude ≈ posterior th ird of STG)
8. th e st riped port ion of Br. area 8 in Fig. 1.1 (fron tal eye field) in itiates volun tar y eye m ovem en ts
to th e opposite direct ion
Brodm an n’s area 44, Wern icke’s area: Lan guage fun ction can n ot be reliably localized on an atom ic
groun ds due to in dividual variabilit y in its exact location ; in order to perform m axim al brain resect ion s w ith m in im al risk of aph asia, tech n iques such as in t ra-operat ive brain m appin g2 or lookin g for
ph ase reversal on in traoperative cort ical SSEP3 sh ould be em ployed.
1.1.3 Medial surface
Fig. 1.2. Th e cin gulate sulcus term in ates posteriorly in th e pars m argin alis (pM) (plural: partes
m argin ales). On axial im agin g, th e pMs: are visible on 95% of CTs an d 91% of MRIs,4 are usually th e
m ost prom in en t of th e paired grooves straddlin g th e m idlin e, an d th ey exten d a greater distan ce in to
th e h em isph eres.4 On axial CT, th e pM is located sligh tly posterior to th e w idest biparietal diam eter 4 ;
on th e t ypically m ore h orizon tally orien ted MRI slices th e pM assum es a m ore posterior position.
Th e pMs cur ve posteriorly in low er slices an d an teriorly in h igh er slices (h ere, th e paired pMs form
th e “pars bracket” – a ch aracteristic “h an dlebar” con figuration straddlin g th e m idlin e).
1.2 Cent ral sulcus on axial im aging
See Fig. 1.3. Iden tificat ion of th e central sulcus is im por tan t to localize th e m otor strip (con tain ed
in th e PreCG). Th e cen tral sulcus (CS) is visible on 93% of CTs an d 100% of MRIs.4 It cur ves posteriorly
as it approach es th e in terh em isph eric fissure (IHF), an d often term in ates in th e paracen tral lobule,
just an terior to th e pars m argin alis (pM) w ith in th e pars bracket (see above)4 (i.e. th e CS often does
n ot reach th e m idlin e).
Gross Anatom y, Cranial and Spine
G
G
Fig. 1.3 Retouched axial FLAIR MRI with labels for
gyri/sulci shown in the left hem isphere, and an
unlabeled mirror image shown as the right hem isphere for reference. The inverted Ω illustrates the
hand “knob” (see text).
See Table 1.1 and Table 1.2 for abbreviations.
F
L
P
P
L
Ω
S
S
F
p
prcs
PM
P
M
PreCG
P
PreC
“motor
“
“moto
strip”
css
PostCG
Pos
hand “k
“knob”
p
pocs
Poin ters:
parieto-occipital sulcus (pos) (or fissure): m ore prom in en t over th e m edial surface, an d on axial
im agin g is lon ger, m ore com plex, an d m ore posterior th an th e pars m argin alis 5
● post-cen t ral sulcus (pocs): usually bifurcates an d form s an arc or paren th esis (“lazy-Y”) cupping
th e pM. Th e an terior lim b does n ot en ter th e pM-bracket an d th e posterior lim b cur ves beh in d th e
pM to en ter th e IHF
●
Han d “Kn ob”: Th e alph a m otor n euron s for h an d m otor fun ct ion are located in th e superior aspect
of th e prefron tal gyrus.6 On axial im agin g, th is appears as a kn ob-like protrusion (sh aped like an
inverted greek letter om ega Ω) of th e precen tral gyrus project in g posterolaterally in to th e cen tral
sulcus 7 Fig. 1.3. On sagittal im aging it h as a posteriorly project in g h ook-like appearan ce an d is
even w ith th e posterior lim it of th e Sylvian fissure.7
1.3 Surface anat om y of t he cranium
1.3.1 Craniom et ric point s
See Fig. 1.4.
Pterion : region w h ere th e follow in g bon es are approxim ated: fron tal, parietal, tem poral an d
sph enoid (greater w in g). Estim ated as 2 finger-breadth s above th e zygom atic arch , an d a th um b’s
breadth beh in d th e fron tal process of th e zygom atic bon e (blue circle in Fig. 1.4).
Asterion : jun ction of lam bdoid, occipitom astoid an d parietom astoid sutures. Usually lies w ith in a
few m illim eters of th e posterior-in ferior edge of th e jun ct ion of th e tran sverse an d sigm oid sin uses
(n ot alw ays reliable 8 – m ay overlie eith er sin us).
Vertex: th e topm ost poin t of th e sku ll.
Lam bda: jun ct ion of th e lam bdoid an d sagittal sut ures.
Steph an ion : jun ction of coron al suture an d superior tem poral lin e.
Glabella: th e m ost for w ard project in g poin t of th e foreh ead at th e level of th e supraorbital ridge
in th e m idlin e.
Opisth ion : th e posterior m argin of th e foram en m agn um in th e m idlin e.
Bregm a: th e jun ct ion of th e coron al an d sagittal sut ures.
Sagittal suture: m idlin e suture from coron al suture to lam bdoid suture. Alth ough often assum ed
to overlie th e superior sagittal sin us (SSS), th e SSS lies to th e righ t of th e sagittal suture in th e m ajorit y of specim en s 9 (but n ever by > 11 m m ).
Th e m ost an terior m astoid poin t lies just in fron t of th e sigm oid sin us.10
1.3.2 Relat ion of skull m arkings t o cerebral anat om y – Taylor-Haught on
lines
Taylor-Haugh ton (T-H) lin es can be con structed on an an giogram , CT scout film , or sku ll x-ray, an d
can th en be recon structed on th e patien t in th e O.R. based on visible extern al lan dm arks.11 T-H lin es
are sh ow n as dash ed lin es in Fig. 1.5.
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Anat om y and Physiology
1
vertex
bregm a
NASAL
prosthion
ZYG
MAXILLA
inferior
alveolar point
gnathion
or m enton
IBLE
D
N
MA
lam bda
TEMPORAL
sm s
pm s
ID
O
s
T
S m
A o
M
ls
L
G
W
S
ophyron
glabella
nasion
rhinion
stl
sqs
C
IP
IT
A
L
TA
N
O
FR
O
C
stephanion
pterion
PARIE
TAL
cs
62
inion
asterion
opisthion
gonion
Fig. 1.4 Craniometric points & cranial sutures.
Named bones appear in all upper case letters.
Abbreviations: GWS = greater wing of sphenoid bone, NAS = nasal bone, stl = superior temporal line, ZYG = zygom atic.
Sutures: cs = coronal, ls = lambdoid, om s = occipitomastoid, pms = parietom astoid, sm s = squam om astoid, sqs =
squamosal
1. Fran kfurt plan e, AKA baselin e: lin e from in ferior m argin of orbit th rough th e upper m argin of th e
extern al auditor y m eat us (EAM) (as distin guish ed from Reid’s base lin e: from in ferior orbital
m argin th rough th e center of th e EAM)12 (p 313)
2. th e distan ce from th e n asion to th e in ion is m easured across th e top of th e calvaria an d is divided
in to quar ters (can be don e sim ply w ith a piece of tape w h ich is th en folded in h alf t w ice)
3. posterior ear lin e: perpen dicular to th e baselin e th rough th e m astoid process
4. con dylar lin e: perpen dicular to th e baselin e th rough th e m an dibular con dyle
5. T-H lin es can th en be used to approxim ate th e sylvian fissure (see below ) an d th e m otor cortex
(also see below )
Sylvian fissure AKA lat eral fissure
Approxim ated by a lin e con n ectin g th e lateral can th us to th e poin t 3/4 of th e w ay posterior alon g
th e arc run n in g over convexity from n asion to in ion (T-H lin es).
Angular gyrus
Located just above th e pin n a, im por tan t on th e dom in an t h em isph ere as part of Wern icke’s area.
Note: th ere is sign ifican t in dividual variabilit y in th e location .2
Gross Anatom y, Cranial and Spine
1
2 cm
3/4
N-I
ce
n
tr
a
l s
u
lc
us
1/2
N-I
N
ia
v
l
sy
n
e
r
u
fis s
63
©2001 Ma rk S Gre e nbe rg, M.D.
All rights re s e rve d.
Una uthorize d us e is prohibite d.
I
EAM
Fra nkfurt
pla ne
pos te rior e a r line
condyla r line
Fig. 1.5 Taylor-Haughton lines and other localizing methods
Angular art ery
Located 6 cm above th e EAM.
Mot or cort ex
Num erous m eth ods utilize extern al lan dm arks to locate th e m otor st rip (pre-cen t ral gyrus) or th e
cent ra l sulcus (Rolan dic fissure) w h ich separates m otor st rip an teriorly from prim ar y sen sor y cortex
posteriorly. Th ese are just approxim ation s sin ce in dividual variabilit y causes th e m otor strip to lie
anyw h ere from 4 to 5.4 cm beh in d th e coron al sut ure.13 Th e cen tral sulcus can n ot even be reliably
iden tified visually at surger y.14
1. m eth od 1: th e superior aspect of th e m otor cortex is alm ost straigh t up from th e EAM n ear th e
m idlin e
2. m eth od 2 15 : th e cen t ral sulcus is approxim ated by con n ectin g:
a) th e poin t 2 cm posterior to th e m idposition of th e arc exten din g from n asion to in ion (illustrated in Fig. 1.5), to
b) th e poin t 5 cm straigh t up from th e EAM
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Anat om y and Physiology
cs
1
B
D1
F
FM
A
V3
Aq
T
D2
V4
O
Twin in g
D3
D4
opis thion
ba s e line
s igmoid s inus
s e lla turcica
Fig. 1.6 Relationship of ventricles to skull landm arks
Abbreviations: (F= frontal horn, B= body, A= atrium, O = occipital horn, T= tem poral horn) of lateral ventricle. FM =
foram en of Monro. Aq = sylvian aqueduct. V3 = third ventricle. V4 = fourth ventricle. cs = coronal suture. Dim ensions
D1–4 see Table 1.3
3. m eth od 3: usin g T-H lin es, th e cen t ral sulcus is approxim ated by con n ecting:
a) th e poin t w h ere th e “posterior ear lin e” in tersects th e circum feren ce of th e sku ll ( Fig. 1.5;
usually about 1 cm beh in d th e ver tex, an d 3–4 cm beh in d th e coron al suture), to
b) th e poin t w h ere th e “con dylar lin e” in tersects th e lin e represen ting th e sylvian fissure
4. m eth od 4: a lin e draw n 45° to Reid’s base lin e start in g at th e pterion poin ts in th e direct ion of th e
m otor strip 16 (p 584–5)
1.3.3 Relat ionship of vent ricles t o skull
Fig. 1.6 sh ow s th e relation sh ip of n on -hydroceph alic ven tricles to th e skull in th e lateral view.
Som e dim en sion s of in terest are sh ow n in Table 1.3.17
In th e n on -hydroceph alic adult , th e lateral ven tricles lie 4–5 cm below th e outer skull surface. Th e
center of th e body of th e lateral ven t ricle sits in th e m idpupillar y lin e, an d th e fron tal h orn is in tersected by a lin e passing perpen dicular to th e calvaria alon g th is lin e.18 Th e an terior h orn s exten d 1–
2 cm an terior to th e coronal sut ure.
Average len gth of th ird ven tr icle≈ 2.8 cm .
Th e m idpoin t of Tw in ing’s lin e (• in Fig. 1.6) sh ould lie w ith in th e 4th ven tr icle.
Gross Anatom y, Cranial and Spine
Table 1.3 Dim ensions from
Fig. 1.6
Dim ension
( Fig. 1.6)
Descript ion
Lower lim it
(m m )
Average
(m m )
Upper lim it
(m m )
D1
length of frontal horn anterior to FM
D2
distance from clivus to floor of 4th ventricle at level
of fastigium a
33.3
36.1
40.0
D3
length of 4th ventricle at level of fastigium a
10.0
14.6
19.0
D4
distance from fastigium a to opisthion
30.0
32.6
40.0
25
a the fastigium is the apex of the 4th ventricle within the cerebellum
Table 1.4 Cervical levels19
Level
Landm ark
C1–2
angle of m andible
C3–4
1 cm above thyroid cartilage (≈ hyoid bone)
C4–5
level of thyroid cartilage
C5–6
crico-thyroid m em brane
C6
carotid tubercle
C6–7
cricoid cartilage
1.4 Surface landm arks of spine levels
Est im ates of cer vical levels for an terior cer vical spin e surger y m ay be m ade using th e lan dm arks
sh ow n in Table 1.4. In tra-operative C-spin e x-rays are essen tial to verify th ese estim ates.
Th e scapular spin e is located at about T2–3.
Th e in ferior scapular pole is ≈ T6 posteriorly.
In tercristal lin e: a lin e draw n bet w een th e h igh est poin t of th e iliac crests across th e back w ill
cross th e m idlin e eith er at th e in terspace bet w een th e L4 an d L5 spin ous processes, or at th e L4 spin ous process itself.
1.5 Cranial foram ina and t heir cont ent s
1.5.1 Sum m ary
Table 1.5 Cranial foramina and their contentsa
Foram en
Contents
nasal slits
anterior ethm oidal nn., a. & v
superior orbital fissure
Cr. Nn. III, IV, VI, all 3 branches of V1 (ophthalm ic division divides into
nasociliary, frontal, and lacrimal nerves); superior ophthalm ic vv.; recurrent
meningeal br. from lacrimal a.; orbital branch of middle m eningeal a.;
sym pathetic filam ents from ICA plexus
inferior orbital fissure
Cr. N. V-2 (m axillary div.), zygomatic n.; filam ents from pterygopalatine
branch of m axillary n.; infraorbital a. & v.; v. between inferior ophthalm ic v. &
pterygoid venous plexus
foramen lacerum
usually nothing (ICA traverses the upper portion but doesn’t enter, 30% have
vidian a.)
carotid canal
internal carotid a., ascending sym pathetic nerves
65
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Anat om y and Physiology
Table 1.5 continued
Foram en
Cont ent s
incisive foram en
descending septal a.; nasopalatine nn.
greater palatine foram en
greater palatine n., a., & v.
lesser palatine foram en
lesser palatine nn.
internal acoustic m eatus
Cr. N. VII (facial); Cr. N. VIII (stato-acoustic) – see text &
hypoglossal canal
Cr. N. XII (hypoglossal); a m eningeal branch of the ascending pharyngeal a.
foram en m agnum
spinal cord (medulla oblongata); Cr. N. XI (spinal accessory nn.) entering the
skull; vertebral aa.; anterior & posterior spinal arteries
foram en cecum
occasional sm all vein
cribriform plate
olfactory nn.
optic canal
Cr. N. II (optic); ophthalmic a.
foram en rotundum
Cr. N. V2 (m axillary div.), a. of foram en rotundum
foram en ovale
Cr. N. V3 (m andibular div.) + portio m inor (motor for CrN V)
foram en spinosum
m iddle m eningeal a. & v.
jugular foram en
internal jugular v. (beginning); Cr. Nn. IX, X, XI
stylomastoid foram en
Cr. N. VII (facial); st ylom astoid a.
condyloid foram en
v. from transverse sinus
m astoid foram en
v. to mastoid sinus; branch of occipital a. to dura m ater
Fig. 1.7
a Abbreviations: a. = artery, aa. = arteries, v. = vein, vv. = veins, n. = nerve, nn. = nerves, br. = branch, Cr. N. = cranial
nerve, fm n. = foramen, div. = division
1.5.2 Porus acust icus
AKA in tern al auditor y can al ( Fig. 1.7)
Th e filam en ts of th e acoust ic portion of VIII pen etrate t iny open in gs of th e lam in a cribrosa of th e
coch lear area.20
Tran sverse crest: separates superior vestibular area an d facial can al (above) from th e in ferior vest ibular area an d coch lear area (below ).20
Vert ical crest (AKA Bill’s bar – n am ed after Dr. William House): separates th e m eatus to th e facial
canal an teriorly (con tain in g VII an d n er vus in term edius) from th e vest ibular area posteriorly (con tainin g th e superior division of vest ibular n er ve). Bill’s bar is deeper in th e IAC th an th e tran sverse
crest.
Th e “5 n er ves” of th e IAC:
1. facial n er ve (VII) (m n em on ic: “7-up” as VII is in superior port ion )
2. n er vus in term edius: th e som at ic sen sor y bran ch of th e facial n er ve prim arily in n er vatin g m ech an oreceptors of th e h air follicles on th e in n er surface of th e pin n a an d deep m ech an oreceptors of
n asal an d buccal cavit ies an d ch em oreceptors in th e taste buds on th e an terior 2/3 of th e tongue
3. acoustic por tion of th e VIII n er ve (m n em on ic: “Coke dow n ” for coch lear por tion )
4. superior bran ch of vestibular n er ve: passes th rough th e superior vest ibular area to term in ate in
th e ut ricle an d in th e am pullæ of th e superior an d lateral sem icircular can als (m n em on ic superior = LSU (Lateral & Superior sem icircular can als an d th e Ut ricule))
5. in ferior bran ch of vest ibular n er ve: passes th rough in ferior vestibular area to term in ate in th e
saccule
facial canal (Cr. N. VII with NI*)
vertical crest (“Bill’s bar”)
Gross Anatom y, Cranial and Spine
67
Fig. 1.7 Right internal auditory canal (porus acusticus) & nerves
* NI= nervus interm edius
1
superior vestibular area
(superior
(to utricle & superior &
vestibular
lateral sem icircular canals) nerve)
ttransverse crest (crista falciform is)
inferior vestibular area
(to saccule)
foramen singulare (to
posterior sem icircular canal)
cochlear area
(inferior
vestibular
nerve)
(acoustic portion
of Cr. N. VIII)
lateral ventricle
head of caudate
INTERNAL CAPSULE
- anterior limb
corticobulbar tract
face
shoulder
arm
hand
hip trunk
foot
putamen
globus pallidus
corticorubral tract
corticospinal tract
}
CAPSULE
}INTERNAL
- genu
frontopontine tract
}
}
}
}
(A)
anterior thalamic
radiation
(B)
superior thalamic
radiation
(C)
posterior thalamic
radiation
(D)
auditory
radiation
}
INTERNAL CAPSULE
- posterior limb
thalamus
lateral geniculate body
medial geniculate body
third ventricle
optic radiation
ascending thalamocortical fibers
descending corticofugal fibers
Fig. 1.8 Internal capsule schematic diagram (left side shows tracts, right side shows radiations)
1.6 Int ernal capsule
1.6.1 Archit ect ural anat om y
For a sch em at ic diagram , Fig. 1.8; Table 1.6 delin eates th e th alam ic subradiation s.
Most IC lesion s are caused by vascular acciden ts (th rom bosis or h em orrh age).
1.6.2 Vascular supply of t he int ernal capsule (IC)
1. an terior ch oroidal: all of retrolen ticular part (in cludes optic radiation ) an d ven t ral part of posterior lim b of IC
2. lateral striate bran ch es (AKA capsular bran ch es) of m iddle cerebral arter y: m ost of an terior
AND posterior lim bs of IC
3. gen u usually receives som e direct bran ch es of th e in tern al carotid arter y
1.7 Cerebellopont ine angle anat om y
For n orm al an atom y of righ t cerebellopon tin e an gle, see
Fig. 1.9.
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Anatom y and Physiology
Table 1.6 Four Thalam ic “subradiations” (AKA thalamic peduncles) , labeled A-D in
Radiat ion
Connection
Fig. 1.8
Com m ent s
anterior
(A)
m edial & anterior thalam ic
nucleus
↔
frontal lobe
superior
(B)
rolandic areas
↔
ventral thalam ic nuclei
posterior
(C)
occipital & posterior parietal
↔
caudal thalam us
inferior
(D)
transverse tem poral gyrus
of Heschl
↔
MGB
re tra ctor
on ce re be lla r
he mis phe re
fora me n of
Lus chka
general sensory fibers from
body & head to term inate in
postcentral gyrus (areas 3,1,2)
(sm all) includes auditory radiation
V
Me cke l's
ca ve
pons
flocculus
choroid
ple xus
VII
IAC
fora me n of
Ma ge ndie
ce re be lla r
tons il
P ICA
VIII
IX
jugula r
fora me n
X
XI
XII
olive
me dulla
Fig. 1.9 Normal anatomy of right cerebellopontine angle viewed from behind (as in a suboccipital approach)20
1.8 Occipit oat lant oaxial-com plex anat om y
Ligam en t s of t h e occip it oat lan t oaxial com p lex. Stabilit y of th e occipitoatlan tal join t is prim arily
due to ligam en ts, w ith lit tle con tribution from bony articulation s an d join t capsules (see Fig. 1.10,
Fig. 1.11, Fig. 1.12):
1. ligam en ts th at con n ect th e atlas to th e occiput:
a) an terior atlan to-occipital m em bran e: ceph alad exten sion of th e an terior lon gitudin al ligam en t. Exten ds from an terior m argin of foram en m agn um (FM) to an terior arch of C1
Gross Anatom y, Cranial and Spine
clivus
ascending
band
right alar
ligament
accessory
(deep) portion
of tectorial
membrane
C1
transverse
band
CRUCIATE
LIGAMENT
descending
band
C2
Fig. 1.10 Sagit tal view of the ligaments of the craniovertebral junction (Modified with permission from “In Vitro
Cervical Spine Biom echanical Testing” BNI Quarterly, Vol.9, No. 4, 1993)
apical
odontoid
ligament
cruciate ligament,
ascending band
anterior
atlantooccipital
membrane
anterior transverse
ligament
longitudinal
ligament
cruciate ligament,
descending band
tectorial
membrane
posterior
longitudinal
ligament
posterior
atlantooccipital
membrane
C1
ligamentum
flavum
spinal
cord
C2
C3
Fig. 1.11 Dorsal view of the cruciate and alar ligaments
Viewed with tectorial m em brane rem oved. (Modified with permission from “In Vitro Cervical Spine Biom echanical
Testing” BNI Quarterly, Vol.9, No. 4, 1993)
69
1
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Anat om y and Physiology
odontoid
process
right alar
ligam ent
transverse
ligam ent
tubercle
Fig. 1.12 C1 viewed from above, showing the transverse and alar ligaments (Modified with perm ission
from “In Vitro Cervical Spine Biom echanical Testing”
BNI Quarterly, Vol.9, No. 4, 199)
tectorial
m em brane
posterior arch C1
b) posterior atlan to-occipital m em -bran e: con n ects th e posterior m argin of th e FM to posterior
arch of C1
c) th e ascen ding ban d of th e cruciate ligam en t
2. ligam en ts th at con n ect th e axis (viz. th e odon toid) to th e occiput:
a) tectorial m em bran e: som e auth ors dist in guish 2 com pon en ts
● superficial com pon en t: ceph alad con tin uat ion of th e posterior lon gitudin al ligam en t. A
st ron g ban d con n ecting th e dorsal surface of th e den s to th e ven tral surface of th e FM
above, an d dorsal surface of C2 & C3 bodies below
● accessor y (deep) por t ion : located laterally, con n ects C2 to occipital con dyles
b) alar (“ch eck”) ligam en ts 21
● occipito-alar port ion : con n ects side of th e den s to occipital con dyle
● atlan to-alar port ion : con n ects side of th e den s to th e lateral m ass of C1
c) apical odon toid ligam en t: con n ects tip of den s to th e FM. Lit tle m ech an ical stren gth
3. ligam en ts th at con n ect th e axis to th e atlas:
a) t r an sve r se (at la n t oa xial) ligam e n t : t h e h or izon t al com p on e n t of t h e cr u ciat e ligam e n t .
Tr ap s t h e d e n s again st t h e an t e r ior at las via a st r ap - like m ech an ism ( Fig. 1 .1 2). Pr o vid es t h e m ajor it y of t h e st r e n gt h (“t h e st r on gest ligam e n t of t h e sp in e ”2 2 )
b) atlan to-alar portion of th e alar ligam en ts (see above)
c) descen din g ban d of th e cruciate ligam en t
Th e m ost im portan t st ructures in m ain tain in g atlan to-occipital stabilit y are th e tectorial m em bran e
an d th e alar ligam en ts. W ith out th ese, th e rem ain ing cruciate ligam en t an d apical den tate ligam en t
are in su cien t.
1.9 Spinal cord anat om y
1.9.1 Dent at e Ligam ent
Th e den tate ligam en t separates dorsal from ven tral n er ve roots in th e spinal n er ves. Th e spinal
accessory n er ve (Cr. N. XI) is dorsal to th e den tate ligam en t.
1.9.2 Spinal cord t ract s
Anat om y
Fig. 1.13 depicts a cross-section of a t ypical spin al cord segm en t, com bin ing som e elem en ts from
di eren t levels (e.g. th e in term ediolateral grey n ucleus is on ly presen t from T1 to ≈ L1 or L2 w h ere
th ere are sym path et ic (th oracolum bar outflow ) n uclei). It is sch em atically divided in to ascendin g
an d descen din g h alves, h ow ever, in actualit y, ascen din g an d descen din g path s coexist on both sides.
Fig. 1.13 also depicts som e of th e lam in ae according to th e sch em e of Rexed. Lam in a II is equivalen t to th e substan tia gelatin osa. Lam in ae III an d IV are th e n ucleus proprius. Lam in a VI is located in
th e base of th e posterior h orn .
Gross Anatom y, Cranial and Spine
MOTOR
(descending
paths)
{
SENSORY
(ascending
paths)
{
{
7
8
S TC
6
III
5
1
S = s ac ral
T = tho rac ic
C = c e rvic al
bi-directional
paths
I
II
intermediolateral
grey nucleus
(sympathetic)
IV
VI
X
9
10
11
12
V
S TC
VII
IX
VIII
IX
CTS
4
3
dentate
ligament
13
14
2
15
cm
4
5
.
2
1
anterior spinal
artery
Fig. 1.13 Schem atic cross-section of cervical spinal cord. See
nam es.
Table 1.7 Descending (motor) tracts (↓ ) in
Table 1.7,
anterior motor
nerve root
Table 1.8 and
71
Table 1.9 for path
Fig. 1.13
Num ber
( Fig. 1.13)
Pat h
Funct ion
Side of body
1
anterior corticospinal tract
skilled m ovement a
opposite
2
m edial longitudinal fasciculus
?
sam e
3
vestibulospinal tract
facilitates extensor muscle tone
sam e
4
m edullary (ventrolateral) reticulospinal
tract
automatic respirations?
sam e
5
rubrospinal tract
flexor muscle tone
sam e
6
lateral corticospinal (pyram idal) tract
skilled m ovem ent
sam e
a The term inal fibers of this uncrossed tract usually cross in the anterior white com missure to synapse on alpha
motor neurons or on internuncial neurons. It is true that some of these fibers do stay on the same side, but it is
felt to be a minority. Also, the anterior corticospinal tract is easily identified only in the cervical and upper thoracic
regions.
72
1
Anatom y and Physiology
Table 1.8 Bi-directional tracts in
Fig. 1.13
Num ber
( Fig. 1.13)
Pat h
7
dorsolateral fasciculus (of Lissauer)
8
fasciculus proprius
Table 1.9 Ascending (sensory) tracts (↑ ) in
Num ber
( Fig. 1.13)
Pat h
9
fasciculus gracilis
10
fasciculus cuneatus
11
Funct ion
short spinospinal connections
Fig. 1.13
Funct ion
Side of body
joint position, fine touch, vibration
same
posterior spinocerebellar tract
stretch receptors
sam e
12
lateral spinothalam ic tract
pain & temperature
opposite
13
anterior spinocerebellar tract
whole limb position
opposite
14
spinotectal tract
unknown, ? nociceptive
opposite
15
anterior spinothalamic tract
light touch
opposite
Sensat ion
Pain and tem perature: body
Receptors: free n er ve en din gs (probable).
1st order n euron : sm all, fin ely m yelin ated a eren ts; som a in dorsal root gan glion (n o syn apse).
En ter cord at dorsolateral t ract (zon e of Lissauer). Syn apse: substan t ia gelatin osa (Rexed II).
2n d order n euron axon cross obliquely in th e an terior w h ite com m issure ascen din g ≈ 1–3 segm en ts w h ile crossing to en ter th e lateral spin oth alam ic t ract .
Syn apse: VPL th alam us. 3rd order n euron s pass th rough IC to postcen tral gyrus (Brodm an n’s
areas 3, 1, 2).
Fine touch, deep pressure and proprioception: body
Fin e touch AKA discrim in ative touch . Receptors: Meissn er’s & pacin ian corpuscles, Merkel’s disks,
free n er ve en din gs.
1st order n euron : h eavily m yelin ated a eren ts; som a in dorsal root gan glion (n o syn apse). Sh ort
bran ch es syn apse in n ucleus proprius (Rexed III & IV) of posterior gray; lon g fibers en ter th e ipsilateral posterior colum n s w ith out syn apsing (below T6: fasciculus gracilis; above T6: fasciculus
cun eat us).
Syn apse: n ucleus gracilis/cun eat us (respect ively), just above pyram idal decussat ion . 2n d order
n euron axon s form in tern al arcuate fibers, decussate in low er m edulla as m edial lem n iscus.
Syn apse: VPL th alam us. 3rd order n euron s pass th rough IC prim arily to postcen tral gyrus.
Light (crude) touch: body
Receptors: as fin e touch (see above), also perit rich ial arborization s.
1st order neuron : large, heavily m yelinated a erents (Type II); som a in dorsal root ganglion (no
synapse). Som e ascend uncrossed in post. colum ns (w ith fine touch ); m ost syn apse in Rexed VI & VII.
2n d order n euron axon s cross in an terior w h ite com m issure (a few don’t cross); en ter an terior
spinoth alam ic t ract .
Syn apse: VPL th alam us. 3rd order n euron s pass th rough IC prim arily to postcen tral gyrus.
1.9.3 Derm at om es and sensory nerves
Derm atom es are ares of th e body w h ere sen sation is subser ved by a sin gle n er ve root.
Periph eral n er ves gen erally receive con tribution s from m ore th an on e derm atom e.
Gross Anatom y, Cranial and Spine
Lesion s in periph eral n er ves an d lesion s in n er ve roots m ay som etim es be dist in guish ed in part
by th e pattern of sen sor y loss. A classic exam ple is splitt in g of th e ring fin ger in m edian n er ve or
uln ar n er ve lesion s, w h ich does n ot occur in C8 n er ve root injuries.
Fig. 1.14 sh ow s an terior an d posterior view, each sch em atically separated in to sen sor y derm atom es (segm en tal) an d periph eral sen sor y n er ve distribution .
ANTE R IO R
trigeminal
nerve
{
V1
V2
V3
P O S T E R IO R
C2
superior clavicular
occipitals
C2
C3
INTERCOSTALS
posterior
lateral
medial
axillary
RADIAL
post. cutaneous
dorsal cutan.
C3
C4
T3
T4
C5
T2
T6
T8
T4
C5
T6
T8
T2
T10
T12
musculocutan.
medial cutan.
L1
©2001 Ma rk S Gre e nbe rg, M.D.
All rights re s e rve d.
Una uthorize d us e is prohibite d.
4
T1
2
S
T
1
C
6
T1
0
C4
T2
radial
T1
C6
clunials
S5
S3
C8
L2
C7
ilioinguinal
lateral cutan.
nerve of thigh
L3
L4
L5
L3
ulnar
FEMORAL posterior
cutaneous
anterior
cutaneous
saphenous
S
1
SCIATIC
COMMON PERONEAL
lat. cutan.
sup. peroneal
deep peroneal
TIBIAL
sural
plantars
D E R MAT O ME S
( a n t e r io r )
C8
median
{
med.
lat.
C U TAN E O U S
NE R VE S
L4
S1
C7
L4
L5
S1
D E R MAT O ME S
( p o s t e r io r )
Fig. 1.14 Dermatomal and sensory nerve distribution (Redrawn from “Introduction to Basic Neurology”, by Harry
D. Pat ton, John W. Sundsten, Wayne E. Crill and Phillip D. Swanson, © 1976, pp 173, W. B. Saunders Co.,
Philadelphia, PA, with perm ission)
73
1
74
1
Anat om y and Physiology
References
[1] Naid ich TP. MR Im agin g of Brain Su rface An atom y.
Neurorad iology. 1991; 33:S95–S99
[2] Ojem an n G, Ojem an n J, Lettich E, Berger M. Cor tical
Lan guage Localization in Left, Dom in an t Hem isph ere. An Elect rical Stim ulat ion Mapp in g Invest igation in 117 Patients. J Neurosurg. 1989; 71:316–
326
[3] Suzuki A, Yasui N. In t raoperative Localization of th e
Cen tral Su lcus by Cort ical Som atosen sory Evoked
Poten tials in Brain Tum or: Case Repor t. J Neurosurg.
1992; 76:867–870
[4] Naid ich TP, Brigh tbill TC. Th e pars m argin alis, I: A
"bracket" sign for the cen tral sulcus in axial plan e
CT an d MRI. In t J Neurorad iol. 1996; 2:3–19
[5] Valen te M, Naidich TP, Abram s KJ, Blum JT. Di erent iatin g th e pars m argin alis from th e p arieto-occipital sulcus in axial com puted tom ography sect ion s.
In t J Neuroradiol. 1998; 4:105–111
[6] Pen field W , Boldrey E. Som atic m otor and sensor y
represen tation in th e cerebral cortex of m an as
st u died by electrical stim u lation . Brain . 1937;
60:389–443
[7] Yousr y TA, Sch m id UD, Alkadhi H, Sch m idt D, Peraud A, Bu ettn er A, W in kler P. Localization of th e
m otor h an d area to a kn ob on th e precen tral gyrus.
A n ew lan d m ark. Brain . 1997; 120 (Pt 1):141–157
[8] Day JD, Tsch abitsch er M. Anatom ic posit ion of the
asterion . Neu rosu rger y. 1998; 42:198–199
[9] Tubbs RS, Salter G, Elton S, Grabb PA, Oakes W J. Sagittal su tu re as an extern al lan d m ark for th e su p erior
sagittal sin u s. J Neurosurg. 2001; 94:985–987
[10] Barn ett SL, D'Am brosio AL, Agazzi S, van Loveren
HR, Lee JH. In : Petroclival an d Upper Clival Menin giom as III: Com bin ed An terior an d Posterior
Ap p roach . Men in giom as. Lon d on : Sp rin ger-Verlag;
2009:425–432
[11] W illis W D, Grossm an RG. In : Th e Brain an d Its En viron m en t . Med ical Neurobiology. 3rd ed. St. Lou is: C
V Mosby; 1981:192–193
[12] Warw ick R, W illiam s PL. Gray's An atom y. Philadelp h ia 1973
[13] Kid o DK, LeMay M, Levin son AW , Ben son W E. Com p uted tom ograph ic localization of th e precen tral
gyrus. Radiology. 1980; 135:373–377
[14] Mart in N, Grafton S, Viñ uela F, Dion J, et al. Im agin g
Tech n iqu es for Cor tical Fu n ct ion al Localization . Clin
Neu rosu rg. 1990; 38:132–165
[15] An derson JE. Grant's Atlas of An atom y. Baltim ore:
W illiam s an d W ilkin s; 1978; 7
[16] W ilkin s RH, Ren gach ar y SS. Neurosurger y. New
York 1985
[17] Lusted LB, Keats TE. Atlas of Roen tgen ographic
Measu rem en t . 3rd ed . Ch icago: Year Book Medical
Publish ers; 1972
[18] Gh ajar JBG. A Guide for Ven tricular Cath eter Placem en t: Tech n ical Note. J Neurosurg. 1985; 63:985–
986
[19] Watkin s RG. In : Anterior Cer vical Approach es to the
Spine. Surgical Approaches to th e Spin e. New York:
Sprin ger-Verlag; 1983:1–6
[20] Rh oton AL, Jr. Th e cerebellopon tin e an gle an d posterior fossa cran ial n er ves by th e retrosigm oid
ap proach . Neu rosu rgery. 2000; 47:S93–129
[21] Dvorak J, Panjabi MM. Fun ct ional An atom y of the
Alar Ligam en ts. Spin e. 1987; 12:183–189
[22] Dickm an CA, Craw ford NR, Bran tley AGU, Son n tag
VKH, Koen em an JB. In vitro cervical spin e biom ech an ical test in g. BNI Qu arterly. 1993; 9:17–26
Vascular Anat om y
75
2 Vascular Anat om y
2
2.1 Cerebral vascular t errit ories
Fig. 2.1 depicts approxim ate vascular dist ribution s of th e m ajor cerebral arteries. Th ere is con siderable variabilit y of th e m ajor arteries 1 as w ell as th e cen tral distribution . Th e len ticulostr iates m ay
h ave origin s o of di eren t segm en ts of th e m iddle or an terior cerebral artery). Recurren t ar ter y of
Heubn er (RAH) (AKA m edial st riate arter y) origin : jun ct ion of th e ACA an d a-com m in 62.3%, proxim al A2 in 23.3%, A1 in 14.3%.2
2.2 Cerebral art erial anat om y
2.2.1 General inform at ion
Th e sym bol “ ” is used to den ote a region supplied by th e in dicated arter y. See An giography (cerebral) (p. 236) for an giograph ic diagram s of th e follow in g an atom y.
2.2.2 Circle of Willis
See Fig. 2.2. A balan ced con figuration of th e Circle of W illis is presen t in on ly 18% of th e populat ion . Hypoplasia of 1 or both p -com m s occurs in 22–32%, absen t or hypoplastic A1 segm en ts occurs
in 25%.
Key poin t: th e an terior cerebral arteries pass over th e superior surface of th e opt ic ch iasm .
2.2.3 Anat om ical segm ent s of int racranial cerebral art eries
1. carotid artery: th e t radition al n um berin g system 3 w as from rostral to caudal (coun ter to th e
direct ion of flow, an d to th e n um berin g sch em e of th e oth er arteries). A n um ber of system s h ave
been described to addresses th is in con sistency an d also to iden tify an atom ically im por tan t segm en ts of th e ICA th at w ere n ot origin ally delin eated (e.g. see Table 2.1 4 ). Also see below for
m ore detail
AXIAL VIEW
CORONAL VIEW
a nte rior ce re bra l
a rte ry
middle ce re bra l
a rte ry
RAH
MCA
AChA
inte rna l ca rotid
PCommA
ba s ila r a rte ry
a nte rior choroida l
a rte ry
poste rior cere bra l
a rte ry
Fig. 2.1 Vascular territories of the cerebral hemispheres. RAH = recurrent artery of Heubner.
76
Anat om y and Physiology
optic n.
(Cr. N. II)
2
central retinal a.
ACAs
a-comm a.
(hidden)
ophthalmic a.
pituitary
ICA
superior hypophyseal a.
MCA
medial &lateral
lenticulostriate aa.
anterior choroidal a.
p-comm a.
PCA
oculomotor n.
(Cr. N. III)
SCA
{
2
P
P1
choroid plexus
pons
pontine aa.
AICA
basilar a.
vertebral a.
PICA
anterior spinal a.
Fig. 2.2 Circle of Willis viewed from in front of and below the brain
2. an terior cerebral5 :
a) A1 (precom m un icating): ACA from origin to ACoA
b) A2 (postcom m un icat in g): ACA from ACoA to bran ch -poin t of callosom argin al
c) A3 (precallosal): from bran ch -poin t of callosom argin al cur vin g aroun d th e gen u of th e corpus
callosum to superior surface of corpus callosum 3 cm posterior to th e gen u
d) A4: (supracallosal)
e) A5: term in al bran ch (postcallosal)
3. m iddle cerebral6 :
a) M1: MCA from or igin to bifu rcat ion (h orizon t al segm en t on AP an giogram ). A classical
bifu rcat ion in to relat ively sym m et r ical su p er ior an d in fer ior t r u n ks is seen in 50%, n o
bifu rcat ion occu rs in 2%, 25% h ave a ver y p roxim al bran ch (m id d le t ru n k) ar isin g from t h e
su p e rior (15%) or t h e in ferior (10%) t r u n k creat in g a “p seu d o-t r ifu rcat ion ”, a p seu d o -tet rafu rcat ion occu rs in 5%
Vascular Anat om y
77
Table 2.1 Segm ents of the ICA
Cincinnati syst em
Syst em of Fischer
C1 (cervical)
Not described
C2 (petrous)
C3 (lacerum )
C5
C4 (cavernous)
C4 + part of C5
C5 (clinoid)
C3
C6 (ophthalm ic)
C2
C7 (comm unicating)
C1
lateral fron to-orbital an d prefron tal bran ch es arise from M1 or superior M2 t run k
● precen tral, cent ral, an terior an d posterior parietal arteries arise from a superior (60%) or
m iddle (25%) or in ferior (15%) trun k
● th e superior M2 trun k does n ot give any bran ch es to th e tem poral lobe
b) M2: MCA trun ks from bifurcat ion to em ergen ce from Sylvian fissure
c) M3–4: distal bran ches
d) M5: term in al bran ch
4. posterior cerebral (PCA) (several n om en clature sch em es exist 5,7 ):
a) P1: PCA from th e origin to posterior com m un icatin g ar ter y (AKA m esen ceph alic, precom m un icating, circular, pedun cular, basilar…). Th e lon g an d sh or t circum flex an d th alam operforatin g ar teries arise from P1
b) P2: PCA from origin of p -com m to th e origin of in ferior tem poral arteries (AKA am bien t , postcom m un icatin g, perim esen ceph alic), P2 traverses th e am bien t cistern , Hippocam pal, an terior
tem poral, pedun cular perforatin g an d m edial posterior ch oroidal arteries arise from P2
c) P3: PCA from th e origin of th e in ferior tem poral bran ch es to th e origin of th e term in al
bran ch es (AKA quadrigem in al segm en t). P3 t raverses th e quadrigem in al cistern
d) P4: segm en t after th e origin of th e parieto-occipital an d calcarin e ar teries, in cludes th e cort ical bran ch es of th e PCA
●
2.2.4 Ant erior circulat ion
Anat om ic variant s
Bovin e circulation : th e com m on carotids arise from a com m on trun k o th e aorta.
Ext ernal carot id
1. superior thyroid a.: 1st an terior bran ch
2. ascen din g ph aryn geal a.
a) n eurom en ingeal t run k of th e ascen din g ph ar yn geal a.: supplies IX, X & XI (im por tan t w h en
em bolizin g glom us tum ors, 20% of low er cran ial n er ve palsy if th is bran ch is occluded)
b) ph ar yn geal bran ch : usually th e prim ar y feeder for jugular foram en tum ors (essen tially th e
only cause of hypertrophy of th e ascen din g ph ar yn geal a.)
3. lin gual a.
4. facial a.: bran ch es an astam ose w ith oph th alm ic a.; im portan t in collateral flow w ith ICA occlusion (p. 1265)
5. occipital a. posterior scalp
6. posterior auricular
7. superficial tem poral
a) fron tal bran ch
b) parietal bran ch
8. (in tern al) m axillar y a. – in itially w ith in parotid glan d
a) m iddle m en in geal a.
● an terior bran ch
● posterior bran ch
2
78
2
Anat om y and Physiology
b) accessory m en ingeal
c) in ferior alveolar
d) in fra-orbital
e) oth ers: distal bran ch es of w h ich m ay an astom ose w ith bran ch es of oph th alm ic artery in th e
orbit
Int ernal carot id art ery (ICA)
Lies posterior & m edial to th e extern al carotid (ECA).
Segm ents of the ICA and its branches
See Fig. 2.3 for bran ch es, an d referen ce.4
1. C1 (cer vical): begin s in n eck at carotid bifurcat ion w h ere th e com m on carotid ar ter y divides in to
in tern al an d extern al carot ids. Travels in carotid sh eath w ith IJV an d vagal n er ve, en circled w ith
postganglion ic sym path etic n er ves (PGSN). C1 en ds w h ere th e ICA en ters carotid can al of petrous
bon e. No bra nches
2. C2 (petrous): still surroun ded by PGSNs. En ds at th e posterior edge of th e foram en lacerum (fLac) (in ferom edial to th e edge of th e Gasserian gan glion in Meckel’s cave). Th ree division s:
anterior cerebral
anterior choroidal
posterior parietal
angular artery
posterior
temporal
central
artery
PCal
CM
LS
ACom
FP
RH
LS
ascending
frontal
anterior
temporal
orbitofrontal
ophthalmic
OF
PCom
internal carotid
Fig. 2.3 Internal carotid arteriogram (AP view).
ACom: anterior com municating artery
CM: callosom arginal artery
FP: frontopolar artery
LS: lenticulostriate arteries
OF: orbitofrontal artery
PCal: pericallosal artery
PCom : posterior com municating artery
RH: recurrent artery of Heubner (Reprinted courtesy of Eastman Kodak Company)
Vascular Anat om y
3.
4.
5.
6.
7.
8.
a) vert ical segm en t: ICA ascen ds th en ben ds as th e…
b) posterior loop: an terior to coch lea, ben ds an tero-m edially becom ing th e…
c) h orizon tal segm en t: deep an d m edial to greater an d lesser superficial petrosal n er ves, an terior to t ym pan ic m em bran e (TM)
C3 (lacerum ): th e ICA passes over (but n ot th rough ) th e f-Lac form ing th e lateral loop. Ascen ds in
th e can alicular portion of th e f-Lac to juxtasellar position , piercin g th e dura as it passes th e petrolin gual ligam en t to becom e th e cavern ous segm en t. Bran ch es (usually n ot visible
an giograph ically):
a) caroticot ym pan ic (in con sisten t) t ym pan ic cavit y
b) pter ygoid (vidian ) bran ch : passes th rough foram en lacerum , presen t in on ly 30%, m ay con tin ue as artery of pter ygoid can al
C4 (cavern ous): covered by vascular m em bran e lin in g sin us, still surroun ded by PGSNs. Passes
an teriorly th en supero-m edially, ben ds posteriorly (m edial loop of ICA), t ravels h orizon tally, an d
ben ds an teriorly (part of an terior loop of ICA) to an terior clinoid process. En ds at th e proxim al
dural rin g (in com pletely en circles ICA). Many bran ch es, m ain on es in clude:
a) m en in gohypophyseal trun k (MHT) (largest & m ost proxim al). 2 causes of a prom in en t MHT:
1) tum or (usually petroclival m en ingiom a – see below ), 2) dural AVM (p.1251)
● a. of ten torium (AKA ar tery of Bern ascon i & Cassin ari): th e blood supply of petroclival
m en in giom as
● dorsal m en in geal a. (AKA dorsal clival a.)
● in ferior hypophyseal a. (
posterior lobe of pit uitar y): post-part um occlusion causes pit uitar y in farcts (Sh eeh an’s n ecrosis), h ow ever, DI is rare because th e stalk is spared
b) anterior m en ingeal a.
c) a. to in ferior portion of cavern ous sin us (presen t in 80%)
d) capsular aa. of McCon n ell (in 30%): supply th e capsule of th e pituitar y 8
C5 (clin oid): begin s at proxim al dural rin g, en ds at distal dural rin g (w h ich com pletely en circles
ICA) w h ere th e ICA becom es in t radural
C6 (oph th alm ic): begin s at distal dural ring, en ds just proxim al to p -com m . Bran ch es:
a) oph th alm ic a.: th e origin from th e ICA is distal to th e cavern ous sin us in 89%(in t racavern ous
in 8%, th e oph th alm ic ar ter y is absen t in 3%9 ) an d can var y from 5 m m an terior to 7 m m posterior to th e an terior clin oid.8 Passes th rough th e optic can al in to th e orbit (th e in tracran ial
course is ver y sh ort , usually 1–2 m m 8 ). Has a ch aracteristic bayon et-like “kin k” on lateral
an giogram
b) superior hypophyseal a. bran ch es an terior lobe of pituitar y & stalk (1st bran ch of supraclin oid ICA)
C7 (com m un icating): begin s just proxim al to p -com m origin , t ravels bet w een Cr. N. II & III, term in ates just below an terior perforated substan ce w h ere it bifurcates in to th e ACA & MCA
a) posterior com m un icatin g a. (p -com m )
● few an terior th alam operforators (
optic tract, ch iasm & posterior hypoth alam us): below
● plexal segm en t: en ters supracorn ual recess of tem poral h orn ,
on ly th is port ion of ch oroid
plexus
● cistern al segm en t: passes th rough crural cistern
b) anterior ch oroidal arter y 10 : takeo 2–4 m m distal to p -com m
(variable) por tion of optic
t ract , m edial globus pallidus, gen u of in tern al capsule (IC) (in 50%), in ferior h alf of posterior
lim b of IC, un cus, retrolen ticular fibers (optic radiation ), lateral gen iculate body; for occlusion
syn drom es (p. 1265)
“Carotid siph on ”: n ot a segm en t, but a region in corporatin g th e cavern ous, oph th alm ic an d com m un icating segm en ts. Begin s at th e posterior ben d of th e cavern ous ICA, an d en ds at th e ICA
bifurcation
Different iat ing p -com m from ACh on art eriogram
1.
2.
3.
4.
p-comm origin is proxim al to that of the anterior choroidal artery (ACh)
p-comm is usually larger than ACh
p-comm usually goes up or down a lit tle, then straight back & usually bifurcates
ACh usually has a superior “hump” (plexal point) where it pass through the choroidal fissure to
enter the ventricle
79
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Anat om y and Physiology
Ant erior cerebral art ery (ACA)
2
Passes bet w een Cr. N. II an d an terior perforated substan ce. See Fig. 2.4. Bran ches:
1. recurren t arter y (of Heubn er): t ypically arises from th e area of th e A1/A2 jun ct ion . Various statistics can be foun d in th e literature regardin g th e percen tage th at arise from distal A1 vs. proxim al
A2.11 It m ost im portan t to be m in dful th at th e takeo is variable, e.g. w h en treatin g an eur ysm s
(on e of th e larger m edial len ticulostriates, rem ain der of len ticulostr iates m ay arise from th is
artery) h ead of caudate, putam en , an d an terior in tern al capsule
2. m edial orbitofron tal ar ter y
3. fron topolar ar ter y
4. callosom argin al
a) in tern al fron tal bran ch es
● an terior
● m iddle
● posterior
b) paracen tral arter y
5. pericallosal arter y (con tin uation of ACA)
a) superior in tern al parietal (precun eate) ar ter y
b) in ferior in tern al parietal arter y
Anatom ic variants
Hyp oid : h avin g on ly on e an terior cerebral arter y (as in a h orse).
Middle cerebral art ery (MCA)
See Fig. 2.5 an d an atom y (p. 76). Bran ch es var y w idely, 10 com m on on es:
1. m edial (3–6 per side) an d lateral len ticulostriate ar teries
2. an terior tem poral
3. posterior tem poral
4. lateral orbitofron tal
5. ascen din g fron tal (can delabra)
6. precen tral (prerolan dic)
7. cent ral (rolan dic)
8. an terior parietal (post rolan dic)
9. posterior parietal
10. an gular
Post erior circulat ion
Anatom ic variants
Fetal circulation : 15–35% of patien ts supply th eir posterior cerebral artery on on e or both sides prim arily from th e carotid (via p -com m ) in stead of via th e vertebrobasilar system .
Vertebral artery (VA)
Th e VA is th e first an d usually th e largest bran ch of th e subclavian ar ter y. Varian t: th e left VA arises
o th e aor tic arch in ≈ 4%. Diam eter ≈ 3 m m . Mean blood flow ≈ 150 m l/m in . Th e left VA is dom in an t
in 60%. Th e righ t VA w ill be hypoplastic in 10%, an d th e left w ill be hypoplastic in 5%. Th e VA is atretic
an d does n ot com m un icate w ith th e BA on th e left in 3%, an d on th e righ t in 2% (th e VA m ay term in ate in PICA).
Four segm en ts:
● V1 prevertebral: from subclavian ar tery, courses superiorly an d posteriorly an d en ters th e foram en tran sversarium , usually of th e 6th ver tebral body
● V2 ascen ds vertically w ith in th e tran sverse foram in a of th e cer vical vertebrae surroun ded by sym path et ic fibers (from th e stellate gan glion ) an d a ven ous plexus. It is sit uated a nter ior to th e cervical roots. It turn s laterally to en ter th e foram en w ith in th e t ran sverse process of th e axis
● V3 exits th e foram en of th e axis an d cur ves posteriorly an d m edially in a groove on th e upper surface of th e atlas an d en ters th e foram en m agn um
● V4 pierces th e dura (location som ew hat variable) an d im m ediately en ters th e subarach n oid space.
Join s th e con tralateral VA at th e ver tebral con fluen s located at th e low er pon tin e border to form
th e basilar arter y (BA)
Vascular Anat om y
superior
(precuneate)
paracentral
Internal frontal
posterior
inferior
}
internal
parietal
middle
anterior
callosomarginal
pericallosal
frontopolar
anterior choroidal
medial
orbitofrontal
choroid crescent
of eye
ophthalmic
tuberculum sellae
posterior communicating
internal carotid
Fig. 2.4 Anterior cerebral arteriogram (lateral view) (Reprinted courtesy of Eastm an Kodak Com pany)
central
ascending
frontal
posterior parietal
angular
posterior
temporal
lateral
orbitofrontal
anterior temporal
internal carotid
Fig. 2.5 Middle cerebral arteriogram (lateral view) (Reprinted courtesy of Eastman Kodak Com pany)
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Anat om y and Physiology
Branches
P-comm
left PCA
III
SCA
IV
V
AICA
VI
VII/VIII
tvt
BA
IX
X
XII
left PICA
{
cs
lm
tm
am
2
An t er ior m en in geal. Arises at body of C2 (axis), m ay feed ch ordom as or foram en m agn um m en in giom as, m ay also act as collateral in vascular occlusion
Post er ior m en in geal. May be a source of blood for som e dural AVMs (p. 1251)
Med u llar y (bu lbar ) aa
Post er ior sp in al
Post er ior in fer ior cerebellar ar t er y (PICA) (largest bran ch ). Usually arises ≈10 m m distal to poin t
w h ere VA becom es in t radural, ≈ 15 m m proxim al to th e vertebrobasilar jun ct ion ( Fig. 2.6)
1. an atom ic varian ts:
a) in 5–8% th e PICA h as an extradural origin
b) “AICA-PICA”: origin is o basilar trun k (w h ere AICA w ould usually origin ate)
2. 5 segm en ts 12 (som e system s som e describe on ly 4). Durin g surgery, th e first th ree m ust be preser ved, but th e last 2 m ay usually be sacrificed w ith m in im al deficit 13 :
a) an terior m edullary: from PICA origin to in ferior olivar y prom in en ce. 1 or 2 sh ort m edullary
sh ort circum flex bran ch es ven tral m edulla
b) lateral m edullar y: to origin of n er ves IX, X & XI. Up to 5 bran ch es th at supply brain stem
c) ton sillom edullar y: to ton sillar m idport ion (con tain s ca uda l loop on an gio)
left
VA
XI
Fig. 2.6 Intradural VA and PICA segments (lateral view) (Modified with perm ission from : Lewis SB, Chang DJ, Peace
DA, Lafrentz PJ, Day AL. Distal posterior inferior cerebellar artery aneurysms: clinical features and managem ent. J
Neurosurg 2002;97(4):756-66)
Vascular Anat om y
d) teloveloton sillar (supraton sillar): ascen ds in ton sillom edullar y fissure (con tain s cra nia l loop
on angio)
e) cort ical segm en ts
3. 3 bran ch es
a) ch oroidal a. (BRANCH 1) arises from cran ial loop (choroida l point), ch oroid plexus of 4th
ven tr icle
b) term in al bran ch es:
● ton silloh em isph eric (BRANCH 2)
● in ferior verm ian (BRANCH 3) in ferior in flect ion = copula r point on an gio
An t er ior sp in al
Basilar artery (BA)
Form ed by th e jun ct ion of th e 2 vertebral arteries. Bran ch es:
1. an terior in ferior cerebellar arter y (AICA): from low er par t of BA, run s posterolaterally an terior to
VI, VII & VIII. Often gives o a loop th at run s in to th e IAC an d gives o th e labyrin th in e artery an d
th en em erges to supply th e an terolateral in ferior cerebellum an d th en an astom oses w ith PICA
2. in tern al auditor y (labyrin th in e)
3. pon tin e bran ch es
4. superior cerebellar a. (SCA)
a) sup. verm ian
5. posterior cerebral: join ed by p -com m s ≈ 1 cm from origin (th e p -com m is th e m ajor origin of th e
PCA in 15%an d is term ed “fetal” circulat ion , bilateral in 2%).
3 segm en ts (n am ed for surroun din g cistern ) an d th eir bran ch es:
a) pedun cular segm en t (P1)
● m esen ceph alic perforatin g aa. (
tectum , cerebral pedun cles, an d th ese n uclei: EdingerWestph al, oculom otor an d t roch lear)
● in terpedun cular th alam operforators (1st of 2 groups of posterior th alam operforatin g aa.)
● m edial post . ch oroidal (m ost from P1 or P2)
● “ar ter y of Perch eron”: a rare an atom ic varian t 14 in w h ich a solitar y arterial t run k arisin g
from th e proxim al segm en t of on e PCA supplies th e param edian th alam i an d rostral m idbrain bilaterally
b) am bien t segm en t (P2)
● lateral post . ch oroidal (m ost from P2)
● th alam ogen iculate th alam operforators (2n d of 2 groups of posterior th alam operforatin g
aa.) geniculate bodies + pulvinar
● an terior tem poral (an astam oses w ith an terior tem poral br. of MCA)
● posterior tem poral
● parieto-occipital
● calcarin e
c) quadrigem in al segm en t (P3)
● quadrigem in al & gen iculate bran ches
quadrigem in al plate
● post. pericallosal (splen ial) (an astom oses w ith pericallosal of ACA)
Posterior cerebral artery (PCA)
See
Fig. 2.7.
Carot id-vert ebrobasilar anast om oses
P-com m artery: th e “n orm al” (m ost com m on ) an astom osis.
Persisten t fetal an astam oses 15 ( Fig. 2.8) result from failure to involute as th e VAs an d p -com m s
develop (order of involution : otic, hypoglossal, prim it ive t rigem in al, proatlan tal). Most are asym ptom at ic. How ever, som e m ay be associated w ith vascular an om alies such as an eur ysm s or AVMs, an d
occasion ally cran ial n er ve sym ptom s (e.g. t rigem in al n euralgia w ith PPTA) can occur.
Four t ypes (from cran ial to caudal – th e 1st 3 are n am ed for th e associated cran ial n er ve):
1. persisten t prim itive t rigem in al arter y (PPTA): seen in ≈ 0.6%of cerebral an giogram s. Th e m ost
com m on of th e persisten t fetal an astom oses (83%). May be associated w ith trigem in al n euralgia
(p. 479). Con n ects th e cavern ous carotid to th e basilar arter y. Arises from th e ICA proxim al to th e
origin of th e m en in gohypophyseal t run k (50% go th rough sella, 50% exit th e cavern ous sin us &
course w ith th e trigem in al n er ve) an d con n ects to th e upper basilar ar ter y betw een AICA & SCA.
Th e VAs m ay be sm all. Saltzm an t ype 1 varian t: th e p -com m s are hypoplastic an d th e PPTA provides sign ifican t blood supply to th e dist ribution s of th e distal BA, PCA an d th e SCAs (th e basilar
83
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Anat om y and Physiology
posterior
choroidals
posterior cerebral
superior cerebellar
thalamoperforators
posterior
communicating
anterior temporal
posterior pericallosal
parieto-occipital
{
lateral
medial
calcarine
superior vermian
posterior
temporal
hemispheric
branches
lateral marginal
basilar
tvt cs
lm
am
{
lateral branch
AICA medial branch
tm
}
choroidal branch
inferior vermian
hemispheric branch
tonsillar branch
P ICA
bra nche s
PICA segments
am = anterior medullary
lm = lateral medullary
tm = tonsillomedullary (w/caudal loop)
tvt = telovelotonsillar (supratonsillar) (w/cranial loop)
cs = cortical segments
vertebral arteries
Fig. 2.7 Vertebrobasilar arteriogram (lateral view) (Reprinted courtesy of Eastman Kodak Com pany)
P-Comm
Fig. 2.8 Carotid-vertebrobasilar anastomoses
PCA
SCA
trigeminal
otic
AICA
PICA
hypoglossal
proatlanta
roatlantal
C1
C2
ICA
VA
artery is often hypoplastic). Salt zm an t ype 2: p -com m supplies PCA. Saltzm an t ype 3: PPTA join s
th e SCA (in stead of th e BA). It is crit ical to recogn ize a PPTA before doing a Wada test (p.1553)
because of th e risk an esth et izing th e brain stem , an d in doing t ran ssph en oidal surgery because of
risk of arterial injur y. May rarely be an explan ation of posterior fossa sym ptom s in a patien t w ith
carotid disease
2. otic: th e first to involute, an d th e rarest to persist (8 cases reported). Passes th rough IAC to con n ect petrous carotid to basilar artery
3. hypoglossal: con n ects petrous or distal cervical ICA (origin usually betw een C1-C3) to VA. Traverses th e hypoglossal can al. Does n ot cross foram en m agn um
Vascular Anat om y
85
4. proatlan tal in tersegm en tal: con n ects cer vical ICA to VA. May arise from : bifurcation of com m on
carotid, ECA, or ICA from C2-C4. An astom osis w ith VA in suboccipital region . 50%h ave hypoplast ic proxim al VA. 40 cases reported
2
2.3 Cerebral venous anat om y
2.3.1 Suprat ent orial venous syst em
Major veins and t ribut aries
See Fig. 2.9 for an giogram an d bran ch es.
Th e left an d righ t in tern al jugular vein s (IJVs) are th e m ajor source of outflow of blood from th e
in tracran ial com part m en t. Th e r ight IJV is usually dom in an t. Oth er sources of outflow in clude orbital
vein s an d th e ven ous plexuses aroun d th e vertebral arteries. Diploic an d scalp vein s m ay act as collateral path ways, e.g. w ith superior sagittal sin us obstruct ion .16 Th e follow in g outlin e t races th e
ven ous drain age back from th e IJVs.
Inferior petrosal sinus
Term in ates (i.e. drain s to) ≤ 1 cm of jun ction of sigm oid an d tran sverse sin uses.
Sigm oid sinus
superior petrosal sinus
Drain s to IJV n ear jun ct ion w ith sigm oid sin us
anterior caudate vein
thalamostriate vein
inferior
sagittal
sinus
superior
sagittal
sinus
superior anastamotic
vein (of Trolard)
direct lateral v.
internal cerebral v.
posterior septal v.
great cerebral
vein (of Galen)
vein of
posterior horn
straight sinus
TC
IVs
septal vein
superficial middle
cerebral vein
sphenoparietal sinus
cavernous sinus
deep middle cerebral vein
basal cerebral
vein (of Rosenthal)
inferior anastamotic
vein (of Labbé)
Torcular herophili
transverse sinus
sigmoid sinus
TC = transverse caudate veins
IVs = insular veins
Fig. 2.9 Internal carotid venogram (lateral view) (Reprinted courtesy of Eastman Kodak Com pany)
86
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Anat om y and Physiology
Transverse sinus
R > L in 65%.
V. of Labbe. (In ferior an astom ot ic v.)
Con flu en s of sin u ses. (Torcular h eroph ili)
1. occipital sin us
2. superior sagittal sin us
a) v. of Trolard (superior an astom otic v.): th e prom in ent superficial vein on th e non-domina nt
side (Labbé is m ore prom in en t on th e dom in an t side)
b) cort ical vein s
3. st raigh t sin us
a) in ferior sagit tal sin us
b) great cerebral v. (of Galen )
● pre-cen t ral cerebellar v.
● basal vein of Rosen th al
● in tern al cerebral v.: join ed at th e foram en of Mon ro (ven ous an gle) by:
an terior septal v.
th alam ostriate v.
Cavernous sinus
Origin ally n am ed for its superficial resem blan ce to th e corpora cavern osa. Alth ough classical teach in g depicts th e cavern ous sin us as a large ven ous space w ith m ultiple t rabeculation s, inject ion studies 17 an d surgical experien ce 18 in stead supports th e con cept of th e cavern ous sin us as a plexus of
vein s. It is h igh ly variable betw een in dividuals an d from side-to-side. Fig. 2.10 is an oversim plified
sch em atic of on e sect ion th rough th e righ t cavern ous sin us.
1. in flow in g vein s:
a) superior & in ferior oph th alm ic vein s
b) superficial m iddle cerebral vein s
c) sph enoparietal sin us
d) superior & in ferior petrosal sin us
2. outflow :
a) sph enoparietal sin us
b) superior petrosal sin us
c) basilar plexus (w h ich drain s to th e in ferior petrosal sin us)
d) pter ygoid plexus
e) th e righ t an d left cavern ous sin uses com m un icate an teriorly an d posteriorly via th e circular
sin us
3. con ten ts19
a) Oculom otor n . (III)
b) Troch lear n . (IV)
Diaphragm a
sellae
Optic chiasm
CAVERNOUS
SINUS
Internal
carotid artery
Oculom otor (III)
Outer layer (dura propria)
Inner mem branous layer
Pituitary
}
Sphenoid
air sinus
Fig. 2.10 Right cavernous sinus (coronal section)
Trochlear (IV)
Triangular space
(of Parkinson)
Abducent (VI)
Ophthalm ic (V1)
Maxillary (V2)
Cords of Willis
Vascular Anat om y
c) Oph th alm ic division of t rigem in al (V1)
d) Maxillar y division of t rigem in al (V2): th e on ly n er ve of th e cavern ous sin us th at doesn’t exit
th e skull th rough th e superior orbital fissure (it exits th rough foram en rotun dum )
e) Carotid arter y (ICA). 3 segm en ts w ith in th e cavern ous sin us
● posterior ascen din g segm en t: im m ediately after ICA en ters th e sin us
● h orizon tal segm en t: after ICA t urn s an teriorly (th e lon gest segm en t of th e in t racavern ous
ICA)
● an terior ascen ding segm en t: ICA turn s superiorly
f) Abducen s n . (VI): th e on ly n er ve NOT attach ed to lateral dural w all, som etim es referred to as
th e on ly cran ial n er ve in side th e cavern ous sin us
4. t rian gular space (of Parkin son ): superior border form ed by Cr. N. III & IV, an d th e low er m argin
form ed by V1 & VI (a lan dm ark for surgical en tran ce to th e cavern ous sin us)20,21 (p 3007)
2.3.2 Posterior fossa venous anat om y
See
Fig. 2.11.
2.4 Spinal cord vasculat ure
See Fig. 2.12.
Alth ough a radicular arter y from th e aorta accom pan ies th e n er ve root at m any levels, m ost of
th ese con tribute lit tle flow to th e spin al cord itself. Th e an terior spin al arter y is form ed from th e
jun ction of t w o bran ch es, each from on e of th e ver tebral arteries. Major con tributors of blood supply
to th e an terior spin al cord is from 6–8 radicular ar teries at th e follow in g levels (“radiculom edullar y
arteries”, th e levels listed are fairly con sisten t, but th e side varies 22 (p 1180–1)):
1. C3 – arises from vertebral ar ter y
2. C6 an d C8 (≈ 10% of population lack an an terior radicular artery in low er cervical spin e 23 )
a) C6 – usually arises from deep cervical ar tery
b) C8 – usually from costocervical t run k
3. T4 or T5
4. artery of Adam kiew icz AKA arteria radicularis an terior m agn a
a) th e m ain ar terial supply for th e spin al cord from ≈ T8 to th e con us
b) located on th e left in 80%24
c) sit uated betw een T9 & L2 in 85% (betw een T9 & T12 in 75%); in rem ain ing 15% betw een T5 &
T8 (in th ese latter cases, th ere m ay be a supplem en tal radicular ar tery furth er dow n )
great cerebral vein (Galen)
precentral cerebellar v.
posterior mesencephalic v.
lateral mesencephalic v.
anterior pontomesencephalic v.
tuberculum sellae
transverse
pontine vein
brachial vein
internal occipital v.
superior vermian v.
transverse sinus
superior hemispheric v.
straight sinus
inferior hemispheric v.
inferior vermian v.
superior petrosal sinus
anterior medullary v.
petrosal vein
vein of the lateral recess of the 4th ventricle
Fig. 2.11 Vertebrobasilar venogram (lateral view) (Reprinted courtesy of Eastman Kodak Com pany)
87
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88
Anat om y and Physiology
basilar artery
spinal cord
2
radicular artery at C3
anterior spinal artery
radicular artery at C6
right vertebral
artery
right common
carotid
left vertebral
artery
left common
carotid
right
subclavian
brachiocephalic trunk
deep cervical artery
costocervical trunk
radicular artery at C8
left subclavian
left posterior spinal artery
}
radicular artery at T5
aorta
posterior intercostal artery
(dorsal branch)
posterior
spinal arteries
radicular
artery
aorta
Axia l vie w
posterior
intercostal
artery
anterior
spinal
artery
intercostal arteries
artery of
Adamkiewicz
(arteria radicularis
anterior magna)
arteria radicularis
magna
(posterior branch)
Fig. 2.12 Schem atic diagram of spinal cord arterial supply (Modified from Diagnostic Neuroradiology, 2nd ed.,
Volume II, pp. 1181, Taveras J M, Woods EH, editors, © 1976, the William s and Wilkins Co., Baltimore, with
perm ission))
d) usually fairly large, gives o ceph alic an d caudal bran ch (latter is usually larger) giving a ch aracteristic h air-pin appearan ce on an giography
Th e paired posterior spin al arteries are less w ell defin ed th an th e an terior spin al arter y, an d are fed
by 10–23 radicular bran ch es.
Th e m idth oracic region h as a tenuous vascular supply (“w atersh ed zon e”), possessin g on ly th e
above n oted arter y at T4 or T5. It is th us m ore susceptible to vascular in sults.
An at om ic var ian t s. Arcade of Lazorth es: n orm al varian t w h ere th e an terior spinal artery join s
w ith th e paired posterior spin al ar teries at th e con us m edullaris.
Vascular Anat om y
89
References
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Dragovic L. Variability of th e Territories of th e Major
Cerebral Arteries. J Neurosurg. 1992; 77:927–940
[2] Lou kas M, Louis RG, Jr, Ch ilds RS. An atom ical exam in ation of th e recurren t artery of Heubner. Clin An at.
2006; 19:25–31
[3] Fisch er E. Die Lageabw eich ungen d er Vorderen Hirn ar terie im Gefässbild. Zen tralbl Neurochir. 1938;
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[4] Bou th illier A, van Loveren HR, Keller JT. Segm en ts
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[5] Krayen bü h l HA, Yasargil MG. Cerebral An giograp hy.
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Georg Th iem e Verlag; 1979:38–246
[7] Ecker A, Riem en sch n eid er PA. An giograph ic Localization of In t racran ial Masses. Sprin gfield, Illin ois:
Ch arles C. Th om as; 1955
[8] Gibo H, Len key C, Rh oton AL. Microsurgical An atom y of th e Su praclin oid Port ion of th e In tern al Carotid Artery. J Neu rosu rg. 1981; 55:560–574
[9] Ren n W H, Rh oton AL. Microsurgical An atomy of th e
Sellar Region. J Neurosurg. 1975; 43:288–298
[10] Rh oton AL, Jr. Th e su praten torial ar teries. Neu rosu rgery. 2002; 51:S53–120
[11] An atom ical exam in ation of th e recurren t artery of
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[12] Lister JR, Rh oton AL, Matsu sh im a T, et al. Microsu rgical An atom y of the Posterior In ferior Cerebellar
Artery. Neurosurgery. 1982; 10:170–199
[13] Getch CC, O'Sh augh n essy BA, Ben dok BR, Parkin son
RJ, Batjer HH. Surgical m an agem en t of in tracran ial
an eur ysm s involvin g th e p osterior in ferior cerebellar artery. Con tem p Neu rosu rg. 2004; 26:1–7
[14] Perch eron G. Th e an atom y of th e ar terial sup p ly of
th e h um an th alam us an d its use for the in terpretat ion of th e th alam ic vascular path ology. Z Neu rol.
1973; 205:1–13
[15] Luh GY, Dean BL, Tom sick TA, Wallace RC. Th e persisten t fetal carotid-vertebrobasilar an astom oses.
AJR Am J Roen tgen ol. 1999; 172:1427–1432
[16] Sch m id ek HH, Au er LM, Kap p JP. Th e Cerebral
Ven ou s System . Neurosurger y. 1985; 17:663–678
[17] Taptas JN. The So-Called Cavernous Sin us: A Review
of the Cont roversy an d Its Im plication s for Neurosu rgeon s. Neu rosu rger y. 1982; 11:712–717
[18] Sekh ar LN, Sch ram m VL. In : Operative Man agem en t
of Tum ors Involvin g th e Cavern ou s Sin us. Tu m ors of
th e Cran ial Base: Diagn osis an d Treatm en t. Mou n t
Krisco: Futura Publish in g; 1987:393–419
[19] Um an sky F, Nath an H. Th e Lateral Wall of th e Cavern ous Sin us: w ith Special Referen ce to the Nerves
Related to It. J Neurosurg. 1982; 56:228–234
[20] van Loveren HR, Keller JT, El-Kallin y M, Scodary DJ,
Tew JM. The Dolen c Tech n ique for Cavern ous Sin us
Exp loration (Cad averic Prosect ion ). J Neurosurg.
1991; 74:837–844
[21] Youm an s JR. Neurological Surgery. Ph iladelph ia
1982
[22] Taveras JM, Wood EH. Diagn ostic Neuroradiology.
2n d ed. Balt im ore: W illiam s an d W ilkin s; 1976
[23] Turnbull IM, Breig A, Hassler O. Blood Supply of th e
Cervical Spin al Cord in Man . A Microan giograph ic
Cadaver Stu d y. J Neurosurg. 1966; 24:951–965
[24] El-Kallin y M, Tew JM, van Loveren H, Du n sker S.
Surgical approach es to th oracic disk h ern iation s.
Acta Neu roch ir. 1991; 111:22–32
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3 Neurophysiology and Regional Brain Syndrom es
3.1 Neurophysiology
3
3.1.1 Blood-brain barrier
General inform at ion
Th e passage of w ater-soluble substan ces from th e blood to th e CNS is lim ited by t igh t jun ction s (zon ulae occluden tes) w h ich are foun d bet w een cerebral capillar y en doth elial cells, lim itin g pen etrat ion
of th e cerebral paren chym a (blood-brain barrier, BBB), as w ell as bet w een ch oroid plexus epith elial
cells (blood-CSF barrier).1 A n um ber of specialized m ediated tran sport system s allow t ran sm ission
of, am ong oth er th in gs, glucose an d certain am in o acids (especially precursors to
n eurotran sm itters).
Th e e cacy of th e BBB is com prom ised in certain path ological states (e.g. tum or, in fect ion , t raum a, st roke, h epatic en cephalopathy…), an d can also be m an ipulated ph arm acologically (e.g. hyperton ic m an n itol in creases th e perm eabilit y, w h ereas steroids reduce th e pen etrat ion of sm all
hydroph ilic m olecules).
Th e BBB is absen t in th e follow in g areas: ch oroid plexus, hypophysis, t uber cin ereum , area postrem a, pin eal an d preoptic recess.
Mean s of assessing th e in tegrit y of th e BBB:
● visible dyes: Evan’s blue, fluorescein
● radioopaque dyes (im aged w ith CT scan 2 ): iodin e (protein -boun d con trast agen t)
● param agnetic (im aged on MRI): gadolin ium (protein -boun d con trast agen t)
● m icroscopic: h orseradish peroxidase
● radiolabeled: album in , sucrose
Cerebral edem a and t he blood brain barrier
Th ree basic t ypes of cerebral edem a; di usion -w eigh ted MRI (p. 232) m ay be able to di eren tiate:
1. cytotoxic: BBB is closed, th erefore n o protein extravasation , th erefore n o en h an cem en t on CT or
MRI. Cells sw ell th en sh rin k. Seen e.g. in h ead injur y
2. vasogen ic: BBB disrupted. Protein (serum ) leaks out of vascular system , an d th erefore m ay
en h an ce on im agin g. Extracellular space (ECS) expan ds. Cells are stable. Respon ds to cort icosteroids (e.g. dexam eth ason e). Seen e.g. surroun din g m etastat ic brain tum or
3. isch em ic: a com bin ation of th e above. BBB closed in itially, but th en m ay open . ECS sh rin ks th en
expan ds. Fluid extravasates late. May cause delayed deterioration follow in g in t racerebral h em orrh age (p. 1337).
3.1.2 Babinski sign and Ho m ann sign
Int roduct ion
Alth ough th e Babin ski sign is regarded as th e m ost fam ous sign in n eurology, th ere is st ill disagreem en t over w h at con stitutes a n orm al respon se an d w h en abn orm al respon ses sh ould occur.3 Th e
follow in g represen ts on e in terpretation .
The plantar reflex (PR) (AKA Babinski sign after Joseph François Félix Babinski (1857–1932) a French
neurologist of Polish descent) is a prim itive reflex, present in infancy, consisting of extension of the great
toe in response to a noxious stim ulus applied to the foot. The sm all toes m ay fan, but this is not a consistent nor clinically important component. The PR disappears usually at ≈ 10 m onths age (range: 6 m os to
12 yrs), presum ably under inhibitory control as myelination of the CNS occurs, and the norm al response
then converts to plantarflexion of the great toe. An upper m otor neuron (UMN) lesion anyw here along
the pyram idal (corticospinal) tract from the motor strip dow n to ≈ L4 w ill result in a loss of inhibition,
and the PR w ill be “unm asked” producing extension of the great toe. With such an UMN lesion, there
m ay also be exaggeration of flexor synergy resulting in dorsiflexion of the ankle, and flexion of the knee
and hip (AKA triple flexor response) in addition to extension of the great toe.
Neuroanatom y
Th e a eren t lim b of th e reflex origin ates in cutan eous receptors restricted to th e first sacral derm atom e (S1) an d travels proxim ally via th e t ibial n er ve. Th e spin al cord segm en ts involved in th e
reflex-arc lie w ith in L4-S2. Th e e eren t lim b to th e toe exten sors t ravels via th e peronea l ner ve.
Neurophysiology and Regional Brain Syndrom es
91
Di erent ial diagnosis
Etiologies
Lesion s producin g a PR n eed n ot be structural, but m ay be fun ct ion al an d reversible. Th e roster of
possible etiologies is exten sive, som e are listed in Table 3.1.
Elicit ing t he PR, and variat ions
Th e optim al st im ulus con sists of stim ulat ion of th e lateral plan tar surface an d t ran sverse arch in a
sin gle m ovem en t lastin g 5–6 secon ds.4 Oth er m ean s for applyin g n oxious st im uli m ay also elicit th e
plan tar reflex (even outside th e S1 derm atom e, alth ough th ese do n ot produce toe flexion in n orm als). Described m an euvers in clude: Chaddock (scratch th e lateral foot; positive in 3%w h ere plan tar
st im ulation w as n egative), Sch ae er (pin ch th e Ach illes ten don ), Oppen h eim (slide kn uckles dow n
sh in ), Gordon (m om en tarily squeeze low er gastrocn em ius), Bing (ligh t pin pricks on dorsolateral
foot), Gon da or St ron sky (pull th e 4th or 5th toe dow n an d out an d allow it to sn ap back).
Ho m an’s (or Ho m ann’s or Ho m ann) sign
Attributed to Joh an n Ho m an n , a Germ an n eurologist pract icin g in th e late 1800. May sign ify a sim ilar UMN in terruption to th e upper extrem ities. Elicited by flicking dow nw ard on th e n ail of th e m iddle or rin g fin ger: a positive (path ologic) respon se con sists of involun tar y flexion of th e adjacen t
fin gers an d/or th um b (m ay be w eakly presen t in n orm als).5 Di ers from th e plan tar reflex sin ce it is
m on osyn aptic (syn apse in Rexed lam in a IX).
Can som etim es be seen as n orm al in youn g in dividual w ith di usely brisk reflexes & positive jaw
jerk, usually sym m etric. W h en present path ologically, represen ts disin h ibition of a C8 reflex, in dicates lesion above C8.
Ho m ann sign was observed in 68% of patients operated for cervical spondylotic myelopathy.5 In 11
patients presenting with lum bar sym ptom s but no myelopathy, a bilateral Ho m an sign was associated
w ith occult cervical spinal cord com pression in 10 (91%).5 The Ho m ann test has a sensitivity of 33-68%,
specificity of 59-78%, a positive predictive value of 26-62% and negative predictive value of 67-75%.6
3.1.3 Bladder neurophysiology
Cent ral pat hw ays
Th e prim ar y coordin at in g center for bladder fun ct ion resides w ith in th e n ucleus locus coeruleus of
th e pon s. Th is cen ter syn chron izes bladder con tract ion w ith relaxation of th e ureth ral sph incter durin g voidin g.7
Volun tary cort ical con trol prim arily involves in h ibition of th e pon t in e reflex, an d origin ates in th e
an terom edial port ion of th e fron tal lobes an d in th e genu of th e corpus callosum . In an un in h ibited
bladder (e.g. in fan cy) th e pon t in e voidin g center fun ct ion s w ith out cort ical in h ibition an d th e detrusor m uscle con tracts w h en th e bladder reach es a crit ical capacit y. Volun tary suppression from th e
cortex via th e pyram idal tract m ay con tract th e extern al sph in cter an d m ay also in h ibit detrusor
contract ion . Cortical lesion s in th is location → urgen cy in con tin en ce w ith in abilit y to suppress th e
m ict urition reflex.8 (p 1031)
E eren ts to th e bladder t ravel in th e dorsal portion of th e lateral colum n s of th e spin al cord
(shaded areas in Fig. 3.1).
Table 3.1 Di erential diagnosis of the plantar reflex (PR)
Et iologies
●
●
●
●
●
●
●
●
●
●
●
spinal cord injuriesa
cervical spinal m yelopathy
lesions in motor strip or internal capsule (stroke, tumor, contusion…)
subdural or epidural hem atom a
hydranencephaly
toxic-m etabolic coma
seizures
traum a
TIAs
hemiplegic m igraine
motor neuron disease (ALS)
a in spinal cord injuries, the PR m ay initially be absent during the period of spinal “shock” (p. 931)
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Anat om y and Physiology
Fig. 3.1 Location of spinal cord bladder efferents
(shaded)
3
Mot or
Th ere are t w o sph in cters th at preven t th e flow of urin e from th e bladder: in tern al (auton om ic, involun tar y con trol), an d extern al (st riated m uscle, volun tar y con trol).
Parasym pathet ics (PSN)
Th e detrusor m uscle of th e bladder con tracts an d th e in tern al sph in cter relaxes un der PSN st im ulat ion . PSN pregan glion ic cell bodies reside in th e in term ediolateral grey of spin al cord segm en ts S2–4.
Fibers exit as ven t ral n er ve roots an d travel via pelvic splan ch n ic n er ves (n er vi erigen tes) to term in ate on ganglia w ith in th e w all of th e detrusor m uscle in th e body an d dom e of th e bladder.
Som atic nerves
Som atic volun tary con trol descen ds in th e pyram idal t ract to syn apse on m otor n er ves in S2–4, an d
th en t ravels via th e puden dal n er ve to th e extern al sph incter. Th is sph in cter m ay be volun tarily con t racted, but relaxes reflexly w ith open in g of th e in tern al sph in cter at th e in it iation of m icturit ion .
Prim arily m ain tain s con tin en ce durin g ↑ vesical pressure (e.g. valsalva).
Sym pathetics
Sym path etic cell bodies lie w ith in th e in term ediolateral gray colum n of lum bar spin al cord from segm en ts T12 —L2. Preganglion ic axon s pass th rough th e sym path et ic ch ain (w ith out syn apsing) to th e
in ferior m esen teric ganglion . Postganglion ic fibers pass th rough th e in ferior hypogast ric plexus to
th e bladder w all an d in tern al sph incter. Sym path et ics h eavily in n er vate th e bladder n eck an d trigon e. Sym path et ics h ave litt le e ect on bladder m otor activity, but alph a adren ergic stim ulation
results in bladder n eck closure w h ich is n ecessar y for bladder filling.
Pelvic n er ve st im ulation → in creased sym path et ic ton e → detrusor relaxation & in creased bladder
n eck ton e (allow in g larger volum e to be accom m odated).
Sensory
Less w ell un derstood th an m otor in n er vation . Bladder w all stretch receptors sen se bladder fillin g
an d sen d a eren t sign als via pelvic, puden dal an d hypogastric n er ves to spin al cord segm en ts T10L2 & S2–4. Fibers ascen d prim arily in th e spinoth alam ic t ract .
Urinary bladder dysfunct ion
Th e term n eurogen ic bladder describes bladder dysfun ct ion due to lesion s w ith in th e cen tral or
periph eral n er vous system s. Som e use th e term syn onym ously w ith detrusor areflexia.
Dorsal (sen sory) roots lesion s in terrupt th e a eren t lim b, producin g an aton ic bladder th at fills
un til dribbling an d overflow in con tin en ce occur. No sen sation of bladder fulln ess is appreciated. Volun tar y voidin g is still possible, but is usually in com plete.
Det rusor hyperreflexia
Can result from in terruption of e eren ts anyw h ere from cortex to sacral cord. W h en a critical volum e is attain ed, reflex bladder em pt ying occurs. Clin ically associated w ith frequen t, un con trollable,
Neurophysiology and Regional Brain Syndrom es
93
precipitous voidin g. Cerebral lesion s in clude: st roke, h ead injur y, brain tum ors, hydroceph alus, Parkin son’s disease, various dem en tias, an d MS. Cord lesion s in clude anyth in g th at causes m yelopathy
(p.1407).
Detrusor areflexia
Clin ically correlates w ith di cult y in itiatin g m icturit ion , in terrupted flow, an d sign ifican t residual
urin e. In con tin en ce m ay result from over-disten tion of th e bladder (overflow in con t in en ce), or m ay
be associated w ith absen ce of sph in cter ton e. Et iologies in clude: ch ron ic in fect ion , lon g-term bladder
cath eterizat ion , certain drugs (especially ph en oth iazin es), injur y or tum or of th e cauda equin a or
con us m edullaris, m yelom en ingocele, an d diabetes m ellitus (auton om ic n europathy).
Specific injuries a ecting t he bladder
In general, regarding discrete n eurologic lesion s a ect in g th e bladder 9 :
1. supraspin al (lesion s above th e brain stem ): loss of cent rally m ediated in h ibition of th e pon tin e
voidin g reflex. Usually produces involun tar y bladder con tract ion s w ith sm ooth an d striated
sph in cter syn ergy, often w ith preser ved sen sation an d volun tar y striated sph in cter fun ction .
Sym ptom s: urin ar y frequen cy or urgen cy, urgen cy in con tin en ce, and n octuria.7 If sen sor y path w ays are in terrupted, un con scious in con t in en ce occurs (in con tin en ce of th e un aw ares t ype).
Sin ce m uscles are coordin ated, n orm al bladder pressures are m ain tain ed an d th ere is low risk of
h igh -pressure related ren al dysfun ct ion . Volun tar y bladder em pt yin g is usually m ain tain ed, an d
t im ed voidin g togeth er w ith an tich olin ergic m edication s (see below ) are used in m an agem en t.
Areflexia m ay som etim es occur
2. com plete (or n ear com plete) spin al cord lesion s:
a) suprasacral (lesion a bove th e S2 spin al cord level, w h ich is ≈ T12/L1 vertebral body level in an
adult): th e sacral voidin g center is located in th e con us m edullaris. Etiologies: spin al cord
injuries, t um ors, tran sverse m yelit is.
● In itially follow in g spin al cord injur y, th ere m ay be spin al sh ock. Durin g spinal sh ock
(p. 931), th e bladder is acon tract ile an d areflexic (detru sor areflexia); sph in cter ton e usually
persists an d urin ar y reten tion is th e rule (urin ar y in con tin en ce gen erally does n ot occur
except w ith overdisten tion )
● After spin al sh ocksubsides, m ost develop det rusor hyper reflexia → involun tar y bladder con tract ion s w ith out sen sation (autom atic bladder), sm ooth sph in cter syn ergy, but st riated
dyssyn ergy (involun tar y con traction of th e extern al sph in cter durin g voidin g w h ich produces a fun ction al outlet obstruct ion w ith poor em pt ying an d h igh vesical pressures). Bladder
fills an d em pties spon tan eously (or in respon se to low er extrem it y cutan eous st im ulation ).
Bladder com plian ce is often reduced. Man aged by in term itten t
cath eterizat ion s + an t ich olin ergics
b) in frasacral lesion s (lesion below th e S2 spin al cord level): in cludes injur y to con us m edullaris,
cauda equin a or periph eral n er ves (form erly referred to as low er m otor n euron lesion s). Etiologies: large HLD, traum a w ith com prom ise of spin al can al. Usually develop detrusor areflexia,
and do n ot h ave involun tar y bladder con traction s. Reduced urin ar y flow rate or reten tion
results, an d volun tar y voidin g m ay be lost. Overflow in con tin en ce develops. Th ere m ay be
reduced com plian ce durin g fillin g, an d paralysis of th e sm ooth sph incter (th e n eurologic basis
of th is h as n ot been settled, an d m ay be due to sym path et ic or PSN involvem en t). Usually
associated w ith loss of bulbocavern osus an d an al w in k reflex (preser ved in suprasacral
lesion s, except w h en spin al sh ock is presen t (p. 931) ) an d perin eal sen sor y loss
3. in terruption of th e periph eral reflex arc: m ay produce disturban ces sim ilar to low spin al cord
injur y w ith det rusor areflexia, low com plian ce an d in abilit y to relax th e striated sph in cter
4. h ern iated lum bar disc (p. 1046): m ost con sist in it ially of di cult y voidin g, st rain ing, or urin ar y
reten tion . Later, irritative sym ptom s m ay develop
5. spinal sten osis (lum bar or cer vical): urologic sym ptom s var y, an d depen d on th e spin al level(s)
involved an d th e t ype of involvem en t (e.g. in cer vical spin al sten osis, detrusor hyperact ivity or
un deractivit y m ay occur depen din g on w h eth er th e involvem en t of th e m icturit ion n eural axis is
com pression of th e in h ibitor y reticulospin al t racts or m yelopathy involving th e posterior
fun iculus)
6. cauda equin a syn drom e (p.1050): usually produces urin ar y reten tion , alth ough som etim es
in con tin en ce m ay occur (som e cases are overflow in cont in en ce)
7. periph eral n europath ies: such as w ith diabetes, usually produce im paired detrusor activit y
8. n eurospin al dysraph ism : m ost m yelodysplastic patien ts h ave an areflexic bladder w ith an open
bladder n eck. Th e bladder usually fills un til th e restin g residual fixed extern al sph in cter pressure
is exceeded an d th e leakage occurs
3
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Anat om y and Physiology
9. m ultiple sclerosis: 50–90% of pat ien ts develop voidin g sym ptom s at som e tim e. Th e dem yelin ation prim arily involves th e posterior an d lateral colum n s of th e cer vical spin al cord. Detrusor
hyperreflexia is th e m ost com m on urodyn am ic abn orm alit y (in 50–99%of cases), w ith bladder
areflexia bein g less com m on (5–20%)
Urinary retent ion
3
Etiologies of urin ar y reten tion :
1. bladder outlet obstruction (a brief di eren tial diagn osis list is presen ted h ere)
a) ureth ral stricture: reten tion tends to be progressive over tim e
b) prostatic en largem en t in m ales:
● ben ign prostatic hypertrophy (BPH) & prostate can cer: reten tion ten ds to be progressive
over tim e
● acute prostatitis: on set of reten tion m ay be sudden
● rare: extruded prostat ic ston e
c) w om en m ay develop a cystocele w h ich can produce a ureth ral kin k
d) rare: ureth ral can cer
2. detrusor areflexia (p.93) or hypoton ia
a) spinal cord injur y
b) cauda equin a syn drom e (p. 1050)
c) ch ronic in fect ion
d) lon g-term bladder cath eterizat ion
e) certain drugs (n arcotics, ph en oth iazin es)
f) injur y of th e cauda equin a or con us m edullaris, or of th e spin al cord at or below th e sacrum
● traum a
● tum or
● m yelom en ingocele
g) diabetes m ellitus (auton om ic n europathy)
h ) h erpes zoster at th e level of th e sacral dorsal root ganglia 9 (p 967)
i) in com plete open in g of th e bladder n eck durin g voidin g: occurs alm ost exclusively in youn g
an d m iddle-aged m ales w ith lon gstan ding obstruct ive an d irritative sym ptom s 9 (p 968)
j) in itially follow in g severe bladder over disten tion or w ith ch ronic disten tion an d decom pression from any of th e above
3. postoperative reten tion : w ell-recogn ized but poorly un derstood. More com m on after low er urin ar y t ract , perin eal, gyn ecologic an d an orectal operat ion s. An esth esia an d an algesia m ay con tribute to a n um ber of factors 9 (p 969)
4. psych ogen ic
Evaluat ion of bladder funct ion
Urodynam ics
Usually com bined w ith x-ray (cystom etrogram (CMG))or fluoro (videourodyn am ics). Measures
in travesicular pressures durin g retrograde bladder filling th rough a ureth ral catheter, usually com bin ed w ith sph in cter electrom yography. Presen ce or absen ce (detrusor areflexia, see below ) of det rusor reflex is detected. If presen t , procedure is repeated, askin g pat ien t to suppress th e urge to
void. In abilit y to suppress is called an un in h ibited det rusor reflex (AKA detrusor hyperreflexia, see
above).
Sphincter electrom yography (EMG)
Eith er via n eedle electrodes, or w ith extern ally m oun ted surface elect rodes. Volun tar y sph in cter
con tract ion tests in tact n ess of supraspin al in n ervation . W h en com bin ed w ith CMG, detects elect rical
act ivit y in sph in cters durin g associated ph ases of detrusor con tract ion .
Voiding cystourethrogram and intravenous pyelography (IVP)
Voidin g cystoureth rogram (VCUG) detect s urethral path ology (diverticula, strictures…), abn orm alities of bladder (divert icula, det rusor trabeculation s associated w ith lon gstan ding con tract ion s
again st h igh resistan ce…), an d vesical-ureteral reflux.
Neurophysiology and Regional Brain Syndrom es
95
Pharm acologic Treat m ent
Goals are to preser ve ren al fun ct ion (w h ich usually involves preven tion of UTIs, ren al calculi, an d
ureteral reflux due to h igh in t ravesicular pressures) an d opt im ization of urin ar y con tin en ce. Pat ien ts
w ith in adequate em pt yin g or in creased bladder pressure are often m an aged by in term itten t cath eterizat ion s an d an t ich olin ergics (see below ). An tich olin ergics an d beh avioral th erapy are used for
patien ts w ith m ain tain ed volun tar y bladder em ptyin g w ith urin ar y frequen cy or urgen cy
in con t in en ce.
Th e m ajorit y of th e n eurologic involvem en t in bladder con tract ion is ACh -m ediated stim ulation
of postganglion ic parasym path etic m uscarin ic ch olin ergic receptors on bladder sm ooth m uscle.
Detrusor hyperreflexia
Th e follow in g are all syn th et ic an tich olin ergics th at block postgan glionic syn apses (m uscarin ic
act ion ) w ith out blockin g skeletal n eurom uscular or auton om ic ganglia (n icot in ic jun ct ion s). Th is
in creases th e volum e at w h ich autom at ic (reflex) con tract ion occurs in th e n eurogen ic (un in h ibited)
bladder, e ect ively in creasing bladder capacit y. Th ese agen ts in crease th e th resh old at w h ich involun tar y bladder con traction occurs, but th ey do n ot in crease th e w arn ing t im e an d th ey do n ot
in crease th e abilit y to suppress con tract ion , th erefore, urgen cy an d in con tin en ce w ill still occur
un less t reatm en t is com bin ed w ith a regim en of tim ed voidin g.9 (p 972)
All are con train dicated in glaucom a as th e an tich olin ergic e ects in clude m ydriasis. Overdosage
results in th e classic an tich olin ergic sym ptom s (“red as a beet, h ot as a stove, dr y as a rock, m ad as a
h atter”). Use is often lim ited by side e ect s such as dr y m outh .
Drug info : Oxybut ynin (Dit ropan®)
Probably the most widely prescribed agent. Com bines anticholinergic activit y with independent musculotropic relaxant e ect and local anesthetic activit y.
Adults: usual dose is 5 m g BID-TID (maxim um 4 times daily). Peds: not recom mended for
age < 5 years; usual dose is 5 m g BID (maximum 5 mg TID). Supplied: 5 mg tablets, 5 mg/5 ml syrup.
Drug info : Tolt erodine (Det rol®)
Milder side e ects than oxybut ynin, but m ay also be less e ective.10
2 m g PO BID. Can be lowered to 1 m g PO BID in som e patients. Supplied: 1 & 2 mg tablets.
Detrol® LA 2 & 4 m g capsule
Drug info : Flavoxat e HCl (Urispas®)
Weak anticholinergic. Direct smooth muscle inhibitor. Few reported side e ects. Som e studies have
shown no benefit in the elderly population.9 (p 974)
Adult: 100–200 m g PO TID-QID.
Drug info : Im ipram ine HCl (Tofranil®)
A tricyclic antidepressant. Mechanism of beneficial e ect is controversial. Does possess som e anticholinergic activit y as well as other porperties.9 (p 977) Appears to decrease bladder contractility and
increase outlet resistance.
3
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Anat om y and Physiology
Det rusor areflexia
Drug info : Bet hanechol (Urecholine®)
3
A parasympathomimetic agent, primarily m uscarinic with lit tle nicotinic activit y; related to acet ylcholine but not destroyed by cholinesterase. Increases the tone of the detrusor muscle, aiding bladder
emptying. Also increases gastric motilit y. Sub-Q administration produces a more intense e ect on
the bladder than PO. Always have atropine available when giving by sub-Q route. E ects occur within
30–90 m inutes after PO dose, and within 15 m inutes of sub-Q dose.
Indicated for acute post-op non-obstructive urinary retention and for neurogenic atony due to spinal cord injury or dysfunction.
Side e ect s: sweating and diarrhea are not uncommon but of little danger. Can precipitate severe
bronchospasm in asthm atics. Nausea may be reduced by giving with an empty stom ach. Atropine is a
specific antidote for overdosage (atropine sub-Q: 0.6 mg in adults, or 0.01 mg/kg in children < 12
yrs).
Start with 5–10 mg PO, and increase hourly until desired e ect obtained or 50 mg given. Then,
continue minim um e ective dosage TID-QID (usual: 10–50 mg PO TID-QID). Sub-Q (have atropine
available): 0.5–1 ml, repeat q 15 mins until desired response or 4 doses given; continue minimal e ective dose TID-QID. Supplied: 5, 10, 25 & 50 mg tabs. Injection: 5.15 mg/ml (for sub-Q use only).
Bladder m anagem ent aft er cauda equina com pression
In situation s w h ere th ere is urin ar y reten tion w ith som e prospect of return of fun ct ion (e.g. follow in g surger y for acute cauda equin a com pression ) th e follow in g bladder m an agem en t regim en m ay
be em ployed:
● teach th e patien t or a fam ily m em ber to perform clean in term itten t cath eterizat ion s (CIC), if CICs
can be don e:
○ h ave th em m on itor post-void residuals (PVR)
○ start tam sulosin (Flom ax®) 0.4 m g PO q d (see below )
○ if PVRs ever fall to < 75 cc, discon tin ue CICs
● if CICs can n ot be perform ed, m an age w ith an in dw ellin g Foley cath eter for a w eek, an d ch eck th e
PVR after th at tim e
● if after 1 w eek th e PVR is ≥ 75 cc, D/C tam sulosin if used, an d refer th e patien t to a urologist for
urodyn am ics (urodyn am ics earlier th an th is t im e w ill usually n ot result in a ch ange in
m an agem en t)
Drug info : Tam sulosin (Flom ax®)
A prostate alpha 1Aadrenoreceptor antagonist. Used to treat voiding di culties resulting from outlet
obstruction due to benign prostatic hypertrophy (BPH). Has been shown to have som e e ectiveness
in wom en via other mechanisms. Sim ilar to terazosin (Hytrin®) and doxazosin (Cardura®), but has an
advantage for acute relief because the dose of tamsulosin does not need to be gradually ram ped up
(it can be started at the therapeutic dose). It takes at least 5–7 days to work.
Side e ect s : very few. Rhinitis, retrograde or dim inished ejaculation, or postural hypotension m ay
occur.11
: 0.4 m g PO q d (usually given 30 minutes after the sam e meal each day). If there is no response
by 2–4 weeks, a dose of 0.8 m g PO q d can be tried.11
3.2 Regional brain syndrom es
Th is sect ion ser ves to briefly describe t ypical syn drom e associated w ith lesion s in various areas of
th e brain . Un less oth erw ise n oted, lesion s con sidered are destr uctive.
3.2.1 Overview
1. fron tal lobe
a) un ilateral injur y:
● m ay produce few clin ical fin dings except w ith ver y large lesion s
● bilateral or large un ilateral lesion s: apathy, abulia
Neurophysiology and Regional Brain Syndrom es
th e fron tal eye field (for con tralateral gaze) is located in th e posterior fron tal lobe (Br. area
8, sh ow n as th e st riped area in Fig. 1.1). Destructive lesion s im pair gaze to th e con tralateral side (patien t looks towa rds th e side of th e lesion ), w h ereas irritative lesions (i.e. seizures) cause th e cen ter to activate, producin g con tralateral gaze (patien t looks a wa y from
th e side of th e lesion ). See also Ext raocu lar m u scle (EOM) system (p. 565) for m ore
details.
b) bilateral injur y: m ay produce apathy, abulia
c) olfactor y groove region : m ay produce Foster Ken n edy syn drom e (see below )
d) prefron tal lobes con trol “executive fun ct ion ”: plan n in g, prioritizing, organ izin g th ough ts, sup pressin g im pulses, un derstan ding th e con sequen ces of decision s
parietal lobe: m ajor features (see below for details)
a) eith er side: cort ical sen sor y syn drom e, sen sor y extin ct ion , con tralateral h om onym ous h em ianopia, con tralateral n eglect
b) dom in an t parietal lobe lesion (left in m ost): lan guage disorders (aph asias), Gerstm an n’s syn drom e (p. 98), bilateral astereogn osis
c) n on -dom in an t parietal lobe lesion s: topograph ic m em or y loss, an osogn osia an d dressin g
apraxia
occipital lobe: h om onym ous h em ian opsia
cerebellum
a) lesion s of th e cerebellar h em isph ere cause ataxia in th e ipsila tera l lim bs
b) lesion s of th e cerebellar verm is cause trun cal ataxia
brain stem : usually produces a m ixture of cran ial n er ve deficits an d lon g tract fin din gs (see below
for som e specific brain stem syn drom es)
pin eal region
a) Parin aud’s syn drom e (p. 99)
97
●
2.
3.
4.
5.
6.
3.2.2 Pariet al lobe syndrom es
See referen ce.12 (p 308–12)
Pariet al lobe anat om y
Th e parietal lobe is located beh in d th e cen tral sulcus, above th e Sylvian fissure, m ergin g posteriorly
in to th e occipital lobe (th e border on th e m edial surface of brain is defin ed by a lin e con n ecting th e
parieto-occipital sulcus to th e pre-occipital n otch ).
Pariet al lobe neurophysiology
eith er side: an terior parietal cortex organ izes tactile precepts (probably con tralateral) an d in tegrates w ith visual an d auditor y sen sation to build aw aren ess of body an d its spatial relation s
● dom in an t side (on left in 97% of adults): un derstan ding lan guage, in cludes “cross-m odal m atch in g” (auditory-visual, visual-tactile, etc.). Dysph asia present w ith dom in an t lobe lesion s often
im pedes assessm en t
● n on -dom in an t side (righ t in m ost): in tegrates visual an d proprioceptive sen sation to allow m an ipulation of body an d objects, an d for cer tain con struct ion al activit ies
●
Clinical syndrom es of pariet al lobe disease
Overview
1. unila tera l parietal lobe disease (dom in an t or n on -dom in an t):
a) cort ical sen sor y syn drom e (see below ) an d sen sor y extin ct ion (n eglecting 1 of 2 sim ultan eously presen ted st im uli). Large lesion → h em ian esth esia
b) congen ital injur y → m ild h em iparesis & con tralateral m uscle atrophy
c) h om onym ous h em ian opia or visual in atten t iven ess
d) occasion ally: an osogn osia
e) n eglect of con tralateral h alf of body an d visual space (m ore com m on w ith righ t side lesion s)
f) abolition of optokinetic nystagmus to on e side
2. addition al e ects of dom in an t parietal lobe lesion (left in m ost):
a) lan guage disorders (aph asias)
b) speech -related or verbally m ediated fun ct ion s, e.g. cross-m odal m atch ing (e.g. patien t un derstan ds spoken w ords an d can read, but can n ot un derstan d sen ten ces w ith elem en ts of
relation sh ips)
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Anat om y and Physiology
c) Gerstm an n’s syn drom e, classically:
● agraph ia w ith out alexia (patien ts can read but can n ot w rite)
● left-righ t con fusion
● digit agn osia: in abilit y to iden tify fin ger by n am e
● acalculia
d) tact ile agn osia (bilateral astereogn osis)
e) bilateral ideom otor apraxia (in abilit y to carr y out verbal com m an ds for act ivit ies th at can oth erw ise be perform ed spon tan eously w ith ease)
3. addit ion al e ects of n on -dom in an t parietal lobe lesion s (usually righ t):
a) topograph ic m em or y loss
b) anosogn osia an d dressin g apraxia
Cort ical sensory syndrom e
Lesion of postcen tral gyrus, especially area th at m aps to h an d.
● sen sor y deficits:
a) loss of position sen se an d of passive m ovem en t sen se
b) in abilit y to localize tact ile, th erm al, an d n oxious st im uli
c) astereogn osis (in abilit y to judge object size, sh ape, an d iden tit y by feel)
d) agraph esth esia (can n ot in terpret n um bers w rit ten on h an d)
e) loss of t w o poin t discrim in ation
● preser ved sen sation s: pain , touch , pressure, vibration , tem perature
● oth er features
a) easy fat igabilit y of sen sor y perception s
b) di cult y dist in guish in g sim ultan eous st im ulat ion s
c) prolongation of superficial pain w ith hyperpath ia
d) touch h allucin ation s
Ant on-Babinski syndrom e
A un ilateral asom atagn osia. May seem m ore com m on w ith n on -dom in an t (usually righ t) parietal
lesion s because it m ay be obscured by th e aph asia th at occurs w ith dom in an t (left) sided lesion s.
1. an osogn osia (in di eren ce or un aw aren ess of deficits, patien t m ay deny th at paralyzed extrem it y
is th eirs)
2. apathy (in di eren ce to failure)
3. alloch eiria (on e-sided st im uli perceived con tralaterally)
4. dressin g apraxia: n eglect of on e side of body in dressin g an d groom in g
5. extin ct ion : patien t is un aw are of con tralateral stim ulus w h en presen ted w ith double-sided
sim ultan eous stim ulation
6. in attent ion to an en tire visual field (w ith or w ith out h om onym ous h em ian opia), w ith deviation
of h ead, eyes, an d torsion of body to un a ected side
Pariet al lobe aphasias
1. Wern icke’s aph asia: lesion of auditor y association areas or th eir separat ion from an gular gyrus
an d prim ar y auditor y cortex. A fluent aph asia (n orm al sen ten ce len gth & in ton ation , devoid of
m ean in g). May in clude paraph asias. Lesion in region of Wern icke’s area (Brodm an n areas 40 &
39, Fig. 1.1)
2. Broca’s (m otor) aph asia: in realit y, “apraxia” of m otor sequen cin g for speech (speech an d ph on at ion m uscles aren’t paralyzed, an d fun ction for oth er act ivities), producin g falterin g, dysarth ric
speech . Lesion in region of Broca’s area (Brodm an n area 44, Fig. 1.1)
3. global aph asia: usually due to lesion th at destroys large por tion of lan guage cen ter; all aspect s of
speech an d lan guage a ected
a) un able to speak except for som e clich és, h abitual ph rases, or explet ives
b) an om ia (in abilit y to n am e objects or parts of objects)
c) verbal an d m otor perseveration
d) un able to un derstan d all except for a few w ords
e) in abilit y to read or w rite
4. con duction aph asia: due to disruption of con n ection s betw een fron tal an d tem poral speech
areas, usually involving supram argin al gyrus. Sim ilar to Wern icke’s (fluen t spon tan eous speech
an d paraph asias), but pat ien ts un derstan d spoken or w ritten w ords, an d are aw are of th eir deficit. Repetition is severely a ected
Neurophysiology and Regional Brain Syndrom es
99
5. pure w ord blin dn ess: AKA alexia w ith out agraph ia (rare) due to lesion in parieto-occipital lobe
th at in terrupts con n ect ion s bet w een left an gular gyrus an d both occipital lobes. Patien ts can
w rite, but are un able to read w h at th ey’ve w rit ten , an d frequen tly seem un con cern ed about th is.
Often accom pan ied by loss of abilit y to n am e colors. Readin g an d n am in g n um bers usually
preser ved
3.2.3 Fost er Kennedy syndrom e
Nam ed after n eurologist Robert Foster Ken n edy. Usually from olfactor y groove or m edial th ird sph en oid w in g tum or (usually m en in giom a). Now rare due to early detect ion by CT or MRI. Classic t riad:
1. ipsilateral an osm ia
2. ipsila tera l cen tral scotom a (w ith opt ic a t rophy due pressure on optic n er ve)
3. cont ra la tera l papilledem a (from elevated ICP)
Occasion ally ipsilateral proptosis w ill also occur due to orbital invasion by tum or.
3.2.4 Brain st em and relat ed syndrom es
Weber’s syndrom e
Cr. N. III palsy w ith con tralateral h em iparesis; also see Lacun ar st rokes (p. 1267). Th ird n er ve palsies
from paren chym al lesion s m ay be relatively pupil sparin g.
Benedikt’s syndrom e
Sim ilar to Weber’s, plus red n ucleus lesion . Cr. N. III palsy w ith con tralateral h em iparesis except arm
w h ich h as hyperkin esia, ataxia, an d a coarse in ten tion trem or. Lesion : m idbrain tegm en tum involvin g red n ucleus, brach ium conjun ct ivum , an d fascicles of III.
Millard-Gubler syndrom e
Facial (VII) & abducens (VI) palsy + con tralateral h em iplegia (cort icospin al tract) from lesion in base
of pon s (usually isch em ic in farct, occasion ally tum or).
3.2.5 Parinaud’s syndrom e
Definit ion
AKA dorsal m idbrain syn drom e, AKA pretectal syn drom e. As origin ally described, a supran uclear
paralysis of vert ical gaze resultin g from dam age to th e m esen ceph alon .13
Th ere are a n um ber of som ew h at var yin g descript ion s, h ow ever m ost in clude:
● supran uclear upw ard gaze palsy (i.e. upgaze palsy a ect in g both volun tar y saccadic an d pursuit
m ovem en ts, w ith preser vation of vestibulo-ocular or oculoceph alic (doll’s eyes) reflexes in m ost
cases). Horizon tal eye m ovem en ts are spared
● lid retract ion (Collier’s sign ): NB: upgaze palsy + lid retract ion produces th e “settin g sun sign ”
● convergen ce palsy
● accom m odation palsy
● less com m on association s: pseudoabducen s palsy (AKA th alam ic esotropia), see-saw nystagm us,
fixed pupils, dissociated ligh t-n ear respon se (pseudo-Argyll Robertson ), convergen ce spasm , nystagm us retractorius, in tern uclear oph th alm oplegia (INO)
Skew deviation m ay be a un ilateral varian t of Parin aud’s syn drom e.
Syn drom e of th e Sylvian aqueduct: Parin aud’s syn drom e (PS) com bined w ith dow n gaze palsy.
Di erent ial diagnosis
Etiologies
1. m asses pressin g directly on quadrigem in al plate (e.g. pin eal region tum ors)
2. elevated ICP: secon dar y to com pression of m esen ceph alic tect um by dilated suprapin eal recess,
e.g. in hydroceph alus
3
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Anat om y and Physiology
3. st roke or h em orrh age in upper brain stem
4. m ultiple sclerosis (MS)
5. occasion ally seen w ith toxoplasm osis
3
Con dition s a ect in g ocular m otilit y th at could m im ic th e upgaze palsy of PS:
1. Guillain -Barré syn drom e
2. m yasth en ia gravis
3. botulism
4. hypothyroidism
5. th ere m ay be a gradual ben ign loss of upgaze w ith sen escen ce
3.3 Jugular foram en syndrom es
3.3.1 Applied anat om y
Th e jugular foram en (JF) is on e of a pair of open in gs bet w een th e lateral par t of th e occipital bon e
an d th e pet rous par t of th e tem poral bon e. Th e foram en is usually divided in 2 by a bony spin e from
th e pet rous tem poral bon e th at attach es via a fibrous bridge (w h ich is bony in 26%) to th e jugular
process of th e occipital bon e.14 Th e righ t JF is usually larger th an th e left.14,15 Th e carot id ridge separates th e JF from th e n earby carotid can al. Con ten ts of jugular foram en (JF): Cr. N. IX, X, XI, petrosal
sin us, sigm oid sin us, som e m en in geal bran ch es from th e ascen din g ph ar yn geal an d occipital
arteries.16
Nearby: Cr. N. XII passes th rough th e hypoglossal can al just above th e occipital con dyle. Th e carot id artery w ith th e sym path et ic plexus en ters th e carotid can al.
Com part m en talizat ion of th e jugular foram en rem ain s con troversial. As m any as 4 foram in a h ave
been described over th e years. Alth ough it h ad been recogn ized previously, an early 2-com par tm en t
description w as publish ed in 1967 by Hovelacque.17 In th is, th e bony spin e (± its fibrous septum )
divide th e foram en in to:
● pars vascularis: th e larger posterolateral com par tm en t con tain in g th e vagal n er ve (an d bran ch in g
Arn old’s n er ve), spin al accessory n er ve an d th e in tern al jugular vein
● pars n er vosa: th e sm aller an terom edial com part m en t con tain in g th e glossoph aryn geal n er ve (an d
bran ch in g Jacobson’s n er ve), in ferior petrosal sin us an d m en in geal bran ch of th e ascendin g ph ar yn geal artery
A publication in 1997 described th ese 3 com part m en ts 18 :
● Sigm oid: large posterolateral com part m en t con tain in g sigm oid sin us
● Pet rosal: sm aller an terom edial com part m en t con tain in g petrosal sin us
● In trajugular or n eural: CN 9, 10 an d 11
3.3.2 Clinical syndrom es
General inform at ion
A n um ber of eponym ous syn drom es w ith som e con flict in g fin din gs in th e literature h ave been
described. See Table 3.2 for a sum m ar y an d Fig. 3.2 for a sch em atic diagram of deficits in various
JF syn drom es.
Vernet’s syndrom e: CN IX, X & XI palsy
AKA syn drom e of th e jugular foram en . Usually due to in tracran ial lesion .
Etiologies in clude: jugular foram en t um ors, ICA dissect ion s, m ycotic an eur ysm s of th e extern al
carotid, th rom bosis of th e jugular vein , follow in g carotid en darterectomy.
Sym ptom s: un ilateral paralysis of th e palate, vocal cords, stern ocleidom astoid, trapezius, w ith
loss of taste in th e posterior 1/3 ton gue, an esthesia of th e soft palate, lar yn x an d ph ar yn x.
Collet -Sicard syndrom e
Palsies of CN IX, X, XI & XII w ith out sym path etic involvem en t. More likely w ith lesion outside skull.
If caused by an in tracran ial lesion , it w ould h ave to be of such a large size th at it w ould usually produce brain stem com pression → lon g t ract fin din gs.
Neurophysiology and Regional Brain Syndrom es
101
Table 3.2 Cranial nerve dysfunction in jugular foram en syndromes
Nerve
Result of lesion
Syndrom e
Vernet
Collet
Sicard
Villaret
Tapia
Jackson
Schm idt
IX
loss of taste and sensation in posterior
third of tongue
X
X
X
X
paralysis of vocal cords & palate,
anesthesia of pharynx & larynx
X
X
X
X
X
X
XI
weak trapezius & SCM
X
X
X
±
X
X
XII
tongue paralysis & atrophy
X
X
X
X
sym pathetics
Horner’s syndrome
X
±
3
Key: X indicates dysfunction / deficit (lesion) of that nerve; ± indicates involvem ent m ay or may not occur
SS XI
X IX IPS
{
Classical
Taxonomy
3 Com partment Model
{
ju g u la r
fo ra m e n
f
m
o
r
a
a
g
n
m
u
e
n
m
Vernet
Fig. 3.2 Schematic diagram of the
jugular foram en (coronal section
through left jugular foram en viewed
from the front). Includes the classic 2
com partm ent m odel and the 3 com partm ent classification of Katsuta et
al.18 Jugular foram en syndromes are
illustrated: a solid line through a
nerve indicates a deficit, dashed line
indicates ± involvement.
IJV
XII
Schm idt
hypoglossal
al
canal
ColletSicard
Jackson
k
to
pharynx
p
pha
arynx
Tapia
sympatheticss
(on carotid)
Villaret
to laryn
larynx
Etiologies in clude: con dylar an d Je erson’s fract ures, in tern al carotid dissect ion , prim ar y an d
m etastatic t um ors, Lym e disease an d fibrom uscular dysplasia.
Sym ptom s: un ilateral paralysis of th e palate, vocal cords, stern ocleidom astoid, t rapezius, tongue,
loss of taste in posterior 1/3 tongue, an esth esia of soft palate, lar yn x an d ph ar yn x.
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Anat om y and Physiology
Villaret’s syndrom e : CN IX, X, XI & XII palsy + sym pat het ic dysfunct ion
3
AKA posterior retropharyngeal syndrom e, AKA the nervous syndrom e of the posterior retroparotid
space). Collet-Sicard syndrom e with sympathetic involvem ent. Usually due to retropharyngeal leasions.
Etiologies in clude: parotid t um ors, m etastases, extern al carotid an eur ysm an d osteom yelitis of
th e skull base.
Sym ptom s: as w ith Collet-Sicard + Horn er’s syn drom e.
Tapia syndrom e : CN X & XII palsy (± XI)
AKA Matador’s disease (first described in a bullfigh ter by An ton io Garcia Tapia). Som e auth ors
describe an in tracran ial an d extracran ial form .19
Etiologies in clude: oral in t ubation (m ajorit y of cases prior to 2013), m etastases, rarely associated
w ith carotid or vertebral arter y dissection s.
Sym ptom s: h oarsen ess of voice, dysph agia secon dar y to in coordin at ion of tongue an d food bolus
propulsion , un ilateral atrophy an d paralysis of th e tongue, ± paralysis of stern ocleidom astoid & t rapezius, sparin g th e soft palate.
(Hughlings) Jackson’s syndrom e: CN X, XI & XII palsy
First described in 1864 w ith un ilateral paralysis of th e soft palate, lar yn x, stern ocleidom astoid, t rapezius an d tongue.
Schm idt syndrom e : CN X & XI
AKA vago-spin al syn drom e. Sch m idt first described th is in 1892. Un ilateral vocal cord an d paralysis
of stern ocleidom astoid, soft palate, lar yn x an d t rapezius.
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13:797–809
[17] Hovelacqu e A. Osteologie. Paris, Fran ce: G. Doin an d
Cie; 1967; 2
[18] Katsu ta T, Rh oton AL, Jr, Matsush im a T. Th e ju gular
foram en : m icrosurgical an atom y and operative
app roach es. Neu rosurger y. 1997; 41:149–201; d iscussion 201-2
[19] Krasn ian ski M, Neud ecker S, Sch luter A, Krau se U,
W interholler M. Cen tral Tapia's syn drom e ("m atador's disease") cau sed by m etastat ic h em an giosarcom a. Neurology. 2003; 61:868–869
Part II
General and Neurology
II
4
Neuroanesthesia
104
5
Sodium
Hom eostasis and
Osm olalit y
110
6
General
Neurocritical Care
126
7
Sedatives,
Paralytics,
Analgesics
132
8
Endocrinology
144
9
Hem atology
153
10 Neurology for
Neurosurgeons
174
11 Neurovascular
Disorders and
Neurotoxicology
194
104
General and Neurology
4 Neuroanest hesia
4.1 General inform at ion
4
Table 4.1 sh ow s th e Am erican Society of An esth esiologists (ASA) gradin g system to estim ate an esth etic risk for various con dition s.
For issues related to in tracran ial pressure (ICP), cerebral perfusion pressure (CPP), in tracran ial
con stituen ts, etc., see ICP prin ciples (p. 856). For cerebral blood flow (CBF) an d cerebral m etabolic
rate of oxygen con sum ption (CMRO2 ), see CBF an d oxygen utilization (p.1264).
Param eters of prim ar y relevan ce to n eurological surger y th at can be m odulated by th e
an esth esiologist:
1. blood pressure: on e of th e factors th at determ in es CPP as w ell as spin al cord perfusion . May
n eed to be m an ipulated (e.g. reduced w h en w orking on an an eurysm , or in creased to en h an ce
collateral circulation durin g cross clam ping). Measurem en t by arterial lin e is m ost accurate an d
depen din g on th e patien t’s presentation an d th e plan n ed procedure, often sh ould be placed prior to in duct ion of an esth esia. For in tracran ial procedures, th e ar terial lin e sh ould be calibrated
at th e extern al auditor y m eatus to m ost closely reflect in tracran ial blood pressure
2. jugular ven ous pressure: on e of th e factors th at in fluen ces ICP
3. ar te rial CO2 te n sion (PaCO2 ): CO2 is t h e m ost p ot en t cerebral vasod ilator. Hyp er ven t ilat ion
red u ces PaCO2 (h yp ocap n ea) w h ich d ecreases CBV bu t also CBF. Goal is gen e rally en d t id al
CO2 (ETCO2 ) of 25–30 m m Hg w it h a correlat in g PaCO2 of 30–35. Use w it h care for stereot act ic p roced u res to m in im ize sh ift of in t racran ial con ten t s w h en u sin g th is m et h od to con t rol ICP4
4. arterial O2 ten sion
5. h em atocrit: in n eurosurger y it is critical to balan ce oxygen carr ying capacit y (decreased by an em ia) again st im proved blood rh eology (im paired by elevated Hct )
6. patien t tem perature: m ild hypotherm ia provides som e protect ion again st isch em ia by reducing
th e cerebral m etabolic rate of oxygen (CMRO2 ) by ≈ 7% for each 1° C drop
7. blood glucose level: hyperglycem ia exacerbates isch em ic deficits 5
8. CMRO2 : reduced w ith cer tain n euro-protect ive agen ts an d by hypotherm ia w h ich h elps protect
again st isch em ic injur y
9. in cases w h ere a lum bar drain or a ven tr icular drain h as been placed: CSF out put
10. elevation of th e h ead of th e pat ien t: low erin g th e h ead in creases arterial blood flow, but also
in creases ICP by im pairin g ven ous outflow
11. in travascular volum e: hypovolem ia can im pair blood flow in n eurovascular cases. In surgery in
th e pron e position , excessive fluids m ay con tribute to facial edem a w h ich is on e of th e risk factors for PION (p. 1056)
12. position in g injuries: during th e procedure, th e patien t’s position m ay ch ange an d be un n ot iced
due to drapin g. Careful an d frequen t exam in ation of th e patien t’s position m ay preven t injuries
associated w ith prolonged m alposition in g
13. post operative n ausea an d vom it in g (PONV): m ay adversely a ect ICP an d m ay n egatively
im pact recen t cer vical surgical procedures. Avoidan ce of an esth etic agen ts kn ow n to cause
PONV or pretreatm en t to preven t PONV m ay be pruden t
4.2 Drugs used in neuroanest hesia
4.2.1 Inhalat ional agent s
General inform at ion
Most r e d u ce ce r eb r al m et ab olism (exce p t n it r ou s oxid e ) by su p p r essin g n e u r on al act ivit y.
Th ese age n t s d ist u rb ce r eb r al au t or e gu lat ion an d cau se ce r eb r al va sod ilat at ion w h ich
in cr e ase s ce r eb r al blood volu m e (CBV) an d can in cr e ase ICP. W it h ad m in ist r at ion > 2 h rs t h ey
in cr e ase CSF volu m e w h ich can a lso p ot e n t ia lly con t r ib u t e t o in cr e ase d ICP. Most age n t s
in cr e ase t h e CO2 r e act ivit y of ce r eb r al blood ve ssels. Th ese age n t s a ect in t r a- op e r at ive EP
m on it or in g (p . 10 7).
Neuroanest hesia
105
Drug info : Nit rous oxide
A potent vasodilator that markedly increases CBF and m inim ally increases cerebral metabolism. Contributes to post-op N/V.
Nit rous oxide, pneum ocephalus and air em bolism : The solubilit y of nitrous oxide (N2 O) is ≈ 34
times that of nitrogen.6 When N2 O com es out of solution in an airtight space it can increase the pressure which m ay convert pneumocephalus to “tension pneumocephalus.” It m ay also aggravate air
embolism. Thus caution must be used especially in the sit ting position where significant post-op
pneum ocephalus and air embolism are common. The risk of tension pneumocephalus may be
reduced by filling the cavit y with fluid in conjunction with turning o N2 O about 10 minutes prior to
completion of dural closure. See Pneumocephalus (p. 887).
Halogenat ed agent s
Agen ts in prim ar y usage today are sh ow n below. All suppress EEG activit y an d m ay provide som e
degree of cerebral protect ion .
Drug info : Isoflurane (Forane®)
Can produce isoelectric EEG without m etabolic toxicit y. Im proves neurologic outcome in cases of
incomplete global ischem ia (although in experim ental studies on rats, the am ount of tissue injury
was greater than with thiopental7 ).
Drug info : Desflurane (Suprane®)
A cerebral vasodilator, increases CBF and ICP. Decreases CMRO2 which tends to cause a compensatory
vasoconstriction.
Drug info : Sevoflurane (Ult ane®)
Mildly increases CBP and ICP, and reduces CMRO2 . Mild negative inotrope, cardiac output not as well
maintained as with isoflurane or desflurane.
4.2.2 Int ravenous anest het ic agent s
Agent s generally used for induct ion
1. propofol: exact m ech an ism of action un kn ow n . Sh ort h alf–life w ith n o act ive m etabolites. May
be used for in duct ion an d as a con tin uous in fusion durin g total in traven ous an esth esia (TIVA).
Causes dose depen den t decrease in m ean arterial blood pressure (MAP) an d ICP. See also in form ation oth er th an use in in duct ion (p. 106). Is m ore rapidly cleared th an , an d h as largely
replaced, th iopen tal
2. barbiturates: produce sign ifican t reduct ion in CMRO2 an d scaven ge free radicals am ong oth er
e ect s (p. 1202). Produce dose-depen den t EEG suppression w h ich can be taken all th e w ay to isoelect ric. Min im ally a ect EPs. Most are an ticonvulsan t, but m eth oh exital (Brevital®) (p. 132) can
low er th e seizure th reshold. Myocardial suppression an d periph eral vasodilatat ion from barbiturates m ay cause hypoten sion an d com prom ise CPP, especially in hypovolem ic pat ien ts
sodium th iopen tal (Pen toth al®): th e m ost com m on agen t. Rapid on set, sh ort acting. Min im al
e ect on ICP, CBF an d CMRO2
3. etom idate (Am idate®): a carboxylated im idazole derivative. An esth etic an d am n estic, but n o
an algesic properties. Som etim es produces m yoclon ic act ivit y w h ich m ay be con fused w ith seizures. Im pairs ren al fun ct ion an d sh ould be avoided in patien ts w ith kn ow n ren al disease. May
4
106
General and Neurology
produce adren al in su cien cy. See Miscellan eous drugs in n euroan esth esia (p. 106) for in form ation oth er th an use in in duction .
4. ketam in e: NMDA receptor an tagon ist. Produces a dissociative an esth esia. Main tain s cardiac output. May sligh tly in crease both h eart rate an d blood pressure. ICP in creases in parallel w ith
in creased cardiac out put.
Narcot ics in anest hesia
Nonsynthet ic narcotics
4
Narcotics in crease CSF absorpt ion an d m in im ally reduce cerebral m etabolism . Th ey slow th e EEG but
w ill not produce an isoelect ric t racin g. All n arcotics cause dose-depen den t respirator y depression
w h ich can result in hypercarbia an d con com itan t in creased ICP in n on -ven tilated pat ien ts. Often also
con tribute to post-op N/V
Morph in e: does n ot sign ifican tly cross th e BBB.
Disadvan tages in n euro patien ts:
1. causes h istam in e release w h ich
a) m ay produce hypoten sion
b) m ay cause cerebrovascular vasodilation → in creased ICP8 (p 1593)
c) th e above togeth er m ay com prom ise CPP
2. in ren al or h epatic in su cien cy, th e m etabolite m orph in e-6-glucuron ide can accum ulate w h ich
m ay cause con fusion
Synthetic narcot ics
Th ese do not cause h istam in e release, un like m orph in e an d m eperidin e.
Rem ifen tan il (Ultiva®); see also detailed in form ation (p. 133): reduces CMRO2 , CBV an d ICP.
Large doses m ay be n eurotoxic to lim bic system an d associated areas. May be used for aw ake cran iotom y (p. 1432).
Fen tanyl: crosses th e BBB. Reduces CMRO2 , CBV an d ICP. May be given as bolus an d/or as a con tin uous in fusion .
Sufen tan il: m ore poten t th en fen tanyl. Does n ot in crease CBF. Raises ICP (m ay be due to hypoven tilation – w h ich can occur w ith any n arcotic) an d is th us often n ot appropriate for n eurosurgical
cases. Expen sive.
4.2.3 Miscellaneous drugs in neuroanest hesia
Ben zod iazep in es. Th ese drugs are GABA agon ists an d decrease CMRO2 . Th ey also provide an ticonvulsan t action an d produce am n esia. See also agen ts an d reversal (p. 205).
Etom id at e (p. 105) . Used prim arily for in duct ion (p. 105).
a cerebrovasocon strictor w h ich th erefore: reduces CBF an d ICP; reduces CMRO2 but n o lon ger prom oted as a cerebral protectan t based on experim en tal studies 9 an d a drop in pBtO2 w ith tem porar y MCA clipping 10
● does n ot suppress brain stem act ivity
● suppresses adren ocort ical fun ction cort isol product ion . Th is usually occurs w ith prolonged
adm in istration , but can occur even after single dose for in duct ion an d m ay persist up to 8 h rs (n o
adverse outcom es from sh ort-term suppression h ave been reported)
● in creases activit y of seizure foci w h ich m ay be used for m appin g foci durin g seizure surger y but
m ay also in duce seizures
●
Prop ofol. A sedative hypn otic. Useful for in duct ion (p. 105). Reduces cerebral m etabolism , CBF
and ICP. Has been described for cerebral protect ion (p.1203) an d for sedation (p. 133). Sh ort h alf–life
perm its rapid aw aken in g w h ich m ay be useful for aw ake cran iotom y (p. 1434). Not an algesic.
Lid ocain e. Given IV, suppresses lar yn geal reflexes w h ich m ay h elp blun t ICP elevation s th at n orm ally follow en dotrach eal in tubation or suct ion in g. An t iconvulsan t at low doses, m ay provoke seizures at h igh con cen tration s.
Esm olol. Selective beta-1 adren ergic an tagon ist, blun ts th e sym path et ic respon se to lar yn goscopy
and in tubation . Less sedating th an equipoten t doses of lidocain e or fen tanyl used for th e sam e purpose. Half life: 9 m in utes. See also dosin g, etc. (p.127)
Neuroanest hesia
107
Dexm ed et om id in e (Preced ex®). Alph a 2 adren ergic receptor agon ist, used for con trol of hyperten sion post operat ively, as w ell as for its sedatin g qualit ies durin g aw ake cran iotom y eith er alon e or
in conjun ct ion w ith propofol (p.105). Also used to h elp patien ts tolerate en dotracheal t ube w ith out
sedatives/n arcotics to facilitate extubation .
4.2.4 Paralyt ics for int ubat ion
Paralyt ics (n eu rom u scu lar blockin g agen t s (NMBA)): ad m in istered t o facilit ate t rach eal in t u bat ion an d to im p rove su rgical con d it ion s w h en in d icated . Ad m in ist rat ion of p aralyt ics id eally
sh ou ld alw ays be gu id ed by n eu rom u scu lar t w itch m on itor in g. Also see Sed at ives & p aralyt ics
(p. 132). In ad d it ion to p aralyt ics, all con sciou s p at ien t s sh ou ld also receive a sed at ive to blu n t
aw aren ess.
Paralytics sh ould n ot be given un t il it h as been determ in ed th at patien t can be ven tilated m an ually, un less t reatin g lar yn gospasm (m ay be tested w ith th iopen tal). Use w ith caution in n on -fixated
patien ts w ith un stable C-spin e.
Due to lon g action , pan curon ium (Pavulon ®) is n ot in dicated as th e prim ar y paralyt ic for in tubat ion , but m ay be useful on ce patien t is in t ubated or in low dose as an adjun ct to succinylch olin e.
Drug info : Succinylcholine (Anect ine®)
The only depolarizing agent. May be used to secure airway for em ergency intubation, but due to
possible side e ect s (p. 135), should not be used acut ely following injury or in adolescent s or
children (a short acting nondepolarizing blocker is preferred). May transiently increase ICP. Prior
dosing with 10% of the ED95 dose of a non-depolarizing m uscle relaxant reduces m uscle
fasciculations.
Intubating dose: 1–1.5 mg/kg (supplied as 20 m g/m l → 3.5–5 cc for a 70 kg patient), onset 60–
90 sec, duration 3–10 min, may repeat same dose × 1.
Drug info : Rocuronium (Zem uron®)
Intermediate acting, am inosteroid, non-depolarizing muscle relaxant. The only nondepolarizing neurom uscular blocking agent approved for rapid sequence intubation. Duration of action and onset are
dose dependent.
(p. 135).
Drug info : Vecuronium (Norcuron®)
See details (p. 136).
Aminosteroid with activit y sim ilar to that of rocuronium , however, does not cause histamine
release and is not approved for rapid sequence intubation. .
Drug info : Cisat racurium (Nim bex®)
See details (p. 136).
Metabolized by Ho man degradation (tem perature dependent), intermediate acting, no significant increases in histamine.
4.3 Anest het ic requirem ent s for int ra-operat ive evoked
pot ent ial m onit oring
For details of in t ra-operative evoked poten tial (EP) m on itoring itself, see In t ra-op erat ive evoked
p oten t ials (p. 239).
4
108
4
General and Neurology
All volatile an esth etics produce dose-depen den t reduct ion in SSEP peak am plitu de an d an
in crease in peak laten cy. Adding n it rous oxide in creases th is sen sitivity to an esth etic agen ts.
An esth esia issues related to in tra-operative evoked poten tial (EPs) m on itorin g:
1. in duct ion : m in im ize pen toth al dose (produces ≈ 30 m in utes of suppression of EPs), or use etom idate (w h ich in creases both SSEP am plitu de an d laten cy 11 )
2. total in t raven ous an esth esia (TIVA) is ideal (i.e. n o in h alat ional agen ts)
3. n itrous/n arcot ic tech n ique is a distan t secon d ch oice
4. if in h alation al an esth etic agen ts are required:
a) use < 1 MAC (m axim al alveolar con cen tration ), ideally < 0.5 MAC
b) avoid older agen ts such as Haloth an e
5. n on depolarizing m uscle relaxan ts h ave litt le e ect on EP (in m on keys 12 )
6. propofol h as a m ild e ect on EP: total an esthesia w ith propofol causes less EP depression th an
in h alation al agen ts at th e sam e depth of an esth esia 13
7. ben zodiazepin es h ave a m ild-to-m oderate depressan t e ect on EPs
8. con tin uous in fusion of an esth etic drugs is preferred over in term itten t boluses
9. SSEPs can be a ected by hyper- or hypo-th erm ia, an d ch anges in BP
10. hypocapn ia (dow n to en d tidal CO2 = 21) causes m in im al reduct ion in peak laten cies 14
11. an t iepilept ic drugs: ph enytoin , carbam azipin e an d ph en obarbital do n ot a ect SSEP15
4.4 Malignant hypert herm ia
4.4.1 General inform at ion
Malign an t hyper th erm ia (MH) is a hyperm etabolic state of skeletal m uscle due to idiopath ic block of
Ca + + re-en tr y in to sarcoplasm ic reticulum . Tran sm itted by a m ultifactorial gen et ic predisposition .
Total body O2 con sum ption in creases × 2–3.
In ciden ce: 1 in 15,000 an esth etic adm in istration s in peds. 1 in 40,000 adults. 50% h ad previous
an esth esia w ith out MH. Frequen tly associated w ith adm in istration of h alogen ated in h alation al
agen ts an d th e use of succinylch olin e (fulm in an t form : m uscle rigidit y alm ost im m ediately after succinylch olin e, m ay involve m asseters → di cult y in tubatin g). In it ial attack an d recrudescen ce m ay
also occur post-op. 30% m ortalit y.16
4.4.2 Present at ion
1. earliest possible sign : increa se in en d-tidal pCO2
2. tachycardia (early) an d oth er arrhyth m ias
3. w ith progression :
a) coagulation disorder (DIC) (bleedin g from surgical w oun d an d body orifices)
b) ABG: in creasing m etabolic acidosis & decreasing pO2
c) pulm on ar y edem a
d) elevated body tem perat ure (m ay reach ≥ 44° C (113° F) at rate of 1° C/5-m in ) (n orm al pat ien ts
becom e hypoth erm ic w ith gen eral an esthesia)
e) lim b m uscle rigidit y (com m on , but late)
f) rh abdom yolysis → elevated CPK & m yoglobin (late)
4. term in al:
a) hypoten sion
b) bradycardia
c) cardiac arrest
4.4.3 Treat m ent
1. elim in ate o en din g agen ts (stop th e operation , D/C in h alation an esth esia an d ch ange t ubin g on
an esth esia m ach in e)
2. dan trolen e sodium (Dan trium ®) 2.5 m g/kg IV usually e ect ive, in fuse un til sym ptom s subside,
up to 10 m g/kg
3. hyper ven tilation w ith 100%O2
4. surface an d cavit y cooling: IV, in w oun d, per NG, PR
5. bicarbon ate 1–2 m Eq/kg for acidosis
6. IV in sulin an d glucose (low ers K+, glucose acts as en ergy substrate)
7. procain am ide for arrhyth m ias
8. diuresis: volum e loading + osm otic diuretics
Neuroanest hesia
109
4.4.4 Prevent ion
1. iden tification of patien ts at risk:
a) on ly reliable test: 4 cm viable m uscle biopsy for in -vitro tests at a few region al test cen ters
(abn orm al con tract ure to ca ein e or h aloth an e)
b) fam ily h istor y: any relative w ith syn drom e puts pat ien t at risk
c) related traits: 50% of MH patien ts h ave h eavy m usculature, Duch en n e t ype m uscular dyst rophy, or scoliosis
d) patien ts w h o exh ibit m asseter spasm in respon se to succinylch olin e
2. in patien ts at risk: avoid succinylch olin e (n on depolarizing blockers preferred if paralysis essen t ial), m ay safely h ave n on -h alogen ated an esth etics (n arcotics, barbiturates, ben zodiazepin es, droperidol, n it rous…)
3. prophylact ic oral dan trolen e: 4–8 m g/kg/day for 1–2 days (last dose given 2 h rs before an esth esia) is usually e ect ive
References
[1] Sch n eider AJ. Assessm en t of Risk Factors an d Surgical Ou tcom e. Su rg Clin N Am . 1983; 63:1113–1126
[2] Vacan t i CJ, Van Houten RJ, Hill RC. A Statist ical An alysis of th e Relation sh ip of Physical Stat us to Postoperative Mortalit y in 68,388 Cases. An esth An alg
Cu rr Res. 1970; 49:564–566
[3] Mar x GF, Mateo CV, Orkin LR. Com p uter An alysis of
Postan esth etic Death s. An esth esiology. 1973;
39:54–58
[4] Benveniste R, Germ an o IM. Evaluat ion of factors
predict in g accu rate resect ion of h igh -grad e gliom as
by u sin g fram eless im age-gu id ed stereotactic gu id an ce. Neu rosu rg Focus. 2003; 14
[5] Mar tin A, Rojas S, Ch am orro A, Falcon C, Bargallo N,
Plan as AM. W h y does acute h yperglycem ia w orsen
th e ou tcom e of tran sien t focal cerebral isch em ia?
Role of cort icosteroids, in flam m ation , an d protein
O-glycosylation . Stroke. 2006; 37:1288–1295
[6] Raggio JF, Fleisch er AS, Su n g YF, et al. Exp an din g
Pn eu m oceph alus d ue to Nitrou s Oxide An esth esia:
Case Repor t . Neu rosurger y. 1979; 4:261–263
[7] Dru m m on d JC, Cole DJ, Patel PM, Reyn old s LW .
Focal Cerebral Isch em ia durin g An esthesia w ith Etom idate, Isofluoran e, or Th iopental: A Com parison of
th e Exten t of Cerebral Inju r y. Neurosurger y. 1995;
37:742–749
[8] Sh ap iro HM, Miller RD. In : Neu rosu rgical An esth esia and In t racran ial Hyperten sion . An esth esia. 2n d
ed. New York: Church ill Livingston e; 1986:1563–
1620
[9] Dru m m on d JC, McKay LD, Cole DJ, Patel PM. Th e
role of n it ric oxid e syn th ase in h ibit ion in th e
[10]
[11]
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[13]
[14]
[15]
[16]
ad verse e ects of etom idate in th e settin g of focal
cerebral isch em ia in rats. An esth An alg. 2005;
100:841–6, table of con ten ts
Ho m an W E, Ch arbel FT, Ed elm an G, Misra M, Au sm an JI. Com parison of th e e ect of etom idate and
desfluran e on brain t issue gases an d p H durin g prolon ged m id dle cerebral arter y occlu sion . An esth esiology. 1998; 88:1188–1194
Koh t A, Sch utz W , Sch m idt G, Sch ram m J, Watan abe
E. E ects of etom idate, m idazolam , an d thiopen tal
on m ed ian n er ve som atosen sor y evoked p oten t ials
an d th e add itive e ects of fentan yl an d n it rous
oxide. An esth An alg. 1988; 67:435–441
Sloan TB. Nondepolarizing n eurom uscular blockade
does n ot alter sen sor y evoked poten t ials. J Clin
Mon it. 1994; 10:4–10
Liu EH, Won g HK, Chia CP, Lim HJ, Chen ZY, Lee TL.
E ects of isofluran e and propofol on cort ical som atosen sor y evoked poten tials du rin g com p arable
dep th of anaesth esia as gu ided by bispectral in dex.
Br J An aesth . 2005; 94:193–197
Sch u bert A, Dru m m on d JC. Th e e ect of acute hypocapn ia on h u m an m edian n er ve som atosen sor y
evoked responses. An esth An alg. 1986; 65:240–244
Borah NC, Math esh w ari MC. E ect of an t iepileptic
dru gs on sh ort-latency som atosen sor y evoked
poten tials. Acta Neu rol Scand. 1985; 71:331–333
Nelson TE, Flew ellen EH. Th e Malign an t Hyperth erm ia Syn drom e. N En gl J Med . 1983; 309:416–418
4
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General and Neurology
5 Sodium Hom eost asis and Osm olalit y
5.1 Serum osm olalit y and sodium concent rat ion
Clin ical sign ifican ce of various serum osm olarit y values is sh ow n in
Table 5.1.
Seru m osm olalit y. May be estim ated usin g Eq (5.1).
Osmolarity ðmOsm⁄ LÞ ¼ 2 Â
5
ÈÂ þ Ã Â þ ÃÉ ½BUN ½glucose
Na þ K
þ
þ
2:8
18
ð5:1Þ
(w ith [Na +] in m Eq/L or m m ol/L, an d glucose an d BUN in m g/dl).
NB: term s in square brackets [] represen t th e serum con cen tration s (in m Eq/L for elect rolytes).
Sod iu m con ten t . In th e diet: usually expressed in gram s Na + (n ot NaCl), a low sodium diet is con sidered 2 gm of Na + per day or less.
1 teaspoon of table salt (NaCl) h as 2.3 gm of Na +.
1 m g NaCl h as 17 m Eq Na +. 1 m g Na + h as 43 m Eq Na +.
Norm al salin e h as 0.9 gm of NaCl/100 m l. 3% NaCl h as 3 gm NaCl/100 m l.
5.2 Hyponat rem ia
5.2.1 General inform at ion
Key concept s
definition: serum [Na +] < 135 m Eq/L. Common etiologies:
○ SIADH: hypotonic hyponatremia (e ective serum osmol < 275 mOsm/L) with inappropriately
high urinary conentration (urine osmol > 100 mOsm /L) and euvolemia or hypervolem ia
○ cerebral salt wasting (CSW): similar to SIADH but with extracellular fluid volume depletion due to
renal sodium loss (urinary [Na}> 20 m Eq/L)
● minimum W/U:
serum [Na +], serum osmolalit y, urine osmolalit y, clinical assessment of
volume status. If volume status is high or low: urinary [Na +] TSH (to R/O hypothyroidism)
● treatment: based on acuit y, severity, symptom s & etiology; see SIADH (p. 115) or CSW (p. 118) as
appropriate
● risk of overly rapid correction: osmotic demyelination (including central pontine myelinolysis)
●
Classificat ion . [Na +] < 135 m Eq/L= m ild, < 130 = m oderate, < 125 = severe hypon atrem ia.
Hyp on at r em ia in n eu rosu rgical p at ien t s. Ch iefly seen in :
● syn drom e of in appropriate an t idiuretic h orm on e secretion (p.114), SIADH (p. 114): dilution al
hypon atrem ia w ith n orm al or eleva ted intra va scula r volume. Th e m ost com m on t ype of
Table 5.1 Clinical correlates of serum osm olalit y
Value (m Osm /L)
Com m ent
282–295
normal
< 240 or > 321
panic values
> 320
risk of renal failure
> 384
produces stupor
> 400
risk of generalized seizures
> 420
usually fatal
Sodium Hom eost asis and Osm olalit y
111
hypon atrem ia.1 Usually treated w ith fluid restrict ion. May be associated w ith n um erous in tracran ial abn orm alit ies ( Table 5.2) an d follow in g t ran ssph en oidal surgery
● cerebral salt w ast in g (CSW): in appropriate n atriuresis w ith volume deplet ion. Treated w ith volume
repla cement (opposite to SIADH) an d sodium; sym ptom s from derangem en ts due to CSW m ay be
exacerbated by fluid restrict ion (p.118).2 Etiology of 6%of cases of hypon atrem ia follow in g an eurysm al SAH3
Table 5.2 Etiologies of SIADa
Malignant tum ors
1.
2.
3.
4.
especially bronchogenic sm all-cell Ca
tumors of GI or GU tract
lymphomas
Ewing’s sarcom a
CNS disorders
1.
infection:
a) encephalitis
b) m eningitis: especially in peds
c) TB m eningitis
d) AIDS
e) brain abscess
2. head trauma: 4.6% prevalence
3. increased ICP: hydrocephalus, SDH…
4. SAH
5. brain tum ors
6. cavernous sinus thrombosis
7.
post craniotomy, especially following surgery for pituitary tum ors, craniopharyngiom as, hypothalamic
tum ors
8. MS
9. Guillain-Barré
10. Shy-Drager
11. delirium trem ens (DTs)
Pulm onary disorders
1. infection: pneum onia (bacterial & viral), abscess, TB, aspergillosis
2. asthma
3. respiratory failure associated with positive pressure respiration
Drugs
1. drugs that release ADH or potentiate it
a) chlorpropram ide (Diabinese®): increases renal sensitivit y to ADH
b) carbam azepine (Tegretol®), even more comm on with oxcarbazepine
c) HCTZ
d) SSRIs, TCAs
e) clofibrate
f) vincristine
g) antipsychotics
h) NSAIDs
i) MDMA (“ecstasy”)
2. ADH analogues
a) DDAVP
b) oxytocin: ADH cross activit y, m ay also be contam inated with ADH
Endocrine disturbances
1. adrenal insufficiency
2. hypothyroidism
Miscellaneous
1. anem ia
2. stress, severe pain, nausea or hypotension (all can stimulate ADH release), postoperative state
3. acute interm it tent porphyria (AIP)
a excerpted and m odified 9,1
5
112
5
General and Neurology
Ot h er et iologies of h yp on at rem ia:
● ren al failure
● volum e overload (e.g. as in congest ive h eart failure)
● p seu d oh yp on at rem ia: osm ot ically act ive solu tes (e.g. glu cose, m an n itol, m arked h yp erlip id em ia, or h yp er p rot ein em ia (w h ich can occu r in m u lt ip le m yelom a) 4 ) d raw w ater from cells an d
also red u ce th e w ater fract ion of p lasm a an d p rod u ce ar t ifact u ally low sod iu m valu es (an ar t ifact of in direct lab tech n iqu es). For ever y 100 m g/d l in crease of glu cose, seru m [Na] d ecreases
by 1.6–2.4 m Eq/L. It is n ecessar y to m easu re ser u m osm olalit y to ru le-ou t
p seu d oh yp on at rem ia
● postoperative hypon at rem ia: a rare con dition usually described in youn g, oth erw ise h ealthy
w om en un dergoing elect ive surger y 5 an d m ay be related to adm in istration of even on ly m ildly
hypoton ic fluids (som etim es in m odest am oun ts)6 an d th e act ion s of ADH (w h ich m ay be
in creased due to st ress, pain or m edication s)
5.2.2 Evaluat ion of hyponat rem ia
Fig. 5.1 sh ow s an algorith m for evaluating th e etiology of hypon atrem ia 7 w h ich drives t reatm en t
decision s. Work-up requires assessm en t of:
1. serum sodium : m ust be < 135 m Eq/L to qualify as hypon at rem ia
2. th e e ective serum osm olality(AKA ton icit y) is sh ow n in Eq (5.2)
effective serum osmolality ¼ measured osmolality À
½BUN ðmg⁄ dlÞ
2:8
ð5:2Þ
an d sh ould be used w h en th e blood urea n itrogen (BUN) level is elevated (for a n orm al [BUN] of 7–
18 m g/dl, just subtract 5 from th e m easured osm olality). Values < 275 m Osm /kg in dicate hypoton ic
hypon atrem ia
1. urin e osm olalit y: values > 100 m Osm /kg are in appropriately h igh if serum ton icit y is < 275
m Osm /kg
2. volum e status: di eren tiates SIADH from CSW
a) clin ical assessm ent: better for hyper volem ia (edem a, upw ard t ren d in patien t w eigh ts) but is
in sen sitive in iden tifyin g extracellular fluid depletion as an etiology of hypon at rem ia 8 (look
for dr y m ucous m em bran es, loss of skin turgor, or th ostatic hypoten sion )
b) n orm al salin e in fusion test used in un cert ain cases. If baselin e urin e osm olalit y is < 500
m Osm /kg, it is usually safe to in fuse 2 L of 0.9% salin e over 24–48 h ours. Correct ion of th e
hypon atrem ia suggests extracellular fluid volum e depletion w as th e cause
c) cent ral ven ous pressure (CVP) m ay be used: CVP < 5–6 cm H2 O suggests hypovolem ia in
patien ts w ith n orm al cardiac fun ct ion 3,7
3. ch eck urin ar y [Na +] if volum e status is h igh or low
4. determ in e durat ion of hypon at rem ia:
a) duration docum en ted as < 48 h ours is con sidered acute
b) hypon atrem ia of > 48 h ours durat ion or of un kn ow n duration is ch ron ic
c) hypon atrem ia th at occurs outside th e h ospital is usually ch ronic an d asym ptom atic except in
m arathon ers and MDMA (“ecstasy”) drug users
5.2.3 Sym pt om s
Due to slow com pen sator y m ech anism s in th e brain , a gradual declin e in serum sodium is better
tolerated th an a rapid drop. Sym ptom s of m ild ([Na] < 130 m Eq/L) or gradual hypon atrem ia in clude:
an orexia, h eadach e, di cult y con cen tratin g, irritabilit y, dysgeusia an d m uscle w eakn ess. Severe
hypon atrem ia (< 125 m Eq/L) or a rapid drop (> 0.5 m Eq/h r) can cause n eurom uscular excitabilit y,
cerebral edem a, m uscle t w itch in g an d cram ps, n ausea/vom it in g, con fusion , seizures, respirator y
arrest an d possibly perm an en t n eurologic injur y, com a or death .
5.2.4 Syndrom e of inappropriat e ant idiuresis (SIAD)
Th is term covers excess w ater reten tion in th e face of hypon at rem ia, in cludin g cases due to in appropriate ADH secretion (SIADH) as w ell as oth ers w ith out in creased circulatin g levels of ADH (e.g.
Sodium Hom eost asis and Osm olalit y
113
Hyponatrem ia
(Serum [Na +] < 135 m Eq/L)
275-290
mOsm/kg
Isotonic
hyponatrem ia
Etiologies
> 290
mOsm/kg
< 275
m Osm /kg
Hypotonic hyponatrem ia
• paraproteinemia
• hypertriglyceridem ia
Water intoxication
Effective
serum osm olality*
< 100
mOsm/kg
Hypertonic
hyponatrem ia
(AKA
pseudohyponatrem ia)
Etiologies
• hyperglycemia
• mannitol therapy
Urine
osmolality
Etiologies
> 100
mOsm/kg
• psychogenic polydipsia
Inappropriately concentrated urine
Decreased
Volum e
status†
Increased
Norm al
> 20
m Eq/L
Urinary
sodium
< 10
mEq/L
Renal
solute loss
Extrarenal
solute loss
Etiologies
Etiologies
• CSW
• diuretics
• Addison disease
§
Etiologies
• SIADH§
• K+ loss
• endocrinopathies
• GI tract
• skin
> 20
m Eq/L
Urinary
sodium
< 10
m Eq/L
Edem atous
states
Renal failure
Etiologies
• CHF
• cirrhosis
Fig. 5.1 Evaluation of the etiology of hyponatremia (adapted 7 )
* e ective serum osmolalit y = measured osm olalit y – [BUN]/2.8 (Eq (5.2))
† volum e status is usually assessed clinically, but this may be insensitive to volume depletion
§ SIADH may be associated with euvolemia or hypervolem ia
h eigh ten ed respon se to ADH, cer tain drugs…). A par t ial list of etiologies is sh ow n in Table 5.2 (see
referen ces 1,9 for details).
Th e diagn ost ic criteria of SIAD is sh ow n in Table 5.3. It is critical to mea sure ser um osmola lit y to
rule-out pseudohypon at rem ia (p.112), an art ifact of in direct lab tech n iques.
5
114
General and Neurology
Table 5.3 Diagnostic criteria for SIAD1
Essent ial feat ures
decreased effective serum osm olalit ya (< 275 m Osm /kg of water)
simulatneous urine osm olalit y > 100 mOsm/kg of water
clinical euvolemia
a) no clinical signs of extracellular (EC) volum e orthostatic hypotension (orthostasis, tachycardia, decreased
skin turgor, dry m ucous mem branes…)
b) no clinical signs of excess EC volum e (edema, ascites…)
urinary [Na] > 40 m Eq/L with norm al dietary Na intake
norm al thyroid and adrenal function
no recent diuretic use
●
●
●
●
●
●
5
Supplem ental features
plasm a [uric acid] < 4 mg/dl
[BUN] < 10 mg/dl
fractional Na excretion > 1%; fractional urea excretion > 55%
NS infusion test: failure to correct hyponatremia with IV infusion of 2 L 0.9% saline over 24–48 hrs
b correction of hyponatrem ia with fluid restriction
abnormal result on water load test c:
a) < 80% excretion of 20 m l of water/kg body weight over 5 hours, or
b) inadequate urinary dilution (< 100 m Osm /kg of water)
elevated plasm a [ADH] with hyponatrem ia and euvolemia
●
●
●
●
●
●
●
a effective osm olalit y (AKA tonicit y) = (measured osmolalit y) – [BUN]/2.8 with [BUN] measured in mg/dl
b this test is used in uncertain cases (corrects volum e depletion), and is usually safe when baseline urine osm olalit y
is < 500 m Osm /L
cwater load test & [ADH] levels are rarely recomm ended; see text for details (p. 115)
5.2.5 Syndrom e of inappropriat e ant idiuret ic horm one secret ion
(SIADH)
General inform at ion
Key concept s
definition: release of ADH in the absence of physiologic (osm otic) stimuli
● results in hyponatrem ia with hypervolem ia (occasionally with euvolemia) with inappropriately high
urine osmolalit y (> 100 mOsm/L)
● may be seen with certain malignancies and m any intracranial abnorm alities
● critical to distinguish from cerebral salt wasting which produces hypovolem ia
● treatment: initial guidelines in brief, see details (p. 115)
○ avoid rapid correction or overcorrection to reduce risk of osm otic demyelination (p. 115). Check
serum [Na +] q 2–4 hours and do not exceed 1 mEq/L per hour, or 8 mEq/L in 24 hrs or 18 mEq/L
in 48 hrs
○ severe ([Na +] < 125 mEq/ L of < 48 hrs duration or with severe sym ptoms (coma, Sz): start 3% saline at 1–2 ml/kg body weight/hr + furosemide 20 m g IV qd
○ severe ([Na +] < 125 mEq/ L of duration > 48 hours or unknown without severe sym ptoms: normal
saline infusion @ 100 m l/hr + furosemide 20 mg IV qd
○ chronic or unknown duration and asym ptom atic: fluid restriction ( Table 5.4) with dietary salt
and protein, and, if necessary, adjuvant drugs (dem eclocycline, conivaptan…)
●
SIADH, AKA Sch w art z-Bartter syn drom e, w as first described w ith bron ch ogen ic can cer w h ich is on e
cause of SIAD. SIADH is th e release of an t idiuret ic h orm on e (ADH), AKA argin in e vasopressin (AVP)
(p. 151), in th e absen ce of physiologic (osm otic) st im uli. Result: elevated urin e osm olality, an d
expan sion of th e extracellular fluid volum e leading to a dilution al hypon atrem ia w h ich can produce
fluid overload (hyper volem ia), but SIADH m ay also occur w ith euvolem ia. For un clear reason s, edem a does n ot occur.
Th e hypon atrem ia of SIADH m ust be di eren tiated from th at due to cerebral salt w ast in g (CSW )
due to di eren ces in t reat m en t recom m en dation s (p.118).
Etiologies: Table 5.2.
Sodium Hom eost asis and Osm olalit y
115
Table 5.4 Fluid restriction recommendations1
Solute rat io a
Recom m ended fluid intake
>1
< 500 m l/d
1
500–700 m l/d
<1
< 1 L/d
a solute ratio defined as: urinary ½Na þ urinary ½K
plasm a ½Na
Diagnosis of SIADH
In gen eral, 3 diagn ostic criteria are: hypon at rem ia, in appropriately con cen trated urin e, an d n o eviden ce of ren al or adren al dysfun ct ion . In m ore detail:
1. low serum sodium (hypon atrem ia): usually < 134 m Eq/L
2. low e ect ive serum osm olality: < 275 m Osm /L
3. h igh urin ar y sodium (salt w ast in g): at least > 18 m Eq/L, often 50–150. Note: th ere h as n ot been
an adequate explanation of th e h igh urin ar y sodium in SIADH
4. h igh ratio of urin e:serum osm olalit y: often 1.5–2.5:1, but m ay be 1:1
5. n orm al ren al fun ction (ch eck BUN & creatin in e): BUN com m on ly < 10
6. n orm al adren al fun ct ion (n o hypoten sion , n o hyperkalem ia)
7. n o hypothyroidism
8. n o sign s of dehydrat ion or overhydration (in m any patien ts w ith acute brain disease, th ere is sign ifican t hypovolem ia often due to CSW (p.118) an d as th is is a st im ulus for ADH secretion , th e
ADH release m ay be “appropriate”10 ). In un cert ain cases, th e n orm al salin e in fusion test (p. 112)
m ay be used.
If furth er test ing is required, th e follow in g are opt ion s, but are rarely recom m en ded:
1. m easure serum or urin ar y levels of ADH. Rarely in dicated sin ce urin e osm olality > 100 m Osm /kg
is usually su cien t to in dicate excessive ADH.1 ADH is n orm ally un detectable in etiologies of
hypon atrem ia oth er th an SIADH
2. w ater-load test: con sidered to be th e defin itive test.11 Th e patien t is asked to con sum e a w ater
load of 20 m l/kg up to 1500 m l. In th e absen ce of adren al or ren al in su cien cy, th e failure to
excrete 65% of th e w ater load in 4 h rs or 80%in 5 h rs indicates SIAD.
CONTRAINDICATIONS: th is test is dangerous if th e start in g serum [Na +] is ≤ 124 m Eq/L or if
th e patien t h as sym ptom s of hypon atrem ia
Sym pt om s of SIADH
Sym ptom s of SIADH are th ose of hypon atrem ia (p. 112) an d possibly fluid overload. If m ild, or if
descen t of [Na +] is gradual, it m ay be tolerated. [Na +] < 120–125 m Eq/L is alm ost always sym ptom atic.
Th ese pat ien ts often h ave a paradoxical (in appropriate) th irst.
Treat m ent of hyponat rem ia w it h SIADH
Man agem en t is based on th e severit y an d durat ion of hypon at rem ia, an d th e presen ce of sym ptom s.
Tw o caveats:
1.
be sure th at hypon at rem ia is n ot due to CSW (p. 118) before restrict in g fluids
2. avoid too rapid correction an d avoid correct in g to n orm al or supran orm al (overcorrect ion )
sodium to reduce th e risk of osm otic dem yelin ation syn drom e
Osm ot ic dem yelination syndrom e
A com plication associated w ith som e cases of treatm ent for hyponatrem ia. While excessively slow correction of acute hyponatrem ia is associated w ith increased m orbidity and m ortality,12 som e cases of inordinately rapid treatm ent have been associated w ith osm otic demyelination syndrom e (w hich includes
central pontine myelinolysis (CPM) a rare disorder of pontine w hite m atter 13 ( Fig. 5.2) and extrapontine
myelinolysis ( Fig. 5.3), as well as other areas of cerebral w hite m atter). First described in alcoholics,14
producing insidious flaccid quadriplegia, m ental status changes, and cranial nerve abnorm alities w ith a
pseudobulbar palsy appearance. In one review,15 no patient developed CPM w hen treated slowly as
5
116
General and Neurology
Fig. 5.2 Central pontine myelinolysis (arrowhead).
Axial FLAIR MRI
5
Fig. 5.3 Osm otic demyelination of pons (black
arrowhead) & thalamus (white arrowhead). Coronal
T2WI MRI
outlined below. And yet, the rate of correction correlates poorly w ith CPM; it m ay be that the m agnitude
is another critical variable.16 Features com m on to patients w ho develop CPM are 15:
● delay in th e diagn osis of hypon at rem ia w ith resultan t respirator y arrest or seizure w ith probable
hypoxem ic even t
● rapid correct ion to n orm o- or hyper-n at rem ia (> 135 m Eq/L) w ith in 48 h ours of in itiat in g th erapy
● in crease of serum sodium by > 25 m Eq/L w ith in 48 h ours of in itiation of th erapy
● over-correct in g serum sodium in pat ien ts w ith h epatic en ceph alopath y
● NB: m any patien ts developin g CPM w ere vict im s of ch ron ic debilitatin g disease, m aln ourish m en t,
or alcoh olism an d n ever h ad hypon atrem ia. Many h ad an episode of hypoxia/an oxia 17
● presen ce of hypon atrem ia > 24 h rs prior to treatm en t 16
Th e on ly defin itive t reatm en t is t reatm en t of th e un derlying cause
● if caused by an em ia: usually respon ds to tran sfusion
● if caused by m align an cy, m ay respon d to an tin eoplastic th erapy
● m ost drug related cases respon d rapidly to discon tin uation of th e o en din g drug
Treatm ent algorithm s
Fig. 5.4 depicts an algorith m for select ing th e correct SIADH t reatm en t protocol.
Aggressive t r eat m en t p rotocol. In dication s (also refer to
1. severe hypon atrem ia (serum [Na +] < 125 m Eq/L)
Fig. 5.4):
Sodium Hom eost asis and Osm olalit y
117
Start
Mild to Moderate
erate
Sever
Severe
([Na +] = 125-135 m Eq/L) Degree of ([Na +] < 125 m Eq/L)
Hyponatrem ia
5
no
Symptom s?
(asymptom atic)
yes
Routine
Treatm ent
(see text)
none
≥ 48 hours
Interm ediate
or unknown
Treatm ent
Symptom s
Duration
m oderate or
(see text)
nonspecific
severe
< 48
(H/A,
(com a,
hours
lethargy)
seizures)
Aggressive
Treatm ent
(see text)
Fig. 5.4 Treatment protocol selection for hyponatremia in SIADH
2. AND eith er
a) duration kn ow n to be < 48 h ours
b) or severe sym ptom s (com a, seizures)
Treatm en t
● tran sfer pat ien t to ICU
● in terven tion s
○ 3% salin e: start in fusion 1–2 m l/kg body w eigh t per h our (in fusion rate m ay be doubled to 2–
4 m l/kg/h r for lim ited periods in patien ts w ith com a or seizures 1 )
○ an d furosem ide (Lasix®) 20 m g IV q d (furosem ide accelerates th e in crease in [Na +] an d preven ts volum e overload w ith subsequen t in crease in atrial n atriuretic factor an d resultan t urin ar y dum ping of th e extra Na + bein g adm in istered)
● m on itorin g an d adjust m en ts
○ ch eck serum [Na +] ever y 2–3 h ours an d adjust in fusion rate of 3%salin e
– goal: raise serum sodium by 1–2 m Eq/L/h r 18 (use low er en d of ran ge for hypon at rem ia > 48
h ours duration or un kn ow n durat ion )
– lim its: do n ot exceed 8–10 m Eq/L in 24 h rs an d 18–25 m Eq/L in 48 h rs 1 (use low er en d of
th ese ran ges for hypon atrem ia > 48 h ours duration or un kn ow n duration)
○ m easure K+ lost in urin e an d replace accordingly
118
General and Neurology
○
if sym ptom s of osm otic dem yelin ation occur (early sym ptom s are leth argy an d a ect ive
ch anges, usually after in itial im provem en t): deficits m ay im prove by stopping treatm en t an d
m odestly relow erin g th e serum sodium e.g. w ith DDAVP19,20
In t er m ed iate t reat m en t p rotocol. In dication s (also refer to Fig. 5.4):
1. sym ptom atic n on severe hypon atrem ia (serum [Na +] = 125–135 m Eq/L), or
2. severe hypon atrem ia (serum [Na +] < 125 m Eq/L), AND
a) duration > 48 h ours or un kn ow n AND
b) on ly m oderate sym ptom s or n on specific sym ptom s (e.g. H/A, or leth argy)
5
Treatm en t
1. in terven tion s
a) 0.9%salin e (n orm al salin e) in fusion
b) an d furosem ide (Lasix®) 20 m g IV q d
c) con sider con ivaptan for refractor y cases
2. m on itorin g: ch eck serum [Na +] ever y 4 h ours an d adjust in fusion rate of n orm al salin e
3. goals: [Na +] in crease of 0.5–2 m Eq/L/h r
4. lim its: do not exceed 8–10 m Eq/L in 24 h rs an d 18–25 m Eq/L in 48 h rs 1
Rou t in e t reat m en t p rotocol an d m ain ten an ce t h erap y. In dication s (also refer to
1. asym ptom atic n on severe hypon atrem ia (serum [Na +] = 125–135 m Eq/L), or
2. severe hypon atrem ia (serum [Na +] < 125 m Eq/L) AND
a) duration > 48 h ours or un kn ow n AND
b) asym ptom atic
Fig. 5.4):
Treatm en t
1. in terven tion s
a) fluid restriction Table 5.4 for adults, for peds: 1 L/m 2 /day) w h ile en couraging use of dietar y
salt an d protein . Caution restricting fluids in hypon at rem ia follow in g SAH (p.1166).
b) for refractor y cases, con sider
● dem eclocycline: a tetracycline antibiotic that partially antagonizes the e ects of ADH on the
renal tubules.21,22,23 E ects are variable, and nephrotoxicity m ay occur. 300–600 m g PO BID
● con ivaptan (Vaprisol®): a n onpeptide an tagon ist of V1A & V2 vasopressin receptors. FDA
approved for euvolem ic an d hypervolem ic m oderate-to-severe hypon atrem ia in h ospitalized pat ien ts (NB: severe sym ptom s of seizures, com a, delirium … w arran ts aggressive
treat m en t w ith hyperton ic salin e 1 ). Use in th e n euro-ICU h as been described for t reatin g
elevated ICP w h en serum [Na] is not respon din g to t radition al m eth ods 24 (o -label use –
use w ith caution ). loading dose 20 m g IV over 30 m in utes, follow ed by in fusion s of 20 m g
over 24 h ours × 3 days. If serum [Na +] are n ot rising as desired, th e in fusion m ay be
in creased to th e m axim al dose of 40 m g over 24 h ours. Use is approved for up to 4 days
total. Caution re drug in teract ion s
● lith ium : n ot ver y e ect ive an d m any side e ect s. Not recom m en ded
5.2.6 Cerebral salt w ast ing
Cerebral salt w astin g (CSW ): ren al loss of sodium as a result of in tracran ial disease, producin g hypon atrem ia an d a decrease in extracellular fluid volum e.11 CAUTION: pat ien ts w ith an eur ysm al SAH
m ay h ave CSW w ith hypon atrem ia w h ich m im ics SIADH, how ever th ere is usually also hypovolem ia
in CSW . In th is settin g, fluid restrict ion m ay exacerbate vasospasm in duced isch em ia.11,25,26,27
Th e m ech an ism w h ereby th e kidn eys fail to con ser ve sodium in CSW is n ot kn ow n , an d m ay be
eith er a result of an as yet un iden tified n atriuretic factor or direct n eural con trol m ech an ism s (see
Hypon atrem ia follow in g SAH (p.1166)).
Laboratory tests (serum and urinary electrolytes and osm olalities) m ay be identical w ith SIADH and
CSW.28 Furtherm ore, hypovolem ia in CSW may stim ulate ADH release. To di erentiate: CVP, PCWP, and
plasm a volum e (a nuclear m edicine study) are low in hypovolem ia (i.e. CSW). Table 5.5 compares som e
features of CSW and SIADH, the two m ost important di erences being extracellular volum e and salt balance. An elevated serum [K+] with hyponatrem ia is incom patible with the diagnosis of SIADH.
Treat m en t of CSW
● Goals:
○ volum e replacem en t
○ positive salt balan ce
Sodium Hom eost asis and Osm olalit y
119
Table 5.5 Comparison of CSW and SIADH11
Param eter
CSW
SIADH
Plasm a volum e
↓ (< 35 m l/kg)
↑ or WNL
Salt balance
negative
variable
Signs & sym ptom s of dehydration
present
absent
Weight
↓
↑ or no Δ
PCWP
↓ (< 8 m m Hg)
↑ or WNL
CVP
↓ (< 6 m m Hg)
↑ or WNL
Orthostatic hypotension
+
±
Hem atocrit
↑
↓ or no Δ
Serum osm olalit y
↑ or WNLa
↓
Ratio of serum [BUN]:[creatinine]
↑
WNL
Serum [protein]
↑
WNL
Urinary [Na+]
↑↑
↑
Serum [K+]
↑ or no Δ
↓ or no Δ
Serum [uric acid]
WNL
↓
Abbreviations: ↓ = decreased, ↑ = increased, ↑ ↑ = significantly increased, WNL= within normal limits, no Δ = no
change, [] = concentration, + = present, ± = may or m ay not be present
a In realit y, serum osm olalit y is usually ↓ in CSW
avoid excessively rapid correct ion of hypon atrem ia or overcorrect ion w h ich m ay be associated
w ith osm ot ic dem yelin ation (p. 115) as w ith SIADH (p. 115).
● In terven tion s
○ Hydrate patien t w ith 0.9% NS at 100–125 m l/h r. For severe cases, 3% salin e at 25–50 cc/h r is
occasion ally required.
○ Do n ot give furosem ide.
○ Salt m ay also be sim ultan eously replaced orally.
○ Blood products m ay be n eeded if an em ia is presen t .
○ Medication s
a) Fludrocort ison e acetate acts directly on th e ren al t ubule to in crease sodium absorption . Ben efits of giving 0.2 m g IV or PO q d in CSW h ave been reported,29 but sign ifican t com plicat ion s
of pulm on ar y edem a, hypokalem ia an d HTN m ay occur.
b) Urea: an altern ative t reat m en t usin g urea m ay be applicable to th e hypon at rem ia of eith er
SIADH or CSW , an d th erefore m ay be used before th e cause h as been ascertain ed: urea (Ureaph il®) 0.5 gram s/kg (dissolve 40 gm in 100–150 m l NS) IV over 30–60 m in s q 8 h rs.30 Use
NS + 20 m Eq KCl/L at 2 m l/kg/h r as th e m ain IV un til th e hypon atrem ia is corrected (un like
m an n itol, urea does n ot in crease ADH secretion ). Th ey supplem en ted w ith colloids (viz.
250 m l of 5% album in IV q 8–12 h rs x 72 h rs).
○
5.3 Hypernat rem ia
5.3.1 General inform at ion
Defin ition : serum sodium > 150 m Eq/L. In n eurosurgical patien ts, th is is m ost often seen in th e sett in g of diabetes in sipidus (DI).
Sin ce n orm al total body w ater (TBW ) is ≈ 60% of th e patien t’s n orm al body w eigh t , th e pat ien t’s
curren t TBW m ay be estim ated by Eq (5.3).
5
120
General and Neurology
 þÃ
Na norm al  TBWnorm al 140m Eq=L 0:6  usual body wt ðkg Þ
 þÃ
 þÃ
TBWcurrent ¼
¼
Na current
Na current
ð5:3Þ
Th e free w ater deficit to be replaced is given by Eq (5.4). Correct ion m ust be m ade slow ly to avoid
exacerbating cerebral edem a. One ha lf th e water deficit is replaced over 24 h ours, an d th e rem ain der
is given over 1–2 addition al days. Judicious replacem en t of deficien t ADH in cases of true DI m ust
also be m ade.
5
free water deficit ¼ Â
0:6 ÂÃusual body wt ðkg ÞÀ TBWcurrent
Na þ current À 140mEq=L
 þÃ
¼
 0:6  usual body wt ðkg Þ
Na current
ð5:4Þ
5.3.2 Diabet es insipidus
General inform at ion
Key concept s
due to low levels of ADH (or, rarely, renal insensitivit y to ADH)
● high output of dilute urine (< 200 m Osm ol/L or SG < 1.003) with normal or high serum osmolalit y
and high serum sodium
● often accom panied by craving for water, especially ice-water
● danger of severe dehydration if not m anaged carefully
●
Diabetes in sipidus (DI) is due to in su cien t ADH act ivity at th e kidn eys, an d results in th e excessive
ren al loss of w ater an d elect rolytes. DI m ay be produced by t w o di eren t etiologies:
● cent ral or n eurogen ic DI: subn orm al levels of ADH caused by hypothalam ic-pituitar y axis dysfun ct ion . Th is is th e t ype m ost often seen by n eurosurgeon s
● “n eph rogen ic DI”: due to relative resistan ce of th e kidn ey to n orm al or supra-n orm al levels of
ADH. Seen w ith som e drugs (drugs: l)
Etiologies of DI31 :
1. (n eurogen ic AKA cen tral) diabetes in sipidus
a) fam ilial (autosom al dom in an t)
b) idiopathic
c) postt raum atic (brain injur y, in cludin g surgery)
d) t um or: cran ioph ar yn giom a, m etastasis, lym ph om a…
e) gran ulom a: n eurosarcoidosis, h ist iocytosis
f) in fect ious: m en in gitis, en cephalit is
g) autoim m un e
h ) vascular: an eur ysm , Sh eeh an’s syn drom e (rarely causes DI)
2. n eph rogen ic diabetes in sipidus
a) fam ilial (X-lin ked recessive)
b) hypokalem ia
c) hypercalcem ia
d) Sjögren’s syn drom e
e) drugs: lithium , dem eclocyclin e, colch icin e…
f) ch ronic ren al disease: pyelon eph ritis, am yloidosis, sickle cell disease, polycystic kidn ey disease, sarcoidosis
Cent ral DI
85% of ADH secretor y capacit y m ust be lost before clin ical DI en sues. Ch aracterist ic features: h igh
urin e out put (polyuria) w ith low urin e osm olality, an d (in th e con scious patien t) cravin g for w ater
(polydipsia), especially ice-w ater.
Sodium Hom eost asis and Osm olalit y
121
Di eren tial diagn osis of DI:
1. (n eurogen ic) diabetes in sipidus (true DI)
2. n eph rogen ic diabetes in sipidus
3. psych ogen ic
a) idiopathic: from reset tin g of th e osm ostat
b) psych ogen ic polydipsia (excess free water in take)
4. osm ot ic diuresis: e.g. follow in g m an n itol, or w ith ren al glucose spillin g
5. diuretic use: furosem ide, hydroch loroth iazide…
Cent ral DI m ay be seen in th e follow in g situation s:
1. follow in g tran ssph en oidal surger y or rem oval of cran ioph ar yn giom a: (usually tran sien t, th erefore avoid lon g-act in g agen ts un til it can be determ in ed if lon g-term replacem en t is required).
Injur y to th e posterior pituitar y or stalk usually causes on e of th ree pattern s of DI32 :
a) t ran sien t DI: supra-n orm al urin e output (UO) an d polydipsia w h ich t ypically n orm alizes ≈
12–36 h rs post-op
b) “prolonged” DI: UO stays supra-n orm al for prolonged period (m ay be m on th s) or even perm an en tly: on ly about on e–th ird of th ese pat ien ts w ill n ot return to n ear-n orm al at on e year
post-op
c) “triph asic respon se”: least com m on
● ph ase 1: injur y to pituitar y reduces ADH levels for 4–5 days → DI (polyuria/polydipsia)
● ph ase 2: cell death liberates ADH for th e n ext 4–5 days → t ran sien t n orm alization or even
SIADH-like w ater reten tion ( NB: th ere is a dan ger of in adver tently con tin uin g vasopressin th erapy beyon d th e in itial DI ph ase in to th is ph ase causin g sign ifican t h em odilution )
● ph ase 3: reduced or absen t ADH secretion → eith er t ran sien t DI (as in “A” above) or a “prolon ged” DI (as in “B” above)
2. central h ern iation (p. 303): sh earin g of pit uitar y stalk m ay occur
3. brain death : hypoth alam ic product ion of ADH ceases
4. w ith certain t um ors:
a) pituitar y aden om as: DI is rare even w ith ver y large m acroaden om as. DI m ay occur w ith
pituitar y apoplexy (p.720)
b) cran ioph ar yn giom a: DI usually on ly occurs postoperatively sin ce dam age to pituitar y or low er stalk does n ot preven t product ion an d release of ADH by hypoth alam ic n uclei
c) suprasellar germ cell t um ors
d) rarely w ith a colloid cyst
e) hypoth alam ic t um ors: Lan gerh an s cell h ist iocytosis
5. m ass lesion s pressin g on hypoth alam us: e.g. a-com m an eur ysm
6. follow in g h ead injur y: prim arily w ith basal (clival) skull fract ures (p.884)
7. w ith en ceph alitis or m en in gitis
8. drug in duced:
a) eth an ol an d ph enytoin can in h ibit ADH release
b) exogen ous steroids m ay seem to “brin g out” DI because th ey m ay correct adren al in su cien cy (below ) an d th ey in h ibit ADH release
9. gran ulom atous diseases
a) Wegen er’s gran ulom atosis (p.199): a vasculit is
b) n eurosarcoidosis involvin g th e hypoth alam us (p. 189)
10. in flam m ator y: autoim m un e hypophysit is (p. 1373) 33 or lym ph ocytic in fun dibulon eurohypophysitis 34 (distin ct con dition s)
Diagnosis
Th e follow in g are usually adequate to m ake th e diagn osis of DI, especially in th e appropriate clin ical
sett ing:
1. dilute urin e:
a) urin e osm olalit y < 200 m Osm /L (usually 50–150) or specific gravit y (SG) < 1.003 (m ay be
1.001 to 1.005). (Note th at n orm ally, urin e osm olality averages bet w een 500–800 m Osm /L;
extrem e ran ge: 50–1400.)
b) or th e in abilit y to con cen trate urin e to > 300 m Osm /L in th e presen ce of clinical dehydration
c) NB: large doses of m an n itol as m ay be used in h ead t raum a can m ask th is by producin g a
m ore con cen trated urin e
2. urin e output (UO) > 250 cc/h r (peds: > 3 cc/kg/h r)
3. n orm al or above-n orm al serum sodium
5
122
General and Neurology
©2001 Ma rk S Gre e nbe rg, M.D.
All rights re s e rve d.
Una uthorize d us e is prohibite d.
1400
800
P OLYDIP S IA
600
NORMAL
400
r
i
n
e
o
s
m
o
l
a
l
i
t
y
(
m
O
s
m
/
L
1000
u
5
)
1200
200
DIABETES
INS IP IDUS
0
276
280
284
288
292
296
serum osmolality (mOsm/L)
Fig. 5.5 Interpretation of simultaneous serum vs. urine osm olalit y (Provided by Arnold M. Moses, M.D., used with
perm ission)
4. n orm al adren al fun ct ion : DI can n ot occur in prim ar y adren al in su cien cy because a m in im um
of m in eralocort icoid activit y is n eeded for th e kidn ey to m ake free w ater, th us steroids m ay
“brin g out” un derlyin g DI by correcting adren al in su cien cy
In un certain cases, plot urin e an d sim ultan eous serum osm olality on th e graph in Fig. 5.5.
1. low serum osm olalit y: usually in dicates psych ogen ic polydipsia (path ological drin kin g of w ater)
2. if th e poin t falls in th e “n orm al” ran ge, a super vised w ater deprivation test is n eeded to determ in e
if th e patien t can con cen trate th eir urin e w ith dehydrat ion (caution : see below )
3. h igh serum osm olalit y:
● diagn osis of DI is establish ed an d n o fur th er test in g to establish th e diagn osis is required
● furth er test ing is on ly n eeded to di eren tiate cent ral from n eph rogen ic DI, if desired to di eren tiate cen tral from n eph rogen ic DI, give aqueous Pitressin ® 5 U SQ
● in cen t ral DI th e urin e osm olalit y sh ould double w ith in 1–2 h ours
4. plotting m ore th an on e data poin t m ay h elp as som e patien ts tend to “vacillate” aroun d th e border zon es
Water deprivation test
If st ill un clear, th e diagnosis of DI is con firm ed by a w ater deprivation test ( CAUTION: perform on ly
un der close supervision as rapid an d poten tially fatal dehydration m ay en sue in DI). Th is test is
rarely n ecessar y if serum osm olality > 298 m Osm /L. (Note th at in com pen sated DI, serum osm olality
is m ore likely to be low er an d to overlap w ith n orm al.35 )
Sodium Hom eost asis and Osm olalit y
123
Table 5.6 Highest urinary osmolalit y after Pitressin in water deprivation test
Δ in urinary Osm
Int erpret at ion
< 5% increase
norm al
6–67% increase
partial ADH deficiency
> 67% increase
severe ADH deficiency
Stop IVs an d m ake th e patien t NPO
● Mon itorin g:
○ ch eck urin e osm olality q h r
○ ch eck patien t w eigh t q 1 h r
● con tin ue th e test un t il on e of th e follow in g occurs:
○ n orm al respon se occurs: urin e out put decreases, an d urin e osm olalit y rises to 600–850 m Osm /
L
○ 6–8 h ours lapse
○ urin e osm olalit y plateaus (i.e. ch anges < 30 m Osm in 3 con secutive h ours)
○ patien t loses 3% of body w eigh t
● if th e patien t fails to dem on strate th e n orm al respon se, th en :
○ give exogen ous ADH (5 U aqueous Pitressin ® SQ), w h ich n orm ally in creases urin e osm olalit y
to > 300 m Osm /L
○ ch eck urin e osm olality 30 an d 60 m in utes later
○ com pare h igh est urin e osm olalit y after Pitressin ® to th e osm olalit y just before Pitressin ®
according to Table 5.6
●
Treat m ent of DI
In con sciou s am bu lator y p at ien t
If DI is m ild, an d th e patien t’s n atural th irst m ech an ism is in tact , in struct patien t to drin k only
w h en th irst y an d th ey usually “keep up” w ith losses an d w ill n ot becom e overhydrated.
If severe, th e patien t m ay n ot be able to m ain tain adequate in take of fluid or tolerate th e frequen t
t rips to bath room . In th ese cases, treatm en t t ypically involves a vasopressin an alogue. See below for
a syn opsis of vasopressin an alogues. Typically start w ith eith er:
1. desm opressin (DDAVP®)
a) PO: 0.1 m g PO BID, adjust up or dow n PRN urin e out put (t ypical dosage ran ge: 0.1–0.8 m g/d
in divided doses)
b) n asal spray: 2.5 m cg (0.025 m l) by n asal in su ation BID, t itrate up to 20 m cg BID as n eeded
(th e n asal spray m ay be used for doses th at are m ultiples of 10 m cg)
OR
2. ADH en h an cin g m edication s (w orks prim arily in ch ron ic partial ADH deficien cy. Will n ot w ork in
total absen ce of ADH)
● clofibrate (Atrom id S®) 500 m g PO QID
● ch lorpropram ide: in creases ren al sen sitivit y to ADH
● hydroch loroth iazide: th iazide diuretics m ay act by depletin g Na + w h ich in creases reabsorpt ion
in proxim al tubules an d sh ift in g fluid aw ay from distal t ubules w h ich is w h ere ADH w orks. :
e.g. Dyazide® 1 PO q d (m ay in crease up to 2 per day PRN)
In con sciou s am bu lator y p at ien t w it h im p aired t h irst m ech an ism s
If th irst m ech an ism s are not in tact in con scious am bulator y patien t, th ey run th e risk of dehydration or fluid overload. For th ese patien ts:
1. h ave patien t follow UO an d daily w eigh ts, balan ce fluid in take an d output using an tidiuretic
m edicat ion as n eeded to keep UO reason able
2. ch eck serial labs (approxim ately q w eekly) in cludin g serum sodium , BUN
In n on -am bu lat or y, com at ose/st u p orou s, or brain -d ead p at ien t; see also Medical Man agem en t of
th e Poten tial Organ Don or (p. 313)
1. follow I’s & O’s q 1 h r, w ith urin e specific gravit y (SG) q 4 h rs an d w hen ever urin e out put (UO) >
250 m l/h r
2. labs: serum elect rolytes w ith osm olalit y q 6 h rs
5
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General and Neurology
Table 5.7 Available preparations of vasopressin analogues
Generic nam e
Trade nam e
Route
Concentration
Availabilit y
Manufacturer
desmopressin
DDAVP®
SQ, IM, IV
4 m cg/ml
1 & 10 m l
Aventis
desmopressin
DDAVP® Nasal
Spray
nasal spray
100 m cg/m l,
each spray delivers 10 mcg
50 doses per
bottle
Aventis
desmopressin
DDAVP®
Tablets
PO
0.1 & 0.2 m g
Aventis
arginine vasopressin
aqueous
Pitressin®
SQ, IM
0.5 and 1 ml
Parke-Davis
5
20 U/ml
(50 mcg/m l)
Table 5.8 Mean tim e of hypertonic urine a (relative to plasma)b
Generic nam e
Route
Dose
Mean duration of action c
desm opressin
SQ, IM, IV
0.5 mcg
8 hrs
desm opressin d
SQ, IM, IV
1.0 mcg
12 hrs
desm opressin
SQ, IM, IV
2.0 mcg
16 hrs
desm opressin
SQ, IM, IV
4.0 mcg
20 hrs
desm opressin
intranasal
10 mcg (0.1 ml)
12 hrs
desm opressin
intranasal
15 mcg (0.15 ml)
16 hrs
desm opressin
intranasal
20 mcg (0.2 ml)
20 hrs
arginine vasopressin
SQ, IM
5 U (12.5 m cg)
4 hrs
(range: 4–8)
a provided by Arnold M. Moses, M.D., used with permission
b onset of antidiuretic action of these preparations is 30–45 m inutes following administration (except pituitary
powder in oil which takes 2–4 hrs to start working)
c times m ay vary from patient to patient, but are usually consistent in any individual
d Note: 1 m cg BID of desmopressin is as effective as 4 mcg q d, but would obviously be less expensive
3. IV fluid m an agem en t:
BASE IV: D5 1/2 NS + 20 m Eq KCl/L at appropriate rate (75–100 m l/h r)
PLUS: replace UO above base IV rate m l for m l w ith 1/2 NS
NB: for post-op patien ts, if th e patien t received sign ifican t in traoperative fluids, th en th ey m ay
h ave an a ppropria te post-op diuresis, in th is case use 1/2 NS to replace on ly ≈ 2/3 of UO th at
exceeds th e basal IV rate
4. if un able to keep up w ith fluid loss w ith IV (or NG) replacem en t (usually w ith UO > 300 m l/h r),
th en EITHER
● 5 U argin in e vasopressin (aqueous Pitressin ®) IVP/IM/SQ q 4–6 h rs (avoid tan n ate oil suspen sion due to erratic absorption an d variable duration )
OR
● vasopressin IV drip: start at 0.2 U/m in & t it rate (m ax: 0.9 U/m in )
OR
● desm opressin inject ion SQ/IV t it rated to UO, usual adult dose: 0.5–1 m l (2–4 m cg) daily in 2
divided doses
Vasopressin an alogu es
Table 5.6, Table 5.7 an d
an alogues.
Table 5.8 sh ow s dosin g form s an d durat ion of action of vasopressin
Sodium Hom eost asis and Osm olalit y
125
Pitressin ® is aqueous solution of 8-argin in e vasopressin an d sh ould be used w ith caution in
patien ts w ith vascular disease (especially coron ary arteries).
Caution – soun dalikes: som et im es
pitocin is con fused w ith pit ressin because of sim ilarities of th e n am e.
DDAVP (1-deam in o-8-D-argin in e vasopressin ) AKA desm opressin . More poten t an d lon ger acting
th an vasopressin .
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excessive correct ion of hypon atrem ia. Clin Neph rol.
1999; 51:383–386
Oya S, Tsutsum i K, Ueki K, Kirino T. Reinduct ion of
hyp on atrem ia to t reat central pon t in e m yelin olysis.
Neu rology. 2001; 57:1931–1932
De Troyer A, Dem an et JC. Correct ion of An tid iuresis
by Dem eclocyclin e. N En gl J Med. 1975; 293:915–
918
Perks W H, Mohr P, Liversedge LA. Dem eclocyclin e
in In ap propriate ADH Syn d rom e. Lan cet. 1976; 2
Forrest JN, Cox M, Hon g C, et al. Superiorit y of
Dem eclocyclin e over Lith ium in th e Treatm en t of
Ch ron ic Syn drom e of In approp riate Secretion of
An tid iu retic Horm on e. N En gl J Med. 1978;
298:173–177
Wright W L, Asbur y W H, Gilm ore JL, Sam uels OB.
Con ivap tan for h ypon at rem ia in th e n eurocritical
care u n it. Neu rocrit Care. 2009; 11:6–13
Maroon JC, Nelson PB. Hypovolem ia in Patients w ith
Subarach n oid Hem orrh age: Th erapeut ic Im plicat ion s. Neurosurger y. 1979; 4:223–226
W ijdicks EFM, Verm eulen M, Hijdra A, et al. Hypon atrem ia an d Cerebral In farct ion in Patients w ith
Ru p tu red In tracran ial Aneurysm s: Is Fluid Restrict ion Harm ful? An n Neu rol. 1985; 17:137–140
W ijd icks EFM, Verm eulen M, ten Haaf JA, et al. Volum e Dep letion an d Natriuresis in Patien ts w ith a
Ru p tu red In tracran ial An eur ysm . An n Neurol. 1985;
18:211–216
Nelson PB, Seif SM, Maroon JC, et al. Hypon atrem ia
in Intracranial Disease. Perhaps Not th e Syndrom e
of In appropriate Secretion of An tidiuretic Horm one
(SIADH). J Neurosurg. 1981; 55:938–941
Hasan D, Lin d say KW , W ijd icks EFM, et al. E ect of
Flud rocort ison e Acetate in Patien ts w ith Subarach n oid Hem orrh age. Stroke. 1989; 20:1156–1161
Reeder RF, Harbaugh RE. Adm in istration of In t raven ous Urea an d Norm al Salin e for th e Treatm en t of
Hypon atrem ia in Neurosurgical Patien ts. J Neurosurg. 1989; 70:201–206
Th ibon n ier M, Barrow DL, Selm an W. In : An tid iu retic Horm on e: Regulation , Disorders, an d Clin ical
Evaluation . Neuroen docrinology. Balt im ore: W illiam s an d Wilkin s; 1992:19–30
Verbalis JG, Robin son AG, Moses AM. Postoperat ive
an d Post-Traum atic Diabetes In sip id u s. Fron t Horm
Res. 1985; 13:247–265
Abe T, Matsu m oto K, San n o N, Osam u ra Y. Lym ph ocytic Hypophysitis: Case Report . Neurosurgery.
1995; 36:1016–1019
Im u ra H, Nakao K, Sh im atsu A, et al. Lym p h ocyt ic
In fu n dibulon eurohypoph ysit is as a Cause of Cen tral
Diabetes In sip id u s. N En gl J Med . 1993; 329:683–
689
Miller M, Dalakos T, Moses AM, et al. Recogn ition of
par t ial d efects in an tid iuretic h orm on e secretion .
An n In tern Med . 1970; 73:721–729
5
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6 General Neurocrit ical Care
6.1 Parent eral agent s for hypert ension
Drug info :
6
Nicardipine (Cardene®)
Calcium channel blocker (CCB) that may be given IV. Does not require arterial line, does not raise ICP.
Does not reduce heart rate, but may be used in conjunction with e.g. labetalol or esmolol if that is
desired. Side e ect s: H/A 15%, nausea 5%, hypotension 5%, reflex tachycardia 3.5%.
start at 5 mg/hr IV (o label: 10 mg/hr may be used in situations where urgent reduction is
needed). Increase by 2.5 mg/hr every 5–15 minutes up to a maximum of 15 mg/hr. Decrease to
3 mg/hr once control is achieved. Ampules contain 25 mg and must be diluted before
administration.
Drug info : Nit roglycerin (NTG)
Raises ICP (less than with nitroprusside due to preferential venous action 1 ). Vasodilator, venous > arterial (large coronaries > small). Result: decreases LV filling pressure (pre-load). Does not cause “coronary steal” (cf nitroprusside).
10–20 mcg/m in IV drip (increase by 5–10 mcg/m in q 5–10 min). For angina pectoris: 0.4 m g SL
q 5 min × 3 doses, check BP before each dose.
Drug info : Labet alol (Norm odyne®, Trandat e®)
Blocks α 1 selective, β non-selective (potency < propranolol). ICP reduces or no change.2 Pulse rate:
decreases or no change. Cardiac output does not change. Does not exacerbate coronary ischemia.
May be used in controlled CHF, but not in overt CHF. Contraindicated in asthma. Renal failure: sam e
dose. Side e ect s: fatigue, dizziness, orthostatic hypotension.
Int ravenous (IV)
Onset 5 m ins, peak 10 mins, duration 3–6 hrs.
IV: patient supine; check BP q 5 min; give each dose slow IVP (over 2 min) q 10 minutes until
desired BP achieved; dose sequence: 20, 40, 80, 80, then 80 m g (300 mg total). Once controlled, use
≈ same total dose IVP q 8 hrs.
IV drip (alternative): add 40 ml (200 m g) to 160 ml of IVF (result: 1 mg/ml); run at 2 ml/min
(2 mg/min) until desired BP (usual e ective dose = 50–200 mg) or until 300 mg given; then titrate rate
(bradycardia limits dose, increase slowly since e ect takes 10–20 minutes).
Oral (PO)
Undergoes first pass liver degradation, therefore requires higher doses PO. PO onset: 2 hrs, peak: 4
hrs.
PO: to convert IV → PO, start with 200 mg PO BID. To start with PO, give 100 mg BID, and
increase 100 mg/dose q 2 day; m ax. = 2400 mg/day.
Drug info : Enalaprilat (Vasot ec®)
An angiotensin-converting enzym e (ACE) inhibitor. The active metabolite of the orally adm inistered
drug enalapril (see below). Acts within ≈ 15 m ins of administration.
Side e ect s: hyperkalemia occurs in ≈ 1%. Do not use during pregnancy.
IV: start with 1.25 mg slow IV over 5 m ins, may increase up to 5 mg q 6 hrs PRN.
General Neurocrit ical Care
127
Drug info : Esm olol (Brevibloc®)
Cardioselective short-acting beta blocker. 3 Being investigated for hypertensive emergencies. Metabolized by RBC esterase. Elim ination half-life: 9 mins. Therapeutic response (> 20% decrease in heart rate,
HR< 100, or conversion to sinus rhythm) in 72%. Side e ect s: dose related hypotension (in 20–50%),
generally resolves within 30 m ins of D/C. Bronchospasm less likely than other beta blockers. Avoid in
CHF.
500 mcg/kg loading dose over 1 min, follow with 4 min infusion starting with 50 mcg/kg/m in.
Repeat loading dose and increment infusion rate by 50 mcg/kg/min q 5 mins. Rarely > 100 mcg/kg/
min required. Doses > 200 mcg/kg/m in add little.
Drug info : Fenoldopam (Corlopam ®)
Vasodilator. Onset of action < 5 m inutes, duration 30 mins.
IV infusion (no bolus doses): start with 0.1–0.3 mcg/kg/m in, titrate by 0.1 mcg/kg/m in q 15 min
up to a maxim um of 1.6 mcg/kg/m in.
Drug info : Propranolol (Inderal®)
Main use IV is to counteract tachycardia with vasodilators (usually doesn’t lower BP acutely when used
alone), but esmolol and labetalol are more comm only used for this.
IV: load with 1–10 mg slow IVP, follow with 3 m g/hr. PO: 80–640 mg q d in divided doses.
6.2 Hypot ension (shock)
6.2.1 Classificat ion
1. hypovolem ic: first sign usually tachycardia. > 20–40%of blood volum e loss m ust occur before perfusion of vital organ s is im paired. In cludes:
a) h em orrh age (extern al or in tern al)
b) bow el obstruct ion (w ith th ird spacing)
2. septic: m ost often due to gram n egative sepsis
3. cardiogen ic: in cludes MI, cardiom yopathy, dysrhyth m ias (in cludin g A-fib)
4. n eurogen ic: e.g. paralysis due to spin al cord injur y. Blood pools in ven ous capacitan ce vessels
5. m iscellan eous
a) an aphylaxis
b) in sulin react ion
6.2.2 Cardiovascular agent s for shock
Plasm a expan ders. In cludes:
1. cr ystalloids: n orm al salin e h as less ten den cy to prom ote cerebral edem a th an oth ers; see IV fluids (p. 870), un der con trol of elevated ICP
2. colloids: e.g. h etastarch (Hespan ®). CAUTION: repeated adm in istration over a period of days
m ay prolong PT/PTT an d clott in g t im es an d m ay in crease th e risk of rebleedin g in an eur ysm al
SAH (p. 1167).4
3. blood products: expen sive. Risk of t ran sm issible diseases or t ran sfusion react ion
6
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General and Neurology
Drug info : Dopam ine
See Table 6.1 for a sum mary of the e ects of dopamine (DA) at various dosages. DA is primarily a
vasoconstrictor (β 1 e ects usually overridden by α-activit y). 25% of dopam ine given is rapidly converted to norepinephrine (NE). At doses > 10 mcg/kg/min one is essentially giving NE. May cause significant hyperglycemia at high doses.
Start with 2–5 mcg/kg/m in and titrate.
Table 6.1 Dopam ine dosage
6
Dose
(m cg/kg/m in)
Effect
Result
0.5–2.0 (sometimes up to 5)
dopam inergic
renal, mesenteric, coronary, & cerebral vasodilatation, (+) inotrope
2–10
β1
positive inotrope
> 10
α, β & dopam inergic
releases nor-epi (vasoconstrictor)
Drug info : Dobut am ine (Dobut rex®)
Vasodilates by β 1 (prim ary) and by increased CO from (+) inotropy (β 2 ); result: lit tle or no fall in BP,
less tachycardia than DA. No alpha release nor vasoconstriction. May be used synergistically with
nitroprusside. Tachyphylaxis after ≈ 72 hrs. Pulse increases > 10% may exacerbate myocardial ischemia, more common at doses > 20 mcg/kg/m in. Optim al use requires hemodynamic monitoring. Possible platelet function inhibition.
usual range 2.5–10 mcg/kg/m in; rarely doses up to 40 used (to prepare: put 50 mg in 250 ml
D5 W to yield 200 mcg/m l).
Drug info : Am rinone (Inocor®)
Nonadrenergic cardiotonic. Phosphodiesterase inhibitor, e ects similar to dobutamine (including
exacerbation of myocardial ischem ia). 2% incidence of thrombocytopenia.
0.75 mg/kg initially over 2–3 min, then drip 5–10 m cg/kg/min.
Drug info : Phenylephrine (Neo-Synephrine®)
Pure alpha sympathom im etic. Useful in hypotension associated with tachycardia (atrial tachyarrhythmias). Elevates BP by increasing SVR via vasoconstriction, causes reflex increase in parasympathetic
tone (with resultant slowing of pulse). Lack of β action means non-inotropic, no cardiac acceleration,
and no relaxation of bronchial smooth muscle. Cardiac output and renal blood flow may decrease.
Avoid in spinal cord injuries (p. 950).
pressor range: 100–180 mcg/m in; m aintenance: 40–60 m cg/min. To prepare: put 40 m g (4
amps) in 500 ml D5 W to yield 80 mcg/m l; a rate of 8 ml/hr = 10 m cg/min.
Drug info : Norepinephrine
Prim arily vasoconstrictor (? counterproductive in cerebral vasospasm, ? decreases CBF). β-agonist at
low doses. Increases pulmonary vascular resistance.
General Neurocrit ical Care
129
Drug info : Epinephrine (adrenalin globally)
0.5–1.0 m g of 1:10,000 solution IVP; may repeat q 5 minutes (may bolus per ET tube). Drip: start at
1.0 m cg/min, titrate up to 8 m cg/min (to prepare: put 1 m g in 100 ml NS or D5W).
Drug info : Isoprot erenol (Isuprel®)
Positive chronotropic and inotropic, → increased cardiac O2 consumption, arrhythmias, vasodilatation
(by β1 action) skeletal muscle > cerebral vessels.
Drug info : Levophed
Direct β stim ulation (positive inotropic and chronotropic).
start drip at 8–12 m cg/min; m aintenance 2–4 mcg/min (0.5–1.0 ml/m in) (to prepare: put 2 m g
in 500 ml NS or D5 W to yield 4 mcg/cc).
6.3 Acid inhibit ors
6.3.1 St ress ulcers in neurosurgery
See referen ce.5
Th e risk of developin g st ress ulcers (SU) AKA Cush in g’s ulcers is h igh in crit ically ill patien ts w ith
CNS path ology. Th ese lesion s are AKA Cush in g’s ulcers due to Cush in g’s classic t reatise.6 17% of SUs
produce clin ically sign ifican t h em orrh age. CNS risk factors in clude in tracran ial path ology: brain
injur y (especially Glasgow Com a scale score < 9), brain t um ors, in t racerebral h em orrh age, SIADH,
CNS in fect ion , isch em ic stroke, as w ell as spin al cord injur y. Th e odds are in creased w ith th e coexisten ce of extra-CNS risk factors in cludin g: lon g-term use of steroids (usually > 3 w eeks), burn s > 25%
of body surface area, hypoten sion , respirator y failure, coagulopath ies, ren al or h epatic failure an d
sepsis.
Th e path ogen esis of SUs is in com pletely un derstood, but probably results from an im balan ce of
destruct ive factors (acid, pepsin & bile) relative to protect ive factors (m ucosal blood flow, m ucusbicarbon ate layer, en doth elial cell replen ish m ent & protaglan din s).5 CNS path ology, especially th at
involving th e dien ceph alon or brain stem , can lead to reduct ion of vagal output w h ich leads to
hypersecretion of gast ric acid an d pepsin . Th ere is a peak in acid and pepsin product ion 3–5 days
after CNS injur y.
6.3.2 Prophylaxis for st ress ulcers
Th ere is st ron g eviden ce th at reduct ion of gast ric acid (w h eth er by an tacids or agen ts th at in h ibit
acid secretion ) reduces th e in ciden ce of GI bleedin g from st ress ulcers in critically ill pat ien ts. Elevatin g gast ric pH > 4.5 also in act ivates pepsin .
Oth er th erapies th at don’t involve alteration s of pH th at m ay be e ect ive in clude sucralfate (see
below ) an d en teral n utr it ion (con troversial).5 Titrated an tacids or sucralfate appear to be superior to
H2 an tagon ists in reducing th e in ciden ce of SUs.
Routin e prophylaxis w h en steroids are used is n ot w arran ted un less on e of th e follow in g risk factors are presen t: prior PUD, con curren t use of NSAIDs, h epatic or ren al failure, m aln ourish m en t , or
prolonged steroid th erapy > 3 w eeks.
6.3.3 Possible increased pneum onia and m ort alit y from alt ering gast ric
pH
W h ereas brin gin g gastric pH to a m ore n eut ral level reduces th e risk of SUs, pH > 4 perm its bacterial
colon ization of th e n orm ally sterile stom ach . Th is m ay in crease th e risk of pn eum on ia from aspirat ion , an d th ere is a suggest ion th at m ortalit y m ay also be in creased.7 Sucralfate m ay be as e ect ive
6
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General and Neurology
in reducing bleedin g, but m ay be associated w ith low er rates of pn eum on ia an d m ortalit y. Th ere is
in su cien t data to determ in e th e n et result of sucralfate com pared to n o t reatm en t.7
6.3.4 Hist am ine2 (H2) ant agonist s
Drug info : Ranit idine (Zant ac®)
Adult age ≤ 65 yrs: 150 mg PO BID, or 50 mg IVPB q 8 hrs. For age > 65 with norm al renal function:
50 m g IV q 12 hrs.
IV drip (provides a m ore consistently higher pH without peaks and troughs; som e cont roversy
that this m ay increase gastric bacterial concent ration with increased risk of aspiration pneum onia
has not been borne out ): 6.25 m g/ hr (e.g. inject 150 m g into 42 m l of IVF yielding 3.125 m g/m l,
run at 2 m l/hr).
6
Drug info : Fam ot idine (Pepcid®)
Adult: 20 m g PO q hs for maintenance; 40 m g PO q hs for active ulcer therapy; IV: 20 mg q 12 hrs
(for hypersecretory conditions, 20 mg IVPB q 6 hrs).8 Supplied: 20 & 40 mg tablets, 40 mg/5 m l suspension, and 20 & 40 mg orally disintegrating tablets as Pepcid RPD. Available OTC in 10 mg tablets
as Pepcid AC. Available IV.
Drug info : Nizat idine (Axid®)
300 mg PO q d or 150 mg PO BID. Supplied: 150 & 300 mg pulvules. Available OTC in 75 mg tablets
as Axid AR.
6.3.5 Gast ric acid secret ion inhibit ors (prot on pum p inhibit ors)
Th ese agen ts reduce gastric acid by specific in h ibition of th e fin al step in acid secretion by gastric
parietal cells (by in h ibitin g th e (H+, K+)-ATPase en zym e system on th e cell surface, th e so-called “acid
pum p”). Th ey block acid secretion regardless of th e st im ulus (Zollinger-Ellison syn drom e, hypergast rin em ia…). Full recover y of acid secretion upon discon tin uat ion m ay n ot occur for w eeks.
Not
in dicated for lon g-term treatm en t as th e t roph ic e ects of th e resultan t elevated levels of gastrin
m ay lead to gast ric carcin oid t um ors.
Drug info : Om eprazole (Prilosec®)
Inhibition of some hepatic P-450 enzymes results in reduced clearance of warfarin and phenytoin.
Decreases the e ectiveness of prednisone.
Adult: for peptic ulcers and gastro-esophageal reflux disease (GERD) 20–40 m g PO daily. For Zollinger-Ellison syndrom e: 20 m g PO q d to 120 mg PO TID (dose adjusted to keep basal acid output <
60 mEq/hr). Side e ect s: N/V, H/A, diarrhea, abdominal pain or rash in 1–5% of patients. Supplied:
10, 20 & 40 m g delayed-release capsules. Available OTC in 20.6 mg tablets as Prilosec OTC.
General Neurocrit ical Care
Drug info :
131
Lansoprazole (Prevacid®)
Found not to have an a ect on a number of other drugs metabolized by cytochrome P-450 including:
phenytoin, warfarin and prednisone.
Adult: 15 m g (for duodenal ulcer, GERD, or maintenance therapy) or 30 m g (for gastric ulcer or
erosive esophagitis) PO q d, short-term treatm ent × 4 wks. Supplied: 15 & 30 mg delayed-release
capsules.
Drug info : Pant oprazole (Prot onix®)
PO: 40 mg PO q d for up to 8 wks. IV: 40 mg IV q d × 7–10 d. Supplied: PO: 40 m g delayed-release
capsules.
6.3.6 Miscellaneous
Drug info : Sucralfat e (Carafat e®)
Minimally absorbed from GI tract. Acts by coating ulcerated areas of mucosa, does not inhibit acid
secretion. This m ay actually result in a lower incidence of pneumonia and mortalit y than agents that
a ect gastric pH (see above).
1 gm PO QID on an empty stomach. Do not give antacids within one half-hour of sucralfate.
References
[1] Cott rell JE, Patel K, Tu rn d orf H, et al. ICP Ch an ges
In duced by Sodium Nitropru sside in Patients w ith
In tracran ial Mass Lesion s. J Neurosurg. 1978;
48:329–331
[2] Orlow ski JP, Sh iesley D, Vid t DG, Barn ett GH, et al.
Labetalol to Con t rol Blood Pressure After Cerebrovascular Surgery. Crit Care Med. 1988; 16:765–768
[3] Esm olol - A Sh ort -Act in g IV Beta Blocker. Med Letter. 1987; 29:57–58
[4] Trum ble ER, Muizelaar JP, Myseros JS. Coagu lop ath y
w ith th e Use of Hetastarch in th e Treatm en t of Vasosp asm . J Neu rosu rg. 1995; 82:44–47
[5] Lu W Y, Rh on ey DH, Bolin g W B, et al. A Review of
Stress Ulcer Prophylaxis in th e Neurosurgical In ten sive Care Unit. Neu rosu rger y. 1997; 41:416–426
[6] Cu sh in g H. Pept ic Ulcers an d th e In terbrain . Su rg
Gyn ecol Obstet. 1932; 55:1–34
[7] Cook DJ, Reeve BK, Guyat t GH, et al. Stress Ulcer
Prop hylaxis in Crit ically Ill Patien ts: Resolvin g Discordan t Meta-An alyses. JAMA. 1996; 275:308–314
[8] Fam otid in e (Pep cid). Med Letter. 1987; 29:17–18
6
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7 Sedat ives, Paralyt ics, Analgesics
7.1 Sedat ives and paralyt ics
7.1.1 Richm ond agit at ion-sedat ion scale (RASS)
A validated scale 1,2 th at uses positive n um bers for agitation an d n egative n um bers for sedation as
sh ow n in Table 7.1. Useful for quan t itating th e desired level of sedat ion w h en t itrating sedatives
for agitated patien ts.
Procedure for perform ing RASS assessm en t:
1. on obser vation , patien t is alert , restless or agitated: score 0 to + 4
2. if pat ien t is n ot aler t , state patien t’s n am e an d verbally in st ruct to open eyes an d look at speaker:
score –1 to –3
3. if n o respon se to verbal stim ulus, physically st im ulate by sh aking sh oulder an d/or stern al rub:
score –4 or –5
7
7.1.2 Conscious sedat ion
Use of th ese agen ts requires abilit y to provide im m ediate em ergen cy ven tilator y support (in cluding
in tubation ). Agen ts in clude:
1. m idazolam (Versed®) (p.870) w ith fen tanyl
2. fen tanyl
3. pen tobarbital (Nem butal®): a barbiturate. for 70 kg adult: 100 m g slow IVP
Drug info : Met hohexit al (Brevit al®)
More potent and shorter acting than thiopental (useful e.g. for percutaneous rhizotom y where patient needs to be sedated and awakened repeatedly). Lasts 5–7 m in. Similar cautions with the added
problem that methohexital may induce seizures. May no longer be available in the U.S.
Adult: 1 gm % solution (add 50 ml diluent to 500 mg to yield 10 m g/ml), 2 m l test dose, then 5–
12 m l IVP at rate of 1 m l/5 secs, then 2 to 4 ml q 4–7 m in PRN.
Table 7.1 Richm ond agitation-sedation scale
Score
Term
Description
+4
com bative
overly combative, violent, imm ediate danger to staff
+3
very agitated
pulls or rem oves tubes or catheters; aggressive
+2
agitated
frequent non-purposeful m ovements, fights ventilator
+1
restless
anxious, but movem ents not aggressive /vigorous
0
alert & calm
Agitation
drowsy
not fully alert, but has
sustained awakening (eyeopening/contact) to voice
(≥ 10 seconds)
–2
light sedation
briefly awakens with eye
contact to voice (< 10
seconds)
–3
m oderate sedation
m ovement or eye opening
to voice (no eye contact)
–4
deep sedation
no response to voice, but
m ovement or eye-opening
to physical stim ulation
–1
Sedation
–5
unarousable
no response to voice or
pjysical stimulation
verbal stimulation
physical stim ulation
Sedat ives, Paralyt ics, Analgesics
133
7.1.3 Sedat ion
Gen erally requires in tubation an d m ech an ical ven tilator y support in th e ICU. Doses are gen erally
low er th an th ose used by an esth esiologists for gen eral an esthesia.
Drug info : Thiopent al (Pent ot hal®)
A short acting barbiturate. 1st dose causes unconsciousness in 20–30 secs (circulation tim e), depth
increases up to 40 secs, duration = 5 mins (terminated by redistribution), consciousness returns over
20–30 mins.
Side e ect s: dose related respiratory depression, irritation if extravasated, intra-arterial injection
→ necrosis, agitation if injected slowly, an antianalgesic, m yocardial depressant, hypotension in hypovolem ic patients.
Adult: initial concentration should not exceed 2.5%,
give 50 mg test dose moderately rapid IVP, then if tolerated give 100–200 mg IVP over 20–30 secs
(500 mg m ay be required in large patient).
7
Drug info :
Rem ifent anil (Ult iva®)
Ultrashort acting micro-opioid receptor agonist. Potency similar to fentanyl. Rapidly crosses BBB.
Onset: < 1 m in. O set: 3–10 mins. Lowers ICP. Metabolism : non-hepatic hydrolysis by nonspecific
blood and tissue esterases, no accum ulation. Synergy with thiopental, propofol, isoflurane, midazolam requires reducing doses of these agents by up to 75%. Side e ect s: bradycardia, hypotension
(these side e ects m ay be blunted by pretreatm ent with anticholinergics), N/V, muscle rigidit y, pruritis (aspecially facial) dose dependent respiratory depression at doses > 0.05 mcg/kg/min.
Adult: avoid bolus doses. Start with drip of 0.05 m cg/kg/min. Titrate in 0.025 mcg/kg/min increments tp a maxim um of 0.1–0.2 m cg/kg/min. Add a sedative if adequate sedation not achieved at
maxim um dose. Wean infusion in 25% decrements over 10 m inues after extubation. Supplied: vials of
1, 2 or 5 mg powder to be reconstituted to 1 mg/ml solution.
Drug info : Fent anyl (Sublim aze®)
Narcotic, potency ≈ 100 × morphine. High lipid solubilit y → rapid onset. O set (sm all doses): 20–
30 mins. Unlike morphine and m eperidine, does not cause histamine release. Lowers ICP. Side e ect s:
dose dependent respiratory depression, large doses given rapidly may cause chest wall rigidit y.
Repeated dosing may cause accumulation. Diminished sensitivit y to CO2 stim ulation, may persist longer than the depression of respiratory rate (up to 4 hours).
Adult: 25–100 m cg (0.5–2 m l) IVP, repeat PRN. Supplied: 50 mcg/ml; requires refrigeration.
Drug info :
Propofol (Diprivan®)
A sedative hypnotic. Also useful in high doses during aneurysm surgery as a neuroprotectant (p. 1203).
Protection seems to be less than with barbiturates. O set time increases after ≈ 12 hours of use.
for sedation: start at 5–10 m cg/kg/min. Increase by 5–10 mcg/kg/min q 5–10 minutes PRN
desired sedation (up to a max of 50 mcg/kg/min).
Side e ect s: include Propofol Infusion Syndrom e: hyperkalem ia, hepatomegaly, lipemia, m etabolic acidosis, myocardial failure, rhabdom yolosis, renal failure and som etimes death.3 First identified in
children, but m ay occur at any age. NB: metabolic acidosis of unknown etiology in a patient on propofol is propofol infusion syndrome until proven otherwise. Use with caution at doses > 50 m cg/kg/min
or at any dose for > 48 hrs. Also note that the lipid carrier provides 1.1 kCal/m l and hypertriglyceridem ia m ay occur.
Supplied: 500 mg suspended in a 50 ml bottle of fat em ulsion. The bot tle and tubing must be
changed every 12 hours since it contains no bacteriostatic agent.
134
General and Neurology
Drug info :
Precedex® (Dexm edet om idine)
An alpha-2 adrenoceptor agonist. Acts in locus ceruleur and dorsal root ganglia. Has both sedative
and analgesic properties and dramatically reduce the risk of respiratory depression and the am ount of
narcotic analgesics required. Reduces shivering.
: usual loading dose is 1 mcg/kg IV over 10 minutes (loading dose not needed if patient already
sedated with other agents), followed by continuous IV infusion of 0.2–1.0 mcg/kg/hr titrated to
desired e ect, not to exceed 24 hours (for short sedation or use as a “transition” drug). Side e ects:
clinically significant bradycardia and sinus arrest have occurred in young, healthy volunteers with
increased vagal tone (anticholinergics such as atropine 0.2 m g IV or glycopyrrolate 0.2 m g IV may
help). Use with caution in patients with advanced heart block, baseline bradycardia, using other drugs
that lower heartrate, and hypovolemia. Supplied: 2 m l vials of 100 mcg/ml to be diluted in 48 ml NS
for a final concentration of 4 mcg/m l for IV use.
7
7.2 Paralyt ics (neurom uscular blocking agent s)
7.2.1 General inform at ion
CAUTION: requires ven tilation (in t ubation or Am bu-bag/m ask). Rem in der: paralyzed patien ts m ay
st ill be con scious an d th erefore able to feel pain , th e sim ultan eous use of sedation is th us required
for con scious patien ts.
Early routin e use in h ead-injured patien ts low ers ICP (e.g. from suct ion in g4 ) an d m ortalit y, but
does n ot im prove overall outcom e.5
Neurom uscular blockin g agen ts (NMBAs) are classified clin ically by tim e to on set an d durat ion of
paralysis as sh ow n in Table 7.2. Addition al in form ation for som e agen ts follow s th e table alon g
w ith som e con sideration s for n eurosurgical patien ts.
Table 7.2 Onset and duration of muscle relaxants
Clinical class
Agent
Trade
nam e
(®)
Onset
(m in)
Durat ion
(m in)
Spont aneous
recovery
(m in)
Com m ent
Ultra-short
succinylcholine
Anectine
1
5–10
20
shortest onset and duration; plasm a cholinesterase
dependent; many side effects
Short
rocuronium
Zem uron
1–1.5
20–35
40–60
close to succinylcholine in
onset in large doses; some
vagolytic action in children
Interm ediate
vecuronium
Norcuron
3–5
20–35
40–60
m inimal cardiovascular
side effects (bradycardia
reported); no histamine
release
cisatracurium
Nimbex
1.5–2
40–60
60–80
no histam ine release at
recom mended doses
Sedat ives, Paralyt ics, Analgesics
135
7.2.2 Ult ra-short act ing paralyt ics
Drug info : Succinylcholine (Anect ine®)
The only depolarizing ganglionic blocker (the rest are com petitive blockers). Rapidly inactivated by
plasma pseudocholinesterases. A single dose produces fasciculations then paralysis. Onset: 1 min.
Duration of action: 5–10 m in.
Indicat ions
Due to significant side e ects (see below), use is now limited primarily to the following indications.
Adults: generally recommended only for emergency intubations where the airway is not controlled.
In children: only when intubation is needed with a full stomach, or if laryngospasm occurs during
at tempted intubation using other agents.
Side e ect s
CAUTIONS: usually increases serum K+ by 0.5 mEq/ L (on rare occasion causes severe hyperkalemia
([K+] up to 12 m Eq/ L) in patients with neuronal or muscular pathology, causing cardiac complications
which cannot be blocked), therefore contraindicated in acute phase of injury following major burns,
m ultiple traum a or extensive denervation of skeletal m uscle or upper m otor neuron injury. Do not
use for routine intubations in adolescents and children (may cause cardiac arrest even in apparently
healthy youngsters, many of whom have undiagnosed myopathies). Linked to m alignant hypertherm ia (p. 108).
May cause dysrhythmias, especially sinus bradycardia (treat with atropine). May get autonomic stim ulation from ACh-like action → HTN, and brady- or tachycardia (especially in peds with repeated
doses). The fasciculations may increase ICP, intragastric pressure, and intraocular pressure (contraindicated in penetrating eye injury, especially to anterior chamber; OK in glaucoma).
Precurarization with a “prim ing dose” of a nondepolarizing blocker (usually ≈ 10% of the intubating dose, e.g. pancuronium 0.5–1 mg IV 3–5 m inutes prior to succinylcholine) in patients with elevated ICP or increased intraocular pressure (to ameliorate further pressure increases during
fasciculation phase) and in patients who have eaten recently (controversial6 ). Phase II block (sim ilar to
nondepolarizing blocker) may develop with excessive doses or in patients with abnormal
pseudocholinesterase.
Dosing
Adult: 0.6–1.1 mg/kg (2–3 m l/70 kg) IVP (err on high side to allow tim e for procedure & to avoid
multi-dosing complications), may repeat this dose × 1.
Peds (CAUTION: Not recom mended for routine use, see above) Children: 1.1 mg/kg. Infants (< 1
mos): 2 m g/kg.
Supplied: 20 mg/ml concentration.
7.2.3 Short act ing paralyt ics
Drug info : Rocuronium (Zem uron®)
In large doses, has speed of onset that approaches succinylcholine. However, in these doses, paralysis
usually lasts ≈ 1–2 hrs. Expensive.
Adult: initial dose 0.6–1 mg/kg. May be used as infusion of 10–12 mcg/kg/min.
7
136
General and Neurology
7.2.4 Int erm ediat e act ing paralyt ics
Drug info :
Vecuronium (Norcuron®)
Nondepolarizing (com petitive) NMBA. Adequate paralysis for intubation within 2.5–3 minutes of
administration. About one–third m ore potent than pancuronium, shorter duration of action (lasts ≈
30 minutes after initial dose). Unlike pancuronium , very lit tle vagal (i.e. cardiovascular) e ects. No
CNS active metabolites. Does not a ect ICP or CPP. Hepatically metabolized. Due to active metabolites, paralysis has been reported to take 6 hrs to 7 days to recede following discontinuation of the
drug after ≥ 2 days use in patients with renal failure.7 Must be m ixed to use.
Dosing
7
Supplied: 10 mg freeze-dried cakes requiring reconstitution. Use within 24 hrs of m ixing.
Adult and children > 10 years age: 0.1 m g/kg (for m ost adults use 8–10 mg as initial dose). May
repeat q 1 hr PRN. Infusion: 1–2 mcg/kg/m in.
Pediatric: children (1–10 yrs) require slightly higher dose and more frequent dosing than adult.
Infants (7 weeks – 1 yr): slightly more sensitive on a mg/kg basis than adults, takes ≈ 1.5 × longer to
recover. Use in neonates and continuous infusion in children is insu ciently studied.
Drug info :
Cisat racurium (Nim bex®)
Nondepolarizing (com petitive) blocker. This isom er of atracurium does not release histamine unlike
its parent compound (see below). Provides about 1 hour of paralysis. Also undergoes Hofm ann degradation, with laudanosine as one of its m etabolites.
Adult and children > 12 years age: 0.15 or 0.2 mg/kg as part of propofol/nitrous oxide/oxygen
induction-intubation technique produces muscle paralysis adequate for intubation within 2 or
1.5 m inutes, respectively. Infusion: 1–3 mcg/kg/min.
Pediatric: children (2–12 yrs): 0.1 m g/kg given over 5–10 seconds during inhalational or opioid
anesthesia.
7.2.5 Reversal of com pet it ive m uscle blockade
Reversal is usually n ot attem pted un til patien t h as at least 1 t w itch to a t rain of 4 stim ulus, oth erw ise
reversal m ay be in com plete if patien t is profoun dly blocked an d blockade m ay reoccur as th e reversal w ears o (a respon se of 1/4 in dicates 90% m uscle blockade)
● n eostigm in e (Prostigm in ®): 2.5 m g (m in im um ) to 5 m g (m axim um ) IV
(start low, n o e cacy from > 5 m g an d can produce severe w eakn ess especially if th e m axim um
dose is exceeded in th e absence of n eurom uscular blockade)
● PLUS (to preven t bradycardia…),
○ EITHER
0.5 m g atropin e for each m g of n eostigm in e
○ OR
0.2 m g glycopyrrolate (Robin ul®) for each m g of n eostigm in e
7.3 Analgesics
7.3.1 General inform at ion
For a discussion of t ypes of pain an d pain procedures (p.476).
Th ree t ypes of pain m edicat ion
1. n on -opioid pain m edication (see below )
a) n on steroidal an ti-in flam m ator y drugs: aspirin , ibuprofen …
b) acetam in oph en
2. opioids (p. 138)
a) agon ists
b) partial agon ists
c) m ixed agon ist/an tagon ists
Sedat ives, Paralyt ics, Analgesics
137
3. drugs th at are n ot st rictly an algesics, but w h ich act as adjuvan ts (p.143) w h en added to any of
th e above: tricyclic an tidepressan ts, an ticonvulsan ts, ca ein e, hydroxyzin e, corticosteroids
(p. 143)
7.3.2 Guiding principles
Th e key to good pain con trol is th e early use of adequate levels of e ect ive an algesics. For can cer
pain , sch eduled dosin g is superior to PRN dosin g, an d “rescue” m edication sh ould be available.8 Non opioid an algesics sh ould be con tin ued as m ore poten t m edicat ion s an d invasive tech n iques are
utilized.
7.3.3 Analgesics for som e specific t ypes of pain
Visceral or dea erent at ion pain
May som et im es be e ect ively t reated w ith t ricyclic an tidepressan ts (p. 477).
Tr yptoph an m ay be e ect ive (p. 143).
Carbam azepin e (Tegretol®) m ay be useful for paroxysm al, lan cin atin g pain .
Pain from m et ast at ic bone disease
Steroids, aspirin , or NSAIDs are especially h elpfu l, probably by reducin g prostaglan din m ediated sen sit ization of A-delta an d C fibers, an d th erefore m ay be preferred to APAP.
7.3.4 Nonopioid analgesics
Acet am inophen
Table 7.3 Acetam inophen dosing
Medication
Dosage
acetaminophen
(APAP)
(Tylenol®)
adult dose: 650 or 1000 mg PO/PR q 4–6 hrs, not to exceed
4000 mg/daya
pediatric dose:
infants: 10–15 m g/kg PO/PR q 4–6 hrs
children: 1 grain/yr age (= 65 m g/yr up to 650 m g) PO/PR q 4–6 hrs
not to exceed 15 m g/kg q 4 hrs
a hepatic toxicit y from APAP: usually with doses ≥ 10 gm /day, rare at doses < 4000 m g. However, m ay occur at
lower doses (even at high therapeutic doses) in alcoholics, fasting patients, and those taking cytochrome P-450
enzym e-inducing drugs
Nonst eroidal ant i-inflam m at ory drugs (NSAIDs)
Th e an t i-in flam m ator y propert ies of NSAIDs is prim arily due to in h ibition of th e en zym e cyclooxygen ase (COX) w h ich part icipates in th e syn th esis of prostaglan din s an d th rom boxan es.9
Ch aracterist ics of n on select ive n on steroidal an t i-in flam m ator y drugs:
1. all are given orally except ketorolac t rom eth am in e (Toradol®) (see below )
2. n o depen den ce develops
3. additive e ect im proves th e pain relief w ith opioid an algesics
4. NSAIDs (an d APAP) dem on strate a ceiling e ect: a m axim um dose above w h ich n o furth er an algesia is obtain ed. For aspirin an d APAP, th is is usually betw een 650–1300 m g, an d is often h igh er
for oth er NSAIDs w h ich m ay also h ave a lon ger duration of action
5. risk of GI upset is com m on , m ore serious risks of h epatotoxicit y,10 or GI ulceration , h em orrh age,
or perforation are less com m on
6. takin g m edicat ion w ith m eals or an tacids h as n ot been proven e ect ive in reducin g GI side
e ect s. Misoprostol (Cytotec®), a prostaglan din , m ay be e ect ive in m it igat in g NSAID-in duced
gast ric erosion or peptic ulcer. Con t rain dicated in pregn an cy. 200 m cg PO QID w ith food as lon g
as patien t is on NSAIDs. If n ot tolerated, use 100 m cg. CAUTION: an abortifacien t. Sh ould n ot
be given to pregn an t w om en or w om en of ch ildbearing poten tial
7. m ost reversibly in h ibit platelet fun ct ion an d prolong bleedin g tim e (n on acetlyated salicylates
h ave less an tiplatelet action , e.g. salsalate, t risalicylate, n abum etom e). Aspirin , un like all oth er
7
138
General and Neurology
NSAIDS, ir reversibly bin ds to cyclooxygen ase an d th us in h ibits platelet fun ct ion for th e 8–10 day
life of th e platelet
8. all cause sodium an d w ater reten tion an d carr y th e risk of NSAID-in duced n eph rotoxicit y 11 (by
reducing syn th esis of ren al vasodilator prostaglan din s → reduced ren al blood flow w h ich can →
ren al in su cien cy, in terstitial n eph rit is, n eph rotic syn drom e, hyperkalem ia)
9. n on -aspirin NSAIDs in crease th e risk of h eart attack or stroke 12
Drug info : Ket orolac t rom et ham ine (Toradol®)
7
The only parenteral NSAID approved for use in pain control in the U.S. Analgesic e ect is more potent
than anti-inflam matory e ect. Half-life ≈ 6 hrs. May be useful to control pain in the following
situations:
1. where the avoidance of sedation or respiratory depression is critical
2. when constipation cannot be tolerated
3. for patients who are nauseated by narcotics
4. where narcotic dependency is a serious concern
5. when epidural morphine has been used and further analgesia is needed without risk of respiratory
depression (agonist t ype narcotics are contraindicated)
6. cautions:
a) not indicated for use > 72 hrs (complications have been reported prim arily with prolonged use
of the oral form)
b) use with caution in postoperative patients since (as with m ost NSAIDs) bleeding tim e is prolonged by platelet function inhibition (risk of GI or op-site hemorrhage is small, but is
increased in patients > 75 yrs old, when used > 5 days, and when used in higher doses13 )
c) even though IM dosing circumvents the GI system , gastric mucosal irritation and erosions m ay
occur as with all NSAIDs (avoid use with PUD)
d) as with all NSAIDs, use with caution in patients at risk for renal side e ects
Parenteral:For single dose adm inistration: 30 mg IV or 60 m g IM in healthy adult. For multiple dosing: 30 mg IV or IM q 6 hrs PRN. Maximum dosage: 120 mg/day. Parenteral use should not exceed 5
days (3 days may be a better guideline).
For patient weight < 50 kg, age > 65 yrs, or reduced renal function (creatinine clearance < 50 ml/
min), all of the above dosages are halved (max daily dose: 60 mg). Creatinine clearance can be estimated using the Cockcroft-Gault equation 14 shown in Eq (7.1), with normal values ≥ 60 ml/m in.
Creatinine clearance ðml⁄ min Þ ¼
½140 À age ðyearsÞ Â ideal wt ðkg Þ
 ð0:85 for fem alesÞ
72 Â serum creatinine ðmg⁄ dlÞ
ð7:1Þ
PO: Indicated only as a continuation of IVor IM therapy, not for routine use as an NSAID. Switching
from IM to PO: start with 10 m g PO q 4–6 hrs (combined PO and IM dose should be ≤ 120 mg on the
day of transition). Supplied: 10 m g tablets.
7.3.5 Opioid analgesics
General inform at ion
Narcotics are m ost com m on ly used for m oderate to severe acute pain or can cer pain (som e exper ts
ch aracterize can cer pain as recurren t acute pain an d n ot ch ron ic pain ).
Ch aracterist ics of n arcotics:
1. n o ceilin g e ect (p. 137): i.e. in creasin g dosage in creases th e e ect iven ess (alth ough w ith w eak
opioids for m oderate pain , side e ect s m ay lim it dosages to relatively low levels 8 )
2. w ith ch ron ic use, toleran ce develops (physical an d psych ological)
3. overdose possible (p.207), w ith th e poten tial for respirator y depression w ith all, an d seizures
w ith som e
Sedat ives, Paralyt ics, Analgesics
139
Table 7.4 Nonsteroidal anti-inflamm atory drugs (NSAIDs)a
Generic nam e
Proprietary
(®)
Typical adult oral dose b
Tabs/caps
availabilit y
(m g)c
Daily m axim um dose
(m g)
aspirin d
(many)
500–1000 m g PO q 4–6 hrs (ceiling
dose ≈ 1 gm)
325, 500
4000
diclofenac
Voltaren,
Cataflam
start at 25 m g QID; additional dose q hs
PRN; increase up to 50 mg TID or QID,
or 75 mg BID
25, 50, 75
200
for acute pain: 200–400 m g q 6–8 hrs
200, 300 caps,
400 tabs
1200
200 m g q 4–6 hrs; for rheumatoid
arthritis 300–600 m g TID-QID
200, 300, 600
3200
50 m g TID-QID or 100 mg TID
50, 100
300
im m ediate
release
start at 75 mg TID or 50 m g QID,
↑ to 150–300 mg daily DIV TID-QID
25, 50, 75
300
extended
release
150 m g q d
ERc 150
see below
see below
400–800 m g QID (ceiling dose:
800 m g)
300, 400, 600,
800
3200
indomethacin
25 mg TID, ↑ by 25 m g total per day
PRN
25, 50, SR 75
150–200
m eclofenam ate
50 mg q 4–6 hrs; ↑ to 100 m g QID if
needed
50, 100
400
etodolac
fenoprofen
Nalfon
flurbiprofen
ketoprofen
ketorolac
ibuprofen e
Motrin
m efenam ic
Ponstel
500 m g initial; then 250 m g q 6 hrs
250
nabumetom e f
Relafen
1000–2000 mg/d given in 1 or 2 doses
500, 750
2000
naproxen
Naprosyn
500 m g, then 250 m g q 6–8 hrs
250, 375, 500
< 1250
naproxen sodium
Anaprox
550 m g, followed by 275 mg q 6–8 hrs
275, DS = 550
1375
oxaprozin
Daypro
1200 m g q d (1st day m ay take 1800)
600
1800
piroxicam
Feldene
10–20 mg q d (steady state takes 7–12
d)
10, 20
sulindac
200 m g BID; ↓ to 150 BID when pain
controlled
150, 200
salsalate
3000 m g divided BID-TID (e.g. 500 mg
2-tabs TID)
500, 750
tolmetin
400 m g TID (bioavailability is reduced
by food)
200, DS = 400,
600
400
1800
a NSAIDs increase the risk of cardiovascular thrombotic events (heart at tack or stroke)12
b when dosage ranges are given, use the smallest effective dose
cabbreviations: DS = double strength; SR= slow release; ER= extended release; DOC = drug of choice
d aspirin: has unique effectiveness in pain from bone m etastases
e ibuprofen: is available as a suspension (PediaProfen®) 100 mg/m l; dose for children 6 mos to 12 yrs age is
5–10 m g/kg with a m aximum of 40 m g/kg/day (not FDA approved for children because of possible Reye’s
syndrome)
funlike most NSAIDs, nabum etom e does not interfere with platelet function
7
140
General and Neurology
Mild t o m oderat e pain
Table 7.5 Weak opioids for m ild to m oderate pain
Medicat ion
Dosage
codeine
usual adult dose: 30–60 m g IM/PO q 3 hrs PRN; use with caution in nursing mothers a
and children
(30 mg PO is equivalent to 300 m g aspirin)
pediatric dose: 0.5–1 m g/kg/dose q 4–6 hrs PO or IV PRN
pentazocine
pentazocine is a mixed agonist-antagonist
tram adol (Ultram ®)
7
Talwin®
→ 12.5 m g pentazocine, 325 m g ASA.
: 2 PO TID-QID PRN
with naloxone
→ 50 m g pentazocine, 0.5 m g naloxone. : 1–2 PO q 3–4 hrs PRN
up to 12 tabs/day
(see below)
a 1–28% of wom en are ultrafast m etabolizers of codeine and the resultant m orphine may be passed on to the
infant via the breast m ilk
Som e useful m edicat ion s are sh ow n in Table 7.5.
Codein e an d congen er pen tazocin e, are usually n o m ore e ect ive th at ASA or APAP an d are usually com bin ed w ith th ese drugs.
Drug info : Tram adol (Ult ram ®)
An oral opioid agonist that binds to µ-opioid receptors, and is also a centrally acting analgesic that
inhibits reuptake of norepinephrine and serotonin. For acute pain, 100 mg is com parable to codeine
60 m g with ASA or APAP.15,16 There has been no report of respiratory depression when oral dosing
recommendations are followed. Seizures and opioid-like dependence have been reported.16
50 to 100 mg PO q 4–6 hrs PRN pain up to a maxim um of 400 mg/day (or 300 mg/d for older
patients). For m oderately severe acute pain, an initial dose of 100 m g followed by 50 mg doses m ay
su ce. Supplied: 50 mg tabs.
Moderat e t o severe pain
Table 7.6 Opioids for moderate to severe pain
Medicat ion
Dosage
hydrocodone
(Vicodin®, Lorcet®, Lortab®…): 5 mg hydrocodone + 500 mg acetam inophen;
(Vicodin ES®, Lortab 7.5/500®): 7.5 m g hydrocodone + 500 m g APAP;
1 tab PO q 6 hrs PRN (may increase up to 2 tabs PO q 3–4 hrs not to exceed 8
pills/24 hrs).
(Lorcet® Plus, Lorcet® 10/650): 7.5 or 10 m g hydrocodone (respectively) + 650
m g APAP;
1 tab PO q 6 hrs PRN (not to exceed 6 tabs in 24 hrs).
(Lortab® 10/500: 10 mg. hydrocodone + 500 m g APAP);
: 1–2 PO q 4 hrs PRN up to 6 tabs/day.
(Norco®): 10 m g hydrocodone + 325 m g APAP scored tabs;
: 1 PO q 4 hrs PRN up to 6 tabs/day.
oxycodone
Supplied : usually available in com bination as:
aspirin 325 mg with oxycodone 5 m g (Percodan®)
or acetam inophen (APAP) (Tylox® = APAP 500 m g + oxycodone 5 m g)
(Percocet® = oxycodone/APAP in 2.5/325, 5/325, 7.5/500, 10/650)
dose: 1 PO q 3–4 hrs PRN (m ay increase up to 2 PO q 3 hrs a )
Sedat ives, Paralyt ics, Analgesics
141
Table 7.6 continued
Medication
Dosage
Supplied :also available alone as OxyIR® 5 mg, OxyFast® oral solution of 20 m g/
ml, or in controlled-release tablets as OxyContin® 10, 20, 40, 80 b & 160 b mg
(which last 12 hours, achieving steady state in 24–36 hours).
Adult: OxyContin® tablet s are taken whole and are not to be divided, chewed
or crushed. It is intended for m anagem ent of m oderate to severe pain when
continuous around-the-clock analgesic is needed for an extended period of tim e
and is not intended for use as a PRN analgesic. For opiate naive patients, start with
10 m g PO q 12 hrs. For patients on narcotic m edications, a conversion table is
provided below for som e m edications. Titrate dose every 1–2 days, increasing
dose by 25–50% q 12 hrs.
Conversion t able for st arting OxyCont in®
Preparation currently
being used
Dose
Suggested starting dose of
OxyContin®
oxycodone com bination pills (Tylox, Percodan…) or Lortab,
Vicodin or Tylenol #3
1–5 pills/day
10–20 mg PO q 12 hrs
6–9 pills/day
20–30 mg PO q 12 hrs
10–12 pills/day
30–40 mg PO q 12 hrs
IV PCA m orphine
determine total
MSO4 dose
used per 24 hrs
multiply total MSO4 dose in 24 hrs ×
1.3 for total OxyContin dose in 24 hrs
hydrom orphone
Dilaudid®: (see
Table 7.7)
m orphine
used in low doses (see
Table 7.7)
a not to exceed 4000 mg of acetam inophen/24 hrs (see footnote to
Table 7.3)
b for use only in opioid-tolerant patients
Severe pain
Table 7.7 Equianalgesic doses for SEVERE pain, AGONISTopioids (parenteral route is referenced to 10 mg IM
morphine)
Drug nam e:
generic
(propriet ary®)
Route
Dose
(m g)
Peak
(hrs)
Durat ion
(hrs)
Com m ent s
morphine
IM
10
0.5–1
4–6
PO
20–60 a
1.5–2
4–7
respiratory depression
long acting PO form s: MS Contin®,
Avinza® (see below)
codeine (not recomm ended at
these doses)
IM
130
PO
200
methadone b
(Dolophine®)
IM
10
PO
20
IM
15
PO
30
PO
oxycodone
(e.g. Tylox®c)
(OxyContin®)
oxymorphone
hydrom orphone
(Dilaudid®)
3–5
these high doses cause unacceptable
side effect s
0.5–1
4–6
long half-life b
1.5–2
4–7
1
3–4
combination (Tylox®) or liquid
30–40
12
OxyContin, see
IM
1
3–5
available as suppository
PR
10
IM
1.5
0.5–1
3–4
Table 7.6
7
142
General and Neurology
Table 7.7 continued
Drug nam e:
generic
(propriet ary®)
Route
Dose
(m g)
Peak
(hrs)
Durat ion
(hrs)
Com m ent s
PO
7.5
1.5–2
3–4
supplied: 1, 2, 3, & 4 m g tabs
fentanyl
(Sublimaze®)
IV
0.1
1–2
not recom mended for acute pain
control, esp. in narcotic naive pts.
transdermal
fentanyl patch
(Duragesic®)d
transdermal
e
72
patches of 25, 50, 75, 100 or
125 m cg/hr (use lowest effective)
12–24
a IM:PO potency ratio for m orphine is 1:6 for single doses, but changes to 1:2–3 with chronic dosing
b due to long half-life, repeated dosing can lead to accumulation and CNS depression (m ust reduce dose after ≈ 3
7
days, even though the analgesic half-life does not change), especially in the elderly or debilitated patient. Use
should be lim ited to physicians with experience using these drugs
cmay not be practical for use in severe pain since 1 Tylox® contains only 5 m g oxycodone (the acetam inophen
lim its the dosage), m ay use OxyContin® for higher doses of oxycodone
d
should not be used as routine post-op analgesic (risk of respiratory depression). Apply 1 patch to upper torso,
replace q 72 hrs PRN.
e conversion from total daily parenteral m orphine as follows:
8–27 mg MSO4/day → Duragesic 25 m cg/hr
28–37 m g MSO4/day → Duragesic 50 m cg/hr
38–52 m g MSO4/day → Duragesic 75 m cg/hr
53–67 m g MSO4/day → Duragesic 100 m cg/hr
68–82 m g MSO4/day → Duragesic 125 m cg/hr
Table 7.8 Equianalgesic doses for SEVERE pain, AGONIST/ANTAGONISTopioids (referenced to 10 m g IM
morphine)
Drug nam e: generic (propriet ary®)
Rout e
Dose
(m g)
buprenorphine
(Buprenex®)
IM
0.4
SL
0.3
Peak
(hrs)
Durat ion
(hrs)
Com m ents
partial agonist
Mixed agonist/antagonist a
butorphanol
IM
2
0.5–1
4–6
nalbuphine
IM
10
1
3–6
IV
140
m cg/kg
0.5
2–5
IMb
20–40
0.5–1
4–6
POb
180
(start @
50)
1.5–2
4–7
pentazocine
(Talwin®c)
no sigma receptor
occupation b
a all can precipitate withdrawal sym ptom s in patients physically dependent on agonists
b most agonist/antagonist drugs occupy sigma receptors (Stadol > Nubain), which m ay cause hallucinations
cTalwin injectable (for IM use) contains only pentazocine. Talwin® Com pound tablets contain ASA, therefore for
high PO doses, use Talwin Nx which contains no ASA ( Table 7.5)
Sedat ives, Paralyt ics, Analgesics
143
Drug info : Avinza® (ext ended release m orphine)
Once daily oral morphine form ulation using a spherical oral drug absorption system (SODAS) (numerous ammonio-methacrylate copolymer beads, ≈ 1 mm dia.). Potential for overdosage and/or abuse.
: Dosage is titrated based on patient’s opioid tolerance and degree of pain. Taken as 1 capsule p.
o. q d. Not to be taken “PRN.” Not for post-op pain. CAUTION: To prevent potentially fatal doses of
morphine, capsules are to be swallowed whole, and are not to be chewed, crushed or dissolved. However, the contents of the capsule (the beads) m ay be sprinkled on apple-sauce for those unable to
swallow the capsules, but the beads are not to be chewed or crushed. Side e ects:Due to the potentially nephrotoxic e ect of fum aric acid used in SODAS, the m aximum dose of Avinza is 1600 m g/d.
Doses ≥ 60 mg are for opioid tolerant patients only. Supplied:30, 60, 90 & 120 mg capsules.
7.3.6 Adjuvant pain m edicat ions
Th e follow in g m ay h ave e cacy in en h an cin g th e e ect iven ess of opioid an algesics (an d th ereby
m ay reduce th e required dose).
Tricyclic an tidepressan ts:
Tr yptoph an : an am in o acid an d a precursor of seroton in , m ay w ork by in creasing seroton in levels.
Requires h igh doses an d h as hypn otic e ects, th erefore 1.5–2 gm given usually q h s. Must give daily
MVI as ch ron ic tr yptoph an th erapy depletes vitam in B6.
An tih istam in es: h istam in es play a role in n ociception . An tih istam in es, w h ich are also an xiolyt ic,
an t iem etic, an d m ildly hypn otic, are e ect ive as an algesics or as adjuvan ts. Hydroxyzin e (Atarax®,
Vistaril®): start w ith 50 m g PO q AM an d 100 m g PO q h s. May in crease up to ≈ 200 m g daily.
An ticonvulsan t-class drugs: carbam azepin e, clon azepam , ph enytoin , gabapen tin or pregabalin
ten d to be m ore e ect ive in n europath ic pain , e.g. from diabetic n europathy, t rigem in al n euralgia,
post-h erpetic n euralgia, glossoph ar yn geal n euralgia, an d n euralgias due to n er ve injur y or in filtrat ion w ith can cer.16 See in dex for en tries.
Phenothiazines: some cause m ild reduction in nociception. Most are tranquilizing and antiem etic. Best
know n for this use is fluphenazine (Prolixin®), usually given with a tricyclic antidepressant for neuropathic pain, Diabetic n europathy, Treatm en t (p.545). Phenothiazines m ay reduce the seizure threshold.
Cort icosteroids: in addit ion to th e reduct ion of toxic e ect s of radiation or ch em oth erapy, th ey
m ay poten tiate n arcotic an algesics. Th ere are also a n um ber of n on specific ben eficial e ect s:
in creased appetite, sen se of w ell being, an tiem etic. Side e ects m ay lim it usefuln ess (p. 146).
Ca ein e: alth ough it possesses n o in trin sic an algesic properties, doses of 65–200 m g en h an ce
th e an algesic e ect of APAP, ASA or ibuprofen in for pain in cludin g: H/A, oral surger y pain an d postpartum pain .
References
[1] Sessler CN, Gosn ell MS, Grap MJ, Brop hy GM, O'Neal
PV, Kean e KA, Tesoro EP, Elsw ick RK. Th e Rich m on d
Agitation -Sedation Scale: validity an d reliabilit y in
ad ult in ten sive care u n it p atien ts. Am J Resp ir Crit
Care Med . 2002; 166:1338–1344
[2] Ely EW , Trum an B, Sh in tan i A, Th om ason JW ,
W h eeler AP, Gordon S, Fran cis J, Spero T, Gautam
S, Margolin R, Sessler CN, Ditt us RS, Bernard GR.
Mon itorin g sed ation status over t im e in ICU
patien ts: reliability an d valid it y of th e Rich m on d
Agitation -Sedation Scale (RASS). JAMA. 2003;
289:2983–2991
[3] Kang TM. Propofol infusion synd rom e in critically ill
patients. Ann Ph arm acoth er. 2002; 36:1453–1456
[4] Werba A, Wein stabi C, Petricek W , et al. Vecu ron iu m
Preven ts Increases in Intracran ial Pressu re Du ring
Rou tine Trach eobron chial Su ction ing in Neu rosurgical Patien ts. Anaesthetist. 1991; 40:328–331
[5] Hsian g JK, Ch esn u t RM, Crisp CD, et al. Early, Rout in e Paralysis for In tracran ial Pressu re Con t rol in
Severe Head In jury: Is It Necessary? Crit Care Med.
1994; 22:1471–1476
[6] Oh lin ger MJ, Rh on ey DH. Neurom u scular Blockin g
Agen ts in th e Neurosurgical In ten sive Care Unit .
Surg Neurol. 1998; 49:217–221
[7] Segred o V, Caldw ell JE, Matth ay MA, et al. Persisten t
Paralysis in Critically Ill Patien ts After Lon g-Term
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
Adm inistration of Vecuron ium . N Engl J Med. 1992;
327:524–528
Marsh all KA. Man aging Can cer Pain : Basic Prin ciples an d Invasive Treatm en t . Mayo Clin Proc. 1996;
71:472–477
Celecoxib for Arth rit is. Med Letter. 1999; 41:11–12
Helfgot t SM, San d berg-Cook J, Zakim D, Nestler J.
Diclofen ac-Associated Hepatotoxicit y. JAMA. 1990;
264:2660–2662
Hen rich W L. An algesic Nep h ropathy. Am J Med Sci.
1988; 295:561–568
U.S. Food an d Drug Adm in istration (FDA). FDA Dru g
Safet y Com m u n ication : FDA st ren gth en s w arn in g
th at non-aspirin n on steroidal an t i-in flam m atory
dru gs (NSAIDs) can cau se h eart attacks or strokes.
2015
Strom BL, Berlin JA, Kin m an JL, et al. Paren teral
Ketorolac an d Risk of Gastroin test in al and Operative
Site Bleedin g. JAMA. 1996; 275:376–382
Cockcroft DW, Gault MH. Pred iction of creatin in e
clearan ce from serum creatin in e. Neph ron . 1976;
16:31–41
Tram ad ol - A n ew oral an algesic. Med Letter. 1995;
37:59–60
Drugs for Pain . Med Letter. 1998; 40:79–84
7
144
General and Neurology
8 Endocrinology
8.1 Cort icost eroids
8.1.1 General inform at ion
Un der n orm al, basal con dition s, th e zon a fasciculata of th e adren al cortex secretes 15–25 m g/day of
cort isol (hydrocort ison e is th e n am e for th e iden tical ph arm aceutical com poun d for adm in istration ),
an d 1.5–4 m g/day of cort icosteron e. Cort isol h as a h alf-life of ≈ 90 m in utes. Th e release of cort isol by
th e adren al glan ds is stim ulated by adren ocort icotroph ic h orm on e (ACTH) from th e pit uitary w h ich
in turn is st im ulated by cort icot ropin releasing h orm on e (CRH) from th e hypoth alam us.
8.1.2 Replacem ent t herapy
8
In prim ar y adren ocort ical in su cien cy (Addison’s disease), both glucocor ticoids an d m in eralocor ticoids m ust be replaced. In secon dar y adren al in su cien cy caused by deficien t corticotropin (ACTH)
release by th e pituitar y, m in eralocort icoid secretion is usually n orm al an d on ly glucocorticoids n eed
to be replaced.
Table 8.1 sh ow s equivalen t daily cort icosteroid doses for replacem en t th erapy.
Physiologic replacem en t (in th e absen ce of stress) can be accom plish ed w ith eith er:
1. hydrocort ison e: 20 m g PO q AM an d 10 m g PO q PM
2. or predn ison e: 5 m g PO q AM an d 2.5 m g PO q PM
Cort isol an d cort ison e are useful for ch ronic prim ar y adren ocor tical in su cien cy or for Addison ian
crisis. Because of m in eralocort icoid act ivit y, use for ch ron ic th erapy of oth er con dition s (e.g. hypopit uitarism ) m ay result in salt an d fluid reten tion , hyper ten sion an d hypokalem ia.
8.1.3 Hypot halam ic-pit uit ary-adrenal axis suppression
General inform at ion
Ch ron ic steroid adm in istration suppresses th e hypothalam ic-pituitar y-adren al (HPA) axis, an d even t ually causes adren al atrophy. W h en th e HPA is suppressed, if exogen ous steroids are abru ptly
Table 8.1 Equivalent corticosteroid dosesa
St eroid: generic
(propriet ary)
Equiv dose
(m g)
Rout e
Dosing
Mineralocort icoid pot ency
Oral dosing
form s
cortisone acetate
25
PO, IM
2/3 in AM,
1/3 in PM
2+
tabs: 5, 10 &
25 mg
hydrocortisone
AKA cort isol
(Cort ef®)
20
PO
2/3 in AM,
1/3 in PM
2+
tabs: 5, 10 &
20 mg
divided
BID-TID
1+
tabs: 1, 2.5, 5,
10, 20, 50 mg c
0
Tabsd : 2, 4, 8,
16, 24, 32 mg
0
scored tabs:
0.25, 0.5, 0.75,
1.5, 4, 6 m g
IV, IMb
(Solu-Cortef®)
prednisone
5
PO only
m ethylprednisolone
4
PO, IV, IM
dexam ethasone
0.75
PO, IV
divided
BID-QID
a doses given are daily doses. Steroids listed are used prim arily as glucocorticoids: equivalent glucocorticoid PO or
IV dose is given; IM m ay differ
b IM route recommended only for em ergencies where IV access cannot be rapidly obtained
cSterapred Uni-Pak® contains 21 tabs of 5 m gs prednisone and tapers dosage from 30 to 5 mgs over 6 days; “DS”
contains 10 m g tabs and tapers from 60 m g to 10 m g over 6 days; “DS 12-Day” contains 48 10 m g tabs and
tapers from 60 m g to 20 m g over 12 days
d Medrol Dosepak® contains 21 tabs of 4 mgs m ethylprednisolone and tapers dosage from 24 mg/d to 4 m g/d
over 6 days
Endocrinology
145
stopped or if acute illn ess develops (w h ich in creases th e steroid requirem en ts), sym ptom s of adren ocor tical in su cien cy (AI) m ay en sue Table 8.2. Severe cases of AI m ay progress to Addison ian
crisis (p.147). Recover y of adren al cortex lags beh in d th e pit uitar y, so basal ACTH levels in crease
before cort isol levels do.
HPA su p p r ession d ep en d s on t h e sp e cific glu cocor t icoid u sed , t h e r ou t e, fr e qu en cy, t im e,
an d d u rat ion of t r e at m en t . Su p p r ession is u n likely w it h < 4 0 m g p re d n ison e (or equ ivalen t ) given in t h e m or n in g for less t h an ≈ 7 d ays, or w it h eve r y- ot h er -d ay t h e rapy of < 40 m g for ≈ 5
w eeks.1 Som e ad ren al at rop h y m ay occu r afte r 3 –4 d ays of h igh d ose st e roid s, an d som e a xis
su p p ression w ill alm ost cer t ain ly occu r aft er 2 w e eks of 4 0–60 m g h yd r ocor t ison e (or e qu ivale n t ) d aily. Aft e r a m on t h or m or e of ste r oid s, t h e HPA a xis m ay be d ep r essed for as lon g as
on e year.
Measurin g m orn ing plasm a hydrocor tison e can evaluate th e degree of recover y of basal adren ocort ical fun ction , but does not assess adequacy of stress respon se.
St eroid w it hdraw al
See referen ce.1
In addition to th e above dan gers of hypocort isolism in th e presen ce of HPA suppression , too rapid
a taper m ay cause a flare-up of th e un derlyin g con dition for w h ich steroids w ere prescribed.
W h en th e risk of HPA suppression is low (as is th e case w ith sh ort courses of steroids for less th an
≈ 5–7 days 2 gen erally prescribed for m ost n eurosurgical in dicat ion s) abrupt discon tin uation usually
carr ies a low risk of AI. For up to ≈ 2 w eeks of use, steroids are usually safely w ith draw n by tapering
over 1–2 w eeks. For lon ger t reatm en t , or w h en w ith draw al problem s develop, use th e follow in g conser va tive ta per:
1. m ake sm all decrem en ts (equivalen t to 2.5–5 m g predn ison e) ever y 3–7 d. Patien t m ay experien ce
m ild w ith draw al sym ptom s of3 :
a) fatigue
b) an orexia
c) n ausea
d) or th ostatic dizzin ess
2. “backtrack” (i.e. in crease th e dose an d resum e a m ore gradual taper) if any of th e follow in g
occur:
a) exacerbation of th e un derlying con dition for w h ich steroids w ere used
b) evidence of steroid w ith draw al sym ptom s ( Table 8.2)
c) in tercurren t in fect ion or n eed for surger y; see St ress doses (p. 146)
3. on ce “physiologic” doses of glucocorticoid h ave been reach ed (about 20 m g hydrocort ison e/day
or equivalen t ( Table 8.1):
a) th e patien t is sw itch ed to 20 m g hydrocort ison e PO q AM (do n ot use lon g acting
preparation s)
b) after ≈ 2–4 w eeks, a m orn in g cort isol level is ch ecked (prior to th e AM hydrocor tison e dose),
an d th e hydrocortison e is tapered by 2.5 m g w eekly un til 10 m g/d is reach ed (low er lim its of
physiologic)
c) th en , ever y 2–4 w eeks, th e AM cort isol level is draw n (prior to AM dose) un til th e 8 AM cort isol is > 10 m cg/100 m l, in dicat in g return of baselin e adren al fun ct ion
d) w h en th is return of baselin e adren al fun ction occurs:
● daily steroids are stopped, but st ress doses m ust st ill be given w h en n eeded (see below )
● m on t h ly cosyn t rop in st im u lat ion (p. 735) test s are p erfor m ed u n t il n or m al. Th e n eed
for st ress d oses of steroid s ce ases w h en a p osit ive t est is obtain ed . Th e r isk for ad ren al
in su cien cy p ersist ≈ 2 years after cessat ion of ch ron ic steroid s (esp ecially t h e first
year)
Table 8.2 Symptoms of adrenal insu ciency (AI)
●
●
●
●
●
●
●
●
●
●
fatigue
weakness
arthralgia
anorexia
nausea
hypotension
orthostatic dizziness
hypoglycemia
dyspnea
Addisonian crisis (p. 147) (if severe; with risk of death)
8
146
General and Neurology
St eroid st ress doses
Durin g physiologic “st ress” th e n orm al adren al glan d produces ≈ 250–300 m g hydrocor tison e/day.
W ith ch ron ic glucocorticoid th erapy (eith er at presen t , or w ith in last 1–2 yrs), suppression of th e
n orm al “stress-respon se” n ecessitates supplem en tal doses.
In patien ts w ith a suppressed HPA axis:
● for m ild illn ess (e.g. UTI, com m on cold), sin gle den tal extract ion : double th e daily dose (if o steroids, give 40 m g hydrocortison e BID)
● for m oderate stress (e.g. flu), m in or surger y un der local an esth esia (en doscopy, m ultiple den tal
extract ion s…): give 50 m g hydrocor tison e BID
● for m ajor illn ess (pn eum on ia, system ic in fect ion s, h igh fever), severe traum a, or em ergen cy surger y un der gen eral an esthesia: give 100 m g hydrocort ison e IV q 6–8 h rs for 3–4 days un t il th e
st ress is resolved
● for elective surger y, see
Table 8.3 for guidelin es
8.1.4 St eroid side e ect s
8
Alth ough deleterious side e ects of steroids are m ore com m on w ith prolonged adm in istration ,4
som e can occur even w ith sh ort treat m en t courses. Som e evidence suggests th at low -dose glucocort icoids (≤ 10 m g/d of predn isolon e or predn ison e equivalen t) for rh eum atoid arth rit is does n ot
in crease osteoporotic fract ures, blood pressure, cardiovascular disease, or peptic ulcers,5 but w eigh t
gain an d skin ch anges are com m on . Possible side e ects in clude 3,6 :
● cardiovascular an d ren al
○ hyperten sion
○ sodium an d w ater reten tion
○ hypokalem ic alkalosis
● CNS
○ progressive m ultifocal leukoen ceph alopathy (PML) (p. 331)
○ m en tal agitat ion or “steroid psych osis”
○ spinal cord com pression from spin al epidural lipom atosis (p.1408): rare
○ pseudotum or cerebri, Idiopath ic in tracran ial hyperten sion (IIH) (p. 766)
● en docrin e
○ caution : because of grow th suppressan t e ect in ch ildren , daily glucocort icoid dosing over prolon ged periods sh ould be reserved for th e m ost urgen t in dication s
○ secon dar y am en orrh ea
○ suppression of hypothalam ic-pituitar y-adren al axis: reduces en dogen ous steroid production →
risk of adren al in su cien cy w ith steroid w ith draw al (see above)
○ Cush in goid features w ith prolonged usage (iatrogen ic Cush in g’s syn drom e): obesit y, hyperten sion , h irsutism …
● GI: risk in creased on ly w ith steroid th erapy > 3 w eeks duration an d regim en s of predn ison e > 400–
1000 m g/d or dexam eth ason e > 40 m g/d 7
○ gast rit is an d steroid ulcers: in ciden ce low ered w ith th e use of an tacids an d/or H2 an tagon ists
(e.g. cim etidin e, ran it idin e…)
○ pan creatitis
Table 8.3 Steroid stress doses for elective surgery
On day of surgery, 50 m g cort isone acet at e IM, followed by 200 m g hydrocort isone IV infused over 24 hrs
Post -op day
Hydrocort isone (m g)
8 AM
4 PM
10 PM
1
50
50
50
2
50
25
25
3
40
20
20
4
30
20
10
5
25
20
5
6
25
15
–
7
20
10
–
Endocrinology
in testin al or sigm oid diverticular perforation 8 : in ciden ce ≈ 0.7%. Sin ce steroids m ay m ask sign s
of periton itis, th is sh ould be con sidered in patien ts on steroids w ith abdom in al discom fort ,
especially in th e elderly an d th ose w ith a h istory of diverticular disease. Abdom in al x-ray usually sh ow s free in traperiton eal air
● in h ibition of fibroblasts
○ im paired w oun d h ealin g or w oun d breakdow n
○ subcutan eous tissue atrophy
● m etabolic
○ glucose in toleran ce (diabetes) an d dist urban ce of n itrogen m etabolism
○ hyperosm olar n on ketotic com a
○ hyperlipidem ia
○ ten d to in crease BUN as a result of protein catabolism
● oph th alm ologic
○ posterior subcapsular cataracts
○ glaucom a
● m usculoskeletal
○ avascular n ecrosis (AVN) of th e h ip or oth er bon es: usually w ith prolonged adm in istration
→cush ingoid h abit us an d in creased m arrow fat w ith in th e bon e 9 (predn ison e 60 m g/d for several m on th s is probably th e m in im um n ecessar y dose, w h ereas 20 m g/d for several m on th s w ill
probably not produce AVN10 ). Many cases blam ed on steroids m ay in stead be due to alcoh ol
use, cigarette sm oking,11 liver disease, un derlyin g vascular in flam m ation …
○ osteoporosis: m ay predispose to vertebral com pression fract ures w h ich occur in 30–50% of
patien ts on prolonged glucocor ticoids. Steroid in duced bon e loss m ay be reversed w ith cyclical
adm in istration of etidron ate 12 in 4 cycles of 400 m g/d 14 days follow ed by 76 days of oral
calcium supplem en ts of 500 m g/d (n ot proven to reduced rate of VB fract ures)
○ m uscle w eakn ess (steroid m yopathy): often w orse in proxim al m uscles
● in fect ious
○ im m un osuppression : w ith possible superin fect ion , especially fun gal, parasitic
○ possible reactivation of TB, ch icken pox
● h em atologic
○ hypercoagulopathy from in h ibition of tissue plasm in ogen activator
○ steroids cause dem argin at ion of w h ite blood cells, w h ich m ay artifactually elevate th e W BC
coun t even in th e absen ce of in fect ion
● m iscellan eous
○ h iccups: m ay respon d to ch lorprom azin e (Th orazin e®) 25–50 m g PO TID-QID
2–3 days (if
sym ptom s persist, give 25–50 m g IM)
○ steroids readily cross th e placen ta, an d fetal adren al hypoplasia m ay occur w ith th e adm in istrat ion of large doses during pregn an cy
147
○
8.1.5 Hypocort isolism
General inform at ion
AKA adren al in su cien cy.
Assessm en t: 8 A.M. serum cortisol level is th e best w ay to test for hypocort isolism . Each lab
sh ould provide a low er lim it of n orm al for th eir lab, w h ich m ay be broken dow n furth er by age an d
gen der.
Addisonian crisis
General inform ation
AKA adren al crisis. An adren al in su cien cy em ergency.
Sym ptom s: m en tal status ch anges (con fusion , lethargy, or agitation ), m uscle w eakn ess.
Sign s: postural hypoten sion or sh ock, hyperth erm ia (as h igh as 105° F, 45.6 C)
Labs
Hypon atrem ia, hyperkalem ia, hypoglycem ia.
Treatm ent of Addisonian crisis
If possible, draw serum for cort isol determ in ation (do n ot w ait for th ese results to in stit ute th erapy).
Give fluids su cien t for dehydration an d sh ock.
8
148
General and Neurology
For “glu cocor t icoid em er gen cy”
● hydrocort ison e sodium succin ate (Solu-Cortef®): 100 m g IV STAT an d th en 50 m g IV q 6 h rs
AND
● cort ison e acetate 75–100 m g IM STAT, an d th en 50–75 m g IM q 6 h rs
For “m in eralocor t icoid em ergen cy”
Usually n ot n ecessary in secon dar y adren al in su cien cy (e.g. pan hypopituitarism )
● desoxycort icosteron e acetate (Doca®): 5 m g IM BID
OR
● fludrocort ison e (Florin ef®): 0.05- 0.2 m g PO q d
m ethylpredn isolon e is NOT recom m en ded for em ergen cy treat m en t .
8.2 Hypot hyroidism
8.2.1 General inform at ion
8
Ch ron ic prim ar y hypothyroidism m ay result in (n on -path ologic) en largem en t of th e pit uitar y glan d.
Plasm a TSH determ in ation w ill dist in guish prim ar y hypothyroidism (h igh TSH) from secon dar y
hypothyroidism (low TSH). Woun d h ealing an d cardiac fun ction m ay be com prom ised, an d surger y
un der gen eral an esth esia sh ould be postpon ed if possible un t il thyroid levels are n orm alized. E ects
of an esth esia m ay be m arkedly prolonged, an d dosages sh ould be adjusted accordin gly.
8.2.2 Thyroid replacem ent
Caut ion in pat ient s w it h adrenal insu ciency
Prim ar y hypothyroidism m ay be associated w ith im m un ologic destruction of adren al cortex
(Sch m idt syn drom e). Secon dary hypothyroidism m ay be associated w ith an d m ay m ask reduced
adren al fun ction .
Thyroid replacem en t w ith out adren al replacem en t in patien ts w ith adren al
in su cien cy (as m ay occur in pan hypopit uitarism ) m ay precipitate adren al crisis (th us give ≈ 300–
400 m g hydrocor t ison e IV over 24 h rs in addit ion to thyroid replacem en t).
8.2.3 Rout ine t hyroid replacem ent dosing
Drug info : Levot hyroxine (Synt hroid®)
Almost pure T4 (contains no T3 as most T3 is produced peripherally from T4).
Dose required to prevent myxedem a com a (not to achieve euthyroidism):
● Maintenance:
0.05 mg po q d
● when patient has been hypothyroid:
start at 0.05 mg po q d and increase by 0.025 m g every 2–3
weeks
For euthyroidism (approximate dose, follow levels and clinical evaluation):
for most adults < 60 years age: 0.18 mg/day
● for elderly patients:
0.12 mg/day
●
Drug info : Desiccat ed t hyroid (e.g. Arm our t hyroid®)
Typical dose:
60 m g (1 grain) to 300 mg daily.
Thyroid replacem ent in m yxedem a com a
Myxedem a com a is an em ergency of hypothyroidism an d carries 50% m or talit y.
Sym ptom s: altered m en tal status or un respon siven ess.
Endocrinology
149
Sign s: hypoten sion , bradycardia, hypon atrem ia, hypoglycem ia, hypoth erm ia, hypoven tilation ,
occasion ally seizures.
Treatm ent
Drugs m ay n eed to be given IV due to reduced gastric m otilit y.
1. gen eral supportive care:
a) hypoten sion : t reat w ith IV fluids (respon ds poorly to pressors un til thyroid replacem en t
accom plish ed)
b) hypon atrem ia: w ill correct w ith thyroid replacem en t; avoid hyperton ic salin e
c) hypoglycem ia: IV glucose
d) sym ptom s of hypocor tisolism : thyroid replacem en t m ay precipitate adren al crisis (see ca ution
a bove); give 300–400 m g hydrocort ison e IV over 24 h rs
e) hypoth erm ia: avoid active w arm ing sin ce th is in creases m etabolic dem an d, use blan kets to
w arm gradually
f) hypoven tilation : ch eck ABG, in tubate if n ecessar y
2. thyroid replacem en t (for average -sized adult):
a) IV replacem en t: 0.5 m g of levothyroxin e IV, follow ed by 0.05–0.2 m g/d IV un t il patien t able
to tolerate PO or NG m eds
b) n asogastric replacem en t: liothyron in e (Cytom el®) is prim arily T3 , h as a rapid on set of act ion ,
m uch sh orter h alf-life th an T4, an d sh ould be reserved for em ergen cies.
: liothyron in e 0.05–0.1 m g per NG in itially, follow ed by 0.025 m g BID per NG
8.3 Pit uit ary em bryology and neuroendocrinology
8.3.1 Em bryology and derivat ion of t he pit uit ary gland
Th e posterior pituitar y (n eurohypophysis) derives from dow nw ard evagin ation of n eural crest cells
(brain n euroectoderm ) from th e floor of th e th ird ven tricle. Th e residual recess in th e floor of th e
th ird ven tr icle is called th e m edian em in en ce. Th e an terior pituitar y glan d (aden ohypophysis) develops from an evagin ation of epith elial ectoderm of th e oroph ar yn x, th e evagin ation is kn ow n as
Rathke’s pouch an d is even tually separated from th e oroph ar yn x by th e sph en oid bon e. Cleft-like
rem n an ts of Rath ke’s pouch separates th e aden ohypophysis an d n eurohypophysis. Th e aden ohypophysis is com prised of th e pars distalis (an terior lobe), th e pars in term edia (in term ediate lobe)
an d th e pars tuberalis (exten sion of aden ohypophyseal cells on th e an terior aspect of th e pituitar y
stalk). Th e pituitar y glan d is fun ction ally outside th e blood-brain barrier.
8.3.2 Pit uit ary horm ones, t heir t arget s and t heir cont rols
General inform at ion
Th e pit uitar y glan d releases 8 h orm on es, 6 from th e an terior pituitar y, 2 from th e posterior pit uitar y
( Fig. 8.1). Th e an terior pituitar y is on e of on ly t w o sites in th e body h aving a por tal circulation (th e
oth er bein g th e liver). 6 hypoth alam ic h orm on es released in a pulsat ile fash ion are conveyed in
blood from hypoth alam ic capillaries th rough th is portal circulation via th e pit uitar y stalk to a secon d
capillar y bed in th e an terior pit uitar y w h ere th ey con trol release of h orm on es by aden ohypophyseal
glan d cells.
Horm on es released from th e posterior pituitar y (ADH & oxytocin ) are syn th esized in neurons in
th e hypoth alam us (not glan d cells) an d are conveyed alon g th eir a xons also in th e pituitar y stalk to
th e posterior pituitar y glan d w h ere th ey are released.
Th e com plete h om eostat ic loop (in cluding n egative feedback of th e hypoth alam ic h orm on es) w ill
n ot be covered h ere, an d th e reader is referred to physiology texts.
Propiom elanocort in (POMC), AKA proopiom elanocort in
241 am in o acid polypept ide h orm on e precursor syn th esized prim arily in cort icot roph cell of th e
an terior pituitar y (but also foun d in th e hypoth alam us). Con tain s am in o acid sequen ces for ACTH,
alph a-m elan ocyte-stim ulating h orm on e (α -MSH), β-lipot ropin , γ-lipotropin , β-en dorph in an d m eten keph alin .
8
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150
General and Neurology
) ni c ot yx O(
) HDA(
Endocrinology
151
Cort icot ropin AKA adrenocort icot rophic horm one (ACTH)
A 39 am in o acid t roph ic h orm on e syn th esized from POMC. Th e first 13 am in o acids at th e am in o
term in al of ACTH are iden tical to α -MSH. Active h alf-life is ≈ 10 m in utes. Produces a diurn al peak in
cort isol (th e h igh est peak occurs in th e early m orn in g, w ith a secon d, lesser peak in th e late aftern oon ) an d also in creases in respon se to st ress.
Con t r ol: CRH from th e hypoth alam us stim ulates th e release of ACTH.
Prolact in (PRL)
AKA som atom am m otropin . 199 am in o-acid protein w eigh in g 23,000 dalton s. Levels are h igh er in
fem ales th an m ales, an d are h igh er st ill in pregn an cy (see Table 46.3). Secreted in pulsatile fash ion
w ith a frequen cy an d am plitu de th at varies during m en strual cycle (range: 5–27 n g/m l) (≈ 9 pulses/
24 h ours in th e late luteal ph ase, ≈ 14 pulses/24 h ours in th e late follicular ph ase, th e pulse am plit ude in creases from early to late follicular an d luteal ph ases). Th ere is also diurn al variation : levels
begin to rise 1 h our after th e on set of sleep, peak ≈ 5:00–7:00 AM, an d n adir in m idm orn in g after
aw aken in g. Heterogen eit y of th e m olecule m ay produce di eren t results betw een bioassays an d
im m un oassays.
Con trol: PRL is th e on ly pit uitar y h orm on e predom in an tly un der inhibitor y con trol from th e
hypoth alam us by prolact in in h ibitor y factors (PRIFs), w ith dopam in e bein g th e prim ar y PRIF. Prolactin releasin g factors (PRFs) in clude: thyrotropin -releasin g h orm on e (TRH) an d vasoact ive in testin al
peptide (VIP). Th e physiologic role of PRFs is n ot establish ed. For DDx of hyperprolact in em ia see
Table 46.4.
Grow t h horm one (GH)
A 191 am in o-acid polypeptide t roph ic h orm on e. GH n orm ally h as pulsat ile secretion (≈ 5–10 pulses/
24 h ours, prim ar ily at n igh t , up to 30 m cg/L), levels m ay be un detectable (< 0.2 m cg/L) by stan dard
assays bet w een pulses.13 In sulin -like grow th factor-1 (IGF-1) (form erly AKA som atom edin -C) is th e
protein secreted prim arily by th e liver in respon se to GH th at is respon sible for m ost of GH’s system ic
e ect s (see levels (p.736)). GH also acts directly on epiphyseal en d-plates of lon g bon e to st im ulate
ch on drocyte proliferation .
Con trol: GH is un der dual hypoth alam ic con trol via th e hypophysial portal system . GH-releasing
h orm on e (GHRH) from the arcuate n ucleus st im ulates pit uitary secretion an d synthesis of GH an d
in duces GH gen e tran scription . Som atostatin from th e periven tricular n ucleus suppresses GH relea se
on ly, an d h as n o e ect on syn th esis. GH relea se is also st im ulated by gh relin ,14 a peptide syn th esized
prim arily in th e GI t ract in respon se to certain n utrien ts (m ay act part ially or totally via hypoth alam ic GHRH).
Thyrot ropin AKA t hyroid st im ulat ing horm one (TSH)
Glycoprotein troph ic h orm on e secreted by thyrotroph cells of th e an terior pituitar y.
Con trol: TSH is also un der dual hypoth alam ic con trol. TRH stim ulates product ion an d release of
TSH. Som atostatin in h ibits th e release of TSH.
Gonadot ropins
Follicle stim ulating h orm on e (FSH) an d lutein izin g h orm on e (LH) (AKA lut ropin ) are released from
th e pit uitar y in respon se to gon adot ropin releasin g h orm on e 1 (Gn RH, form erly lutein izin g h orm on e
releasin g h orm on e LH-RH) syn th esized prim arily in th e preoptic area of th e hypothalam us.
Ant idiuret ic horm one (ADH)
AKA argin in e vasopressin (AVP). Th e m ajor source of th is n an opept ide h orm on e is th e m agn ocellular
port ion of th e supraoptic n ucleus of th e hypothalam us. It is conveyed alon g a xons in th e supraopt ichypophyseal t ract to th e posterior pit uitary glan d w h ere it is released in to th e system ic circulat ion .
All action s of ADH result from bin din g of th e h orm on e to specific m em bran e boun d receptors on th e
surface of target cells.15 On e of th e m ajor e ect s of ADH is to in crease th e perm eabilit y of th e distal
ren al t ubules resultin g in in creased reabsorpt ion of w ater, dilutin g th e circulatin g blood an d producin g a con cen trated urin e. Th e m ost pow erful physiologic st im ulus for ADH release is an in crease in
serum osm olality, a less poten t st im ulus is a reduct ion of in travascular volum e. ADH is also released
in glucocorticoid deficien cy, an d is in h ibited by exogen ous glucocort icoids an d adren ergic drugs.
ADH is also a poten t vasocon st rictor.
8
152
General and Neurology
Oxyt ocin
A n on apept ide. Oxytocin is a n eurotran sm itter as w ell as a h orm on e. Th e hypothalam us is th e m ain
source of pituitar y oxytocin w h ich is stored in n er ve en dings in th e n eurohypophysis an d is involved
in th e m ilk letdow n reflex for breastfeeding as w ell as in uterin e con traction durin g labor.
References
8
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62:806–810
[7] Lu W Y, Rh on ey DH, Bolin g W B, et al. A Review of
Stress Ulcer Prophylaxis in the Neurosurgical Inten sive Care Unit. Neurosurger y. 1997; 41:416–426
[8] Wein er HL, Rezai AR, Cooper PR. Sigm oid Divert icular Perforation in Neurosurgical Patien ts Receiving
High-Dose Cor t icosteroids. Neurosurger y. 1993;
33:40–43
[9] Zizic TM, Marcoux C, Hun gerfold DS, et al. Cort icosteroid Th erap y Associated w ith Isch em ic Necrosis
[10]
[11]
[12]
[13]
[14]
[15]
of Bone in System ic Lupus Er yth em atosus. Am J
Med. 1985; 79:597–603
Zizic TM. Avascu lar Necrosis of Bon e. Cu rren t Opin ion s in Rh eu m atology. 1990; 2:26–37
Matsu o K, Hiroh ata T, Sugioka T, et al. In flu en ce of
Alcoh ol In take, Cigarette Sm okin g an d Occu pation al
Stat us on Idiopathic Necrosis of th e Fem oral Head.
Clin Orth op . 1988; 234:115–123
Stru ys A, Sn eld er AA, Muld er H. Cyclical Etidron ate
Reverses Bon e Loss of th e Sp in e an d Proxim al
Fem ur in Patients W ith Establish ed Cor t icosteroidIn duced Osteoporosis. Am J Med. 1995; 99:235–242
Peacey SR, Toogood AA, Veld h uis JD, Th orn er MO,
Sh alet SM. Th e relation sh ip bet w een 24-h our
grow th horm on e secretion an d in sulin -like grow th
factor I in patien ts w ith successfu lly t reated acrom egaly: im pact of surgery or radioth erapy. J Clin
En docrinol Metab. 2001; 86:259–266
Tan n enbaum GS, Epelbaum J, Bowers CY. Interrelat ion sh ip bet w een th e n ovel peptide gh relin an d
som atostatin /grow th h orm on e-releasin g h orm on e
in regu lation of p ulsatile grow th h orm on e secret ion . En d ocrinology. 2003; 144:967–974
Th ibonn ier M, Barrow DL, Selm an W . In: Antidiuretic Horm on e: Regulation , Disord ers, an d Clin ical
Evalu ation . Neu roen d ocrin ology. Balt im ore: William s an d W ilkin s; 1992:19–30
Hem at ology
153
9 Hem at ology
9.1 General inform at ion
Circulatin g blood volum es for adults an d peds are sh ow n in
Table 9.1.
9.2 Blood com ponent t herapy
9.2.1 Massive t ransfusions
Defin ition : replacem en t of > 1 blood volum e (in average adult ≈ 20 U) in < 24 h rs for adult, or > 2 × circulatin g blood volum e in peds, m ay cause dilution of e ect ive platelets an d coagulation factors.
W h en operatin g on a pediatric patien t, you can usually safely replace up to 1.5 × th e circulatin g blood
volum e before problem s w ith coagulopathy en sue.
Blood com pon en t th erapy required for m assive tran sfusion s:
1. PRBCs
2. platelets (4 U in adult)
3. FFP
9.2.2 Cellular com ponent
Red blood cell t herapy
9
General inform ation
Major h istocom patibilities of blood are sh ow n in
Table 9.2.
Whole blood
1 U (≈ 510 cc) = 450 cc blood + 63 cc preservat ive.
Recom m en ded tran sfusion criteria:
● exch ange t ran sfusion s in n eon ates
● acute burn debridem en t an d graft ing in ch ildren
Packed red blood cells (PRBCs)
Recom m en ded t ran sfusion criteria:
1. acute blood loss ≥ 15% of patien t’s blood volum e
2. in asym ptom at ic patien t: h em oglobin (Hb) ≤ 8 gm or Hct ≤ 24%
Table 9.1 Circulating blood volum e
Age
Vol (cc/kg a )
prem ature infant
85–100
term infant < 1 month
85
infant > 1 m os (& adult)
75
a cc per kg of body weight
Table 9.2 Blood com patibilit y (AB0)
Blood t ype
Antibody present
Com patible blood
(PRBC)
Com patible plasm a
Com pat ible platelets
or cryoprecipitat e
A
B
A, 0
A, AB
0
B
A
B, 0
B, AB
AB
none
AB, A, B, 0
AB
0
A, B
0
AB, A, B, 0
154
General and Neurology
3. sym ptom s of an em ia at rest
4. preoperative Hb ≤ 15 gm or Hct < 45% in th e n eon ate
Am oun t to t ran sfuse:
Adult: 1 U (250–300 cc) raises Hct by 3–4%.
For peds, use Eq (9.1).
ðestimated blood volum e ½ml Þ Â ðHct increment desired ½% Þ
70%
(where the Hct of PRBCs ranges 70–80%)
m l of PRBC to transfuse ¼
ð9:1Þ
Give n o faster th an 2–3 cc/kg/h r.
Autologous blood transfusion
Predon ated w h ole blood m ay be stored 35 days. PRBCs m ay be stored 42 days.
Pat ien ts m ay don ate ever y 3 days to 1 w eek as lon g as th ey m ain tain Hct ≥ 34% (supplem en t w ith
ferrous sulfate). Th e follow in g patien ts require physician release before don atin g: patien ts w ith coron ar y arter y disease, an gin a, cerebrovascular disease, seizure disorder, pregn an cy (because of possible vasovagal episode) or patien ts w ith m align an cy.
Tr y to t im e last don ation > 72 h rs prior to surger y to allow patien t to replen ish som e of th e
depleted RBCs before surgery.
9
9.2.3 Plat elet s
General inform at ion
Norm al platelet coun t (PC) is 150K-400K (abbreviation used h ere: 150K= 150,000/m m 3 = 150 × 109/
l). Th rom bocytopen ia is defin ed as PC< 150K. Bleeding (spon tan eously or w ith invasive procedures)
is rarely a problem w ith PC > 50K. Spon tan eous h em orrh age is ver y likely w ith PC< 5K. Spon tan eous
in t racran ial h em orrh age is un com m on w ith PC> 30K, an d is m ore com m on in adults th an ch ildren .
Based on patien ts w ith ITP, th e risk of fatal h em orrh age in patien ts w ith PC< 30K is 0.0162–0.0389
cases per pat ien t-year 1 (risk of death from in fect ion is h igh er). In tracran ial bleeding is usually subarach n oid or in traparen chym al, w ith petech ial h em orrh ages com m on .
1 un it of platelets con tains 5.5 × 1010 (m in im um ) to 10 × 1010 platelets. Th e volum e of 6 un its is
250–300 m l. Platelets m ay be stored up to 5 days.
Recom m ended plat elet t ransfusion crit eria
In dication s for platelet t ran sfusion 2 :
1. th rom bocytopenia due to ↓ product ion (w ith or w ith out in creased destruction ) (th e m ost com m on causes are aplastic an em ia an d leukem ia)
a) PC< 10K even if n o bleedin g (prophylactic t ran sfusion to preven t bleedin g)
b) PC< 20K an d bleeding
c) PC< 30K an d patien t at risk for bleedin g: com plain ts of H/A, presen ce of con fluen t (c.f. scattered) petech iae, con tin uous bleedin g from a w oun d, in creasing retin al h em orrh age
d) PC< 50K AND
● m ajor surger y plan n ed w ith in 12 h ours
● PC rapidly fallin g
● patien t < 48 h ours post-op
● patien t requires lum bar pun ct ure
● acute blood loss of > 1 blood volum e in < 24 h ours
2. platelet t ran sfusion s h ave lim ited usefuln ess w h en th rom bocytopen ia is due to platelet destruction (e.g. by an t ibodies as in ITTP) or con sum pt ion (if product ion is adequate or in creased, platelet tran sfusion usually w ill n ot be useful)
3. docum en ted platelet dysfun ct ion in a patien t sch eduled for surger y or in a patien t w ith advan ced
h epatic an d/or ren al in su cien cy (con sider ph arm acologic en h an cem en t of platelet fun ct ion , e.g.
desm opressin 3 )
Oth er in dication s for platelet t ran sfusion :
1. patien ts w h o have been on Plavix® or aspirin w h o n eed urgen t surgery th at can n ot be postpon ed
for ≈ 5 days to allow n ew platelets to be syn th esized
Hem at ology
155
Dosage
Approxim ately 25%of platelets are lost just w ith t ran sfusion .
Peds: 1 U/m 2 raises PC by ≈ 10K, usually give 4 U/m 2 .
Adult: 1 U raises platelet coun t by ≈ 5–10K. Typical dose for th rom bocytopen ic bleedin g adult: 6–
10 U (usual order: “8-pack”). Altern atively, 1 U of ph eresed platelets m ay be given (obtain ed from a
sin gle don or by aph eresis, equivalen t to 8–10 U of pooled don or platelets).
Ch eck PC 1–2 h rs after tran sfusion . Th e in crease in PC w ill be less in DIC, sepsis, splen om egaly,
w ith platelet an tibodies, or if th e patien t is on ch em otherapy. In th e absence of in creased con sum p t ion , platelets w ill be n eeded q 3–5 days.
9.2.4 Plasm a prot eins
FFP (fresh frozen plasm a)
General inform ation
1 bag = 200–250 m l (usually referred to as a “un it”, n ot to be con fused w ith 1 un it of factor activit y
w h ich is defin ed as 1 m l). FFP is plasm a separated from RBCs an d platelets, an d con tain s all coagulation factors an d n atural in h ibitors. FFP h as an out-date period of 12 m on th s. Th e risk of AIDS an d
h epatitis for each un it of FFP is equal to th at of a w h ole un it of blood.
Recom m ended transfusion criteria
Recom m en dat ion s (m odified 2 ):
1. h istor y or clin ical course suggestive of coagulopathy due to congen ital or acquired coagulation
factor deficien cy w ith act ive bleedin g or pre-op, w ith PT > 18 sec or APTT > 1.5 × upper lim it of
n orm al (usually > 55 sec), fibrin ogen fun ct ion in g n orm ally an d level > 1 g/l, an d coagulation factor
assay < 25% act ivity
2. proven coagulation factor deficien cy w ith act ive bleedin g or sch eduled for surgery or oth er invasive procedure
a) congen ital deficien cy of factor II, V, VII, X, XI or XII
b) deficien cy of factor VIII or IX if safe replacem en t factors un available
c) von W illebran d’s disease un respon sive to DDAVP
d) m ultiple coagulat ion factor deficien cy as in h epatic dysfun ct ion , vitam in K depletion or DIC
3. reversal of w arfarin (Coum adin ®) (p. 166) e ect (PT > 18 sec, or INR > 1.6) in patien t actively
bleedin g or requiring em ergen cy surgery or procedure w ith in su cien t tim e for vitam in K to
correct (w h ich usually requires > 6–12 h rs)
4. deficien cy of an tith rom bin III, h eparin cofactor II, or protein C or S
5. m assive blood t ran sfusion : replacem en t of > 1 blood volum e (≈ 5 L in 70 kg adult) w ith in several
h ours w ith evidence of coagulat ion deficien cy as in (1) an d w ith con tin ued bleedin g
6. t reatm en t of th rom botic th rom bocytopen ic purpura, h em olytic urem ic syn drom e
7.
because of associated h azards an d suitable altern atives, th e use of FFP as a volum e expan der is
relatively con train dicated
Dosage
Usual start in g dose is 2 bags of FFP (400–600 m l). If PT is 18–22 secs or APTT is 55–70 secs, 1 bag
m ay su ce. Doses as h igh as 10–15 m l/kg m ay be n eeded for som e pat ien ts. Mon itor PT/PTT (or specific factor assay) an d clin ical bleedin g. Sin ce factor VII h as a sh orter h alf-life (≈ 6 h rs) th an th e oth er
factors, PT m ay becom e prolonged before APTT.
Rem em ber: if patien t is also receivin g platelets, th at for ever y 5–6 un its of platelets th e patien t is
also receivin g coagulat ion factors equivalen t to ≈ 1 bag of FFP.
Album in and plasm a protein fraction (PPF, AKA Plasm anate®)
Usually from outdated blood, treated to in act ivate h epatitis B virus. Ratio of album in :globulin percentage in “album in ” is 96%:4%, in PPF it is 83%:17%. Available in 5% (on cotically an d osm ot ically
equivalen t to plasm a) an d 25%(con train dicated in dehydrated pat ien ts). 25%album in m ay be diluted
to 5% by m ixin g 1 volum e of 25% album in to 4 volum es of D5 W or 0.9% NS ( caution : m ixin g w ith
sterile w ater w ill result in a hypoton ic solution th at can cause h em olysis an d possible ren al failure).
Expen sive for use sim ply as a volum e expan der (≈ $60–80 per un it). In dicated on ly w h en total
protein < 5.2 gm % (oth er w ise, use cr ystalloid w h ich is equally e ect ive). Rapid in fusion (> 10 cc/m in )
h as been reported to cause hypoten sion (due to Na-acetate an d Hagem an factor fragm en ts). Use in
ARDS is con troversial. In n eurosurgical pat ien ts, m ay be con sidered as an adjun ct for volum e
9
156
General and Neurology
expan sion (alon g w ith cr ystalloids) for hyperdyn am ic th erapy (p. 1186) w h en th e h em atocrit is < 40%
follow in g SAH w h ere th ere is con cern about in creasin g th e risk of rebleedin g e.g. w ith th e use of
h etastarch (p.1165).
Cryoprecipitate
Recom m en ded tran sfusion criteria:
1. h em oph ilia A
2. von W illebran d disease
3. docum en ted fibrin ogen /factor VIII deficien cy
4. docum en ted dissem in ated in travascular coagulation (DIC): alon g w ith oth er m odes of th erapy
Prot hrom bin com plex concent rat e (PCC) (Kcent ra® and ot hers)
Derived from fresh -frozen h um an plasm a, con tain s clot ting factors II, VII, IX an d X, w ith protein C &
S to preven t th rom bosis. Prim ary in dication is to be given IV to reverse w arfarin in em ergen cy sit uat ion s. How ever it is also used in oth er settin gs. Requires m uch low er volum e th an FFP to w ork. Also,
w h en th e INR gets dow n to about 1.4, PCC w ill con tin ue to reduce th e INR w h ereas FFP w ill h ave
little or n o ben efit.
Optim al dosin g is n ot kn ow n . Doses of 15-50 IU/kg h ave been given to h em oph iliacs but th e clott in g deficit di ers in vitam in -K depletion th an in clot t in g factor absen ce. A reason able dose th at is
often used is 25 IU/kg.
9
9.2.5 Ant icoagulat ion considerat ions in neurosurgery
General inform at ion
Most of th ese issues h ave n ot been st udied in a rigorous, prospective fash ion . Yet, th ese question s
frequen tly arise. Th e follow in g is to be con sidered a fram ework of guidelin es, an d is n ot to be con st rued as a stan dard of care. Table 9.3 acts as an in dex to th e topics discussed below.
Cont raindicat ions t o heparin
Con train dication s to h eparin th erapy are con stan tly being reevaluated. Massive PE producing h em odyn am ic com prom ise sh ould be treated w ith an ticoagulat ion in m ost cases despite in tracran ial risks.
Con train dication s to full an ticoagulation w ith h eparin in clude:
● recen t severe h ead injur y
● recen t cran iotom y: see below
● patien ts w ith coagulopath ies
● h em orrh agic in farct ion
● bleedin g ulcer or oth er in accessible bleedin g site
Table 9.3 Anticoagulation issues in neurosurgery
General neurosurgical contraindications to full anticoagulation with heparin (p. 156)
St art ing/cont inuing ant icoagulation in t he presence of t he following neurosurgical condit ions
●
●
●
●
●
●
●
●
incidental aneurysm (p. 157)
subarachnoid hemorrhage (p. 157)
brain tumor (p. 157)
following craniotom y (p. 157)
acute epidural/subdural hem atom a
chronic subdural hem atom a
ischemic stroke
○ after tPA (p. 1287)
○ for prevention of (p. 1270)
intracerebral hemorrhage (p. 1341)
Managing pat ients who are already ant icoagulat ed who need a neurosurgical procedure
●
●
●
●
warfarin (Coum adin®) (p. 157)
heparin (p. 160)
LMW-heparin (p. 160)
antiplatelet drugs (aspirin, Plavix, NSAIDs) (p. 160)
Recom m endat ions for DVT prophylaxis in neurosurgical pat ient s (p. 168)
Hem at ology
157
un con trollable hyperten sion
● severe h epatic or ren al disease
● < 4–6 h ours before an invasive procedure (see below )
● brain tum or: see below
●
Pat ient s w it h unrupt ured (incident al) cerebral aneurysm s
An ticoagulation m ay n ot in crease th e risk of h em orrh age (i.e. rupture), h ow ever, sh ould rupture
occur, an t icoagulation w ould m ost likely in crease volum e of h em orrh age an d th us in crease m orbidit y an d m or talit y.
Th e decision to star t/con tin ue an t icoagulan t depen ds on th e in dication for th e drugs, th e size of
th e an eur ysm (a sm all an eur ysm < 4 m m is n ot as w orrisom e). Pat ien ts n eeding Plavix® for drugelut in g cardiac sten ts sh ould probably be left on th eir drugs.
Pat ient s on ant icoagulat ion/ant iplat elet drugs w ho develop SAH
Coum adin an d an t iplatelet drugs are usually reversed.
In pat ient s w it h brain t um or
Som e auth ors are reluctan t to adm in ister full-dose h eparin to a patien t w ith a brain tum or,4
alth ough a n um ber of st udies foun d n o h igh er risk in th ese patien ts w h en t reated w ith h eparin or
oral an ticoagulation 5,6,7 (PT sh ould be follow ed ver y closely, on e study recom m en ded m ain tain in g
PT ≈ 1.25 × con trol7 ).
Post -operat ively follow ing craniot om y
Requires in dividualization based on th e reason for th e cran iotom y. Surgery for paren chym al lesion s
w h ere th e surger y disrupts sm all vessels (e.g. brain tum or) is probably h igh er risk for h em orrh age
th an e.g. an eur ysm surgery (expert opin ion ). Option s:
Full an t icoagulation : m ost n eurosurgeon s w ould probably n ot fully an ticoagulate patien ts < 3–5
days follow in g cran iotom y,8 an d som e recom m en d at least 2 w eeks. How ever, on e st udy foun d n o
in creased in ciden ce of bleeding w h en an t icoagulation w as resum ed 3 days post cran iotom y.9
Low -dose (prophylact ic) an ticoagulat ion : eith er w ith m in i-dose h eparin (5000 U SQ 2 h rs prior to
cran iotom y an d con tin uing q 12 h rs post-op × 7 d) or en oxaparin (Loven ox) (30 m g SQ BID or as a
single dose of 40 MG SQ q d). – RPDB study 10 : assessed sa fet y (n ot e cacy), 55 patien ts un dergoin g
cran iotom y for t um or received m in i-dose h eparin as in dicated h ad n o in creased bleedin g ten den cy
by any of th e param eters m easured. RPNB study 11 : in ciden ce of post-op h em orrh age in creased to
11%w ith en oxaparin .
Managem ent of ant icoagulant s prior t o neurosurgical procedures
Pre-operative laborator y assessm en t of th e coagulat ion path w ay an d platelet fun ct ion is routin ely
used even th ough th ese studies rarely con tribute crit ical in form ation in th e patien t w ith a n egative
h istor y for bleedin g ten den cies. Th ere are n o ran dom ized studies to assess th e value of coagulation
laboratory m easurem en ts to patien t care. Th is sect ion en com passes th e use of an tiplatelet an d an ticoagulation m edicin es, th eir m on itoring, an d th eir reversal.
Table 9.4 sum m arizes th is in form at ion .
Warfarin
Managem ent guidelines
Pat ien ts on w arfarin w h o m ust be an ticoagulated as lon g as possible (e.g. m ech an ical h eart valves)
m ay be “bridged“ to LMW h eparin inject ion s, e.g. Loven ox (p. 165), as follow s: stop w arfarin at least
3 days prior to th e procedure, an d begin self-adm in istered LMW h eparin inject ion s w h ich are discon tin ued as outlin ed in Table 9.4.
Pat ien ts w ith less critical an t icoagulation n eeds (e.g. ch ron ic a-fib) can usually stop th e w arfarin
at least 4–5 days before th e procedure, an d a PT/INR is th en ch ecked on adm ission to th e h ospital.
Pat ien ts m ust be advised th at durin g th e tim e th at th ey are n ot an t icoagulated, th ey are at risk of
possible com plication s from th e con dition for w h ich th ey are receivin g th e agen ts (a nnua l risk for
m ech an ical valve: ≈ 6%; for a-fib: depen ds on several factors in cludin g age & h istor y of prior st roke,
an average for patien ts > 65 years age is ≈ 5–6%; see details (p. 1304).
9
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Hem at ology
159
9
160
General and Neurology
Table 9.5 Recom m endations for holding new oral anticoagulants prior to invasive procedures related to renal
function.31
Dabigat ran
Apixaban
Rivoraxaban
CrCl > 80 m l/m in
≥ 72 hr
≥ 48 hr
≥ 48 hr
CrCl 50–80 ml/m in
≥ 72 hr
≥ 48 hr
≥ 48 hr
CrCl 30–49 ml/m in
≥ 96 hr
≥ 72 hr
≥ 72 hr
CrCl < 30 ml/m in
≥ 120 hr
≥ 96 hr
≥ 96 hr
The recommended m inimum interval bet ween last dose and procedure is based on renal function and procedure
risk. Generally, neurosurgical procedures including minor procedures such as LPs are considered interventions
with a high bleeding risk
For non-em ergent neurosurgical procedures
For procedures w h ere post-op m ass e ect from bleedin g w ould pose serious risk (w h ich in cludes
m ost n eurosurgical operation s), it is recom m en ded th at th e PT sh ould be ≈ ≤ 13.5 sec (i.e. ≤ upper
lim its of n orm al) or th e INR sh ould be ≈ ≤ 1.4 (e.g. for referen ce, th is INR is con sidered safe for perform ing a percutan eous n eedle liver biopsy). See also reversal of an t icoagulat ion (p.166).
9
For em ergent neurosurgical procedures
Give FFP (start w ith 2 un its) an d vitam in K (10–20 m g IV at ≤ 1 m g/m in ) as soon as possible; see also
reversal of an ticoagulat ion (p. 166). Th e tim ing of surger y is th en based on th e urgen cy of th e sit uat ion an d th e n ature of th e procedure (e.g. th e decision m igh t be to evacuate a spin al epidural h em atom a in an acutely paralyzed pat ien t before an ticoagulation is fully reversed).
Heparin
For em ergen cies: if it w ould be deleterious to w ait 4–6 h ours after discon tin uing h eparin an d th en
repeating th e PTT to verify th at an ticoagulation h as been corrected, th en h eparin can be reversed
w ith protam in e (p.166).
For non-em ergencies
IV h eparin : stop th e drip ≈ 4–6 h ours prior to th e plan n ed procedure. Option : rech eck PTT just prior
to start in g th e procedure.
“Min i-dose” SQ h eparin : n ot m an dator y to stop for cran iotom y, but if desired to discon tin ue, th en
give last dose ≥ 12 h ours prior to surger y.
Low-m olecular weight heparins (LMWH)
For em ergen cies: can be reversed w ith protam in e (p. 166).
Non -em ergen cies: See Table 9.4. Lon ger t im es are n eeded in ren al failure. A factor Xa level can
be used to ch eck an t icoagulation status, but th is usually m ust be sen t out , m akin g it un suitable for
acute m an agem en t.
Antiplatelet drugs and neurosurgical procedures
Platelet m echanistics and platelet function tests
Platelets are important for m aintaining vascular endothelial in tegrity and are constan tly involved w ith
hem ostasis in conjunction w ith coagulation factors. Severe throm bocytopenia can result in petechial
hem orrhages or spontaneous intracerebral hem orrhage (ICH). Vascular w all disturbance is the initial
stim ulus for platelet deposition and activation. Platelets adhere to collagen via surface receptors GPIbV-IX and von Willebrand factor. This adhesion sets o a cascade of reactions, w hich result in platelet
aggregation form ing a hem ostatic plug. Historically, bleeding tim e (BT) was used as the screening test
for abnorm alities of platelet function. Due to un reliabilit y, m any institutions have replaced the BT w ith
the platelet function assay (PFA) using the PFA-100 (platelet function analyzer). There are lim ited studies confirm ing its use according to the International Society of Throm bosis and Hem ostasis.12,13
In th e PFA-100, prim ar y h em ostasis is sim ulated un der “h igh -sh ear” flow by m ovem en t of
citrated blood th rough a m em bran e-im pregn ated capillar y in t w o collagen -coated cart ridges; on e
stim ulates platelets w ith aden osin e diph osph ate (ADP) an d th e oth er w ith epin eph rin e.14 Th is in teract ion w ith th e collagen in duces a platelet plug, w h ich closes an apert ure. Results are reported as
Hem at ology
161
closure t im e in secon ds. Th is m eth od is eligible as a screen ing test for prim ar y h em ostatic disease
such as von W illebran d disease as w ell as for m on itorin g th e e ect of an tiplatelet th erapy. Th e PFA100 w orks for test in g w ith aspirin but n ot w ith th ien opyridin e drug class (e.g. clopidogrel). New ly
available PFA cart ridges detect P2Y12 receptor blockade in patien ts on th ein opyridin e drugs.15 VerifyNow ® m easures agon ist-in duced aggregation as an in crease in ligh t tran sm itt an ce. Th e system
con tain s a preparat ion of h um an fibrin ogen -coated beads, w h ich cause a ch ange in ligh t tran sm ittan ce by ADP-in duced platelet aggregat ion .15 Th ere is lit tle correlation betw een PFA-100 results an d
VerifyNow Assay.
Agent s
Plavix® (clop idogrel) (p.1275) an d asp irin . Cause perm anen t in hibition of platelet fun ction th at
persists ≈ 5 days after discontin uation of th e drug an d can in crease the risk of bleeding. For elective
cases, 5–7 days o th ese drugs is recom m ended (surveys of Germ an n eurosurgeons 16,17 : an average of
7 days was used for low -dose ASA, w ith a few w h o do spine surgery even w hile the patient is on ASA).
Cardiac sten ts: dual an tiplatelet th erapy (e.g. ASA+ Plavix®) are m an datory for 4 w eeks (90 days
is preferable 18 ) after placem en t of a bare m etal cardiac stent , an d for at least 1 year w ith drug-elutin g
stents (DES) (th e risk declin es from ≈ 6% to ≈ 3%).19 Even sh ort gaps in drug th erapy (e.g. to perform
n eurosurgical procedures) is associated w ith sign ifican t risk of acute stent occlusion (an d th erefore
elect ive surger y durin g th is tim e is discouraged 20 ). DES are so e ect ive in suppressing en doth elialization th at lifetim e dual an t iplatelet th erapy m ay be required. Bridgin g DES patien ts w ith an tith rom bin , an ticoagulan ts, or glycoprotein IIb/IIIa agen ts has n ot been proven e ect ive.20
Reversal of an t ip latelet d r u gs: W h ile h eparin an d w arfarin can be reliably an d m easurably
reversed, th e situation is less clear w ith an tiplatelet agen ts.21 Agents used pre-op to reverse th ese
drugs in clude: Desm opressin (p. 166) (DDAVP®)16,17 an d FFP.16
Reversal of Plavix for em ergen cy surger y (p. 154): platelets m ay be given , h ow ever, Plavix e ects
persists for up to a couple of days after th e last dose, an d can actually in h ibit platelets given after th e
drug is discon tin ued (th e h alf-life of aspirin is low er an d sh ould n ot be an issue after 1 day). In cases
w ith con tin ued oozing in th e first day or so after discon tin uing Plavix, th e follow in g regim en is an
option :
1. recom bin an t activated coagulation factor VII (rFVIIa): even th ough th e defect is in th e platelets,
rFVIIa w orks, via a m ech an ism n ot m ediated by protein clot t ing factors. Ver y expen sive
(≈ $10,000 per dose), but th is m ust be balan ced again st th e cost of repeat cran iotom y, in creased
ICU stay an d addition al m orbidit y
a) in itial dose 22 : 90–120 m cg/kg
b) sam e dose 2 h rs later
c) 3rd dose 6 h rs after in itial dose
2. platelets ever y 8 h ours for 24 h ours, either
a) 6 U of regular platelets
b) if patien t is on fluid or volum e restriction : 1 un it of ph eresed platelets
Her bal p rod u ct s an d su p p lem en t s. Herbal products an d supplem en ts often a ect platelet aggregation an d th e coagulat ion cascade by m ean s th at can n ot be detected by laborator y tests. Th e
in creasing popularit y of th ese un regulated products requires screen in g patien ts for th eir use. Th ere
are lim ited studies regardin g th e use of h erbal supplem en ts in n eurosurger y an d for an elect ive operation w ait in g 7–14 days after cessation of th eir use is w arran ted.
Fish Oil (Om ega-3 Fatt y Acids) is w idely used am on g th e cardiac an d gen eral population for treatm en t of dyslipidem ia an d hypert riglyceridem ia. Fish oil m ay a ect platelet aggregat ion by a reduction in arach n adon ic acid an d th om boxan e an d aden osin e diph osph ate receptor blockade. Fish oil
m ay also poten tially len gth en bleedin g t im es.23,24,25
Garlic (Allium sativum ) h as in creased in popularit y as a supplem en t. Purported ben efits in clude:
low erin g blood pressure, preven tin g in fect ion an d m yocardial in farct ion , an d treating hyperch olesterolem ia. Garlic h as an an t iplatelet a ect th rough ADP receptor blockade, an d reducin g calcium an d
th rom boxan e.26 Th ere is par ticular con cern w ith garlic as it m ay poten tiate th e an t iplatelet or an ticoagulan t a ect of aspirin or w arfarin .27
Gin kgo (Gin kgo biloba)h as also becom e a popular supplem en t foun d in m any form ulat ion s from
capsules to en ergy drin ks. Gin kgo h as been used to t reat a n um ber of ailm en ts in cludin g m em or y
loss, depression , an xiet y, dizziness, claudication , erect ile dysfun ct ion , tin n itus an d h eadach e. Gin kgo
a ects bleedin g via an an t iplatelet e ect an d an tagon ism of platelet-activating factor.28,29 See Gin kgo
biloba un der Spon tan eous subdural h em atom a (p. 901).
Gin sen g (Pan ax gin sen g)h as also been foun d to h ave an t iplatelet activit y th rough th rom boxan e
in h ibition an d platelet-act ivatin g factor.30
Som e auth ors also advocate cautious use of gin ger an d vit am in E w h en plan n in g surger y, but th e
exact an tiplatelet m ech an ism is un clear.25
9
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163
9
164
General and Neurology
Table 9.7 Recom m ended INRs39
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●
●
m echanical prosthetic heart valve
prevention of recurrent MI
INR
2.5–3.5
antiphospholipid antibody syndrom e (p. 1270) 40
≥3
all other indications (DVT prophylaxis and treatm ent, PE, atrial fibrillation, recurrent system ic
em bolism , tissue heart valves)
2–3
Ant icoagulant s
See also platelet fun ction in h ibitors (p. 164).
Warfarin
Drug info : Warfarin (Coum adin®)
9
An oral vitam in K antagonist. To anticoagulate average weight patient, give 10 mg PO q d × 2–4 days,
then ≈ 5 mg q d. Follow coagulation studies, titrate to PT= 1.2–1.5 × control (or INR ≈ 2–3) for most
conditions (e.g. DVT, single TIA). Higher PT ratios of 1.5–2 × control (INR ≈ 3–4) may be needed for
recurrent systemic embolism , m echanical heart valves…(the recommended ranges for the International Normalized Ratio (INR) are shown in Table 9.7).
Starting warfarin: During the first ≈ 3 days of warfarin therapy, patients may actually be hypercoagulable (secondary to reduction of vitamin-K dependent anticoagulation factors protein C and protein S),
putting them at risk of “Coumadin necrosis.” Therefore patients should be “bridged” by starting either
Lovenox (p. 165) which can be self-administered as an outpatient, or heparain (with a therapeutic PTT).
Supplied: scored tabs of 1, 2, 2.5, 5, 7.5 and 10 mg. IV form: 5 m g/vial.
Heparin
Drug info : Heparin
Full anticoagulation in an average weight patient, give 5000 U bolus IV, follow with 1000 U/hr IV
drip. Titrate to therapeutic anticoagulation of APTT= 2–2.5 × control (for DVT, some recommend
1.5–2 × control41 ).
prophylactic AKA low-dose (“mini-dose”) heparin: 5000 IU SQ q 8 or 12 hrs. Routine monitoring of
APTT is usually not done, although occasionally patients may become fully anticoagulated on this regimen.
Side e ect s: (see Anticoagulant considerations in neurosurgery above): hem orrhage, throm bosis42
(heparin activates anti-throm bin III and can cause platelet aggregation) which can result in MIs, DVTs,
PEs, strokes, etc. Heparin induced thrombocytopenia (HIT): transient m ild throm bocytopenia is fairly
comm on in the first few days after initiating heparin therapy, however severe throm bocytopenia
occurs in 1–2% of patients receiving heparin > 4 days (usually has a delayed onset of 6–12 days, and is
due to consumption in heparin-induced throm bosis or to antibodies formed against a heparin-platelet
protein complex). The incidence of HIT in SAH is 5–6% and was similar with enoxaparin.43 Consider
use of fondaparinux in thrombocytopenic patients. Chronic therapy may cause osteoporosis.
Low m olecular weight heparins
See referen ces.44,45
Low m olecular w eigh t h eparin s (LMWH) (average m olecular w eigh t = 3000–8000 daltons) are
derived from un fraction ated h eparin (average MW = 12,000–15,000 dalton s). LMW Hs di er from
un fract ion ated h eparin because th ey h ave a h igh er ratio of an ti-factor Xa to an t i-factor IIa (an tith rom bin ) act ivity w h ich th eoretically sh ould produce an tith rom bic e ect s w ith fewer h em orrh agic
com plicat ion s. Realization of th is ben efit h as been ver y m in or in clin ical t rials. LMW H h ave greater
bioavailabilit y after sub-Q inject ion leadin g to m ore predictable plasm a levels w h ich elim in ates th e
n eed to m on itor biologic act ivity (such as APTT). LMWH h ave a lon ger h alf-life an d th erefore require
Hem at ology
165
few er doses per day. LMW H h ave a low er in ciden ce of th rom bocytopen ia. More e ect ive in DVT prophylaxis th an w arfarin in orth opedic surgery.46
Sp in al ep id u r al h em at om as: Th ere h ave been a n um ber of case reports of spin al epidural h em atom as occurrin g in patien ts on LMW H (prim arily en oxaparin ) w h o also un derw en t spin al/epidural
an esth esia or lum bar pun ct ure, prim arily in elderly w om en un dergoing orth opedic surger y. Som e
h ave h ad sign ifican t n eurologic sequelae, in cludin g perm an en t paralysis.47 Th e risk is fur th er
in creased by th e use of NSAIDs, platelet in h ibitors, or oth er an ticoagulan ts, an d w ith t raum atic or
repeated epidural or spin al pun ct ure.
Available low m olecu lar w eigh t h ep ar in s. Drugs in clude:
● en oxaparin (Loven ox®): see below
● dalteparin (Fragm in ®):
2500 an ti-Xa U SQ q d
● ardeparin (Norm iflo®): h alf-life = 3.3 h rs.
50 an ti-Xa U/kg SQ q 12 h rs
● dan aparoid (Orgaran ®): a h eparin oid. Even h igh er an ti-Xa:an ti-IIa ratio th an LMW Hs. Does n ot
require laboratory m on itorin g. 750 an t i-Xa U SQ BID
● tin zaparin (Logiparin ®, In n oh ep®): n ot available in U.S.
175 an ti-Xa U per kg SQ on ce daily
Drug info : Enoxaparin (Lovenox®)
dosage established following hip replacem ent is 30 m g SQ BID × 7–14 days (alternative: 40 mg SQ q
d). Pharmacokinetics: After SQ injection, peak serum concentration occurs in 3–5 hrs. Half-life: 4.5 hrs.
Direct throm bin inhibitors
Drug info : Dabigat ran (Pradaxa®, Rendix®)
An oral anticoagulant in the class of direct thrombin inhibitors. Administered as the prodrug dabigatran etexilate. Must be stopped 24 hrs prior to surgery.
Reversal of an t icoagu lat ion : Praxbin d (idarucizum ab) IV for em ergen cies. Reverses pradaxa w ith in
4 h rs, lasts 24 h rs.48
Drug info : Bivalirudin (Angiom ax® or Angiox®)
A reversible direct thrombin inhibitor (DTI) that increases the rapidit y of plasm inogen activator-m ediated recanalization. No e ective reversal.
: IV loading dose of 0.5 m g/kg IV, followed by continuous infusion of 1.75 m g/kg/hr. Intraarterial:
inject 15 mg in 10 ml of heparinized saline via a m icrocatheter.
Factor Xa inhibitors
Drug info : Fondaparinux (Arixt ra®)
A synthetic analog of the pentasaccharide binding sequence of heparin. Increases factor Xa inhibition
without a ecting factor IIa (thrombin).49 Unlike heparin, fondaparinux does not bind to other plasma
proteins or platelet factor-4 and does not cause heparin-induced thrombocytopenia (HIT) and can
therefore be used in patients with HIT. May be more e ective than enoxaparin (Lovenox®) for preventing post-op DVTs. Side e ect s: Bleeding is the m ost common side e ect (m ay be increased by
concurrent NSAID use). Contraindicated with severe renal impairment (CrCl < 30 ml/min).50
: 2.5 mg SQ injection q d. Supplied: 2.5 mg single-dose syringes. Pharm acokinet ics: Peak activit y occurs in 2–3 hrs. Half-life: 17-21 hrs. Anticoagulation e ect lasts 3-5 half-lives. Elim ination: in
urine (in renal insu ciency reduce dose by 50% for CrCl 30-50 ml/min). STOP: 2-4 days pre-op (longer
with kidney dysfunction)
9
166
General and Neurology
Coagulopat hies
Correction of coagulopathies or reversal of anticoagulants
Also refer to recom m en ded n orm al values for coagulat ion studies in n eurosurger y (p. 157).
Platelets
See in dication s an d adm in istration guidelin es (p.154).
Fresh frozen plasm a
To reverse w arfarin an ticoagulat ion , use th e follow in g as a start in g poin t an d rech eck PT/PTT
after w ards:
● w h en patien t is “th erapeutically an t icoagulated” start w ith 2–3 un its FFP (approxim ately 15 m l/kg
is usually n eeded)
● for severely prolonged PT/PTT, start w ith 6 un its FFP
Prothrom bin com plex concentrate (PCC)
Warfarin induced anticoagulation m ay be reversed up to 4 or 5 tim es m ore quickly w ith PCC (Kcentra)
(contain s coag factors II, IX, and X) than w ith FFP.51 Patient m ay becom e hyperth rom botic w ith this.
Drug info : Vit am in K (Mephyt on®)
9
To reverse elevated PT from warfarin , give aqueous colloidal solution of vitamin K1 (phytonadione,
Mephyton®). Doses > 10 mg may produce warfarin resistance for up to 1 week. FFP may be adm inistered concurrently for m ore rapid correction (see above). See recommended levels of PT (p. 157).
adult: start with 10–15 mg IM; the e ect takes 6–12 hrs (in absence of liver disease). Repeat
dose if needed. The average total dose needed to reverse therapeutic anticoagulation is 25–35 m g.
IV administration has been associated with severe reactions (possibly anaphylactic), including
hypotension and even fatalities (even with proper precautions to dilute and administer slowly), therefore IV route is reserved only for situations where other routes are not feasible and the serious risk is
justified. IV (when IM route not feasible): 10–20 mg IV at a rate of injection not to exceed 1 mg/min
(e.g. put 10 m g in 50 m l of D5 W and give over 30 m inutes).
Drug info : Prot am ine sulfat e
For heparin: 1 mg protam ine reverses ≈ 100 U heparin (give slowly, not to exceed 50 mg in any 10 m in
period). Therapy should be guided by coagulation studies.
Reversal of low m olecular weight heparins (LMWH): slow IV injection of a 1% solution of protam ine can also be used to reverse LMWHs as follows:
Enoxaparin (Lovenox®): ≈ 60% of Lovenox can be reversed with 1 mg of protamine for every mg of
Lovenox given (maximum dose = 50 mg) within the last 8 hrs, and 0.5 m g of protamine for every mg of
Lovenox given from 8–12 hrs prior. Protamine is probably not needed for Lovenox given > 12 hrs earlier.
Dalteparin (Fragmin®) or ardeparin (Normiflo®): 1 mg of protamine for every 100 anti-Xa IU of
the LMWH (maximum dose = 50 mg) with a second infusion of 0.5 mg protam ine for every 100 antiXa IU of LMWH if the APTT rem ains elevated 2–4 hours after the first dose is com pleted.
Danaparoid and Hirudin: no known reversing agent.
Drug info : Desm opressin (DDAVP®)
Causes an increase in factor III coagulant activit y and von Willebrand factor which helps coagulation
and platelet activit y in hemophilia A and in von Willebrand’s disease Type I (where the factors are
norm al in makeup but low in concentration, but may cause throm bocytopenia in von Willebrand’s
disease Type IIB where factors m ay be abnorm al or missing).
0.3 mcg/kg (use 50 ml of diluent for doses ≤ 3 mcg, use 10 m l for doses > 3 mcg) given over 15–
30 m inutes 30 minutes prior to a surgical procedure.
Hem at ology
167
Elevated pre-op PTT
In a patien t w ith n o h istory of coagulopathy, a sign ifican tly elevated pre-op PTT is com m on ly due to
eith er a factor deficien cy or to lupus an ticoagulan t. Work-up:
1. m ixin g study
2. lupus coagulan t
If th e m ixin g st udy corrects th e elevated PTT, th en th ere is probably a factor deficien cy. Con sult a
h em atologist.
Lu p u s an t icoagu lan t : If th e test for lupus an t icoagulan t is positive, th en th e m ajor risk to th e pat ien t w ith surger y is not bleedin g, rath er it is th rom boem bolism . Man agem en t recom m en dation s:
1. as soon as feasible post-op, start patient on heparin (p.164) or LMW heparin (p.164), e.g. Lovenox
2. at th e sam e tim e start w arfarin , an d m ain tain th erapeutic an t icoagulat ion for 3–4 w eeks (th e risk
of DVT/PE is act ually h igh est in th e first few w eeks post-op)
3. m obilize as soon as possible post-op
4. con sider ven a-cava in terruption filter in patien ts for w h om an ticoagulation is con train dicated
Dissem inated intravascular coagulation (DIC)
Abn orm al in travascular coagulat ion w h ich con sum es clotting factors an d platelets, coupled w ith
abn orm al act ivation of fibrin olytic system . Head t raum a is an in depen den t risk factor for DIC, possibly because th e brain is rich in th rom boplast in w h ich m ay be released in to system ic circulat ion w ith
t raum a.52 Oth er risk factors: sh ock, sepsis.
Presentation
Di use bleedin g, cutan eous petech ia, sh ock.
Labs
1. fibrin ogen degradation products (FDP) > 16 m cg/m l (1–8 = n orm al; 8–16 = borderlin e; 32 = defin itely abn orm al; som e labs require > 40 for diagn osis of DIC) (th e m ost com m on abn orm alit y)
2. fibrin ogen < 100 m cg/dl (som e use 130)
3. PT > 16; PTT > 50
4. platelets < 50,000 (relatively un com m on )
Chronic DIC
PT & PTT m ay be n orm al; platelet & fibrin ogen low, fibrin split products elevated.
Treatm en t
1. rem ove in cit in g st im ulus if possible (treat in fect ion s, debride injured t issue, stop t ran sfusion s if
suspected)
2. vigorous fluid resuscitation
3. an ticoagulan ts, if n ot con train dicated (p. 156)
4. FFP if PT or PTT elevated, or fibrin ogen < 130
5. platelet t ran sfusion if platelet coun t < 100 K
Pseudo-DIC
In creased fibrin split products, n orm al fibrin ogen .
Seen in con dition s such as liver failure.
Throm boem bolism in neurosurgery
Deep-vein throm bosis (DVT)
DVT is of con cern prim arily because of th e poten tial for m aterial (clot, platelet clum ps…) to dislodge
an d form em boli (in cludin g pulm on ar y em boli, (PE)) w h ich m ay cause pulm on ar y in farct ion , sudden
death (from cardiac arrest), or cerebral in farct ion (from a paradoxical em bolus, w h ich m ay occur in
th e presen ce of a paten t foram en ovale, see Cardiogen ic brain em bolism (p. 1304)). Th e reported
m ortalit y from DVT in th e LEs ran ges from 9–50%.53 DVT lim ited to th e calf h as a low th reat (< 1%) of
em bolization , h ow ever, th ese clots later exten d in to th e proxim al deep vein s in 30–50% of cases,53
from w h ere em bolizat ion m ay occur (in 40–50%), or th ey m ay produce postph lebit ic syn drom e.
Neurosurgical patien ts are particularly pron e to developin g DVTs (estim ated risk: 19–50%) due at
least in par t to th e relatively h igh frequen cy of th e follow in g:
1. lon g operating tim es of som e procedures
2. prolonged bed rest pre- an d/or post-op
9
168
General and Neurology
3. alteration s in coagulation status
a) in patien ts w ith brain tum ors (see below ) or h ead injur y 54
● related to th e con dition itself
● due to release of brain th rom boplastin s durin g brain surgery
b) in creased blood viscosit y w ith con com itan t “sludging”
● from dehydration th erapy som etim es used to reduce cerebral edem a
● from volum e loss follow in g SAH (cerebral salt w astin g)
c) use of h igh -dose glucocort icoids
Specific “n eurological” risk factors for DVT an d PE in clude 53 :
1. spinal cord injur y (p. 952)
2. brain tum or: autopsy prevalen ce of DVT = 28%, of PE = 8.4%. In ciden ce using 125I-fibrin ogen 55 :
m en in giom a 72%, m align an t gliom a 60%, m etastasis 20%. Risk m ay be reduced by pre-op use of
aspirin 56
3. subarach noid h em orrh age
4. h ead traum a: especially severe TBI (p. 918)
5. st roke: in ciden ce of PE = 1–19.8%, w ith m or talit y of 25–100%
6. n eurosurgical operat ion : risk is h igh er follow in g cran iotom y for supraten torial tum ors (7% of 492
patien ts) th an p -fossa t um ors (0 out of 141)57
Prophylaxis against DVT
9
Option s in clude:
1. gen eral m easures
a) passive ran ge of m otion
b) am bulate appropriate patien ts as early as possible
2. m ech an ical tech n iques (m in im al risk of com plicat ion s):
a) pn eum at ic com pression boots 58 (PCBs) or sequen t ial com pression devices (SCDs): reduces th e
in ciden ce of DVTs an d probably PEs. Do n ot use if DVTs already presen t. Con tin ue use un t il
patien t able to w alk 3–4 h rs per day
b) TED Stockin gs®: (TEDS) applies graduated pressure, h igh er distally. As e ect ive as PCB. No
evidence th at th e ben efit is additive.53 Care sh ould be taken to avoid a tourn iquet e ect at th e
proxim al en d (n ote: TEDS® is a registered tradem ark. “TED” stan ds for th rom boem bolic
disease)
c) elect rical st im ulat ion of calf m uscles
d) rotating beds
3. an ticoagulat ion ; see also con train dication s an d con sideration s of an ticoagulat ion in n eurosurgery (p. 156)
a) full an t icoagulation is associated w ith perioperative com plication s 59
b) “low -dose” an t icoagulation 60 (low -dose h eparin ): 5000 IU SQ q 8 or 12 h rs, startin g 2 h rs preop or on adm ission to h ospital. Poten tial for h azardous h em orrh age w ith in brain or spin al
can al h as lim ited its use
c) low m olecular w eigh t h eparins an d h eparin oids (p. 164): n ot a h om ogen eous group. E cacy
in n eurosurgical prophylaxis has n ot been determ in ed
d) aspirin : role in DVT prophylaxis is lim ited because ASA in h ibits platelet aggregation , an d platelets play on ly a m in or role in DVT
4. com bin ation of PCBs an d “m in i-dose” h eparin start in g on th e m orn in g of post-op day 1 (w ith n o
evidence of sign ifican t com plication s) 61
Recom m endations
Recom m en ded prophylaxis varies w ith th e risk of developin g DVT, as illustrated in
also details of prophylaxis in cer vical spin al cord injuries (p. 952).
Table 9.8.53 See
Diagnosis of DVT
(For PE, see below ). Th e clin ical diagn osis of DVT is ver y un reliable. A patien t w ith th e “classic sign s”
of a h ot, sw ollen , an d ten der calf, or a positive Hom an s’ sign (calf pain on dorsiflexion of th e an kle)
w ill h ave a DVT on ly 20–50% of th e tim e.53 50–60% of patien ts w ith DVT w ill n ot h ave th ese fin din gs.
Laboratory t est s
● con trast ven ography: th e “gold stan dard”, h ow ever it is invasive an d carr ies risk of iodin e reaction , occasion ally produces ph lebit is, n ot readily repeated
Hem at ology
169
Table 9.8 Risk & prophylaxis of DVT in neurosurgical patientsa
Risk group
Est im ated risk
of calf DVT
Typical neurosurgical patients
Treatment recom m endat ion
low risk
< 10%
age < 40 yrs, m inim al general risk factors,
surgery with < 30 m inutes general anesthesia
no prophylaxis, or
PCB/TEDS
moderate
risk
10–40%
age ≥ 40 yrs, m alignancy, prolonged bed rest,
extensive surgery, varicose veins, obesit y, surgery > 30 minutes duration (except simple
lum bar discectomy), SAH, head injury
PCB/TEDs; or for patients without ICH or
SAH, mini-dose
heparin
high risk
40–80%
history of DVT or PE, paralysisb (para- or
quadriplegia or hemiparesis), brain tum or
(especially meningiom a or m alignant gliom a)
PCB/TEDS + (in patients without ICH or
SAH) mini-dose
heparin
a abbreviations: DVT= deep venous throm bosis, PCB= pneumatic com pression device, TEDS = TED (thromboem -
bolic disease) Stockings®, ICH = intracerebral hem orrhage, SAH = subarachnoid hem orrhage
b see specifics regarding DVT prophylaxis in cervical SCI (p. 952)
Doppler ult rasoun d w ith h igh -resolution real-tim e B-m ode im agin g: 95% sen sitive an d 99%specific for proxim al DVT. Less e ect ive for calf DVT.62 As a result , it is recom m en ded th at patien ts
w ith in itially n egative studies un dergo repeat st udies over th e n ext 7–10 days to R/O proxim al exten sion . Requires m ore skill on th e part of th e tester th an IPG. May be used in im m obilized or
casted LE (un like IPG). Widely accepted as th e n on -invasive test of ch oice for DVT63
● im pedan ce plethysm ography (IPG): looks for reduced electrical im pedan ce produced by blood
flow from th e calf follow in g relaxation of a pn eum at ic tourn iquet. Good in detect in g proxim al
DVT, n ot sen sitive for calf DVT. A positive st udy in dicates DVT th at sh ould be t reated, a n egative
st udy can occur w ith n on -occlusive DVT or w ith good collaterals, an d sh ould be repeated over a 2
w eek period
● 125I-fibrin ogen : radiolabeled fibrin ogen is in corporated in to th e developin g th rom bus. Better for
calf DVT th an proxim al DVT. Expen sive, an d m any false positives. Risk of HIV t ran sm ission h as
resulted in w ith draw al of use
● D-dim er (a specific fibrin degradation product): h igh levels are associated w ith DVT an d PE64
●
Treatm ent of DVT
1. bed rest, w ith elevation of involved leg(s)
2. un less an ticoagulat ion is con train dicated (p.156): start h eparin as outlin ed in An ticoagulation
(p. 156), aim for APTT = 1.5–2 × con trol; or fixed dose of LMW h eparin oids, e.g. tin zaparin (Logiparin ®,65 or in th e U.S. en oxaparin (Loven ox®) (p.165). Simulta neously in itiate w arfarin th erapy.
Heparin can be stopped after ≈ 5 days 66
3. in patien ts w h ere an t icoagulat ion is con train dicated, con sider in ferior ven a cava in terruption or
placem en t of a filter (e.g. Green field filter)
4. in n on -paralyzed patien ts, cautiously begin to am bulate after ≈ 7–10 days
5. w ear an ti-em bolic stockin g on a ected LE in defin itely (lim b is alw ays at risk of recurren t DVT)
Pulm onary em bolism (PE)
See referen ce.67
Prevention of PE
Preven tion of PE is best accom plish ed by preven tion of DVT (p.168).68
Presentation of PE
Post-op PE gen erally occurs 10–14 days follow in g surger y.68 Th e reported in ciden ce 68 ran ges from
0.4–5%. A series (on a ser vice w ith routin e use of elastic stockings an d, in h igh risk pat ien ts, “m in idose” h eparin ) foun d a post-op in ciden ce of ≈ 0.4%, w ith a doublin g of th is n um ber if on ly patien ts
w ith m ajor path ology (brain tum or, h ead t raum a, or cerebrovascular or spin al path ology) w ere con sidered 68 (an oth er series dealing on ly w ith brain tum ors foun d a 4% in ciden ce 57 ).
Clin ical diagn osis is n on specific (di eren tial diagn osis of sym ptom s is large, an d ran ges from atelect asis to MI or cardiac tam pon ade).
9
170
General and Neurology
Com m on fin din gs: sudden dyspn ea (th e m ost frequen t fin ding), tachypn ea, tachycardia, fever,
hypoten sion , 3rd or 4th h eart soun d. Tr ia d (rare): h em opt ysis, pleurit ic ch est pain , dyspn ea. Auscultation : pleurit ic friction rub or rales (rare). Sh ock an d CHF (m im ics MI) in dicates m assive life-th reaten in g PE. Mor talit y reported ran ges from 9–60%,68 w ith a sign ifican t n um ber of deaths w ith in th e
first h our.
Diagnosis of PE
A n egative D-dim er test (see above) reliably excludes PE in patien ts w ith a low clin ical probabilit y of
PE69 or in th ose w ith n on diagn ostic VQ scan .64
Altern at ively, on e can ch eck for DVT ut ilizin g IPG, Doppler, or ven ography (see above). If positive,
th is in dicates a possible source of PE, an d sin ce th e t reatm en t is sim ilar for both , n o furth er search
for PE n eed be m ade an d treatm en t is started. If n egative, furth er test in g m ay be n eeded (e.g.VQ
scan , see below ).
Laboratory t est s
D-dim er: see above.
General diagnost ic test s
Non e are ver y sen sitive or specific.
● EKG: “classic” S1Q3T3 is rare. Usually just n on specific-ST & T ch anges occur. Tachycardia m ay be
th e on ly fin din g
● CXR: n orm al in 25–30%. W h en abn orm al, usually sh ow s in filtrate an d elevated h em idiaph ragm
● ABG: n ot ver y sen sitive. pO2 > 90 on room air vir t ually excludes ma ssive PE
9
Specific radiograph ic evaluation
● Test of ch oice: con t r ast en h an ced ch est CT. Occasion ally ch est CTA m ay be em ployed . Can p rovid e in sigh t in to alt ern ate d iagn oses
● pulm on ar y an giogram : h istorically, th e “gold stan dard.” Invasive, expen sive, an d labor in ten sive.
3–4% risk of sign ifican t com plication s. Not in dicated in m ost cases
● ven tilation -perfusion scan (VQ scan ): CXR is also n eeded. A perfusion defect w ith n o ven tilation
defect in a pat ien t w ith n o previous h istor y of PE st ron gly suggests acute PE. Equivocal st udies
occur w h en an area of m alperfusion correspon ds to an area of reduced ven tilation (on ven tilation
scan ) or in filtrate (on CXR). Probabilities of PE based on VQ scan are sh ow n in Table 9.9.70 A
tech n ically adequate n orm al VQ scan virt ually rules out PE. Pat ien ts w ith low or in term ediate
probabilit y scan s sh ould h ave a test for DVT or quan t itative D-dim er (see above). If test for DVT is
positive, treat; if it is n egative, th e ch oice is to follow serial IPG or Doppler st udies for 2 w eeks, or
(rarely) to do a pulm on ar y an giogram
● th in -section con trast-en h anced ch est CT: m ore accurate in pat ien ts w ith COPD w h o often h ave an
in determ in ate VQ scan
Treatm en t
If diagn osis is seriously en ter tain ed, start hepa r in – un less con train dicated (p. 156) – w ith out
w aitin g for results of diagn ost ic st udies. For an average 70 kg patien t, begin w ith 5000–7500 un it IV
bolus, follow ed by 1000 U/h r drip (less for sm aller pat ien t). Follow PTT an d titrate drip rate for PTT
1.5 to 2 × con trol.
Th e use of h eparin sh ortly after surger y an d in pat ien ts w ith brain t um ors is con troversial, an d
ven a caval in terruption m ay be an altern ate con siderat ion (e.g. Green field filter).
Pat ien ts w ith m assive PEs m ay be h em odyn am ically un stable. Th ey usually require ICU care, often
w ith PA cath eter an d pressors.
Table 9.9 Probabilit y of PE based on VQ scan
Scan result s
Incidence of PE
high probabilit y
90–95%
intermediate probabilit y or indeterminate
30–40%
low probabilit y
10–15%
norm al
0–5%
Hem at ology
171
9.3 Ext ram edullary hem at opoiesis
9.3.1 General inform at ion
In ch ron ic an em ias (especially th alassem ia m ajor, AKA Cooley’s an em ia), low h em atocrit results in
ch ronic over-stim ulation of bon e m arrow to produce RBCs. Th is results in system ic bony abn orm alities, cardiom yopathy (due to h em och rom atosis caused by in creased breakdow n of defect ive RBCs).
Pert in en t to th e CNS, th ere are th ree sites w h ere extram edullar y h em atopoiesis (EMH) can cause
fin din gs:
● skull: produces “h air-on -en d” appearan ce on skull x-ray
● vertebral bodies: m ay result in epidural cord com pression 71 (see below )
● ch oroid plexus
9.3.2 Epidural cord com pression from EMH
Th e exuberan t tissue is ver y radiosen sitive, h ow ever, th e pat ien t m ay be som ew hat depen den t on
th e h em atopoietic capacit y of th e tissue.
9.3.3 Treat m ent
Surgical excision follow ed by radiation th erapy h as been th e recom m en ded treatm en t. Repeated
blood t ran sfusion s m ay h elp reduce EMH an d m ay be useful post-op in stead of RTX except for refractory cases.71
Surger y on th ese patien ts is di cult because of:
1. low platelet count
2. poor con dition of bon e
3. cardiom yopathy: in creased an esth et ic risk
4. an em ia, coupled w ith th e fact th at m ost of th ese patien ts are “iron -toxic” from m ult iple previous
t ran sfusion s
5. total rem oval of th e m ass is n ot alw ays possible
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10 Neurology for Neurosurgeons
10.1 Dem ent ia
Defin it ion . Loss of in tellect ual abilities previously attain ed (m em or y, judgem en t, abstract
th ough t, an d oth er h igh er cortical fun ct ion s) severe en ough to in terfere w ith social an d/or occupat ion al fun ct ion in g.1 Mem or y deficit is th e cardin al feature, h ow ever, th e DSM-IV defin ition requires
im pairm en t in at least on e oth er dom ain (lan guage, perception , visuospatial fun ct ion , calculation ,
judgem en t, abstraction , problem -solving skills). A ect s 3–11% of com m un it y-dw ellin g adults > 65
yrs of age, w ith a greater presen ce am ong in stitut ion alized residen ts.2
Risk factors: advan ced age, fam ily h istor y of dem en tia, an d apolipoprotein E-4 allele.
Delir iu m vs. d em en t ia (cr it ical d ist in ct ion ). Delirium AKA acute con fusion al state. Distin ct from
dem en tia, h ow ever, patien ts w ith dem en tia are at in creased risk of developin g delirium .3,4 A prim ar y
disorder of atten tion th at subsequen tly a ects all oth er aspects of cogn ition .5 Often represents lifeth reaten in g illn ess, e.g. hypoxia, sepsis, urem ic en ceph alopathy, elect rolyte abnorm alit y, drug in toxication , MI. 50%of pat ien ts die w ith in 2 yrs of th is diagn osis.
Un like dem en tia, delirium h as acute on set, m otor sign s (trem or, m yoclonus, asterixis), slurred
speech , altered con sciousn ess (hyperalert /agitated or leth argic, or fluctuation s), h allucin ation s m ay
be florid. EEG sh ow s pron oun ced di use slow in g.
10
Br ain biop sy for d em en t ia. Clin ical criteria are usually su cien t for th e diagn osis of m ost dem en t ias. Biopsy sh ould be reser ved for cases of a ch ron ic progressive cerebral disorder w ith an un usual
clin ical course w h ere all oth er possible diagn ostic m eth ods h ave been exh austed an d h ave failed to
provide adequate diagn ostic certain t y.6 Biopsy m ay disclose CJD, low grade astrocytom a, an d AD
am ong oth ers. Th e h igh in ciden ce of CJD am on g patien ts selected for biopsy un der th ese criteria
n ecessitates appropriate precaution s; see Creutzfeldt-Jakob disease (p. 367).In a report of 50 brain
biopsies perform ed to assess progressive n eurodegen erative disease of un clear etiology,7 th e diagn ostic yield w as on ly 20% (6% w ere on ly suggest ive of a diagn osis, 66% w ere abn orm al but n on specific, 8% w ere n orm al). Th e yield w as h igh est in th ose w ith focal MRI abn orm alit ies. Am on g th e 10
patien ts w ith diagn ostic biopsies, th e biopsy result led to a m ean in gful th erapeutic in terven t ion in
on ly 4.
Recom m en d at ion s. Based on th e above, th e follow in g recom m en dation s are m ade for patien ts
w ith an oth erw ise un explain ed n eurodegen erative disease:
1. th ose w ith a focal abn orm alit y on MRI: stereotactic biopsy
2. th ose w ith out focal abn orm alit y (possibly in cludin g SPECT or PET scan ): brain biopsy sh ould on ly
be perform ed w ith in an investigat ive protocol
Recom m en d at ion s for specim en . Ideally th e biopsy specim en sh ould 8 :
1. be large en ough (usually 1 cm 3 )
2. be taken from an a ected area
3. in clude grey an d w h ite m atter, pia an d dura
4. be h an dled carefully to m in im ize artifact (elect rocauter y sh ould n ot be used on th e specim en
side of th e in cision )
10.2 Headache
10.2.1 General inform at ion
Headach e (H/A) m ay be broadly categorized as follow s:
1. ch ronic recurring h eadach es
a) vascular t ype (m igrain e): see below
b) m uscle con traction (ten sion ) h eadach es
2. h eadache due to path ology
a) system ic path ology
b) in tracran ial path ology: a w ide variety of etiologies in cludin g:
● subarach noid h em orrh age: sudden on set, severe, usually w ith vom it in g, apoplexy, focal deficits possible;see di eren tial diagnosis of paroxysm al H/A (p. 1158)
Neurology for Neurosurgeons
175
in creased in tracran ial pressure from any cause (tum or, com m un icatin g hydroceph alus,
in flam m at ion , pseudot um or cerebri…)
● irritation or in flam m at ion of m en in ges: m en in gitis
● t um or (p.590): w ith or w ith out elevated ICP
c) local path ology of th e eye, n asoph aryn x, or extracran ial tissues (in cludin g gian t cell arteritis
(p.195)
d) follow in g h ead t raum a: postcon cussive syn drom e (p. 923)
e) follow in g cran iotom y: “syn drom e of th e treph in ed ” (p. 1431)
●
A severe new H/A, or a ch ange in th e pattern of a lon gstan din g or recurren t H/A (in cludin g develop in g associated N/V, or an abn orm al n eurologic exam ) w arran ts fur th er invest igation w ith CT or MRI.9
Un ilateral H/A th at n ever ch anges side over a period ≥ 1 year w arran ts an MRI; th is w ould be
atypical in m igrain e an d m ay be a presentation of an occipital AVM (p. 1239).
10.2.2 Migraine
General inform at ion
Migrain e attacks usually occur in in dividuals predisposed to th e con dition , an d m ay be act ivated by
factors such as brigh t ligh t, stress, diet ch anges, t raum a, adm in istration of radiologic con trast m edia
(especially an giography) an d vasodilators.
Classificat ion
Based on th e 1962 ad h oc com m ittee on h eadache (H/A). See also in dex un der Headach e, e.g. for:
crash m igrain e (th un derclap h eadach e) (p. 1158), post-m yelogram h eadach e (p. 1508)...
Com m on m igraine
Episodic H/A w ith N/V an d ph otoph obia, w ith out aura or n eurologic deficit .
Classic m igraine
Com m on m igrain e + aura. May h ave H/A w ith occasion al focal n eurologic deficit(s) th at resolve com pletely in ≤ 24 h rs.
Over h alf of th e tran sien t n eurologic dist urban ces are visual, an d usually con sist of positive ph en om en a (spark ph otopsia, stars, com plex geom etric pattern s, fort ification spectra) w h ich m ay leave
n egative ph en om en a (scotom a, h em ian opia, m on ocular or bin ocular visual loss…) in th eir w ake.
Th e secon d m ost com m on sym ptom s are som atosen sor y involving th e h an d an d low er face. Less frequen tly, deficits m ay con sist of aph asia, h em iparesis, or un ilateral clum sin ess. A slow ma rch-like progression of deficit is ch aracteristic. Th e risk of stroke is probably in creased in pat ien ts w ith
m igrain e.10
Com plicated m igraine
Occasion al attacks of classic m igrain e w ith m in im al or n o associated H/A, an d com plete resolut ion of
n eurologic deficit in ≤ 30 days.
Migraine equivalent
Neurologic sym ptom s (N/V, visual aura, etc.) w ith out H/A (aceph algic m igrain e). Seen m ostly in ch ildren . Usually develops in to t ypical m igrain e w ith age. Aura m ay be sh or ten ed by open in g an d sw allow in g con ten ts of a 10 m g n ifedipin e capsule.11
Hem iplegic m igraine
H/A t ypically precedes h em iplegia w h ich m ay persist even after H/A resolves.
Cluster headache
AKA h istam in ic m igrain e. Actu ally a n eurovascular even t, distin ct from true m igrain e. Recurren t un ilateral attacks of severe pain . Usually oculofron tal or oculotem poral w ith occasion al radiation in to
th e jaw, usually recurrin g on th e sam e side of th e h ead. Ipsilateral auton om ic sym ptom s (conjun ctival inject ion , n asal congest ion , rh in orrh ea, lacrim ation , facial flush ing) are com m on . Part ial Horn er’s
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syn drom e (ptosis an d m iosis) som et im es occurs. Male:fem ale ratio is ≈ 5:1. 25% of patien ts h ave a
person al or fam ily h istor y of m igrain e.
Headach es ch aracterist ically h ave n o prodrom e, last 30–90 m in utes, an d recur on e or m ore t im es
daily usually for 4–12 w eeks, often at a sim ilar tim e of day, follow in g w h ich th ere is typically a
rem ission for an average of 12 m on th s.12
Prophylaxis for cluster H/A is on ly m in im ally e ect ive:
1. β-adren ergic blockers are less e ect ive
2. lith ium : becom ing drug of ch oice (respon se rate 60–80%). 300 m g PO TID an d follow levels
(desired: 0.7–1.2 m Eq/L)
3. occasion ally ergotam in es are used
4. n aproxen (Naprosyn ®)
5. m ethysergide (San sert®) 2–4 m g PO TID is e ect ive in 20–40%of cases, m ust cycle pat ien t o th e
drug to preven t retroperiton eal fibrosis, etc. (also see below )
Treatm en t for cluster H/A (prophylaxis is on ly m in im ally e ect ive):
Treatm en t is di cult because th ere is n o prodrom e an d th e H/A often stop after 1–2 h rs. Treatm en t of acute attacks in cludes:
● 100% O2 by face m ask w ith pat ien t sit tin g for ≤ 15 m in or un til attack aborted
● ergotam in e: see below
● SQ sum atriptan : usually aborts attack w ith in 15 m in utes (see below )
● steroids: see below
● refractor y cases m ay be con sidered for:
○ percutan eous radiofrequen cy sph en opalatin e ganglion blockade 13
○ occipital n er ve stim ulat ion 14
○ hypoth alam ic deep brain stim ulat ion
10
Basilar artery m igraine
Essen tially restricted to adolescen ce. Recurren t episodes lastin g m in utes to h ours of tran sien t n eurologic deficits in dist ribut ion of vertebrobasilar system . Deficits in clude: ver tigo (m ost com m on ), gait
ataxia, visual dist urban ce (scotom ata, bilateral blin dn ess), dysarth ria, follow ed by severe H/A an d
occasion ally n ausea an d vom it in g.15 Fam ily h istor y of m igrain e is present in 86%.
10.3 Parkinsonism
10.3.1 General inform at ion
Parkin son ism m ay be prim ar y or secon dar y to oth er con dition s. All result from a relative loss of dop am in e m ediated in h ibition of th e e ect s of acet ylch olin e in th e basal gan glia.
10.3.2 Idiopat hic paralysis agit ans (IPA)
Clinical
Classical Parkin son’s disease AKA sh aking palsy. A ect s ≈ 1% of Am erican s > age 50 yrs,16 it is frequen tly un derdiagnosed.17 Male:fem ale ratio is 3:2. Not clearly environ m en tally or gen etically
in duced, but m ay be in fluen ced by th ese factors.
Th e classic t riad is sh ow n in Table 10.1. Oth er sign s m ay in clude: postural in stabilit y, m icrograph ia, m ask-like facies. Gait con sists of sm all, sh u in g steps (m arch e á petits pas) or festin atin g gait.
Clinically dist inguishing IPA from secondary parkinsonism (see below )
May be di cult early. IPA gen erally exh ibits gradual on set of bradykin esia w ith t rem or th at is often
asym m etrical, an d in itially respon ds w ell to levodopa. Oth er disorders are suggested w ith rapid progression of sym ptom s, w h en th e in itial respon se to levodopa is equivocal, or w h en th ere is early
m idlin e sym ptom s (ataxia or im pairm en t of gait an d balan ce, sph in cter disturban ce…) or th e
Table 10.1 Classic triad of Parkinson’s disease
●
●
●
trem or (resting, 4–7/second)
rigidit y (cogwheel)
bradykinesia
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presen ce of oth er features such as early dem en tia, sen sor y fin din gs, profoun d orth ostatic hypoten sion , or abn orm alit ies of extraocular m ovem en ts.18,19
Pat hophysiology
Degen erat ion p r im ar ily of p igm en ted (n eu rom elan in -lad en ) d op am in ergic n eu ron s of t h e p ars
com p act a of t h e su bst an t ia n igra, resu lt in g in red u ced levels of d op am in e in th e n eost r iat u m
(cau d at e n u cle u s, p u t am en , globu s p allid u s). Th is d ecreases t h e act ivit y of in h ibitor y n eu ron s
w ith p red om in an t ly D2 class of d op am in e receptors w h ich p roje ct d irect ly to t h e in te rn al segm en t of t h e glob u s p allid u s (GPi), an d also in creases (by loss of in h ibit ion ) act ivit y of n eu ron s
w it h p red om in an t ly D1 rece ptors w h ich p roject in d irect ly t o t h e globu s p allid u s exter n a (GPe)
an d su bt h alam ic n u cleu s.2 0 Th e n et resu lt is in creased act ivit y in GPi w h ich h as in h ibit or y p ro ject ion s to t h e t h alam u s w h ich t h en su p p resses act ivit y in t h e su p p lem en t al m ot or cor tex
am on g ot h er locat ion s.
Histologically: Lew y bodies (eosinophilic intraneuronal hyaline inclusions) are th e hallm ark of IPA.
10.3.3 Secondary parkinsonism
General inform at ion
Th e di eren tial diagn osis of Parkin son’s disease in cludes th e follow in g etiologies of secon dar y parkin son ism or Parkin son -like con dition s (som et im es of th ese are occasion ally referred to as “Parkin son plus” syn drom es or parkin son ian disorders) (see above for dist in guish in g features):
1. olivopon tocerebellar degen eration (OPC)
2. st riato-n igral degen eration (SND): m ore aggressive th an parkin son ism
3. posten ceph alitic parkin son ism : follow ed an epidem ic of en ceph alit is leth argica (von Econ om o
disease) in th e 1920s, vict im s are n o lon ger living. Dist inguish in g features: oculogyric crisis,
trem or involves n ot on ly extrem ities but also trun k an d h ead, asym m et rical, n o Lew y bodies
4. progressive supran uclear palsy (PSNP): im paired vert ical gaze (see below )
5. m ultiple system atrophy (Shy-Drager syn drom e): see below
6. drug in duced: in cludes:
a) prescription drugs (elderly fem ales seem m ore susceptible)
● an tipsych ot ics (AKA n eurolept ics): h aloperidol (Haldol®) w h ich w orks by blockin g postsyn aptic dopam in e receptors
● ph en oth iazin e an t iem et ics: proch lorperazin e (Com pazin e®)
● m etoclopram ide (Reglan ®)
● reserpin e
b) MPTP (1-m et h yl- 4-p h e n yl- 1,2,3,6-tet rah yd ropyr id in e): a com m ercially available ch em ical in term ed iate w h ich is also a by-p rod u ct of t h e syn t h esis of MPPP (a m ep erid in e an alog) th at w as syn th esized an d self-in jected by a grad u ate st u d en t ,21 an d later p rod u ced
by illicit d r ug m an u fact u rers to be sold as “syn t h et ic h eroin ” an d u nw it t in gly in ject ed by
som e IV d rug abu sers in n or t h er n Califor n ia in 1983 22 (t h ere is also a case rep or t of a
ch em ist w h o w orked w it h MPTP w h o d evelop ed p arkin son ism ).23 MPTP w as su bse quen t ly d iscover ed to be a p ot en t n eu rotoxin for d op am in ergic n euron s (w it h con t in u ed
toxic e ect s th at p ersisted for years 2 4 ). As a r u le, t h e resp on se to levod op a is d ram at ic,
bu t sh or t-lived w it h fre quen t sid e e ects. In con t rast to classic IPA, t h e locu s coer u leu s
an d d orsal m otor vagu s n u cleu s w er e essen t ially n orm al, an d t h e sym ptom s d i er
sligh t ly
c) th ere is an as yet un proven assert ion that m ethylen edioxym eth am ph etam in e (MDMA) AKA
“ecstasy” (on th e st reet), m ay h asten the on set of Parkin son ism (a st udy dem on st ratin g a
lin k h ad to be w ith draw n because of a m islabelin g of drugs)
7. toxic: poison in g w ith
a) carbon m on oxide: sym m et ric low den sities in th e globus pallidus on CT
b) m angan ese: m ay be seen in m in ers, w elders, an d pyrotech nics workers. Mangan ese is
excreted by th e liver, people w ith h epatic in su cien cy are m ore susceptible. Im agin g:
sym m etrical h igh sign al abn orm alit ies on T1W I prim arily in th e globus pallidus w ith essen t ially n o fin din gs on T2W I or GRASS (alm ost path ogn om on ic)
8. isch em ic (lacun es in basal gan glia): produces so-called arteriosclerotic parkin son ism AKA vascular parkin son ism : “low er-h alf” parkin son ism (gait dist urban ce predom in ates 17 ). Also causes
pseudobulbar deficits, em otion al labilit y. Trem or is rare
9. postt raum atic: parkin son ian sym ptom s m ay occur in ch ron ic t raum atic en cephalopathy, see
dem en tia pugilistica (p. 924). Th ere are usually oth er features n ot n orm ally present in IPA (e.g.
cerebellar fin din gs)
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10. n orm al pressure hydroceph alus (NPH): urin ar y in con t in en ce (p.404)…
11. n eoplasm in th e region of th e substan tia n igra
12. Riley-Day (fam ilial dysautonom ia)
13. parkin son -dem en t ia com plex of Guam : classic IPA+ am yot roph ic lateral sclerosis (ALS). Path ologically h as features of parkin son ism an d Alzh eim er’s disease but n o Lew y bodies n or sen ile
plaques
14. Hun tin gton’s disease (HD): w h ereas adults t ypically sh ow ch orea, w h en HD m an ifests in a
youn g person it m ay resem ble IPA
15. (spon tan eous) in tracran ial hypoten sion (p. 389) m ay present w ith fin din gs m im icking IPA
Mult iple syst em at rophy (MSA)
AKA Shy-Drager syn drom e. Parkin son ism (in distin guish able from IPA), PLUS idiopath ic or th ostatic
hypoten sion , PLUS oth er sign s of autonom ic n er vous system (ANS) dysfun ct ion (ANS fin dings m ay
precede parkin son ism an d m ay in clude urin ar y sph in cter disturban ce an d hypersen sitivit y to n oradren alin e or t yram in e in fusion s). Degen eration of pregan glion ic lateral h orn n euron s of th oracic spin al cord. Unlike IPA, m ost do n ot respon d to dopa th erapy. NB: classic IPA m ay even tually produce
orth ostatic hypoten sion from in act ivit y or as a result of progressive auton om ic failure.
Progressive supranuclear palsy (PSNP)
10
AKA Steele-Rich ardson -Olszew ski syn drom e.25
Triad:
1. progressive supran uclear oph th alm oplegia (ch iefly vert ical gaze): paresis of volun tar y ver tical
eye m ovem en t, but still m oves to vert ical doll’s eyes m an euver
2. pseudobulbar palsy (m ask-like facies w ith m arked dysarth ria an d dysph agia, hyperact ive jaw
jerk, em ot ion al in con tin en ce usually m ild)
3. axial dyston ia (especially of n eck an d upper trun k)
Associated fin din gs: subcort ical dem en tia (in con stan t), m otor fin dings of pyram idal, extrapyram idal
an d cerebellar system s. Average age of on set: 60 yrs. Males com prise 60%. Respon se to an ti-parkin son drugs is usually ver y sh ort lived. Average sur vival after diagn osis: 5.7 yrs.
Di eren tiatin g from Parkin son’s disease (IPA):
Pat ien ts w ith PSNP h ave a pseudo-parkin son ism . Th ey h ave m ask facies, but do n ot w alk ben t forw ard (th ey w alk erect), an d th ey do n ot h ave a t rem or. Th ey ten d to fall backw ards.
Course
1. early:
a) m any falls: due to dysequilibrium + dow n gaze palsy (can’t see floor)
b) eye fin din gs m ay be n orm al in itially, subsequen tly m ay develop di cult y lookin g dow n
(especially to com m an d, less to follow in g), calorics h ave n orm al ton ic com pon en t but absen t
nystagm us (cort ical com pon en t)
c) slurred speech
d) person alit y ch anges
e) di cult y eatin g: due to pseudobulbar palsy + in abilit y to look dow n at food on plate
2. late:
a) eyes fixed cen trally (n o respon se to oculoceph alics or oculovestibulars): ocular im m otility is
due to fron tal lobe lesions
b) n eck st i en s in exten sion (retrocollis)
Treat m ent for Parkinson’s disease
Medical t reatm en t for Parkin son’s disease is beyon d th e scope of th is book.
Surgical treatm ent
Before th e in troduct ion of L-dopa in th e late 1960’s, stereotactic th alam otom y w as w idely used for
Parkin son’s disease. Th e locat ion ultim ately targeted for lesionin g w as th e ven trolateral n ucleus. Th e
procedure w orked better for relieving th e trem or th an for th e bradykin esia, h ow ever it w as th e latter
sym ptom th at w as m ost disablin g. Th is procedure can n ot be don e bilaterally w ith out sign ifican t risk
to speech fun ct ion . Th e procedure fell out of favor w h en m ore e ect ive drugs becam e available.26
See Surgical t reatm en t of Parkin son’s disease (p.1524) for fur th er in form at ion .
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10.4 Mult iple sclerosis
Key concept s
an idiopathic dem yelinating disease of the CNS producing exacerbating and rem itting sym ptom s
disseminated in space and time
● classic clinical findings: optic neuritis, paresthesias, INO and bladder symptoms
● diagnostic criteria (McDonald criteria) use clinical and/or lab results (MRI, CSF…) to stratify patients
as: MS, probable MS, or not MS
● MRI: m ultiple usually enhancing lesions involving optic nerves & white matter of brain (especially
periventricular white mat ter), cerebellum and spinal cord
●
10.4.1 General inform at ion
An id iop at h ic d em yelin at in g d isease (t h u s a ect in g on ly w h ite m at ter) of t h e cerebru m , opt ic
n er ves, an d sp in al cord (esp ecially t h e cor t icosp in al t ract s an d t h e p osterior colu m n s). Does not
a ect p er ip h eral m yelin . Pat h ologically p rod u ces m u lt ip le p laques of var iou s age in d i u se locat ion s in th e CNS, esp ecially in t h e p eriven t ricu lar w h ite m at ter. Lesion s in it ially evoke an in flam m ator y resp on se w it h m on ocytes an d lym p h ocyt ic p erivascu lar cu n g, bu t w it h age set t le
d ow n to glial scars.
10.4.2 Epidem iology
Usual age of on set: 10–59 years, w ith th e greatest peak betw een ages 20–40 years. Th e fem ale:m ale
in ciden ce is approxim ately 2:1.27
Prevalen ce varies w ith latitude, an d is < 1 per 100,000 n ear th e equator, an d is ≈ 30–80 per
100,000 in th e n orth ern U.S. an d Can ada.
10.4.3 Classificat ion
Typically causes exacerbation s an d rem ission s in various location s in th e CNS (dissemina tion in spa ce
a nd t ime). Com m on sym ptom s: visual dist urban ces (diplopia, blurring, field cuts or scotom a), spastic
paraparesis, an d bladder disturban ces. Nom en clature for th e tim e course of MS is sh ow n in
Table 10.2.28 Relapsin g-rem it t ing MS is th e m ost com m on pattern (≥ 70%) at on set, an d h as th e
best respon se to th erapy, but > 50% of cases even tu ally becom e secon dar y progressive MS. On ly 10%
h ave prim ar y progressive MS, an d th ese patien ts ten d to be older at on set (40–60 years) an d frequen tly develop progressive m yelopathy.29 Progressive relapsin g MS is ver y un com m on . Deficits
presen t > 6 m on th s usually persist.
Table 10.2 Clinical categories of MS
Cat egory
Definit ion
relapsing-remitting
episodes of acute worsening with recovery and a stable course bet ween
relapses
secondary progressive
gradual neurologic deterioration ± superim posed acute relapses in a patient
who previously had relapsing-rem it ting MS
primary progressive
gradual, nearly continuous neurologic deterioration from the onset of
symptoms
progressive relapsing
gradual neurologic deterioration from the onset of symptom s, but with
subsequent superim posed relapses
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General and Neurology
10.4.4 Clinical signs and sym pt om s
Visual dist urbances
Dist urban ces of visual acuit y m ay be caused by opt ic or retrobulbar n eurit is w h ich is th e presen ting
sym ptom of MS in 15% of cases, an d w h ich occurs at som e tim e in 50% of MS patien ts. Th e percen tage of patien ts w ith an attack of optic n euritis an d n o prior attack th at w ill go on to develop MS
ran ges from 17–87% depen din g on th e series.30 Sym ptom s: acute visual loss in on e or both eyes w ith
m ild pain (often on eye m ovem en t).
Dip lop ia m ay be d u e t o in ter n u clear op h t h alm op legia (INO) (p. 565) from a p laqu e in t h e MLF.
INO is an im p or t an t sign becau se it rarely occu rs in ot h er con d it ion s besid es MS or brain stem
st roke.
Mot or findings
Ext rem it y w eakn ess (m on o, para, or quadriparesis) an d gait ataxia are am on g th e m ost com m on
sym ptom s of MS. Spasticit y of th e LEs is often due to pyram idal tract involvem en t. Scan n in g speech
results from cerebellar lesion s.
Sensory findings
Posterior colum n involvem en t often causes loss of propriocept ion . Paresth esias of extrem ities, t run k,
or face occur. Lh erm it te’s sign (elect ric sh ock-like pain radiatin g dow n th e spin e on n eck flexion ) is
com m on , but is n ot path ogn om on ic. Trigem in al n euralgia occurs in ≈ 2%, an d is m ore often bilateral
an d occurs at a youn ger age th an th e population in general.31
10
Ment al dist urbances
Euph oria (la belle in di eren ce) an d depression occur in ≈ 50%of pat ien ts.
Reflex changes
Hyperreflexia an d Babin ski sign s are com m on . Abdomina l cuta neous reflexes disappear in 70–80%.
GU sym pt om s
Urin ar y frequen cy, urgen cy, an d in con tin en ce are com m on . Im poten ce in m ales an d reduced libido
in eith er sex is often seen .
10.4.5 Di erent ial diagnosis
Th e plethora of possible sign s an d sym ptom s in MS causes th e di eren tial diagn osis to exten d to
alm ost all con dition s causin g focal or di use dysfun ct ion of th e CNS. Con dit ion s th at m ay closely
m im ic MS clin ically an d on diagn ostic test in g in clude:
1. acute dissem in ated en ceph alom yelit is (ADEM) (p. 182): gen erally m on oph asic. May also h ave
CSF- OCB (p. 182). Corpus callosum involvem en t is un com m on
2. CNS lym ph om a (p. 710)
3. oth er closely related dem yelin atin g diseases: e.g. Devic syn drom e (p. 1409)
4. vasculit is
5. en ceph alit is: pat ien ts are usually ver y ill
6. ch ronic w h ite m atter ch anges: seen in older patien ts
10.4.6 Diagnost ic crit eria
No sin gle clin ical feat u re or d iagn ost ic test is ad equ ate for t h e accu rate d iagn osis of MS. Th er efore, clin ical in for m at ion is in tegrat ed w ith p araclin ical st u d ies. Diagn osin g MS after a sin gle,
acu te rem it t in g clin ically isolated syn d rom e (CIS) is ver y r isky. 50–70% of p at ien t s w it h a CIS
suggest ive of MS w ill h ave m u lt ifocal MRI abn or m alit ies ch aracter ist ic of MS. Th e p rese n ce of
t h ese MRI abn or m alit ies in creases t h e r isk of d evelop in g MS in 1–3 years (w ith greater p rogn ost ic sign ifican ce t h an CSF- OCB). Th e m ore MRI lesion s, t h e h igh er th e r isk.32 Criteria for t h e d iagn osis of MS3 3 follow s.
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Definit ions
See referen ces.33,34
Th e follow in g defin ition s are used in th e classification system th at follow s:
1. attack (exacerbation , relapse): n eurologic dist urban ce lastin g > 24 h rs 35 t ypical of MS w h en clin icopath ological st udies determ in e th at th e cause is dem yelin atin g or in flam m ator y lesion s
2. rem ission : ≥ 30 days sh ould separate th e on set of th e first attack from the on set of a secon d
3. h istorical in form at ion : reportin g of sym ptom s by th e patien t (con firm ation by obser ver desirable), adequate to locate a lesion of MS, an d h as n o oth er explan ation (i.e. m an ifestat ion s m ust
n ot be att ributable to an oth er con dition )
4. clin ical evidence (signs): n euro dysfun ct ion recorded by com peten t exam in er
5. paraclin ical eviden ce: tests or procedures dem on stratin g CNS lesion w hich h as n ot produced
sign s; e.g. Uh th o ph en om en on or sign (w orsen ing of sym ptom s w ith h ot bath or sh ow er), BAER,
im agin g procedures (CT, MRI), expert urological assessm en t
6. t ypical of MS: sign s & sym ptom s (S/S) kn ow n to occur frequen tly in MS. Th us excludes gray m atter lesion s, periph eral n er vous system lesion s, an d n on -specific com plain ts such as H/A, depression , convulsive seizures, etc.
7. separate lesion s: S/S can n ot be explain ed on basis of sin gle lesion (optic n eurit is of both eyes
sim ultan eously or w ith in 15 days represen ts single lesion )
8. laboratory support: in th is st udy, th e on ly con siderat ion s w ere CSF oligoclon al ban ds (CSF-OCB)
(see below ) (OCB m ust n ot be presen t in serum ) or in creased CSF IgG product ion (CSF-IgG) (serum IgG m ust be n orm al). Th is assum es th at syph ilis, SSPE, sarcoidosis, etc. h ave been ruled out
Diagnosis of MS
Th e 2010“McDon ald MS Diagn ostic criteria”36 are sh ow n in
Table 10.3.
MRI
MRI is th e preferred im agin g st udy in evaluating MS39 an d can dem on strate dissem in at ion of lesion s
in t im e an d space. Recom m en ded 33 brain MRI criteria for diagn osin g MS are sh ow n in Table 10.3.40,
41 Lesion s are n or m ally > 3 m m d iam eter.33 MRI sh ow s m u lt ip le w h ite m at ter abn orm alit ies in
80% of p at ien t s w it h MS (com p ar ed to 29% for CT).42,43 Lesion s are h igh sign al on T2, an d acu t e
lesion s te n d to en h an ce w it h gad olin iu m m ore t h an old lesion s d o. Per iven t r icu lar lesion s m ay
blen d in w ith t h e sign al from CSF in t h e ven t r icles on T2, t h ese lesion s are sh ow n to bet ter
advan tage on FLAIR (flu id at ten u at ion ) MRI (p. 229). These lesion s are ovoid an d are or ien ted
p er p en d icu lar to t h e ep en dym al su r face an d are som et im es called Daw son ’s fin gers (after n eu rop at h ologist Jam es Daw son ).
Spin al cord lesion s n orm ally sh ow lit tle or n o sw ellin g, sh ould be ≥ 3 m m but < 2 ver tebral segm en ts, occupy on ly a portion of th e cross-sect ion of th e cord, an d m ust be hyperin ten se on T2.44
Specificit y of MRI is ≈ 94%,45 h ow ever, en ceph alit is as w ell as UBOs seen in aging m ay m im ic MS
lesion s. DW I sh ould be n orm al, how ever plaques can som etim es exh ibit “sh in e th rough” (p. 232) so
th e ADC m ap m ust be ch ecked to rule-out in farct.
Focal tum efactive dem yelin atin g lesion s (TDL) m ay occur in isolation or, m ore com m on ly, in
patien ts w ith establish ed MS (con cen tr ic sclerosis of Balo). TDL m ay represen t an in term ediate position betw een MS an d ADEM (p.182).46 TDLs ten d to be sym m etric. TDLs m ay en h an ce, an d sh ow
perilesion al edem a (but less th an MS) and th us be m istaken for n eoplasm s. Biopsy results m ay be
con fusin g. MRS m ay n ot be able to di eren tiate from n eoplasm .47
CSF
CSF an alysis can support th e diagn osis in som e cases, but can n ot docum en t dissem in ation of lesion s
in t im e or space. Th e CSF in MS is clear an d colorless. Th e OP is n orm al. Total CSF protein is < 55 m g/
dl in ≈ 75% of patien ts, an d < 108 m g/dl in 99.7% (values n ear 100 sh ould prom pt a search for an
altern ative diagn osis). Th e W BC coun t is ≤ 5 cells/m cl in 70% of patien ts, an d on ly 1% h ave a coun t >
20 cells/m cl (h igh values m ay be seen in th e acute m yelit is).
In ≈ 90% of patien ts w ith MS, CSF-IgG is in creased relative to oth er CSF protein s, an d a ch aracterist ic pattern occurs. Agarose gel elect roph oresis sh ow s a few IgG ban ds in th e gam m a region (oligoclonal ban ds) th at are n ot presen t in th e serum (h igh er resolution isoelect ric focusin g can
dem on strate 10–15 ban ds). CSF-OCB are n ot specific for MS, an d can occur in CNS in fect ion s an d less
com m on ly w ith strokes or tum ors. Th e predictive value of th e absen ce of IgG in a patien t w ith suspected MS h as n ot been satisfactorily elucidated.
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Table 10.3 2010 McDonald MS Diagnostic Criteria36
The diagnosis of MS requires elim ination of m ore likely diagnoses and dem onstration of lesions dissem inated
in space (DIS) and t im e (DIT)
Clinical (at t acks)
Lesions
Additional crit eria to m ake t he diagnosis
≥2
Objective clinical evidence of ≥ 2 lesions
or objective clinical evidence of 1 lesion
with reasonable historical evidence of a
prior attack
None. If additional tests are done,
results m ust still be consistent with MS
≥2
Objective clinical evidence of 1 lesion
DIS; or wait for further clinical attack
im plicating a different CNS location
1
Objective clinical evidence of ≥ 2 lesions
DIT; or wait for a second clinical attack
1
Objective clinical evidence of 1 lesion
DIS or wait for further clinical attack
implicating a different CNS location and
DIT; or wait for a second clinical at tack
0 (progression from onset)
10
One year of disease progression (retrospective or prospective) and at least 2
of:
● DIS in the brain based on ≥ 1 T2 MRI
lesion in periventricular, juxtacortical
or infratentorial regions
● DIS in the spinal cord based on ≥ 2 T2
MRI lesions
● or positive CSF
Paraclinical evidence in diagnosis of MS
Evidence for DIS37
≥ 1 T2 MRI lesion in at least 2 out of 4 areas of the CNS: periventricular,
juxtacortical, infratentorial or spinal cord
● Gadolinium enhancement of lesions is not required
● If the patient has a brainstem or spinal cord syndrome, the sym ptom atic lesions
are excluded and do not contribute to lesion count
Evidence for DIT38
●
●
Evidence for positive CSF
New T2 and/or gadolinium -enhancing MRI lesion(s) on follow-up MRI, with
reference to a baseline study, irrespective of the tim ing of the baseline MRI
or
Simultaneous presence of asym ptomatic gadolinium-enhancing and nonenhancing lesions at any tim e
Oligoclonal bands in CSF (and not serum ) or elevated IgG index
Recom m en ded criteria h ave been publish ed,48 m ost of w h ich pertain to specifics of laborator y
an alysis, pert in en t clin ical excerpts are sh ow n in Table 10.4.
10.5 Acut e dissem inat ed encephalom yelit is
AKA ADEM. Acu te d em yelin at in g con d it ion , h as been associate d w it h relat ively recen t h ist or y of
vaccin at ion . Like MS, m ay also d em on st rate oligoclon al ban d s in CSF. ADEM is gen erally m on o p h asic, an d lesion s occu r w it h in a cou p le of w eeks. Th e re is u su allly a good resp on se to h igh d ose IV cor t icosteroid s.
10.6 Mot or neuron diseases
10.6.1 General inform at ion
Degen erative diseases of m otor n euron s. See also com parison of upper m otor n euron (UMN) w ith
low er m otor n euron (LMN) (p. 504) an d th e paralysis th ey produce. Five subt ypes of w h ich ALS is th e
m ost com m on (see below ).
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Table 10.4 CSF criteria for MS
1.
qualitative assessment of IgG is the most informative analysis and is best perform ed using IEF with some
form of imm unodetection (blotting or fixation)
2. analysis should be perform ed on unconcentrated CSF and m ust be compared to sim ultaneously run serum
sample in the sam e assay
3. runs should use the sam e amount of IgG from serum and CSF
4. each run should contain positive and negative controls
5. quantitative analysis should be m ade in term s of one of the 5 recognized staining patterns for OCB
6. an individual experienced in the techniques should report the result s
7. all other tests perform ed on the CSF (including WBC, protein & glucose, lactate) should be taken into
consideration
8. evaluation using light chains for im m unodetection may be helpful in certain cases to resolve equivocal
oligoclonal IgG pat terns
9. if clinical suspicion is high but CSF results are equivocal, negative or show only a single band, consider
repeating the LP
10. to m easure IgG levels, nonlinear form ulas that consider integrit y of the blood-CSF barrier should be used (e.
g. the ratio of CSF to serum albumin (AKA Qalb) is a m easure of leakiness)
11. labs analyzing CSF should have internal as well as external qualit y assessm ent controls
12. quantitative IgG is a complementary test, but is not a substitute for qualitative IgG testing which has the
highest sensitivit y and specificit y
Th ree pattern s of involvem en t:
1. m ixed UMN & LMN degen eration : am yotroph ic lateral sclerosis (ALS) (see below ). Th e m ost com m on of th e m otor n euron diseases
2. UMN degen eration : prim ar y lateral sclerosis. Rare, on set after age 50. No LMN sign s. Slow er progression th an ALS (yrs to decades). Pseudobulbar palsy is com m on .49 Usually does n ot sh orten
lon gevity. May present w ith falling due to balan ce problem s or low back an d n eck pain due to
axial m uscle w eakn ess
3. LMN degen eration : progressive m uscular atrophy (PMA) an d spin al m uscular atrophy (SMA)
10.6.2 Am yot rophic lat eral sclerosis
Key concept s
degeneration of anterior horn cells and corticospinal tracts in the cervical spine and medulla (bulb)
of unknown etiology
● a m ixed upper and lower motor neuron disease (UMN → mild spasticit y in LEs; LMN → atrophy and
fasciculations in UEs)
● clinically: progressive muscle wasting, weakness, and fasciculations
● no cognitive, sensory, nor autonomic dysfunction
●
In t h e U.S. am yot rop h ic lateral sclerosis (ALS) is AKA Lou Geh rig’s d isease n am ed after th e New
York Yan kee first basem an w h o an n ou n ced t h at h e h ad t h e d isease in 1939. AKA m otor n eu ron
d isease (sin gu lar).
Epidem iology
See referen ce.30
Prevalen ce: 4–6/100,000. In ciden ce: 0.8–1.2/100,000.
Fam ilial in 8–10% of cases. Fam ilial cases usually follow autosom al dom in an t in h eritan ce, but
occasion ally dem on strate a recessive pattern .
On set usually after 40 years of age.
Pat hology
Etiology is n ot kn ow n w ith certain t y. Histology: degen eration of an terior h orn alph a-m oton euron s
(in th e spinal cord a nd in brain stem m otor n uclei) (LMNs) an d cort icospin al t ract s (UMNs). Produces
m ixed UMN & LMN fin din gs, w ith a great deal of variabilit y depen din g on w h ich predom in ates at
any given tim e.
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Clinical
Ch aracterized by progressive m uscle w astin g, w eakn ess, an d fasciculation s.
Involvem en t is of volun tar y m uscles, sparin g th e volun tar y eye m uscles an d urin ar y sph in cter.
Classically, presen ts in itially w ith w eakn ess an d atrophy of th e h an ds (low er m otor n euron ) w ith
spast icit y an d hyperreflexia of th e low er extrem ities (upper m otor n euron ). How ever, LEs m ay be
hyporeflexic if th e low er m otor n euron deficits predom in ate.
Dysarth ria an d dysph agia are caused by a com bin ation of upper an d low er m otor n euron path ology. Tongue atrophy an d fasciculat ion s m ay also occur.
Although cognitive deficits are generally considered to be absent in ALS, in actuality 1–2% of cases are
associated w ith dem entia, and cognitive changes m ay occasionally predate the usual features of ALS.50
Di erent ial diagnosis
At tim es, it m ay be ver y di cult to distin guish ALS from cer vical spon dylotic m yelopathy; see discussion of di eren tiating features (p.1086).
Diagnostic st udies
EMG
Not absolutely n ecessary to m ake diagn osis in m ost cases. Fibrillation s an d positive sh arp w aves are
foun d in advan ced cases (m ay be absen t early, especially if upper m otor n euron path ology predom in ates). LMN fin din gs in th e LE in th e absen ce of lum bar spin e disease, or fibrillation poten tials in
th e tongue are suggestive of ALS.
LP (CSF)
May h ave sligh tly elevated protein .
10
Treat m ent
Much of care is directed tow ards m in im izing disability:
1. risk of aspiration m ay be reduced w ith
a) t rach eostom y
b) gastrostom y tube to allow con tin ued feeding
c) vocal cord injection w ith Teflon
2. n on invasive ven tilation : e.g. BiPAP spast icit y th at occurs w h en upper m otor n euron deficits predom in ate m ay be treated (usually w ith sh ort-lived respon se) w ith :
a) baclofen (p. 1530): also m ay relieve th e com m on ly occurrin g cram ps
b) diazepam
3. riluzole (Rilutek®): in h ibits presyn aptic release of glutam ate. Doses of 50-200 m g/d in creases t rach eostom y-free sur vival at 9 & 12 m on th s, but th e im provem en t is m ore m odest or m ay be n on existen t by ≈ 18 m on th s 51,52
Prognosis
Most patien ts die w ith in 5 years of on set (m edian sur vival: 3–4 yrs). Th ose w ith prom in en t oroph aryn geal sym ptom s m ay h ave a sh orter life-span usually due to com plication s of aspiration .
10.7 Guillain -Barré syndrom e
10.7.1 General
Key concept s
acute onset of peripheral neuropathy with progressive muscle weakness (more severe proximally)
with areflexia, reaches maximum over 3 days to 3 weeks
● cranial neuropathy: also common, m ay include facial diplegia, ophthalmoplegia
● little or no sensory involvem ent (paresthesias are not uncomm on)
● onset often 3 days-5 weeks following viral URI, immunization, Campylobacter jejuni enteritis, or surgery
● pathology: focal segmental demyelination with endoneurial m onocytic infiltrate
● elevated CSF protein without pleocytosis (albuminocytologic dissociation)
●
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Guillain -Barré syn drom e (GBS) AKA acute polyradiculon eurit is, am ong oth ers, is actually a collect ion
of syn drom es h avin g in flam m ator y polyradiculon europathy in com m on . Its m ost frequen t form is
acute in flam m atory dem yelin atin g polyradiculon europathy (AIDP). First described as an ascendin g
paralysis, m ost form s are ch aracterized by symmetr ic w eakn ess an d areflexia. Mild cases m ay
presen t on ly w ith ataxia, w h ereas fulm in an t cases m ay ascen d to com plete tet raplegia w ith paralysis
of respirator y m uscles an d cran ial n er ves. Th ere are also a n um ber of varian ts (p. 186).
GBS is th e m ost com m on acquired dem yelin atin g n europathy. In ciden ce is ≈ 1–3/100,000. Th e
lifetim e risk for any on e in dividual get ting GBS is ≈ 1/1,000.
GBS is triggered by both hum oral and cell m ediated autoim m une response to an im m une sensitizing event. Frequent (but not essen tial) an teceden ts: viral infection, surgery, im m unization, mycoplasm a infection, enteral infection w ith Cam pylobacter jejuni (≈ 4 days of intense diarrhea). Higher
frequency in th e follow ing conditions than in general population: Hodgkin’s disease, lymphom a, lupus.
Most cases involve an tibodies to gan gliosides an d glycolipids in periph eral m yelin (axon an tibodies occur in som e form s). For un kn ow n reason s serum creatin e kin ase can be m ildly elevated, an d
m ay correlate w ith m uscle t ype pain .53
10.7.2 Diagnost ic crit eria
See referen ce.54
features required for diagn osis:
● progressive m otor w eakn ess of m ore th an 1 lim b (from m in im al w eakn ess ± ataxia to paralysis,
m ay in clude bulbar or facial or EOM palsy). Un like m ost n europath ies, proxim al m uscles are
a ected m ore th an distal
● areflexia (usually un iversal, but distal areflexia w ith defin ite hyporeflexia of biceps an d kn ee jerks
su ces if oth er features con sisten t)
features st ron gly support ive of diagn osis:
clin ical features (in order of im portan ce)
○ progression : m otor w eakn ess peaks at 2 w ks in 50%, by 3 w ks in 80%, an d by 4 w ks in > 90%
○ relative sym m etr y
○ m ild sen sor y sym ptom s/sign s (e.g. m ild paresth esias in h an ds or feet)
○ cra nia l ner ve involvem en t: fa cia l wea kness in 50%, usually bila tera l. GBS presen ts in itially in
EOMs or oth er Cr. N. in < 5% of cases. Oroph ar yn geal m uscles m ay be a ected
○ recover y usually by 2–4 w ks after progression stops, m ay be delayed by m on th s (m ost patien ts
recover fun ction ally)
○ auton om ic dysfun ct ion (m ay fluct uate): tachycardia an d oth er arrhyth m ias, postural hypoten sion , HTN, vasom otor sym ptom s
○ afebrile at on set of n euritic sym ptom s
○ varian ts (n ot ran ked):
– fever at on set of n eurit ic sym ptom s
– severe sen sor y loss w ith pain
– progression > 4 w ks
– cessation of progression w ith out recover y
– sph in cter dysfun ct ion (usually spared): e.g. bladder paralysis
– CNS involvem en t (con troversial): e.g. ataxia, dysarth ria, Babin ski sign s
● CSF: album in ocytologic dissociation (↑ protein w ith out pleocytosis)
○ protein : elevated after 1 w k of sym ptom s, > 55 m g/dl
○ cells: 10 or fewer m on on uclear leukocytes/m l
○ varian ts
– n o CSF protein rise 1–10 w ks after on set (rare)
– 11–50 m on ocytes/m l
– elect rodiagn ostics: 80%h ave NCV slow in g or block at som e t im e (m ay take several w eeks in
som e). NCV usually < 60%of n orm al, but n ot in all n er ves
●
features casting doubt on diagn osis:
m arked, persisten t , asym m etr y of w eakn ess
● persisten t bow el or bladder dysfun ct ion
● > 50 m on ocytes/m l CSF
● PMNs in CSF
● sh arp sen sor y level
●
features of con dition s in th e di eren tial diagn osis (see below )
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General and Neurology
10.7.3 Guillain-Barré variant s
General inform at ion
A n um ber of varian ts h ave been described (som e m ay sim ply be in com plete form s of typical Guillain -Berré). Auton om ic dysfun ct ion m ay occur in som e.
Miller-Fisher variant of GBS
Ataxia, areflexia an d oph th alm oplegia. May also h ave ptosis. 5% of cases of GBS. Serum m arker: an tiGQ1b an t ibodies.
Acut e m ot or axonal neuropat hy (AMAN)
Th is varian t an d AIDP are th e m ost com m on to follow Cam pylobacter jejun i en teritis.
Pharyngeal-cervical-brachial variant
Facial, oroph ar yn geal, cer vical, an d UE w eakn ess, sparin g th e LEs.
Pure sensory variant
Sen sor y loss accom pan ied by areflexia.
At ypical GBS
May be accom pan ied by rh abdom yolysis.55
10
10.7.4 Di erent ial diagnosis
Also see con dition s in th e di eren tial diagnosis un der Myelopathy (p. 1407)
1. Guillain -Barré syn drom e (in cludin g on e of its varian ts)
2. crit ical illn ess polyn europathy (p. 542): EMG: ↓ CMAP & SNAP
3. curren t h exacarbon abuse: volatile solven ts (n -h exan e, m eth yl n -but yl keton e), glue sn i n g
4. acute in term itten t porphyria (AIP): a disorder of porphyrin m etabolism . CSF protein is n ot elevated in AIP. Recurren t pain ful abdom in al crises are com m on . Ch eck urin e delta-am in olevulin ic
acid or porph obilin ogen
5. recen t diph th erit ic in fect ion : diph th erit ic polyn europathy h as a lon ger laten cy an d a slow er crescen do of sym ptom s
6. lead n europathy: UE w eakn ess w ith w rist drop. May be asym m etrical
7. poliom yelitis: usually a symmetr ic, h as m en ingeal irritation
8. hypoph osph atem ia (m ay occur in ch ron ic IV hyperalim en tat ion )
9. botulism : di cult to distin guish clin ically from GBS. Norm al NCV an d a facilitating respon se to
repetitive n er ve stim ulat ion on elect rodiagn ostics
10. toxic n europathy (e.g. from n it rofuran toin , dapson e, th allium or arsen ic)
11. t ick paralysis: m ay cause an ascen din g m otor n europathy w ith out sen sor y im pairm en t. Careful
exam in at ion of th e scalp for t ick(s)
12. ch ronic im m un e dem yelin atin g polyradiculon europathy (CIDP) AKA ch ron ic relapsin g GBS,
ch ronic relapsin g polyn euritis.56 ICD9: 357.81 ch ron ic in flam m ator y dem yelin atin g polyn eurit is. Sim ilar to GBS, but lon g t im e course (sym ptom s m ust be presen t > 2 m os). CIDP produces
progressive, sym m etrical, proxim al & distal w eakn ess, depression of m uscle stretch reflexes,
an d variable sen sor y loss. Cran ial n er ves are usually spared (facial m uscles m ay be involved).
Balan ce di culties are com m on . Need for respirator y support is rare. Peak in ciden ce: age 40–60
yrs. Elect rodiagn ost ics an d n er ve biopsy fin din gs are in dicat ive of dem yelin ation . CSF fin dings
are sim ilar to GBS (see above). Most respon d to im m un osuppressive th erapy (especially predn isolon e & plasm aph eresis) but relapses are com m on . Refractor y cases m ay be treated w ith IV
gam m a-globulin , cyclosporin -A,57 total body lym ph oid irradiation or in terferon -α 58
13. crit ical illn ess m yopathy: ICD9: 359.81 ch ron ic illn ess m yopathy. Muscles n ot excitable w ith
direct st im ulation . EMG: low or n orm al CMAP w ith n orm al SNAP. Muscle biopsy: abn orm alit ies
m ay ran ge from Type II fiber atrophy to n ecrosis (severe n ecrosis m ay n ot recover)
14. m otor n euron disease (p. 182): AKA ALS. Hyperreflexia in LEs
15. m yasth en ia gravis: w eakn ess w orsen s tow ards th e en d of th e day an d w ith repeat e orts. Posit ive assay for circulat in g an ti-acet ylch olin e receptor an tibodies
16. spinal cord injur y
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10.7.5 Im aging
No characteristic finding, however, di use enhancem ent of cauda equina and nerve roots occurs in up to
95% of cases.59 Thought to be due to disruption of the blood-nerve barrier from inflam m ation. Conspicuous nerve root enhancem ent correlates w ith pain, GBS disability grade, and duration of recovery.59
10.7.6 Treat m ent
Im m un oglobulin s m ay be h elpfu l. In severe cases, early plasm aph eresis h asten s th e recover y an d
reduces th e residual deficit . Its role in m ild cases is un certain . Steroids are n ot h elpful.60 Mech an ical
ven tilation an d m easures to preven t aspiration are used as appropriate. In cases of facial diplegia,
th e eyes m ust be protected from exposure (n europaralyt ic) keratit is.
10.7.7 Out com e
Recover y m ay n ot be com plete for several m on th s. 35% of un treated patien ts h ave residual w eakn ess
an d atrophy. Recurren ce of GBS after ach ieving m axim al recover y occurs in ≈ 2%.
10.8 Myelit is
10.8.1 General inform at ion
AKA acute tran sverse m yelitis (ATM). The term in ology is con fusing: m yelitis overlaps w ith “m yelopathy.” Both are pathologic conditions of th e spinal cord. Myelitis indicates inflam m ation , and etiologies include: infectious/post-infectious, autoim m un e, and idiopath ic. Myelopathy is gen erally
reser ved for com pressive, toxic, or m etabolic etiologies 61 ; see also di eren tial diagn osis (p.1407).
10.8.2 Et iology
Many so-called “causes” rem ain un proven . Im m un ologic respon se again st th e CNS (m ost likely via
cell m ediated com pon en t) is th e probable com m on m ech an ism . An im al m odel: experim en tal allergic en ceph alom yelitis (requires m yelin basic protein of CNS, n ot periph eral).
Gen erally accepted etiologies in clude (item s w ith an asterisk * m ay be m ore properly associated
w ith m yelopathy rath er th an m yelitis):
1. in fect ious an d post-in fect ious
a) prim ar y in fect ious m yelit is
● viral: poliom yelit is, m yelitis w ith viral en ceph alom yelitis, h erpes zoster, rabies
● bacterial: in cluding tuberculom a of spin al cord
● spiroch etal: AKA syph ilitic m yelitis. Causes syph ilitic en darteritis
● fun gal (aspergillosis, blastom ycosis, cr yptococcosis)
● parasitic (Ech in ococcus, cysticercosis, paragon im iasis, sch istosom iasis)
b) post-in fect ious: in cluding post-exan th em atous, in fluen za
2. post-traum atic
3. physical agen ts
a) decom pression sickn ess (dysbarism )
b) elect rical injur y*
c) post-irradiation
4. paraneoplastic syn drom e (rem ote e ect of can cer): m ost com m on prim ar y is lun g, but prostate,
ovar y an d rectum h ave also been described 62
5. m etabolic
a) diabetes m ellitus*
b) pern icious an em ia*
c) ch ronic liver disease*
6. toxin s
a) cresyl ph osph ates*
b) in tra-ar terial con trast agen ts*
c) spinal an esth et ics
d) m yelograph ic con trast agen ts
e) follow in g ch em on ucleolysis 63
7. arach n oidit is
8. autoim m un e
a) m ultiple sclerosis (MS), especially Devic syn drom e (p. 1409)
b) follow in g vaccin at ion (sm allpox, rabies)
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General and Neurology
9. collagen vascular disease
a) system ic lupus er yth em atosus
b) m ixed con n ect ive tissue disease
10.8.3 Clinical
Present at ion
34 pat ien ts w ith ATM 64 : age of on set ran ged 15–55 yrs, w ith 66% occurrin g in 3rd an d 4th decade.
12 patien ts (35%) h ad a viral-like prodrom e. Presen ting sym ptom s are sh ow n in Table 10.5, w ith
oth er presen t in g sym ptom s of un specified frequen cy in cludin g 65 : fever an d rash .
Present ing level
Th e levels at presen tat ion in 62 patien ts w ith ATM are sh ow n in Table 10.6.65 Th e th oracic level is
th e m ost com m on sen sor y level. In frequen tly, ATM is th e presen ting sym ptom of MS (≈ 3–6% of
patien ts w ith ATM develop MS).
Progression
Progression is usually rapid, w ith 66% reach in g m axim al deficit by 24 h rs, h ow ever th e in terval
betw een first sym ptom an d m axim al deficit varies from 2 h rs-14 days.65 Fin din gs at th e t im e of
m axim al deficit are sh ow n in Table 10.7.
10.8.4 Evaluat ion
10
Im aging sh ould be don e to rule-out a com pressive lesion . Myelogram , CT & MRI: n o ch aracteristic
fin din g. On e paper repor ts 2 patien ts w ith fusiform cord en largem en t .67 MRI m ay be able to dem on st rate th e area of involvem en t w ith in th e cord. MRI m ay sh ow th e “cen tral dot sign ”,68 an area of
h igh sign al on axial T2WI usually cen trally located w ith a sm all dot of isoin ten se sign al in th e core of
th e hyperin tensit y.
CSF: n orm al durin g acute ph ase in 38% of LPs. Rem ain der (62%) h ad elevated protein (usually > 40
m g%) or pleocytosis (lym ph ocytes, PMNs, or both) or both .
Table 10.5 Presenting symptom s in m yelitis
Sym pt om
Series Aa
Series Bb
pain (back or radicular)
35%
35%
m uscle weakness
32%
13%
sensory deficit or paresthesias
26%
46%
sphincter disturbance
12%
6%
a series A: 34 patients with ATM64
b series B: 52 patients with acute or subacute transverse m yelitis66
Table 10.6 Level of sensory deficit
Level
%
cervical
8%
high thoracic
36%
low thoracic
32%
lumbar
8%
unknown
16%
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Table 10.7 Symptoms at tim e of maximal deficit (62 patients with ATM65 )
Sym pt om
%
sensory deficit or paresthesias
100%
m uscle weakness
97%
sphincter disturbance (hesitancy, retention, overflow incontinence)
94%
pain in back, abdomen, or lim bs
34%
fever
27%
nuchal rigidit y
13%
Evaluat ion schem e
In a pat ien t developin g acute m yelopathy/paraplegia, especially w h en ATM is con sidered likely, th e
first test of ch oice is an em ergen cy MRI. If n ot readily available, a m yelogram (w ith CT to follow )
directed at th e region of th e sen sor y level is perform ed (CSF m ay be sen t in th is circum stan ce on ce
block is ruled out).
10.8.5 Treat m ent
No t reatm en t h as been st udied in a ran dom ized con trolled t rial.
1. steroids: n ot ben eficial for all causes of m yelitis,69 especially w ith ASIA A (com plete loss of spin al
cord fun ct ion ).70 Rx: h igh -dose IV m ethylpredn isolon e 3-5 days (doses quoted in clude 500 m g/d,
an d 1000 m g/d 71 ). Th e decision to in troduce addit ion al t reat m en t m easures is based on th e respon se to steroids an d th e MRI appearan ce after ≈ 5 days of steroids
2. plasm a exch ange (PLEX) for patien ts th at do n ot respon d to steroids w ith in 3-5 days
3. oth er form s of im m un e suppression m ay be attem pted for failure of above th erapies, in cluding:
cycloph osph am ide (usually un der th e direct ion of an on cologist)
4. in cases of focal spin al cord en largem en t, surgical decom pression m ay be con sidered in cases th at
fail to respon d to th e above
10.8.6 Prognosis
In a series of 34 ATM patien ts w ith ≥ 5 yrs follow -up (F/U) 64 : 9 pat ien ts (26%) h ad good recover y
(am bulate w ell, m ild urin ar y sym ptom s, m in im al sen sor y an d UMN sign s); 9 (26%) h ad fair recover y
(fun ct ion al gait w ith som e degree of spast icit y, urin ar y urgen cy, obvious sen sor y sign s, paraparesis);
11 (32%) poor (paraplegic, absen t sph incter con trol); 5 (15%) died w ith in 4 m os of illn ess. 18 patien ts
(62% of sur vivors) becam e am bulator y (in th ese cases, all could w alk w ith support by 3–6 m os).
In a series of 59 patien ts65 (F/U period un specified): 22 (37%) h ad good recover y; 14 (24%) poor; 3
died in acute stage (respirator y in su cien cy in 2, sepsis in 1). Recover y occurred betw een 4 w eeks
an d 3 m os after on set (n o im provem en t occurred after 3 m os).
10.9 Neurosarcoidosis
10.9.1 General
Key concept s
neurologic involvement of sarcoidosis (a system ic granulomatous disease)
● m ay produce multiple cranial nerve palsies
● the most comm on neurologic manifestation is diabetes insipidus
● corticosteroids are beneficial for systemic as well as neurologic involvement
●
Sarcoidosis is a gran ulom atous disease th at is usually system ic, an d m ay in clude th e CNS (so-called
n eurosarcoidosis AKA n eurosarcoid). On ly 1–3% of cases h ave CNS fin dings w ith out system ic m an ifestation s.72 Th e cause of th e disease is un kn ow n . An exaggerated cellular im m un e respon se for
10
190
General and Neurology
un kn ow n reason s is th e curren tly favored hypoth esis. Organ s com m on ly involved in clude lun gs,
skin , lym ph n odes, bon es, eyes, m uscles, an d parotid glan ds.30
10.9.2 Pat hology
CNS sarcoidosis prim arily involves th e leptom en in ges, h ow ever paren chym al invasion often occurs.
Adh esive arachn oiditis w ith n odule form ation m ay also occur (n odules h ave a predilect ion for th e
posterior fossa). Di use m en in git is or m en ingoen ceph alitis m ay occur, an d m ay be m ost pron oun ced
at th e base of th e brain (basal m en ingit is) an d in th e subepen dym al region of th e th ird ven tricle
(in cludin g th e hypothalam us).
Con stan t m icroscopic features of n eurosarcoidosis in clude n on caseating gran ulom as w ith lym ph ocyt ic in filt rates. Lan gh an s gian t cells m ay or m ay n ot be presen t .
10.9.3 Epidem iology
Incidence of sarcoidosis is ≈ 3–50 cases/100,000 population ; n eurosarcoidosis occurs in ≈ 5% of cases
(reported range: 1–27%). In one series, the m edian age of onset of neurologic sym ptom s was 44 years.
10.9.4 Clinical findings
10
Clin ical fin din gs in clude m ultiple cran ial n er ve palsies in 50–70% (particularly facial n ., in cludin g
diplegia), periph eral n europathy, an d m yopathy.73 Occasion ally th e lesion s m ay produce m ass
e ect ,74 an d hydroceph alus m ay result from adh esive basal arachn oiditis. Patien ts m ay h ave low
grade fever. In t racran ial hyper ten sion is com m on an d m ay be dangerous. Hypoth alam ic involvem en t
m ay produce disorders of ADH (diabetes in sipidus, disordered th irst). Rare involvem en t of th e pit uitar y m ay produce pit uitary in su cien cy. Seizures occur in 15%.
0.4% of patien ts w ith sarcoidosis develop spinal cord involvem en t,75 an d in 16% of th ese, th e spin al cord w as th e on ly iden tifiable site of involvem en t.
10.9.5 Laborat ory
CBC: m ild leukocytosis an d eosin oph ilia m ay occur.
Serum an giotensin -convert in g en zym e (ACE): abn orm ally elevated in 83% of patien ts w ith act ive
pulm on ar y sarcoidosis, but in on ly 11% w ith in active disease.76 False positive rate: 2–3%; m ay also
be elevated in prim ar y biliar y cirrh osis.
CSF: sim ilar to any subacute m en in gitis: elevated pressure, m ild pleocytosis (10–200 cells/m m 3 )
m ostly lym ph ocytes, elevated protein (up to 2,000 m g/dl), m ild hypoglycorrh ach ia (15–40 m g/dl),
CSF ACE is elevated in ≈ 55% of cases w ith n eurosarcoidosis (n orm al in pat ien ts w ith sarcoidosis n ot
involving th e CNS).77 No organ ism s are recovered on culture or gram stain .
10.9.6 Im aging
CXR
Usually dem on strates ch aracteristic fin dings of sarcoidosis (hilar aden opathy, m ediast in al lym ph
n odes…).
MRI
Gadolin ium en h an cem en t of th e leptom en in ges an d/or optic n er ve m ay be th e on ly abn orm al fin din g(s). Men in geal en h an cem en t w as seen in 38% of n eurosarcoidosis pat ien ts.78 Leson s m ay be solitar y or m ultiple, an d m ay be located in tra- or extraparen chym al, periven tr icular, an d/or in basal
cistern s. Lesion s m ay be seen on FLAIR th at w ould oth erw ise h ave been m issed. Hydroceph alus m ay
occur.
Gallium scan
Nuclear m edicin e scan w ith 67Ga cit rate (p. 236). Described fin din gs in clude:
1. Pan da sign 79 : uptake in lacrim al glan ds, parotid glan ds & n asoph ar yn x (n orm al). Not specific for
sarcoidosis
2. lam bda distribution 80 : uptake in h ilar lym ph n odes
3. leopard m an sign 81 : di use dappled pattern due to uptake in soft t issues, skin , m uscles, m ediastin um , an d lacrim al glan ds
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Table 10.8 Di erential diagnosis of neurosarcoidosis
1. Hodgkin’s disease
2. chronic granulomatous m eningitis:
a) Hansen’s disease (leprosy)
b) syphilis
c) cryptococcosis
d) tuberculosis
3. m ultiple sclerosis
4. CNS lym phom a
5. pseudotumor cerebri
6. granulom atous angiitis
10.9.7 Di erent ial diagnosis
Di eren tiatin g gran ulom atous an giitis (GA) from n eurosarcoidosis th at involves on ly th e CNS can be
don e on h istologic criteria: th e in flam m ator y react ion in sarcoidosis is n ot lim ited to th e region
im m ediately surroun din g blood vessels as it is in GA, w h ere exten sive disruption of th e vessel w all
m ay occur.
10.9.8 Diagnosis
Makin g th e diagn osis is relatively easy w h en system ic involvem en t occurs: ch aracteristic fin dings on
CXR, biopsy of skin or liver n odules, m uscle biopsy, serum ACE assay.
Isolated n eurosarcoidosis m ay be m ore di cult to diagn ose, an d m ay require biopsy (see below ).
10
10.9.9 Biopsy
In un cert ain cases, biopsy m ay be in dicated. W h en ever possible, MRI sh ould be used to localize a
supraten torial region of involvem en t. If a m ass lesion can n ot be biopsied, a m en ingeal biopsy m ay
be don e an d sh ould in clude all layers of m en in ges an d cerebral cortex. Cult ures an d stain s for fun gus
an d acid-fast bacteria (TB) sh ould be perform ed in addit ion to m icroscopic exam in at ion .
10.9.10 Treat m ent
An tibiotics h ave n ot been proven to be of ben efit. Im m un osuppression prim arily w ith cort icosteroids are ben eficial for system ic as w ell as n eurologic involvem en t. Th erapy m ay be in itiated w ith predn ison e 60 m g PO qd in adults, an d tapered based on respon se. Th erapy w ith cyclosporin e m ay
allow a reduct ion in steroid dosage in refractor y cases.82 Treatm en t for un respon sive cases in clude:
m eth ot rexate, cytoxan , cycloph osph am ide, azath ioprin e, low dose XRT. CSF sh un tin g is in dicated if
hydrocephalus develops.
10.9.11 Prognosis
Usually a ben ign disease. Periph eral an d cran ial n er ve palsies recover slow ly.
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J, Moseley IF, Scaddin g JW , Th om pson EJ, Ch am oun
V, Miller DH, McDon ald W I, Mitch ell D. Cen tral
n er vous system sarcoidosis–diagnosis an d m anagem en t. QJM. 1999; 92:103–117
[79] Kurdziel KA. The Pan da Sign . Radiology. 2000;
215:884–885
[80] Sulavik SB, Spen cer RP, Weed DA, Sh apiro HR, Sh iue
ST, Castriotta RJ. Recognition of distin ctive pattern s
of galliu m -67 d istr ibut ion in sarcoid osis. J Nucl
Med . 1990; 31:1909–1914
[81] Fayad F, Duet M, Orcel P, Liote F. System ic sarcoidosis: th e "leopard -m an " sign . Join t Bon e Sp in e. 2006;
73:109–112
[82] Stern BJ, Sch on feld SA, Sew ell C, et al. The Treatm en t
of Neurosarcoid osis W ith Cyclosp orin e. Arch Neurol. 1992; 49:1065–1072
193
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11 Neurovascular Disorders and Neurot oxicology
11.1 Post erior reversible encephalopat hy syndrom e (PRES)
11.1.1 General inform at ion
AKA reversible posterior leukoen ceph alopathy syn drom e (RPLS). A group of en ceph alopath ies w ith
ch aracteristic pattern of w idespread vasogen ic brain edem a seen on CT or MRI w ith som e predom in an ce in th e parietal an d occipital region s.1 Th e m ost com m on PRES pat tern involves w atersh ed
zon es w ith involvem en t of th e cortex, subcort ical an d deep w h ite m atter to a variable exten t.1 A
sm all n um ber of pat ien ts w ith PRES w ill go on to in farct ion .
Pat ien ts m ay presen t w ith h eadach e, seizures, m en tal status ch anges an d focal n eurologic deficit .
In tracerebral h em orrh age (ICH) an d SAH m ay occur in up to 15%.1
11.1.2 Associat ed findings and condit ions
11
In cludes:
1. hyperten sive en ceph alopathy: com m on ly seen in th e sett ing of subacute blood pressure elevation s (as m ay occur w ith m align an t hyperten sion ). Im aging st udies sh ow sym m etric con fluen t
lesion s w ith m ild m ass e ect an d patchy en h an cem en t prim arily in th e subcort ical w h ite m atter
of th e occipita l lobes2 w h ich m ay produce cort ical blin dn ess
a) m oderate to severe hyper ten sion is seen in ≈ 75% of patien ts w ith PRES1 alth ough th e upper
lim its of autoregulat ion are often n ot reach ed
b) in addition to h em isph eric pattern s of edem a isolated brain stem an d cerebellar edem a h ave
been described. Posterior fossa edem a h as been reported to cause obstruct ive hydroceph alus
in a severe case 3
2. preeclam psia/eclam psia associated w ith cerebral edem a.4 Th e con dition is often tem porar y, but
(perm an en t) in farction s also occur. Restricted di usion on MR im agin g is seen in 11–26%of cases.
Abn orm al DW I areas on MRI m ay be associated w ith a w orse progn osis 5
a) m ay presen t (e.g. w ith blin dn ess) durin g pregn an cy com plicated by preeclam psia or
eclam psia 6
b) m ay develop 4–9 days post-part um an d m ay be associated w ith vasospasm 7 even in patien ts
n ot m eetin g clin ical criteria for th e diagn osis of eclam psia
c) toxem ia is attributed to the placenta. Delivery and rem oval of the placenta is felt to be curative 8
3. in fect ion , sepsis an d sh ock: blood pressure w as n orm al in 40%(edem a w as greater in th e n orm oten sive pat ien ts). Gram positive organ ism s predom in ate 9
4. autoim m un e disease: PRES h as been described in patien ts w ith lupus, scleroderm a, Wegen er’s
gran ulom atosis an d polyarteritis n odosa.1 Th ese patien ts often receive regim en s of im m un osuppressive m edicat ion s (tacrolim us, cyclosporin e), w h ich h ave also been lin ked to cases of PRES
5. can cer ch em oth erapy: PRES occurs in patien ts receiving m ulti-drug h igh dose ch em oth erapy
m ost com m on ly for h em atopoietic m align an cies
6. tran splan tation : PRES h as been reported both w ith bon e m arrow an d solid organ tran splan tat ion
a) in ciden ce: 3–16%w ith bon e m arrow tran splan tation depen din g on th e precon dition in g regim en an d w h eth er or n ot it is m yeloablative 1
b) h igh est in ciden ce in th e first m on th follow in g allogen eic bon e m arrow tran splan t 1
c) low er in ciden ce follow in g solid organ tran splan ts. Occurs earlier follow in g liver tran splan tat ion , usually w ith in 2 m on th s. Occurs later in ren al tran splan ts 1
7. cyclosporin e post-tran splan t n eurotoxicit y 9
11.1.3 Treat m ent
Disordered autoregulat ion m an dates tigh t con trol of blood pressure to reduce th e risk of ICH. Th e
un derlying cause n eeds to be addressed (i.e. con trol HTN, h old im m un osuppressives or ch em oth erapeutics, deliver y of th e placen ta, etc.).
11.2 Crossed cerebellar diaschisis
Hypom etabolism of cerebellar cortex con tralateral to a cerebral h em isph eric lesion (lesion s in clude:
st roke, brain tum or…). Lesion s in th e m otor cortex, an terior coron a radiata, an d th alam us produce
th e m ost m arked suppression of m etabolism . Th eor y: hypom etabolism is due to discon n ection of
Neurovascular Disorders and Neurotoxicology
195
cerebro-pon to-cerebellar path w ays → decreased oxygen an d glucose con sum ption → decreased CO2
product ion → local arterial con striction (dow n -regulat ion of cerebellar blood flow ).
11.3 Vasculit is and vasculopat hy
11.3.1 General inform at ion
Th e vasculitides are a group of disorders ch aracterized by in flam m at ion an d n ecrosis of blood vessels. Vasculit is m ay be prim ar y or secon dary. Th ose th at m ay a ect th e CNS are listed in Table 11.1,
all of th ese cause tissue isch em ia (even after th e in flam m ation is quiescen t) th at m ay ran ge in e ect
from n europraxia to in farct ion .
11.3.2 Giant cell art erit is (GCA)
Key concept s
formerly often referred to as temporal arteritis
● a chronic vasculitis of large and medium caliber vessels, prim arily involving cranial branches of the
arteries arising from the aortic arch
● age > 50 years; a ects women t wice as often as men
● important possible late complications: blindness, stroke, thoracic aortic aneurysms and aortic
dissections
● tem poral artery biopsy is recom mended for all patients suspected of GCA
● corticosteroids are the drug of choice for treatment
●
AKA tem poral ar teritis (TA), AKA cran ial arteritis. A ch ron ic gran ulom atous arteritis of un kn ow n etiology involving prim arily th e cran ial bran ch es of th e aort ic arch (especially th e extern al carotid
artery (ECA)),11 w h ich if un treated, m ay lead to blin dn ess. Takayasu’s arterit is is sim ilar to GCA, but
ten ds to a ect large arteries in youn g w om en ; it h as 2 ph ases: in flam m atory (t reated w ith cort icosteroids) an d sten otic (treated w ith ar terial bypasses).
Epidem iology
Seen alm ost exclusively in Caucasian s > 50 yrs age (m ean age of on set is 70). In ciden ce: 17.8 per
100,000 people ≥ 50 years old 12 (ran ge: 0.49–23). Prevalen ce: ≈ 223 (autopsy in ciden ce m ay be m uch
Table 11.1 Vasculitides that may a ect the CNS10
Vasculit is
Frequency of
neuro
involvem ent
Type of CNS involvem ent a
Acut e encephalopat hy
Seizure
Cranial
nerve
Spinal
cord
ICH or
SAH
periarteritis nodosa b (PAN)C
20–40%
++
++
+
+
+
hypersensitivit y vasculitisb
10%
+
+
0
0
+
giant cell (temporal) arteritisb
10%
+
0
++
0
0
Takayasu’s arteritis
10–36%
+
++
++
+
+
Wegener’s granulom atosisb
23–50%
+
++
++
+
+
lym phom atoid granulom atosisb
20–30%
++
+
++
+
0
isolated angiitis of the CNSb
100%
++
+
++
++
+
Behçet’s disease b
10–29%
++
+
++
+
+
a KEY: 0 = uncom mon or unreported; + = not uncomm on; + + = comm on; ICH = intracerebral hemorrhage;
SAH = subarachnoid hemorrhage
b see section that follows for these topics
cPAN: a group of disorders, frequencies may vary by subgroup
11
196
General and Neurology
h igh er).13 More com m on in n orth ern latitudes an d am ong in dividuals of Scan din avian descen t suggesting a gen et ic an d environ m en tal causes.11 Fem ale:m ale ratio is ≈ 2:1 (reported ran ge: 1.05–
7.4:1). 50% of GCA patien ts also h ave polym yalgia rh eum atica (PMR) (p. 198).
Pat hology
Discon tinuous (so-called “skip lesions”) inflam m atory reaction of lym phocytes, plasm a cells, m acrophages, ± giant cells (if absent, intim al proliferation m ay be prom inent); predom inantly in m edia of
involved arteries. Arteries preferentially involved include the ophthalm ic and posterior ciliary bran ches
an d the entire distribution of the external carotid system (of w hich the STA is a term inal branch). Other arteries in the body m ay be involved (reported involvem ent of abdom inal aorta, fem oral, brachial
an d m esenteric arteries are rarely sym ptom atic). Unlike PAN, GCA generally spares the renal arteries.
Clinical
11
Various com bin ation s of sym ptom s of gian t cell ar teritis are listed in Table 11.2. On set is usually
in sidious, alth ough occasion ally it m ay be abru pt.14
Details of som e fin din gs:
1. H/A: th e m ost com m on presen ting sym ptom . May be n on specific or located in on e or both tem poral areas, foreh ead, or occiput. May be superficial or burn in g w ith paroxysm al lan cin atin g pain
2. sym ptom s relatin g to ECA blood supply (strongly suggestive of GCA, but n ot path ogn om on ic16 ):
jaw claudication , tongue, or ph aryn geal m uscles
3. oph th alm ologic sym ptom s: due to arterit is an d occlusion of bran ch es of oph th alm ic artery or
posterior ciliar y arteries
a) sym ptom s in clude: am aurosis fugax (precedes perm an en t visual loss in 44%), blin dn ess, visual field cuts, diplopia, ptosis, ocular pain , corn eal edem a, ch em osis
b) blin dn ess: in ciden ce is ≈ 7%, an d on ce it occurs, recover y of sigh t is un likely
4. system ic sym ptom s
a) n on specific con stitut ion al sym ptom s: fever (m ay presen t as FUO in 15% of cases), an orexia,
w eigh t loss, fatigue, m alaise
b) 30% h ave n eurologic m an ifestation s. 14%are n europath ies in cludin g m on on europath ies and
periph eral polyneuropath ies of th e arm s or legs 17
c) m usculoskeletal sym ptom s
● PMR (p. 198) is th e m ost com m on (occurs in 40% of patien ts):
● periph eral arth rit is, swellin g & pitting edem a of h an ds & feet in 25%
● arm claudication from sten osis of subclavian an d axillar y arteries
d) th oracic aortic an eur ysm s: 17 t im es as likely in GCA. An n ual CXRs are adequate for screen ing
5. tem poral arteries on ph ysical exam in ation m ay exh ibit ten dern ess, sw ellin g, er yth em a, reduced
pulsation s, or n odularit y. Norm al in 33%
6. th e presen ce of system ic sym ptom s correlates w ith a lower in ciden ce of blin dn ess or stroke
Di erent ial diagnosis
1.
2.
3.
4.
5.
6.
7.
8.
periarteritis n odosa (PAN) (p. 199)
hypersen sit ivit y vasculit is
ath erosclerot ic occlusive disease
m align an cy: sh ares system ic also h as sym ptom s of low grade fever, m alaise an d w eigh t loss
in fect ion
trigem in al n euralgia (p.479)
oph th alm oplegic m igrain e
den tal problem s
Table 11.2 Signs and symptom s of GCA15,11
Frequent
(> 50% of cases)
Occasional
(10–50% of cases)
Rare
(< 10% of cases)
H/A: 66%
tem poral artery tenderness
visual sym ptoms
weight loss
fever (low grade)
proximal myalgias
jaw claudication
facial pain
scalp tenderness
blindness
extrem it y claudication
tongue claudication
ear pain
synovitis
stroke
angina
Neurovascular Disorders and Neurotoxicology
197
Evaluat ion
Laboratory studies
1. ESR > 40 m m /h r (usually > 50) by Westergren m eth od (if > 80 m m /h r w ith above clin ical syn drom es, h igh ly suggestive of GCA). ESR is n orm al in up to 22.5%18
2. C-react ive protein : an other acute ph ase reactan t th at is m ore sen sitive th an ESR. Has th e advan tage th at it can be perform ed on frozen sera
3. CBC: m ay sh ow m ild n orm och rom ic an em ia 19
4. rh eum atoid factor, ANA, an d serum com plem en t usually n orm al
5. LFTs abn orm al in 30% (usually elevated alkalin e ph osph atase)
6. tests for rh eum atoid factor an d ANA are usually n egative
7. tem poral ar ter y an giography n ot h elpfu l (an giography elsew h ere in dicated if suspicion of large
ar tery involvem en t exists)
8. CT: usually n ot h elpfu l, on e report described calcified areas correspon ding to th e tem poral
ar teries20
9. tem poral ar ter y biopsy: see below
Tem poral artery biopsy
Sen sitivity an d specificit y are sh ow n in
Table 11.3.
Indicat ions and t im ing
Curren t recom m en dation s: tem poral artery biopsy in all patien ts suspected of h avin g GCA.11 May be
con troversial. Argum en ts for: toxicit y of a lon g course of steroids in an elderly patien t, an d a h igh
rate of false in itial respon ses of oth er illn esses to steroids. Argum en ts again st: sin ce a n egative biop sy can n ot exclude th e diagn osis, cases w ith a n egative biopsy but a st ron g clin ical suspicion are often
t reated as th ough th ey h ave GCA.22 In gen eral, h ow ever, biopsy is con sidered pruden t before
em barking on a lon g course of h igh -dose steroid th erapy.16 Com plication s of biopsy are rare an d
in clude bleedin g, in fect ion , an d on ly in th e sett in g of active vasculit is h as scalp n ecrosis been
reported (n ot lin ked to biopsy).
In gen eral, perform biopsy before startin g steroids if biopsy can be don e im m ediately.11 Oth erw ise, start steroids to preserve vision an d perform biopsy usually w ith in 1 w eek (path ologic changes
can be seen after m ore th an 2 w eeks of th erapy,23 th erefore do n ot w ith h old steroids to aw ait
biopsy).
Technique of tem poral art ery biopsy
Biopsy side of involvem en t if lateralit y exists. Th e yield is in creased by rem ovin g a port ion of arter y
th at is involved clin ically (a ten der or in flam ed segm en t).24 Mark th e fron tal bran ch of th e STA w ith
a skin m arker (spare th e m ain trun k an d parietal bran ch if possible). In filtrate local an esth etic. Th e
in cision is m ade parallel to th e arter y an d if possible beh in d th e h airlin e. Th e in cision is taken dow n
to th e fascia of th e tem poralis m uscle, to w h ich th e STA is superficial.25 Optim al len gth of STA biop sy: 4–6 cm (if an abn orm al segm en t of STA can be palpated, som e say th at a sm aller biopsy to in clude
th is area m ay be su cien t, but th is is probably un reliable as th e m uscle m ay be ten der, etc.). Step sect ion in g by path ologist th rough th e en tire len gth of th e biopsy specim en also in creases th e yield.
Frozen sect ion s can be perform ed. Biopsy of th e con tralateral side if th e first side is n egative in
cases w h ere clin ical suspicion is h igh in creases th e yield on ly by 5–10%.
Treat m ent
No kn ow n cure. Steroids can produce sym ptom at ic relief an d usually preven t blin dn ess (progression
of ocular problem s 24–48 h rs after in stitution of adequate steroids is rare). Totally blin d patien ts or
th ose w ith lon gstan din g partial visual loss are un likely to respon d to any t reatm en t.
1. for m ost cases:
a) start w ith prednisone , 40–60 m g/d PO divided BID- QID (qod dosing is usually n ot e ect ive in
in itial m an agem en t)
b) if n o respon se after 72 h rs, an d diagn osis certain , ↑ to 10–25 m g QID
Table 11.3 Temporal artery biopsy
sensitivit y
≈ 90% (reported range 15,21 is 9–97%)
specificit y
near 100%
predictive value
≈ 94%
11
198
General and Neurology
c) on ce respon se occurs (usually w ith in 3–7 days), give en tire dose as q AM dose for 3–6 w eeks
un til sym ptom s resolved an d ESR n orm alizes (occurs in 87% of patien ts w ith in ≈ 4 w eeks) or
stabilizes at < 40–50 m m /h r
d) on ce quiescen t, a gradual taper is perform ed to preven t exacerbation s: reduce by 10 m g/d q
2–4 w eeks to 40 m g/d, th en by 5 m g/d q 2–4 w ks to 20 m g/d, th en by 2.5 m g/d q 2–4 w ks to
5–7.5 m g/d w h ich is m ain tain ed for several m on th s, follow ed by 1 m g/d decrem en ts q 1–3
m os (usual len gth of treatm en t is 6–24 m os; do not D/C steroids w h en ESR n orm alizes)
e) if sym ptom s recur durin g treatm en t, predn ison e dose is tem porarily in creased un til sym ptom s resolve (isolated rise in ESR is n ot su cien t reason to in crease steroids 11 )
f) patien ts sh ould be follow ed closely for ≈ 2 years
2. in severely ill patien ts: m ethylpredn isolon e, 15–20 m g IV QID
3. an ticoagulan t th erapy: con troversial
4. acute blin dn ess (on set w ith in 24–36 h rs) in a patien t w ith gian t cell arteritis:
a) con sider up to 500 m g m ethylpredn isolon e IV over 30–60 m in s (n o con trolled studies sh ow
reversal of blin dn ess)
b) som e h ave used in term itten t in h alat ion of 5% carbon dioxide an d oxygen
Out com e
Com plication s of steroid th erapy occur in ≈ 50%of pat ien ts. Most are n ot life th reaten in g, an d in clude
vertebral com pression fract ures in ≈ 36%, peptic ulcer disease in ≈ 12%, proxim al m yopathy, cataract s, exacerbation of diabetes; also see Possible deleterious side e ects of steroids (p. 146).
30–50% of patien ts w ill h ave spon tan eous exacerbation s of GCA (especially durin g th e first 2
years) regardless of th e cort icosteroid regim en .11
Sur vival parallels th at of th e gen eral population . On set of blin dn ess after in itiation of steroid th erapy is rare.
11.3.3 Polym yalgia rheum at ica (PMR)
11
General inform at ion
PMR an d gian t cell arterit is (GCA) (p.195) m ay be di eren t poin ts on a con tin uum of th e sam e disease. Both h ave in in creased frequen cy of HLA-DR4 an d system ic m on ocyte activation . 15% of
patien ts w ith PMR even tually develop GCA.
Epidem iology
See referen ce.11
Both GCA & PMR occur in people ≥ 50 years old. Th e in ciden ce in creases w ith age an d peaks
betw een 70–80 years an d is h igh er at h igh er latitud es.11
PMR is m ore com m on th an GCA. Prevalen ce: 500/100,000).26 In ciden ce: 52.5 per 100,000 people ≥ age 50, h igh er in fem ales (61.7) th an m ales (39.9).27
Feat ures
See referen ce.11
● an in flam m ator y con dition of un kn ow n etiology
● clin ical ch aracterist ics
a) ach ing an d m orn in g st i n ess in th e cer vical region an d sh oulder & pelvic girdles lastin g > 1
m on th . Th e pain usually in creases w ith m ovem en t
○ sh oulder pain : presen t in 70–95% of patien ts. Radiates tow ard elbow
○ h ip & n eck pain : 50–70%. Hip pain radiates tow ards kn ees
b) age ≥ 50 years
c) ESR ≥ 40 m m /h r (7–20% h ave n orm al ESR28 )
d) usually respon ds rapidly to low dose cort icosteroids (≤ 20 m g predn ison e/day) see below
e) system ic sym ptom s (presen t in ≈ 33%): fever, m alaise or fat igue, an orexia an d w eigh t loss
● favorable progn osis: usually rem its in 1–3 years
Treat m ent
PMR respon ds to eith er to low doses of steroids 26 (10–20 m g predn ison e/day) or som etim es to
NSAIDs (respon se to steroids is m uch m ore rapid). Th e in itial dose of steroids is m ain tain ed for 2–4
w eeks, an d th en by ≤ 10%of th e daily dose ever y 1–2 weeks 11 w h ile obser vin g for sign s of GCA.
Neurovascular Disorders and Neurotoxicology
199
11.3.4 Ot her vasculit ides
Periart erit is nodosa
AKA polyarterit is n odosa. Actually a group of n ecrotizin g vasculit ides, in cluding:
● classic periarteritis n odosa (PAN): a m ultisystem disease w ith in flam m atory n ecrosis, th rom bosis
(occlusion ), an d h em orrh age of arteries an d arterioles in ever y organ except lun g & spleen . Nodules m ay be palpated alon g m edium sized m uscular arteries. Com m on ly produces m on on euritis
m ultiplex, w eigh t loss, fever, an d tachycardia. Periph eral n er ve m an ifestation s are att ributed to
arteritic occlusion of vasa n er vorum . CNS m an ifestation s are un com m on an d in clude H/A, seizures, SAH, retin al h em orrh ages, an d stroke in ≈ 13%
● allergic an giitis an d gran ulom atosis (Ch urg-Strauss syn drom e)
● system ic n ecrotizin g vasculit is
Th ese pat ien ts do better w h en treated w ith cycloph osph am ide rath er th an steroids.
Wegener’s granulom at osis
General inform ation
A system ic n ecrotizing gran ulom atous vasculit is involving th e respirator y tract (lun g → cough /h em optysis, an d/or n asal airw ays → serosanguin ous n asal drain age ± septal perforation→ ch aracteristic
“saddle n ose deform it y”) an d frequen tly th e kidn eys (n o reported cases of kidn ey involvem en t w ith out respirator y).29
Nasal obstruct ion an d crustin g are th e usual in itial fin dings. Ar th ralgia (n ot true ar th rit is) is
presen t in > 50%.
Neurologic involvem en t usually con sists of cran ial n er ve dysfun ct ion (usually II, III, IV, & VI; less
often V, VII, & VIII; an d least com m on ly IX, X, XI, & XII) an d periph eral n europath ies, w ith diabetes
in sipidus (occasion ally preceding oth er sym ptom s by up to 9 m on th s). Focal lesion s of th e brain an d
spinal cord occur less frequen tly.
Di erential diagnosis
Di eren tial diagn osis in cludes:
● “leth al m idlin e gran ulom a” (m ay be sim ilar or iden tical to polym orph ic reticulosis) m ay evolve
in to lym ph om a. May cause fulm in an t local destruction of th e n asal tissue. Di eren tiation is crucial
as th is con dition is treated by radiation ; on e sh ould avoid im m un e suppression (e.g. cycloph osph am ide). Probably does n ot involve true gran ulom as. Ren al an d trach eal involvem en t do n ot
occur
● fun gal disease: Sporoth rix sch en ckii & Coccidioides m ay cause iden tical syn drom e
● oth er vasculitides: especially Ch urg-St rauss syn drom e (asth m a an d periph eral eosin oph ilia usually seen ), an d PAN (gran ulom as usually lackin g)
Evaluat ion
Biopsy of upper airw ays con sists of rem ovin g all crusts, an d obtain ing as m uch friable m ucosa as
possible. Th is tissue sh ould be fixed in form aldehyde an d exam in ed path ologically w ith in 24 h rs (do
n ot freeze). A sam ple sh ould also be cultured (in cluding fun gal an d acid-fast cultures). Ren al biopsy
sh ould n ot be don e w h en m ore specific t issue is available from th e upper airw ay.
Treatm ent
Un t reated, Wegen er’s gran ulom atosis is rapidly fatal, w ith a m edian sur vival of 5 m on th s, an d m ore
th an 90% of patien ts are dead w ith in 2 years of diagn osis.30 For fulm in at in g disease: predn ison e 60–
80 m g/d un til disease is con trolled (docum en ted by decreasing ESR an d im provem en t of serum
creatin in e).
W h en disease is stable: cycloph osph am ide (Cytoxan ®) ≈ 2 m g/kg daily (takes 2–3 w eeks to h ave
an e ect ). Con tin ue 1 year beyon d last eviden ce of active disease. Low -dose w eekly m eth otrexate
m ay be an acceptable altern ative to cycloph osph am ide in selected patien ts.30
11.3.5 Lym phom at oid granulom at osis
Rare; a ect s m ain ly th e lun gs, skin (er yth em atous m acules or in durated plaques in 40%) an d n er vous system (CNS in 20%, periph eral n europath ies in 15%). Sin uses, lym ph n odes, an d spleen are usually spared.
11
200
General and Neurology
11.3.6 Behçet ’s syndrom e
Relapsin g ocular lesion s an d recurren t oral an d gen ital ulcers, w ith occasion al skin lesion s, th rom boph lebitis, an d arth rit is.10 H/A occur in > 50%. Neurologic involvem en t in cludes pseudot um or, cerebellar ataxia, paraplegia, seizures, an d dural sin us th rom bosis. On ly 5% h ave n eurologic sym ptom s as
th e presen ting com plain t.
86% h ave CSF pleocytosis an d protein elevation . Cerebral an giography is usually n orm al. CT m ay
sh ow focal areas of en h ancin g low den sit y.
Steroids usually am eliorate ocular and cerebral sym ptom s, but usually have no e ect on skin and genital lesions. Uncontrolled trials of cytotoxic agents → som e benefit. Thalidom ide m ay be e ective (uncontrolled studies), but carries risk of serious adverse e ects (teratogenicity, peripheral neuropathy…).31
Although painful, the disease is usually benign. Neurologic involvem ent portends a worse prognosis.
11.3.7 Isolat ed CNS vasculit is
General inform at ion
AKA isolated an giitis of th e CNS. Rare (≈ 20 cases reported 32 as of 1983); lim ited to vessels of CNS.
Sm all vessel vasculitis is ≈ always presen t → segm en tal in flam m ation an d n ecrosis of sm all leptom en in geal an d paren chym al blood vessels w ith surroun ding tissue isch em ia or h em orrh age.10
Present at ion
Com bin ation s of H/A, con fusion , dem en tia, an d leth argy. Occasion ally seizures. Focal an d m ultifocal
brain disturban ce occurs in > 80%. Visual sym ptom s are frequen t (secon dar y eith er to involvem en t of
ch oroidal an d retin al arteries, or to involvem en t of visual cortex → visual h allucin ation s).
Evaluat ion
11
ESR & W BC count are usually n orm al. CSF m ay be n orm al or h ave pleocytosis an d/or elevated protein . CT m ay sh ow en h an cin g areas of low den sit y.
An giography (required for diagn osis): ch aracterist ically sh ow s m ultiple areas of sym m etrical n arrow in g (“strin g of pearls” con figuration ). If n orm al, it does n ot exclude diagn osis.
Histological diagnosis (recom m en ded): all biopsy m aterial sh ould be cultured. Brain paren chym a
biopsy in frequen tly sh ow s vasculit is. Leptom en ingeal biopsy invariably sh ow s involvem en t.
Treat m ent and out com e
Reportedly fatal if un t reated, but m ay sm older for years.
Rarit y of th is con dition m akes t reatm en t un certain . Recom m en ded: cycloph osph am ide (Cytoxan ®) 2 m g/kg/d an d predn ison e 1 m g/kg/d qod th erapy.
NB: th is con dition is th ough t to be T-cell m ediated, but predn ison e causes m ore B-cell suppression , th erefore breakth rough durin g predn ison e th erapy is n ot un com m on .
11.3.8 Hypersensit ivit y vasculit is
Neurologic involvem en t is n ot a prom in en t feature of th is group of vasculitides, w h ich in clude:
● drug in duced allergic vasculitis: A n um ber of drugs are associated w ith th e developm en t of cerebral vasculitis. Th ese in clude m eth am ph etam in es (“speed”), cocain e (fran k vasculitis occurs 33 but
is rare), h eroin an d eph edrin e
● cutan eous vasculitis
● serum sickn ess: m ay → en ceph alopathy, seizures, com a, periph eral n europathy an d brach ial
plexopathy
● Hen och -Sch ön lein purp ura
11.3.9 Fibrom uscular dysplasia
General inform at ion
A vasculopathy (an giopathy) a ect in g prim arily bran ch es of th e aorta, w ith ren al artery involvem en t
in 85% of cases (th e m ost com m on site) an d com m on ly associated w ith hyper ten sion . Th e disease
h as an in ciden ce of ≈ 1%, an d results in m ult ifocal arterial con striction s an d in terven in g region s of
an eur ysm al dilatation .
Th e secon d m ost com m on ly involved site is th e cer vical in tern al carot id (prim arily n ear C1–2),
w ith fibrom uscular dysplasia (FMD) appearin g on 1% of carotid an giogram s, m akin g FMD th e secon d
Neurovascular Disorders and Neurotoxicology
201
m ost com m on cause of extracran ial carotid sten osis.34 Bilateral cer vical ICA involvem en t occurs in ≈
80% of cases. 50% of patien ts w ith carotid FMD h ave renal FMD. Pat ien ts w ith FMD h ave an in creased
risk of in t racran ial an eur ysm s an d n eoplasm s, an d are probably at h igh er risk of carotid dissect ion .
An eur ysm s an d fibrom uscular dysplasia: Th e reported in ciden ce of an eur ysm s w ith FMD35
ran ges from 20–50%.
Et iology
Th e actual etiology rem ain s un kn ow n , alth ough congen ital defect s of th e m edia (m uscular layer)
an d in tern al elastic layer of th e arteries h as been iden tified w h ich m ay predispose th e arteries to
injur y from oth erw ise w ell-tolerated t raum a. A h igh fam ilial rate of st rokes, HTN, an d m igrain e h ave
supported th e suggestion th at FMD is an autosom al dom in an t trait w ith reduced pen etran ce in
m ales.36
Present at ion
Most patien ts h ave recurren t, m ultiple sym ptom s sh ow n in Table 11.4.
Up to 50% of pat ien ts present w ith episodes of t ran sien t cerebral isch em ia or in farct ion . How ever,
FMD m ay also be an in ciden tal fin din g an d som e cases h ave been follow ed for 5 years w ith out recurren ce of isch em ic sym ptom s suggestin g th at FMD m ay be a relatively ben ign con dition .
Headach es are com m on ly un ilateral an d m ay be m istaken for t ypical m igrain e. Syn cope m ay be
caused by involvem en t of th e carotid sin us.
Horn er’s syn drom e occurs in ≈ 8% of cases. T-wave ch anges on EKG m ay be seen in up to on e–
th ird of cases, an d m ay be due to involvem en t of th e coron ary arteries.
Diagnosis
Th e “gold-stan dard” for th e diagn osis of FMD is th e an giogram . Th e th ree an giograph ic t ypes of
FMD37 are sh ow n in Table 11.5.
11
Treat m ent
Medical th erapy in cludin g an t iplatelet m edication (e.g. aspirin ) h as been recom m en ded.
Direct surgical treatm en t is problem ridden due to th e di cult location (h igh carotid arter y, n ear
th e base of th e sku ll), an d th e friable n ature of th e vessels m akin g an astam osis or arteriotom y closure di cult.
Tran slum in al an gioplast y h as ach ieved som e degree of success. Carotid cavern ous fistulas an d
arterial rupture h ave been reported as com plication s.
Table 11.4 Previous sym ptoms in 37 cases of aortocranial FMD36
Sym pt om
%
H/A
78%
m ental distress
48%
tinnitus
38%
vertigo
34%
cardiac arrhythm ia
31%
TIA
31%
syncope
31%
carotidynia
21%
epilepsy
15%
hearing im pairm ent
12%
abdominal angina
8%
angina/ MI
8%
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General and Neurology
Table 11.5 Angiographic classification of FMD
Type
Findings
1
m ost comm on (80–100% of reported cases). Multiple, irregularly spaced, concentric
narrowings with normal or dilated intervening segm ents giving rise to the so-called “string of
pearls” appearance. Corresponds with arterial m edial fibroplasia
2
focal tubular stenosis, seen in ≈ 7% of cases. Less characteristic for FMD than Type 1, and may
also be seen in Takayasu’s arteritis and other conditions
3
“at ypical FMD.” Rare. May take on various appearances, m ost comm only consisting of
diverticular outpouchings of one wall of the artery
11.3.10 Miscellaneous vasculopat hies
CADASIL
Key concept s
clinical: migraines, dem entia, TIAs, psychiatric disturbances
● MRI: white mat ter abnormalities
● autosomal dom inant inheritance
● anticoagulants controversial, generally discouraged
●
11
An acronym for Cerebral Autosom al Dom in an t Arteriopathy w ith Subcort ical In farcts an d Leukoen ceph alopathy.38 A fam ilial disease w ith on set in early adulth ood (m ean age at on set: 45 ± 11 yrs),
m apped to ch rom osom e 19. Clin ical an d n euroradiologic features are sim ilar to th ose seen w ith m ult iple subcor tical in farcts from HTN, except th ere is n o evidence of HTN. Th e vasculopathy is dist in ct
from th at seen in lipohyalin osis, arteriosclerosis an d am yloid an giopathy, an d causes th icken in g of
th e m edia (by eosin oph ilic, gran ular m aterial) of leptom en in geal an d perforatin g arteries m easurin g
100–400 m cm in diam eter.
Clinical involvem ent
Recurren t subcor tical in farcts (84%), progressive or stepw ise dem en tia (31%), m igrain e w ith aura
(22%), an d depression (20%). All sym ptom at ic an d 18% of asym ptom at ic patien ts h ad prom in en t subcort ical w h ite-m atter an d basal ganglia hyperin tensit ies on T2W I MRI.
Treatm ent
Warfarin (Coum adin ®) is used by som e.
11.3.11 Paraneoplast ic syndrom es a ect ing t he nervous syst em
General inform at ion
Paraneoplast ic syn drom es (PNS), AKA “rem ote e ect s of can cer.” Develop acutely or subacutely. May
m im ic or be m im icked by m etastatic disease. Th e n eurologic disabilit y is usually severe, an d m ay
precede oth er m an ifestation s of th e can cer by 6–12 m os. Often on e part icular n eural cell t ype is predom in an tly a ected. Th e presen ce of a PNS m ay porten d a m ore ben ign course of th e can cer.
16% of patien ts w ith lun g Ca, an d 4% w ith breast Ca w ill develop a PNS.
Path ogen esis un kn ow n . Th eories: ? toxin ; ? com petition for essen tial subst rate; ? opportun istic
in fect ion ; ? auto-im m un e process.
Types of syndrom es
1. a ect ing cerebrum or cerebellum
a) en ceph alit is
● di use
● lim bic an d brain stem : usually due to sm all-cell lun g Ca or test icular Ca 39 as a result of
serum an tin euron al an tibodies
Neurovascular Disorders and Neurotoxicology
203
b) “lim bic en ceph alit is” (m esial): dem en tia (decreased m em or y, psych iatric sym ptom s,
h allucin ation s)
c) pan -cerebellar degen eration (PCD) AKA subacute cerebellar degen eration *: (see below )
d) opsoclon us-m yoclon us syn drom e*: in peds, usually in dicates n euroblastom a
2. a ect ing spin al cord
a) poliom yelitis (an terior h orn syn drom e): m im ics ALS (w eakn ess, hyporeflexia, fasciculation s)
b) subacute n ecrotizing (tran sverse) m yelitis: rapid n ecrosis of spin al cord
c) gan glion it is* (dorsal root gan glion ): ch ron ic or subacute. Pure sen sor y n euron opathy (n ot
n europathy)
3. a ect ing periph eral n er vous system
a) ch ronic sen sor y-m otor: t ypical n europathy (as in DM or EtOH abuse)
b) pure sen sor y (p.1268) 40
c) pure m otor: rare. Alm ost alw ays due to lym ph om a (m ostly Hodgkin’s)
d) acute in flam m ator y dem yelin atin g polyradiculopathy, AKA Guillain -Barré (p. 184)
e) Eaton -Lam bert (EL) m yasth en ic syn drom e*: rare. 66% of patien ts w ith th is syn drom e w ill
h ave can cer, m ost com m on prim ar y is oat cell Ca of lun g. Pre-syn apt ic n eurom uscular jun ction (PSNMJ) blockade due to an tibodies again st th e PSNMJ; NB: t rue m yasth en ia gravis (MG)
is a post-syn aptic block. Worse in AM, im proves durin g day w ith recruit m en t (opposite of
MG, w h ich is w orse at n igh t or w ith exercise due to depletion ). Mostly m otor, but often
accom pan ied by paresth esias. MG is a ects m ostly n icot in ic receptors, but EL also a ect s
m uscarin ic receptors, an d th erefore auton om ic sym ptom s m ay occur: dr y m outh , m ales m ay
h ave im poten ce. Repetitive n er ve st im ulat ion on EMG: for MG use 2–5 Hz st im ulation , for EL
use > 10 Hz, MG: decrem en tal respon se w ith low frequen cy, w ith EL th ere is in crem en tal respon se (m ore respon se w ith repeat stim ulat ion ).
f) m yasth en ia gravis
g) polym yositis: in age > 60 yrs, 25% of pat ien ts w ith th is h ave a m align an cy*, m ost often lin ked
to bron ch ogen ic Ca
h ) t ype IIb m uscle fiber atrophy: th e m ost com m on paran eoplastic syn drom e; m ain ly proxim al
m uscle w eakn ess (sam e as in oth er en docrin e m yopath ies, e.g. hypothyroid, steroid)
* “classic” n eurologic PNS. In a patien t w ith out previous can cer h istory presen ting w ith on e of th ese
syn drom es w ith an asterisk, w ork-up for occult m align an cy h as h igh yield.
Pan-cerebellar degenerat ion
Severe Purkinje cell loss (due to an ti-Purkinje cell an tibody) → severe pan -cerebellar dysfun ct ion .
Presen ts w ith vert igo, gait an d upper an d low er extrem it y ataxia, dysarth ria, N/V, diplopia, oscillop sia, nystagm us, oculom otor dysm etria. Usually n ot t reatable n or rem itting even w ith im m un e sup pression . 20% of patien ts im prove w ith treatm en t of th e prim ary can cer. CT is W NL early, late →
cerebellar atrophy. In 70%of cases, cerebellar fin din gs precede diagn osis of can cer.
Th e m ost com m on prim ar y m align an cies in pan -cerebellar degen eration are sh ow n in
Table 11.6.
Evaluat ion
LP: CSF for cell coun t, cytology an d IgG. Typically W BCs an d IgG are elevated
● Evaluation for prim ar y
○ CT of ch est/abdom en /pelvis
○ lym ph n ode exam
○ pelvic exam an d m am m ogram in w om en
●
Table 11.6 Comm on prim aries with pan-cerebellar degeneration
Wom en
Men
ovarian Ca
breast
uterus
Hodgkin’s lymphom a
lung Ca
Hodgkin’s lym phoma
11
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General and Neurology
11.4 Neurot oxicology
11.4.1 Et hanol
General inform at ion
Th e acute an d ch ron ic e ects of ethyl alcoh ol (eth an ol, EtOH) abuse on th e n er vous system (n ot to
m en tion th e e ects of EtOH on oth er organ system s) are protean ,41 an d are beyon d th e scope of th is
text). Neurom uscular e ect s in clude:
1. acute in toxication : see below
2. e ect s of ch ronic alcoh ol abuse
a) Wern icke’s en cep h alop at hy (p.206)
b) cerebellar degen eration : due to degen eration of Purkinje cells in th e cerebellar cortex, predom in an tly in th e an terior superior verm is
c) cent ral pon tin e m yelin olysis (p. 115)
d) st roke: in creased risk of
● in tracerebral h em orrh age (p.1330)
● isch em ic st roke 42
● possibly an eur ysm al SAH
e) periph eral n europathy (p. 541)
f) skeletal m yopathy
3. e ect s of alcoh ol w ith draw al: usually seen in h abituated drin kers w ith cessation or reduct ion of
eth an ol in take
a) alcoh ol w ith draw al syn drom es: see below
b) seizures: up to 33% of patien ts h ave a gen eralized ton ic-clon ic seizure 7–30 h rs after cessation
of drin kin g – Alcoh ol w ith draw al seizures (p. 464)
c) delirium trem en s (DTs): see below
Acut e int oxicat ion
11
Th e p rim ar y e ect of Et OH on th e CNS is d ep ression of n eu ron al excit abilit y, im p u lse con d u ct ion , an d n eu rot ran sm it ter release d u e to d irect e ect s on t h e cell m em bran es. Table 11.7
sh ow s t h e clin ical e ect s associated w it h sp ecific Et OH con cen t rat ion s. Mellan by e ect : t h e
sever it y of in t oxicat ion is greate r at an y give n level w h e n blood alcoh ol levels are risin g t h an
w h en fallin g.
In m ost jurisdiction s, in dividuals w ith blood eth an ol levels ≥ 21.7 m m ol/l (100 m g/dl) are defin ed
as legally in toxicated, an d a n um ber of states h ave ch anged th is to 80 m g/dl. How ever, even levels of
10.2 m m ol/l (47 m g/dl) are associated w ith in creased risk of involvem en t in m otor veh icle accidents.
Ch ron ic alcoh olism leads to in creased toleran ce; in h abituated in dividuals sur vival w ith levels
exceedin g 1000 m g/dl h as been reported.
Alcohol w it hdraw al syndrom e
General inform ation
Com pen sation for th e CNS depressan t e ects of EtOH occurs in ch ron ic alcoh olism . Con sequen tly,
reboun d CNS hyperact ivit y m ay result from falling EtOH levels. Clin ical sign s of EtOH w ith draw al are
classified as m ajor or m in or (th e degree of auton om ic hyperact ivity an d th e presen ce/absen ce of DTs
di eren tiates th ese), as w ell as early (24–48 h rs) or late (> 48 h rs).
Sign s/sym ptom s in clude: t rem ulousn ess, hyperreflexia, in som n ia, N/V, auton om ic hyperact ivity
(tachycardia, systolic HTN), agitat ion , m yalgias, m ild con fusion . If EtOH w ith draw al seizures (p. 464)
occur, th ey ten d to be early. Percept ual dist urban ces or fran k h allucin osis m ay also occur early.
Table 11.7 Blood ethanol concentrations
[blood EtOH]
Clinical effect
m m ol/lit er
m g/dl
5.4
25
m ild intoxication: altered m ood, im paired cognition, incoordination
> 21.7
100
vestibular and cerebellar dysfunction: increased nystagmus, diplopia, dysarthria, ataxia
> 108.5
500
usually fatal from respiratory depression
Neurovascular Disorders and Neurotoxicology
205
Hallucin osis con sists of visual an d/or auditor y h allucin ation s w ith an oth erw ise clear sen sorium
(w h ich dist in guish es th is from th e h allucin ation s of DTs). DTs can occur 3–4 days after cessation of
drin kin g (see below ).
Suppressed by ben zodiazepin es, resum ption of drin kin g, β-adren ergic an tagon ists, or α 2agon ists.
Prevention of and treatm ent for alcohol withdrawal syndrom e
See referen ce.43
Mild EtOH w ith draw al is m an aged w ith a quiet, support ive environ m en t, reorien tation an d on eto-on e con tact. If sym ptom s progress, in stit ute ph arm acologic t reatm en t.
Ben zod iazep in es
Ben zodiazepin es (BDZs) are th e m ain stay of t reatm en t. Th ey reduce autonom ic hyperact ivity, an d
m ay preven t seizures an d/or DTs. All BDZs are e ect ive. In itial doses are sh ow n in Table 11.8 an d
are h igh er th an th ose used for t reating an xiet y. Sym ptom triggered dosin g w ith repeated evaluation
utilizing a stan dardized protocol (e.g. CIW A-Ar 44 ) m ay be m ore e cacious th an fixed-dose sch edules.45 Avoid IM adm in istration (erratic absorption ).
Adju n ct ive m ed icat ion s
Associated con dition s com m on ly seen in patien ts experien cin g alcoh ol w ith draw al syn drom e
in clude dehydration , fluid an d electrolyte dist urban ces, in fect ion , pan creatitis, an d alcoh olic ketoacidosis, an d sh ould be treated accordingly.
Oth er m edicat ion s used for EtOH w ith draw al itself in clude:
1. drugs useful for con trolling HTN (caut ion : th ese agen ts sh ould n ot be used alon e because th ey do
n ot preven t progression to m ore severe levels of w ith draw al, an d th ey m ay m ask sym ptom s of
w ithdraw al)
a) β-blockers: also treat m ost associated ta chya r rhythmia s
● a tenolol (Ten orm in ®): reduces len gth of w ith draw al an d BDZ requirem en t
●
avoid propran olol (psych otoxic react ion s)
b) α -agon ists: do n ot use togeth er w ith β-blockers
2. ph en obarbital: an altern ative to BDZs. Long acting, an d h elps prophylax again st seizures
3. baclofen : a sm all study 47 foun d 10 m g PO q d X 30 days resulted in rapid reduct ion of sym ptom s
after th e in it ial dose an d con tin ued abstin en ce
4. “support ive” m edicat ion s
a) thia mine : 100 m g IM q d × 3 d (can be given IV if n eeded, but th ere is risk of adverse react ion ).
Ration ale: h igh -con centration glucose m ay precipitate acute Wern icke’s en ceph alopath y in
patien ts w ith th iam in e deficien cy
b) folate 1 m g IM, IV or PO q d × 3 d
c) MgSO4 1 gm × 1 on adm ission : h elpful on ly if m agn esium levels are low, reduces seizure risk.
Be sure ren al fun ct ion is n orm al before adm in isterin g
d) vitam in B12 for m acrocyt ic an em ia: 100 m cg IM (do n ot give before folate)
e) m ultivitam in s: of ben efit on ly if patien t is m aln ourish ed
Table 11.8 Guidelines for BDZ doses for EtOH withdrawala
Drug
Dose
Oral
IV
chlordiazepoxide
(Librium ®)
100 m g initially, then 25–50 mg PO TID-QID, gradually taper over ≈
4 days). Additional doses m ay be needed for continuing agitation,
up to 50 mg PO hourly46
–
lorazepam (Ativan®)
4 mg initially, then 1–2 mg PO q 4 hrs
1–2 m g q
1–2 hrs
diazepam
(Valium ®)
20 mg PO initially, then 10 m g PO BID-QID
5–10 m g
initially
m idazolam
(Versed®)
a modify as appropriate based on patient response
titrate drip to
desired
effect
11
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General and Neurology
5. seizures: see in dication s for treatm en t (p.464)
a) p h en yt oin (Dilan tin ®) (p. 446): load w ith 18 m g/kg = 1200 m g/70 kg
b) con tin ued seizures m ay som et im es be e ect ively t reated w ith pa ra ldehyde if available
6. eth an ol drip: n ot w idely used. 5%EtOH in D5 W , star t at 20 cc/h r, an d t it rate to a blood level of
100–150 m g/dl
Delirium t rem ens (DTs)
W h en DTs occur, th ey usually begin w ith in 4 days of th e on set of EtOH w ith draw al, an d t ypically
persist for 1–3 days.
Sign s an d sym ptom s in clude: profoun d disorien tation , agitation , trem or, in som n ia, h allucin ation s,
severe auton om ic in stabilit y (tachycardia, HTN, diaph oresis, hyperth erm ia).48 Mortalit y is 5–10%
(h igh er in elderly), but can be reduced w ith treat m en t (in cludin g t reating associated m edical problem s an d treat m en t for seizures).
Haloperidol an d ph en oth iazin es m ay con trol h allucin ation s, but can low er th e seizure th resh old.
HTN an d tachyarrhyth m ias sh ould be t reated as outlin e above un der alcoh ol w ithdraw al syn drom e.
Wernicke’s encephalopathy (WE)
General inform ation
11
AKA Wern icke-Korsako en ceph alopath y (n ot to be con fused w ith Korsako ’s syn drom e or Korsako ’s psych osis). Classic triad: en cephalopathy (con sistin g of global con fusion ), oph th alm oplegia, an d
ataxia (NB: all 3 are present in on ly 10–33%of cases).
Due to th iam in e deficien cy. Body stores of th iam in e are adequate on ly for up to ≈ 18 days. May be
seen in :
1. a cer tain susceptible subset of th iam in e deficien t alcoh olics. Th iam in e deficien cy h ere is due to a
com bin ation of in adequate in take, reduced absorption , decreased h epatic storage, an d im paired
utilization
2. hyperem esis (as in som e pregn an cies)
3. star vation : in cludin g an orexia n er vosa, rapid w eigh t loss
4. gast roplication (bariatric surger y)
5. h em odialysis
6. can cers
7. AIDS
8. prolonged IV hyperalim en tat ion
Clinical
Oculom otor abn orm alit ies occur in 96% an d in clude: nystagm us (h orizon tal > vert ical), lateral rectus
palsy, conjugate-gaze palsies.
Gait ataxia is seen in 87%, an d results from a com bin ation of polyn europathy, cerebellar dysfun ct ion , an d vestibular im pairm en t.
System ic sym ptom s m ay in clude: vom iting, fever.
Diagnostic testing
MRI: May show high signal in T2WI and FLAIR im ages in the paraventricular (m edial) thalam us, the floor
of the 4th ventricle, and periaqueductal gray of the m idbrain. These changes m ay resolve w ith treatm ent.49 Atrophy of the m am m illary bodies m ay also be seen. Norm al MRI does not R/O the diagnosis.
Treatm ent
Wern icke’s en ceph alopathy (WE) is a m edical em ergency. W h en W E is suspected, 100 m g th iam in e
sh ould be given IM or IV (oral route is un reliable, see above) daily for 5 days. IV glucose can precip itate acute W E in th iam in e deficien t patien ts, give th iam in e before glucose.
Th iam in e adm in istration im proves eye fin din gs w ith in h ours to days; ataxia an d con fusion
im prove in days to w eeks. Many patien ts th at survive are left w ith h orizon tal nystagm us, ataxia, an d
80% h ave Korsako ’s syn drom e (AKA Korsako ’s psych osis), a disabling m em or y dist urban ce involvin g retrograde an d an terograde am n esia.
11.4.2 Opioids
In cludes h eroin (w h ich is usually injected IV, but th e pow der can be sn orted or sm oked) as w ell as
prescription drugs. Opioids produce sm all pupils (m iosis).
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207
Overdose m ay produce:
1. respirator y depression
2. pulm on ar y edem a
3. com a
4. hypoten sion an d bradycardia
5. seizures
6. fatal overdose m ay occur w ith any agen t, but is m ore likely w ith syn th et ic opioids such as fen tan yl (Sublim aze®) am ong users un fam iliar w ith th eir h igh poten cy
Reversal of in toxication 50
A test dose of n aloxon e (Narcan®) 0.2 m g IV avoids sudden com plete reversal of all opioid e ect s.
If n o sign ifican t react ion occurs, an addition al 1.8 m g (for a total dose of 2 m g) w ill reverse th e toxicit y of m ost opioids. If n eeded, th e dose m ay be repeated q 2–3 m in utes up to a total of 10 m g,
although even larger doses m ay be n eeded w ith pen tazocin e or bupren orph in e (Bupren ex®). Naloxon e m ay precipitate n arcotic w ith draw al sym ptom s in opioid depen den t patien ts, w ith an xiet y or
agitation , piloerect ion , yaw n in g, sn eezin g, rh in orrh ea, n ausea, vom it in g, diarrh ea, abdom in al
cram ps, m uscle spasm s… w h ich are un com fortable but n ot life th reaten in g. Clon idin e (Catapres®)
m ay be h elpfu l for som e n arcotic w ith draw al sym ptom s.
W ith lon ger act in g opioids, especially m eth adon e (Doloph in e®), repeat doses of n aloxon e m ay be
obviated by th e use of n alm efen e (Revex®), a lon g-act in g n arcotic an tagon ist w h ich is n ot appropriate for th e in itial t reatm en t of opioid overdosage.
11.4.3 Cocaine
Cocain e is extracted from Er yth roxylon coca leaves (an d oth er Er yth roxylon species) an d is th us
un related to opioids. It blocks th e re-uptake of n or-epin ephrin e by presyn aptic adren ergic n er ve term in als. It is available in 2 form s: cocain e hydroch loride (h eat labile an d w ater soluble, it is usually
taken PO, IV or by n asal in su ation ) an d as th e h igh ly purified cocain e alkaloid (free base or crack
cocain e, w h ich is h eat stable but in soluble in w ater an d is usually sm oked).
Peak toxicit y occurs 60–90 m in utes after in gestion (except for “body packers”), 30–60 m in utes
after sn ort in g, an d m in utes after IV inject ion or sm okin g (freebase or crack).50
Acut e pharm acologic e ect s of cocaine
E ects on body system s outside th e n er vous system in clude: tachycardia, acute m yocardial in farct ion , arrhyth m ias, rupture of ascen din g aor ta (aort ic dissect ion ), abru ptio placen ta, hyperth erm ia,
in testin al isch em ia, an d sudden death .
Acu t e p h arm acologic e ect s p er t in en t to t h e n er vou s syst em in clu d e:
1. m en tal status: in itial CNS st im ulation th at first m an ifests as a sen se of w ell-being an d euph oria.
Som etim es dysph oric agitation results, occasion ally w ith delirium . St im ulation is follow ed by
depression . Paran oia an d toxic psych osis m ay occur w ith overdosage or ch ronic use. Addiction
m ay occur
2. pupillar y dilatat ion (m ydriasis)
3. hyper ten sion : from adren ergic stim ulat ion
Non -p h ar m acologic e ect s r elated to t h e n er vou s system
1. pituitar y degen erat ion : from ch ron ic in tran asal use
2. cerebral vasculitis: less com m on th an w ith am ph etam in es
3. seizures: possibly related to th e local an esth et ic properties of cocain e
4. st roke 51
a) in tracerebral h em orrh age: see In tracerebral h em orrh age, Etiologies (p. 1332)
b) subarach noid h em orrh age 52,53 : possibly as a result of HTN in th e presen ce of an eurysm s or
AVMs, h ow ever, som etim es n o lesion is dem on strated on an giography.54 May possibly be due
to cerebral vasculitis
c) isch em ic st roke 55 : m ay result from vasocon strict ion
d) th rom botic stroke 50
e) TIA56
5. an terior spin al ar tery syn drom e 56
6. e ect s of m atern al cocain e use on th e fetal n er vous system in clude 57 : m icroceph aly, disorders of
n euron al m igration , n euron al di eren tiation an d m yelin ation , cerebral in farction , subarach n oid
an d in tracerebral h em orrh age, an d sudden in fan t death syn drom e (SIDS) in th e postn atal period
11
208
General and Neurology
Treatm ent of toxicit y
Most cocain e toxicit y is too sh or t-lived to be treated. An xiety, agitation or seizures m ay be t reated
w ith IV ben zodiazepin es, e.g. lorazepam (p. 471). Refractor y HTN m ay be treated w ith n icardipin e
(p. 126) or ph en tolam in e (Regit in e®) (p. 655). IV lidocain e used to treat cardiac arrhyth m ias m ay
cause seizures.50
11.4.4 Am phet am ines
Toxicit y is sim ilar to th at of cocain e (see above), but lon ger in duration (m ay last up to several h ours).
Cerebral vasculit is m ay occur w ith prolonged abuse w h ich m ay lead to cerebral in farct ion .
Elim in at ion of am ph etam ines requires adequate urin e out put. An tipsych ot ic drugs such as h aloperidol (Haldol®) sh ould n ot be used because of risk of seizures.
11.4.5 Carbon m onoxide
General inform at ion
Carbon m on oxide (CO) is th e largest source of death from poison in g in th e U.S.A.
Norm al cellular fun ct ion requires ≈ 5 m l O2 /100 m l blood. Blood n orm ally con tain s ≈ 20 m l O2 /
100 m l.
CO bin ds to h em oglobin (Hb) w ith an a n it y ≈ 250 t im es th at of O2 , an d it causes a left sh ift of
th e Hb/O2 dissociation cur ve. It also bin ds to in tracellular m yoglobin .
On ly ≈ 6% of patien ts sh ow th e classic “ch err y-red” color of blood.
Clinical findings
Clin ical fin din gs related to CO-Hb levels are sh ow n in
11
Table 11.9.
Diagnostic st udies
EKG ch anges are com m on , usually n on -specific ST-T w ave ch anges.
In cases of severe in toxication , CT m ay sh ow sym m et rical low atten uat ion in th e globus pallidus;
see di eren tial diagn osis (p.1386).
Out com e
Progn osticators
1. outcom e is m ore closely correlated w ith hypoten sion th an w ith actual CO-Hb level
2. com a
3. m etabolic acidosis
4. EEG
5. CT/MRI ch anges: in on e st udy, th e presen ce of MRI lesion s after 1 m on th did n ot accurately predict subsequen t outcom e
6. CO-Hb level
7. oth er factors probably h ave an e ect , in cluding: age, severit y of exposure
Approxim ately 40% of patien ts exposed to sign ifican t levels of CO die. 30–40% h ave t ran sien t sym ptom s but m ake a full recover y. 10–30%h ave persisten t n eurological sequelae in cludin g CO-en ceph alopathy (m ay be delayed in on set) – im paired m em or y, irritabilit y, parietal lobe sym ptom s in cluding
various agn osias.
Brain lesion s:
1. w h ite m at ter lesion s:
a) m ultifocal sm all n ecrotic lesion s in deep h em isph eres
b) exten sive n ecrotic zon es alon g lateral ven tr icles
c) Grin ker’s m yelin opathy (n ot n ecrosis)
2. grey m at ter lesion s:
a) bilateral n ecrosis of globus pallidus
b) lesion s of h ippocam pal form at ion an d focal cort ical n ecrosis
Neurovascular Disorders and Neurotoxicology
209
Table 11.9 Levels of CO-Hb
CO-Hb level
(%)
Signs/sym ptom s a
0–10
none
10–20
m ild H/A, mild DOE
20–30
throbbing H/A
30–40
severe H/A, dizziness, dim ming of vision, impaired judgement
40–50
confusion, tachypnea, tachycardia, possible syncope
50–60
syncope, seizures, com a
60–70
com a, hypotension, respiratory failure, death
> 70
rapidly fatal
a NB: sm okers may have CO-Hb levels of 15% without signs or sym ptom s
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Part III
Im aging and Diagnost ics
12 Plain Radiology and
Cont rast Agents
212
13 Im aging and
Angiography
227
14 Electrodiagnostics
238
III
212
Im aging and Diagnostics
12 Plain Radiology and Cont rast Agent s
12.1 C-Spine x-rays
12.1.1 Norm al findings
For radiograph ic sign s of cer vical spin e t raum a, see
clin ical in stabilit y, see Table 65.4.
Table 63.2, an d for guidelin es for diagn osin g
Cont our lines
On a lateral C-spin e x-ray, th ere are 4 con tour lin es (AKA arcuate lin es). Norm ally each sh ould form a
sm ooth , gen tle cur ve ( Fig. 12.1):
1. posterior m argin al lin e (PML): alon g posterior cort ical surfaces of vertebral bodies (VB). Marks
th e an terior m argin of spin al can al
2. an terior m argin al lin e (AML): alon g an terior cort ical surfaces of VBs
WCCL
ha rd pa la te
McR
CL
B
O
12
C1
McG
C2
KEY
B = basion, O = opisthion
C3
Ba s ila r Line s *
McR = McRae's line
McG = McGregor's line
CL = Chamberlain's line
WCCL = Wackenheim's
clivus-canal line
CONTOUR
AML (a nte rior
LINES
ma rgina l line )
P ML (pos te rior
ma rgina l line )
Fig. 12.1 Spinal contour lines and lines used to diagnose basilar invagination
Lateral view through craniocervical junction.
* See discussion of the basilar lines (p. 218)
P S L (pos te rior
s pinous line )
S LL (s pinola mina r line )
Plain Radiology and Cont rast Agent s
213
Table 12.1 Norm al ADI
Pat ient
ADI
adults
m ales
≤ 3 mm
females
≤ 2.5 m m
pediatrics7 (≤ 15 yrs)
≤ 4 mm
3. spinolam in ar lin e (SLL): alon g base of spin ous processes. Th e posterior m argin of th e spin al can al
4. posterior spin ous lin e (PSL): alon g t ips of spin ous processes
Relat ion of at las t o occiput
See also criteria for atlan tooccipital dislocat ion (AOD) (p.965).
Relat ion of at las t o axis
Th ese m easurem en ts are useful for atlan toaxial subluxation /dislocat ion (p. 968) e.g. in t raum a, rh eum atoid arth rit is (p. 1134) or Dow n syn drom e (p.1138).
12.1.2 Rule of Spence
On AP or open -m outh odon toid x-ray, if th e sum total overh ang of both C1 lateral m asses on C2 is ≥ 7
m m (x + y in Fig. 12.7), th e tran sverse atlan tal ligam en t (TAL) is probably disrupted 1,2 (w h en corrected for an 18% m agn ificat ion factor, it h as been suggested th at th e criteria be in creased
to ≥ 8.2 m m 3 )
12.1.3 (Ant erior) at lant odent al int erval (ADI)
Note: th e term ADI usually refers to th e an terior atlan toden tal in ter val (th ere is also a posterior ADI
(p.213) an d a lateral ADI w h ich can be seen on AP radiograph s).
AKA preden tal space. Th e distan ce betw een th e an terior m argin of th e den s an d th e closest poin t
of th e an terior arch of C1 (“C1 button”) on a lateral C-spin e x-ray ( Fig. 12.2). Th e n orm al m axim al
ADI is variously given in th e ran ge of 2 to 4 m m .4,5 Com m on ly accepted upper lim its are sh ow n in
Table 12.1. An abn orm ally in creased ADI is a surrogate m arker for TAL disruption 6
12.1.4 Post erior at lant odent al int erval (PADI)
AKA th e n eural can al w idth (NCW ).8 Th e PADI is th e AP diam eter of th e bony can al at C1 an d is m easured from th e back of th e odon toid to th e an terior aspect of th e posterior C1 rin g ( Fig. 12.2). It is
m ore useful th an th e ADI for som e con dition s, e.g. AAS in rh eum atoid arth rit is (p. 1134) or Dow n
syn drom e (p.1138).
Fig. 12.2 The atlantodental interval (ADI) (p. 213) and
posterior atlantodental interval (PADI) on a lateral C-spine
x-ray
PADI
ADI
C1
C2
12
214
Im aging and Diagnostics
Table 12.2 Normal prevertebral soft tissue
Space
Level
Maxim um norm al widt h (m m )
Adult s
MDCT
retrotracheal
Lat eral X-Ray
C1
8.5
10
C2–4
6–7 a
5–7
C5–7
18
22
retropharyngeal
Peds
unreliable
14
a CT data was deemed unreliable at C4 11
Canal diam et er
Norm al can al diam eter on lateral C-spin e x-ray (from spin olam in ar lin e (SLL) to posterior ver tebral
body w ith 6 foot tube to film distan ce) 9 : 17 ± 5 m m . In th e presen ce of osteophytic spurs, m easure
from th e back of th e spur to th e SLL.
Cer vical spin al stenosis: various cuto s for th e n orm al m in im um AP diam eter h ave been suggested.10 On a plain lateral C-spin e x-ray th is is usually m easured from th e posterior vertebral body
(or th e posterior aspect of an osteophyte) to th e spin olam in ar lin e. Som e use 15 m m . Most agree th at
stenosis is presen t w h en th e AP diam eter is < 12 m m in an adult. Th is m easurem en t is less critical
th an it once w as, it is a surrogate m arker for sten osis severe en ough to com press th e spin al cord,
w h ich n ow m ay be dem on st rated directly w ith MRI (or m yelography).
Prevert ebral soft t issue
12
Abn orm ally in creased prevertebral soft tissue (PVST) m ay in dicate th e presen ce of a vertebral fract ure, dislocation , or ligam en tous disruption .12 Norm al values for lateral C-spin e x-ray an d CT scan
are sh ow n in Table 12.2. Plain film s are subjcet to errors due to m agn ification an d rotation . Multidetector CT (MDCT) elim in ates th ese sh ortcom ings.11
In creased PVST is m ore likely w ith an terior th an posterior injuries.13 NB: th e sen sitivit y of th ese
m easurem en ts is on ly ≈ 60% at C3 an d 5% at C6.12 False positives m ay occur w ith basal skull/facial
fract ures, especially w ith fract ure of th e pter ygoid plates. An ET-tube m ay allow fluid to accum ulate
in th e posterior oroph ar yn x w h ich can obscure th is m easurem en t. In th is sett in g, on e can look for a
th in fat layer betw een th e prevertebral m uscles an d th e posterior ph ar yn x on cer vical CT; th e prevertebral t issue (posterior to th is lin e) w ill be th icken ed (n o m easurem en ts available at th is t im e).
MRI can also dem on strate abn orm al sign al w ith in the prever tebral tissue.
Int erspinous dist ances
C-spin e AP: a fract ure/dislocat ion or ligam en t disruption m ay be diagn osed if th e in terspin ous distan ce is 1.5 t im es th at at both adjacen t levels (m easured from cen ter of spin ous processes ).14 Also
look for a m alalign m en t of spin ous processes below a certain level w h ich m ay be evidence of rotat ion due to a un ilaterally locked facet.
C-spin e lateral: look for “fan n in g” or “flar in g” w h ich is an abn orm al spread of on e pair of spin ous
processes th at m ay also in dicate ligam en t disruption .
12.1.5 Pediat ric C-spine
C1 (at las)
Ossification cen ters 15 : usually 3 ( Fig. 12.3)
● 1 (som et im es 2) for body (n ot ossified at birth ; appears on x-ray durin g 1st yr)
● 1 for each n eural arch (appear bilaterally ≈ 7th fetal w eek)
Syn ch on droses 15 :
● syn ch on drosis of th e spin ous process: fuses by ≈ 3 yrs age
● 2 n eurocen tral syn ch on droses: fuse by ≈ age 7 yrs
Plain Radiology and Cont rast Agent s
AP VIEW
neurocentral
synchondrosis
Fig. 12.3 Pediatric C1 (atlas)
neural
arch
body
215
body
neural
arch
VIEWED
FROM ABOVE
synchondrosis of
spinous process
neurocentral
synchondrosis
os term inale
neural
arch
neural
arch
neural
arch
dens
neural
arch
body
dentocentral
synchondrosis
VIEWED FROM ABOVE
neurocentral
synchondrosis
AP VIEW
Fig. 12.4 Pediatric C2 (axis)
Th e ossification cen ters of C1 fail to com pletely close in 5% of adults (usually posteriorly). W h en
presen t, th e rare an terior defect is usually associated w ith a posterior defect .
C2 (axis)
Developm en tally th ere are 5 ossification cen ters. Th e t w o h alves of th e odon toid fuse togeth er in th e
m idlin e (dash ed lin e in Fig. 12.4) at 7 m on th s developm en t, so th at at birth th ere are 4 prim ary
ossification cen ters ( Fig. 12.4):
● odon toid process
● vertebral body
● 2 n eural arch es
Th e posterior arch es fuse together by 2-3 years of age. Th e an terior syn chon droses n orm ally fuse
betw een 3-6 years of age. How ever, th e den tocen tral syn ch on drosis (AKA subden tal syn chon drosis)
m ay be visible on x-ray un til ≈ 11 years of age. A secon dar y ossificat ion cen ter (os term in ale) appears
at th e sum m it of th e den s bet w een 3–6 years of age, an d fuses w ith th e den s by age 12 years.15
C3–7
3 ossification cen ters at bir th 16 (see
● vertebral body
● 2 n eural arch es
Fig. 12.5).
12
216
Im aging and Diagnostics
neurocentral
synchondroses
Fig. 12.5 Pediatric C3-7
body
neural
arches
posterior
synchondrosis
VIEWED FROM ABOVE
Th e 2 n eural arch es fuse togeth er posteriorly by 2-3 years age.
Th e n eural arch es each fuse to th e body by 3-6 years age.
Cer vical bodies are n orm ally sligh tly w edge sh aped in pediatric population (n arrow er an teriorly).
Wedgin g decreases w ith age.
12.2 Lum bosacral (LS) spine x-rays
12
L4–5 is n orm ally th e lum bar disc space w ith th e greatest vert ical h eigh t. Also see Norm al LS spin e
m easurem en ts (p.1102).
AP view : look for defect or n on visualization of th e “ow l’s eyes” w h ich is due to pedicle erosion
w h ich m ay occur w ith lyt ic tum ors (com m on w ith m etastatic disease).
Oblique view s: look for discon tin uit y in n eck of “Scott y dog” for defect in pars in terar ticularis.
Bu t t erfly ver t ebra: An un com m on congen ital an om aly th ough t to arise from failure of fusion of
th e lateral h alves of th e VB due to persistent n otoch ord tissue, producin g a “butterfly” appearan ce
on AP x-rays or coron al CT scan recon struct ion s. Th e involved VB is w iden ed, an d adjacen t vertebrae
m ay sh ow a com pen sator y deform it y as if to fill in som e of th e gap. May be associated w ith oth er
spinal an d rib m alform at ion s.17 On lateral view s m ay sim ulate com pression fract ure. In severe cases,
th ere m ay be sign ifican t kyph osis an d/or scoliosis. Often asym ptom atic, requirin g n o treatm en t. May
be associated w ith lipom yelom en ingocele (p. 269).
12.3 Skull x-rays
Water’s view : AKA subm en tal vertex view. X-ray tube angled up 45° (perpen dicular to clivus).
Tow n e’s view : x-ray tube an gled dow n 45°, to view occiput .
12.3.1 Sella t urcica
Norm al adult dim ensions on skull x-ray
Techn ique: t rue lateral, 91 cm target to film distan ce, central ray 2.5 cm an terior an d 1.9 cm superior
to EAM. Table 12.3 sh ow s n orm al values ( Fig. 12.6 sh ow s h ow m easurem en ts are m ade).
Depth (D): defin ed as th e greatest m easurem en t from floor to diaph ragm a sellae.
Len gth (L): defin ed as th e greatest AP diam eter.
Abnorm al findings
Pituit ar y aden om as ten d to en large th e sella, in con trast to cran ioph ar yn giom as w h ich erode th e
posterior clinoids. Em pt y sella syn drom e tends to balloon th e sella sym m etrically, an d also does n ot
erode th e clin oids. Tuberculum m en in giom as usually do n ot en large th e sella, an d m ay be associated
w ith en largem en t of th e sph enoid sin us; see sph en oid pn eum osin us dilatan s (p.1372).
Plain Radiology and Cont rast Agent s
217
Table 12.3 Norm al sella turcica dim ensions ( Fig. 12.6)
Dim ension
Max
Min
Avg
D (depth) (mm )
12
4
8.1
L (length) (mm )
16
5
10.6
diaphragma
sellae
L
Fig. 12.6 Measurem ents of the sella turcica (lateral
view)
D
L = length
D = depth
“J” sh aped sella suggests optic n er ve gliom a. It can also occur congen itally in Hurler syn drom e (a
m ucopolysacch aridosis).
12.3.2 Basilar invaginat ion and basilar im pression (BI)
Term inology
Th e term s basilar im pression an d basilar invagin ation are often used in terch angeably in th e literat ure: h istorically, basilar invagin ation (AKA cran ial settling) den oted upw ard in den tation of sku ll
base usually due to acquired soften ing of bon e (see below ), often associated w ith atlan to-occipital
fusion , w h ile basilar im pression im plied n orm al bon e. Making a distin ct ion seem s poin tless (th e
abbreviation (BI) w ill be used for eith er). Com m on feature: upw ard displacem en t of th e upper cer vical spin e (in cludin g odon toid process, AKA cran ial m igration of th e odon toid) th rough th e foram en
m agn um in to th e p -fossa.
Plat ybasia: flatten ing of th e skull base. Origin ally assessed on plain x-rays (w h ich are subject to
error due to skull rotation or di cult y iden tifyin g lan dm arks), n ow m ore com m on ly evaluated on
CT or MRI. May or m ay n ot be associated w ith BI, an d m ay occur in association w ith cran iofacial
abn orm alit ies, Ch iari m alform at ion , Paget’s disease…
Quan titated by m easurin g th e basal an gle, w h ich on plain x-rays, m easured th e an gle betw een
lin es draw n from th e n asion to cen ter of sella an d th en to th e an terior foram en m agn um ,18 but on
MRI w as felt to be better represen ted by th e an gle betw een a lin e draw n alon g th e floor of th e an terior fossa to th e dorsum sellae an d a secon d lin e draw n alon g th e posterior clivus.19 Norm al m ean
basal an gle: 130°. Plat ybasia: > 145° (abn orm ally obtuse basal an gle).
Tw o subt ypes of BI
See referen ce.20
Type I: BI w ith out Ch iari m alform ation . Tip of odon toid ten ds to be above CL, McR, an d W CCL in
Fig. 12.7. Brain stem com pression is due to odon toid process invagin at ion . 85% can be reduced w ith
t ract ion . Treatm en t: tran soral surger y is recom m en ded, usually accom pan ied by posterior fusion
Type II: BI + Ch iari m alform at ion . Odon toid t ip ten ds to be above CL, but n ot McR or WCCL. Brain stem com pression is due to reduced p -fossa volum e. On ly 15% can be reduced w ith traction . Foram en m agn um decom pression is appropriate
12
218
Im aging and Diagnostics
m astoid process
digastric notch
FDGL
C1
x
y
C2
FBML
odontoid process
C1 lateral m ass
C2 lateral m ass
Fig. 12.7 AP view through craniocervical junction
FDGL= Fischgold’s digastric line, FBML= Fischgold’s bim astoid line, x + y = total overhang of C1 on C2; see Rule of
Spence (p. 970)
Measurem ent s used in BI
12
( Fig. 12.1 an d Fig. 12.7):
1. McRae’s lin e (“McR” in Fig. 12.1): draw n across foram en m agn um (tip of clivus (basion ) to opisth ion ).21 Th e m ean position of th e odon toid tip below th e lin e is 5 m m (± 1.8 m m SD) on CT an d
4.6 m m (± 2.6 m m SD) on MRI.22 No part of odon toid sh ould be above th is lin e (th e m ost accurate
m easure for BI).
2. Ch am berlain’s lin e (“CL” in Fig. 12.1)23 : posterior h ard palate to posterior m argin of foram en
m agn um (opisth ion ). Less th an 3 m m or h alf of den s sh ould be above th is lin e, w ith 6 m m being
defin itely path ologic. Seldom used because th e opisth ion is often h ard to see on plain film an d
m ay also be invagin ated. On CT24 an d MRI22 th e n orm al odon toid tip is 1.4 m m (± 2.4) below th e
lin e
3. McGregor’s baselin e (“McG” in Fig. 12.1)25 : posterior m argin of h ard palate to m ost caudal
poin t of occiput . No m ore th an 4.5 m m of den s sh ould be above th is. On CT24 an d MRI22 th e n orm al odon toid t ip is 0.8 m m (± 2.4) above th e lin e
4. Wacken h eim ’s clivus-can al lin e (“WCCL” in Fig. 12.1): th e odon toid sh ould be tan gen tial to or
below th e lin e th at exten ds th e course of th e clivus (th e clivus baselin e). If th e clivus is con cave
or convex, th is baselin e is draw n to con n ect th e basion to th e base of th e posterior clin oids on th e
clivus 26
5. (Fisch gold’s) digastric lin e (“FDGL” in Fig. 12.7): join s th e digastric n otch es. Th e n orm al distan ce
from th is lin e to th e m iddle of th e atlan to-occipital join t is 10 m m (decreased in BI).27 No par t of
odon toid sh ould be above th is lin e. More accurate th an th e bim astoid lin e (FBML)
6. Fisch gold’s bim astoid lin e (“FBML” in Fig. 12.7): join s tips of m astoid processes. Th e odon toid
tip averages 2 m m above th is lin e (range: 3 m m below to 10 m m above) an d th is lin e should cross
th e atlan to-occipital join t
Condit ions associat ed w it h BI
1. congen ital con dition s (BI is th e m ost com m on congenital an om aly of th e cran iocer vical jun ct ion ,
it is often accom pan ied by oth er an om alies 28 (p 148–9))
a) Dow n syn drom e
b) Klippel-Feil syn drom e (p. 271)
c) Ch iari m alform at ion (p.277): in a series of 100 patien ts, 92 h ad BI29
d) syrin gom yelia
2. acquired con dit ion s
a) rh eum atoid arth rit is (in part due to in com peten ce of tran sverse ligam en t, see Basilar im pression in rh eum atoid arth rit is (p. 1137)
b) post-traum atic
3. con dition s w ith BI associated w ith soften in g of bon e in clude 30 :
a) Paget’s disease
Plain Radiology and Cont rast Agent s
219
b) osteogen esis im perfecta: patien ts h ave blue discolored sclera an d early h earing loss an d due
to a genetic defect th at causes defect ive Type 1 collagen . Bon es are w eak (”brit tle-bon e disease”). Autosom al dom in an t in h eritan ce. Th ere are 4 com m on t ypes of OI an d som e un com m on on es
c) osteom alacia
d) rickets
e) hyperparathyroidism
12.4 Cont rast agent s in neuroradiology
Also see In traoperative dyes (p. 1426) for visible dyes useful in th e operat in g room .
12.4.1 Iodinat ed cont rast agent s
General precaut ions
Water-soluble con trast agen ts h ave superseded n on -w ater-soluble on es such as Pan topaque® (ethyl
iodoph enylun decylate or ioph en dylate m eglum in e).
Caution : iodin ated con trast (IV or in t ra-arterial) m ay delay excret ion of m etform in (Glucoph age®, Avan dam et®), an oral hypoglycem ic agen t used in diabetes t ype II, an d can be associated
w ith lact ic acidosis an d ren al failure (part icularly in patien ts w ith CHF or th ose con sum ing alcoh ol).
Th e m an ufact urer recom m en ds w ith h olding m etform in 48 h rs prior to an d follow in g con trast
adm in istration (or lon ger if th ere is evidence of declin ing ren al fun ct ion follow in g use of con trast).
Metform in sh ould also be h eld ≈ 48 h ours before any surger y, an d sh ould n ot be restarted post-op
un til th e patien t h as fully recovered an d is eatin g an d drin kin g n orm ally.
Maxim um dose of iodin e w ith n orm al ren al fun ct ion is ≈ 86 gm in a 24 h our period.
Int rat hecal contrast agent s
Inadvertent intrathecal injection of unapproved cont rast agents
Caution : serious react ion s can occur w ith in adverten t in trath ecal inject ion (e.g. for m yelography,
cistern ography, ven triculography…) of iodin ated con trast m edia th at are n ot specifically in dicated
for in t rath ecal use (in cludin g ion ic con trast agen ts as w ell as som e n on -ion ic agen ts (e.g. Optiray®,
Ren o-60…)). Th is can cause un con trollable seizures, in tracerebral h em orrh age, cerebral edem a,
com a, paralysis, arach n oidit is, m yoclon us (ton ic-clon ic m uscle spasm s), rh abdom yolysis w ith subsequen t ren al failure, hyper th erm ia, an d respirator y com prom ise, w ith a sign ifican t fatalit y rate.31
Man agem en t suggestion s for in adverten t in trath ecal injection in clude:
1. im m ediately rem ove CSF + con trast if th e error is recogn ized w h en th e opport un it y is available
(e.g. w ith draw fluid th rough m yelography n eedle)
2. elevate h ead of bed ≈ 45° (to keep con trast out of h ead)
3. if th ere is a question about w h at m ay h ave occurred (i.e. it is n ot certain if an in appropriate con trast agen t w as used) sen d blood an d CSF w ith con trast for h igh -perform an ce liquid ch rom atography for iden tification of agen t 32
4. an tih istam in es: e.g. diph en hydram in e (Ben adr yl®) 50 m g deep IM
5. respiration : supplem en tal oxygen , an d if n eeded, in t ubation
6. con trol HTN
7. IV hydrat ion
8. IV steroids
9. sedation if patien t is agitated
10. treat fever w ith acetam in oph en an d if n eeded w ith a coolin g blan ket
11. ph arm acologic paralysis if n ecessar y to m an age m uscle activit y
12. an ticonvulsan t m edication : m ore th an on e agen t m ay be required (e.g. ph enytoin + ph en obarbital + a ben zodiazepin e)
13. con sider un en h an ced brain CT scan : m ay h elp assess if con trast h as di used in t racran ially, but
th is requires placing patien t flat an d m ay n ot be advisable
14. in sert lum bar subarach noid drain w ith CSF drain age (e.g. 10 cc q h r)
15. m on itor: elect rolytes, an ticonvulsan t levels, creatin e kin ase (CK)
16. repeat EEGs to assess seizure act ivit y w h ile sedated/paralyzed
Iohexol (Om nipaque®)
Th e prim ar y approved agen t em ployed for in t rath ecal use today is ioh exol (Om n ipaque®).
12
220
Im aging and Diagnostics
A n on -ion ic t riiodin ated com poun d. Con cen t ration is expressed as follow s: e.g. Om n ipaque 300
contain s th e equivalen t of 300 m g of organ ic iodin e per m l of m edia (300 m gI/m l).
Used for m yelography, cistern ography as w ell as IV con trasted CT. Uses an d con cen tration s are
sh ow n in Table 12.4.
In t rat h ecal u se
NB: on ly Om n ipaque 180, 210, 240 an d 300 are labeled for in trath ecal use. 140 an d 350 are not
FDA approved for in trathecal use, h ow ever, som e n euroradiologists w ill use Om n ipaque 140 or
diluted 180 e.g. for CT ven triculography (o -label usage).
Con sider discon tin uing n eurolept ic drugs (in cludin g: ph en oth iazines, e.g. ch lorprom azin e, proch lorperazin e, an d prom eth azin e) at least 48 h ours prior to procedure. Elevate HOB≥ 30° for th e first
few h ours after th e procedure. Hydrate orally or IV.
Use w ith caution in patien ts w ith seizure h istor y, severe cardiovascular disease, ch ron ic alcoh olism or m ultiple sclerosis.
Ioh exol un dergoes slow di usion from th e in t rath ecal space to th e system ic circulat ion an d is
elim in ated by ren al excret ion w ith n o sign ifican t m etabolism or deiodin at ion .
Maxim um dosage: a total dose of 3060 m g iodin e sh ould n ot be exceeded in an adult durin g a
sin gle m yelogram (som e say up to 4500 m g is OK) (e.g. 15 cc of Om n ipaque 300 = 15 m l × 300 m gI/
m l= 4500 m g of iodin e).
Iopam idol (e.g. Isovue 300, Isovue 370®)
Triiodin ated, n on -ion ic, w ater-soluble. Used for in t ravascular an d in t rath ecal radiograph ic con trast.
Isovue 300 an d 370 con tain s 300 an d 270 m g iodin e/m l, respect ively.
Table 12.4 Iohexol concentrations for adults
12
Procedure
Concent rat ion
(m gI/m l)
Volum e
(m l)
lumbar m yelography
via LP
180
240
10–17
7–12.5
thoracic myelography
via LP or cervical injection
240
300
6–12.5
6–10
cervical m yelography
via LP
240
300
6–12.5
6–10
cervical m yelography
via C1–2 puncture
180
240
300
7–10
6–12.5
4–10
com plete myelography
via LP
240
300
6–12.5
6–10
cerebral arteriographya
300
≈ 6–12 ml/vessel
IV contrast enhanced CT scan of the brain
240
350
120–250 ml IV drip
70–150 m l bolusb
CT cisternography
via LP or C1–2 puncture
300
350
12
12
CT ventriculography via ventricular catheter
180 c
2–3
plain film ventriculography via ventricular catheter
180
2–3
plain film “shunt-o-gram ” injected via shunt into ventricles
180
2–3
plain film “shunt-o-gram ”
injected via shunt distal to valve so as not to enter into ventricles (to
check distal shunt function)
300
350
10–12
10–12
a m ost centers use Optiray®, see text
b follow with 250 ml bolus of 0.45% NS to rehydrate patient
c180 will be very dense on CT, and som e use 1–3 m l of 140 or diluted 180%(dilute approxim ately 2 parts contrast
to 1 part preservative-free norm al saline)
Plain Radiology and Cont rast Agent s
221
Non-int rat hecal contrast agent s
For in adverten t in trath ecal injection of con trast agen ts not in ten ded for in t rath ecal use, see above.
Ioversol (Optiray®)
Not for in t rathecal use (see above).
Uses an d con cen tration s in clude:
● arteriography: Optiray 300 (ioversol 64%) or Optiray 320 (ioversol 68%). Total procedural dose
sh ould n ot usually exceed 200 m l
● IV con trast en h an ced CT scan of brain :
a) adult: 50–150 m l of Optiray 300, 320, or 100–250 m l of Optiray 240.
Typically: 100 m l of Optiray 320
b) pediatrics: 1–3 m l/kg of Optiray 320
Ioprom ide (Ultravist®)
Not for in trath ecal use (see above). Available in 150, 240, 300 & 370 m g iodin e/m l. Osm olalit y of
Ult ravist 300 is 607.
Cerebral an giography (300 m g/m l): m axim um dose is 150 m l per procedure.
Con trast en h an ced CT (CECT) (300 m g/m l). Pedia tr ics (> 2 years age): t ypical dose in is 1–2 m l/
kg IV, m axim um dose is 3 m l/kg per procedure. Adult:t ypical dose is 50–200 m l, m axim um dose is
200 m l.
Iodixanol (Visipaque®)
Not for in t rathecal use (see above). Triiodin ated, n on -ion ic, isosmola r to blood. For in travascular
use. FDA approved for CECT, som e an giograph ers use Visipaque 270 for cerebral an giography
(sligh tly low er opacification , but also sligh tly low er iodin e dose). Available in 270 an d 320 m g
iodin e/m l.
Iodinat ed cont rast w it h allergies or renally insu ciency
Allergy prep
In dicated for patien ts w ith previous h istor y of react ion to IV iodin ated con trast m aterial. Min or previous reaction s such as h ives an d itch in g m erit preparation w ith th is regim en w h en ever possible.
Pat ien ts w ith an aphylact ic sh ock or severe edem a causin g com prom ise of th e airw ay sh ould probably n ot receive IV iodin e even w ith th is prep, un less absolutely n ecessary. Caut ion : in spite of th is
regim en , th e patien t m ay st ill h ave serious react ion (m odified 33 ). Th is prep h as also been used for
th e rare gadolin ium allergy.
1. utilize n on -ion ic con trast m edium (e.g. ioh exol) w h en ever possible
2. h ave em ergen cy equipm en t available durin g st udy
3. m edicat ion s:
a) steroid ( Table 8.1 for fur th er details of steroid dosing)
● predn ison e 50 m g PO: 20–24 h rs, 8–12 h rs & 2 h rs before st udy
● equivalen t dose of IV Solum edrol® (m ethylpredn isolon e): ≈ 25 m g
b) diph en hydram in e (Ben adr yl®) 50 m g, EITHER IM 1 h r before,
OR IV 5 m in before study
c) option al: H2 an tagon ist, e.g. cim etidin e 300 m g PO or IV 1 h r before study
Medicat ion s for an emergency scan w h en 24 h our prep is n ot possible:
● hydrocort ison e 100 m g IV th en scan w ith in 2 h ours
Prep for renal insu ciency or patients with DM
For pat ien ts w ith DM or m ild ren al in su cien cy (e.g. sligh t serum creatin in e elevation , > 1.2 m g/dl
(U.S.) w h ich is > 100 m cm ol/L) 1 m g/dl of creatin in e (used in th e U.S.) = 88.4 m cm ol/L, to m itigate
again st iodin e con trast-in duced n eph ropathy:
● N-acet yl cystein e (Mucom yst; th e act ual e
cacy of NAC h as n ot been proven , an d m ay be n o better th an hydration alon e): regim en s all accom pany hydration an d in clude:
a) 800 m g PO q 8 h rs for 24 h ours before th e st udy,34 follow ed by 600 m g PO BID for 24 h ours
after th e st udy
b) 600 m g PO BID X 2 days before th e st udy, 600 m g PO BID for 24 h ours after
c) 600-m g IV bolus before th e study, an d 600 m g PO BID for 48 h ours after 35
12
222
Im aging and Diagnostics
●
hydration : 1 L of sterile w ater w ith 3 am ps of sodium bicarbon ate IV at 100 m l/h r, start 1 h our
prior to th e study, an d con tin ue un til en tire L given
12.4.2 React ions t o int ravascular cont rast m edia
General inform at ion
See also t reatm en t of in adverten t in trath ecal inject ion of ion ic con trast agen ts (p.219)
Beta blockers
Beta blockers can in crease th e risk of con trast m edia react ion s, an d m ay m ask som e m an ifestation s
of an an aphylactoid react ion . Th ey also m ake use of epin eph rin e in advisable sin ce th e alph a e ects
of epin eph rin e w ill predom in ate (bron ch ospasm , vasocon st rict ion , in creased vagal ton e). If treatm en t is required for hypoten sion after beta-blocker adm in istration , m ay t r y glucagon 2–3 m g IV
bolus, follow ed by 5 m g IV drip over 1 h our (glucagon h as positive in otropic an d ch ron otropic e ect
th at is n ot m ediated th rough adren ergic path ways).
Idiosyncrat ic react ions and t reat m ent
Hypotension with tachycardia (anaphylactoid reaction)
12
1. m ild: Tren delen burg position . IV fluids
2. if n o respon se but rem ain s m ild:
epin eph rin e (use w ith caution in patien ts w ith coron ar y ar tery disease, lim ited cardiac reserve,
hyperten sion , or un clipped cerebral an eur ysm )
a) 0.3–0.5 m l of 1:1000 SQ (0.3–0.5 m g) q 15–20 m in s (peds: 0.01 m g/kg)
b) or, ASEP recom m en dation s (especially for elderly or patien ts in sh ock): 10 m l of 1:100,000 IV
over 5 to 10 m in (put 0.1 m l of 1:1000 in 10 m l of NS, or dilute 1 am p of 1:10,000 to 10 m l
w ith NS)
3. m oderate to severe or w orsen in g (an aphylaxis): add:
a) IV colloidal fluids, e.g. h etastarch (Hespan ®) 6%(colloids are required sin ce th ere is extravascular sh ift of fluids due to see page, th ese agen ts also carr y a sm all risk of allergic react ion )
b) epin eph rin e (see above). May repeat × 1
c) O2 2–6 L/m in per NC. In tu bate if n ecessary
d) EKG to R/O isch em ic ch anges
4. if sh ock develops: add dopam in e (p. 128), star t at 5 m cg/kg/m in
Hypotension with bradycardia (vasovagal react ion)
1. m ild:
a) Tren delen burg position
b) IV fluids
2. if n o respon se, add:
a) atropin e 0.75 m g IV, m ay repeat up to 2–3 m g over 15 m in s PRN. Use w ith caution in patien ts
w ith un derlying h eart disease
b) EKG an d/or cardiac m on itor: especially if atropin e or dopam in e are used
3. if n o respon se: add dopam in e (p.128), star t at 5 m cg/kg/m in
Urticaria
1. m ild: self lim ited. No treatm en t n ecessar y
2. m oderate:
a) diph en hydram in e (Ben adr yl®) 50 m g PO or deep IM (avoid IV, can cause an aphylaxis itself)
b) cim et idin e (Tagam et®) 300 m g PO or IV diluted to 20 m l an d given over 20 m in s. H2 receptors
con tribute to w h eal an d flare of reaction
3. severe: treat as above for m oderate react ion , an d add:
a) epin eph rin e (see above)
b) m ain tain IV lin e
Facial or laryngeal angioedem a
1. epin eph rin e: see above. May repeat up to 1 m g
2. if respirator y distress: O2 2–6 L/m in . In tu bate if n ecessary (orotrach eal m ay be ver y di cult due
to sw ellin g of tongue, n asotrach eal in t ubation or em ergen cy cricothyrotom y m ay be required)
Plain Radiology and Cont rast Agent s
3.
4.
5.
6.
7.
223
diph en hydram in e: see above
cim etidin e: see above
if an gioedem a is accessible, add ice pack
m ain tain IV lin e
steroids are usually e ect ive on ly for chronic an gioedem a
Bronchospasm
1. m ild to m oderate:
a) epin eph rin e: see above. May repeat up to 1 m l
b) if respirator y distress: O2 2–6 L/m in . In tu bate if n ecessary
c) m ain tain IV lin e
d) in h alat ion al th erapy w ith a β-adren ergic agon ist, e.g. albuterol (Proven til®) if respirator y
th erapy is available, oth erw ise, m etered dose in h aler e.g. pirbuterol (Maxair®) or m etaproteren ol (Metaprel®), 2 pu s
2. severe: treat as above for m oderate react ion , an d add:
a) am in ophyllin e 250–500 m g in 10–20 cc NS slow IV over 15–30 m in s. Mon itor for hypoten sion
an d arrhyth m ias
b) in tubate
3. prolonged: add th e follow in g (w ill n ot h ave im m ediate e ect ):
a) hydrocort ison e 250 m g IV
b) diph en hydram in e: see above
c) cim et idin e: see above
Pulm onary edem a
1.
2.
3.
4.
5.
O2 2–6 L/m in per NC. In tu bate if n ecessary
raise h ead an d body
furosem ide (Lasix®) 40 m g IV
EKG
if hypoxia develops (m ay m an ifest as agitation or com bativen ess), add:
a) m orph in e 8–15 m g IV. May cause respirator y depression , be prepared to in t ubate
b) epin eph rin e: see above. CAUTION: use on ly if MI can be R/O as cause of th e pulm on ar y edem a. Pat ien ts w ith acute in t racran ial path ology m ay be at risk of n eurogen ic pulm on ar y edem a
(p.1178)
Seizures
If seizure is n ot self lim ited, start w ith lorazepam (Ativan ®) 2–4 m g IV for an adult . Take precaution s
for status epilept icus (p.470) an d proceed to oth er drugs as in dicated (p.471).
12.5 Radiat ion safet y for neurosurgeons
12.5.1 General inform at ion
Radiation exposure h as both a determ in ist ic com pon en t (exposure over a certain th reshold w ill
cause a specific injur y) as w ell as a stoch ast ic com pon en t (any dose in creases th e cha nces of an
adverse even t, an d th e h igh er th e cum ulative dose, th e h igh er th e ch an ces).
12.5.2 Unit s
See referen ce.36
Absorbed dose: th e am oun t of en ergy absorbed per un it m ass. Expressed in Gray or rads.
Gray (Gy): th e SI un it . 1 Gy = 100 cGy = 100 rads = an absorbed dose of 1 Joule/kg.
Rad: 1 rad = an absorbed dose of 100 ergs/gram = 0.01 joule/kg = 0.01 Gy = 1 cGy.
Th e biological e ect (dose equivalen t) of radiation : can be expressed in rem or Sieverts.
Sievert (Sv): th e SI un it . Th e dose equivalen t in sieverts is equal to th e absorbed dose in grays
m ultiplied by a “qualit y factor” (Q) w h ich di ers for di eren t sources of radiation , e.g. h igh -en ergy
proton s h ave a Q of 10, x-rays h ave a Q of 1. 1 Sv=100 rem s.
Roen tgen -equivalen t m an (rem ): th e absorbed dose in rads m ult iplied by Q. 1 rem is estim ated to
cause ≈ 300 addit ion al cases of can cer per m illion person s (on e th ird of w h ich are fatal). 1 rem = 0.01
sievert.
12
224
Im aging and Diagnostics
12.5.3 Typical radiat ion exposure
Th e average an n ual exposure to radiation is 360 m rem (about 30 m rem are due to backgroun d cosm ic radiation , ≈ 20% of th e total dose is due to radioact ive potassium -40 w h ich is in ever y cell).
Exposure from a t ran scon tin en tal airlin e fligh t is ≈ 5 m rem .
CXR: causes about 0.01–0.04 rem of exposure to th e ch est.
Spin e x-ray w ith obliques: 5 rem .
CAT scan (brain , n on con trast): m edian e ect ive dose to th e h ead = 0.2 rem , but th e ran ge varied
13 fold w ith in an d across in stitution s.37
Spin e CT: 5 rem .
Cerebral arteriogram : ≈ 10–20 rem (in cludin g fluoroscopy).38
Cerebral em bolizat ion : 34 rem .
Bon e scan : 4 rem .
C-arm fluoroscopy 39 : exposure is sh ow n in Table 12.5.
Doses durin g a m in im ally invasive TLIF40 :
Pat ien t exposure: m ean 60 m Gy to th e skin in th e AP plan e (ran ge: 8–250 m Gy), 79 m Gy in th e
lateral plan e.
Surgeon exposure: 76 m rem to dom in ant h an d, 27 m rem at th e w aist un der a lead apron , an d 32
m rem to an un protected thyroid level detector.
12.5.4 Occupat ional exposure
12
Th e U.S. Nuclear Regulator y Com m ission (NRC) m axim al recom m en ded an n ual occupation al dose
lim its for radiation are sh ow n in Table 12.6.41 Th e 1990 recom m en dation s of th e In tern at ion al
Com m ission on Radiological Protect ion (ICRP) w as to keep exposure ≤ 2 rem /year averaged over 5
years.42
ALARA: an acronym for “As Low As Reason ably Ach ievable” by w h ich th e NRC m ean s m akin g
ever y reason able e ort to keep radiation dose as far below th e lim its as possible con sisten t w ith th e
purp ose for w h ich th e licen sed act ivity is un dertaken .43
Steps to reduce occupat ion al radiation dose (to sta ) durin g surgery:
1. in crease th e distan ce from th e radiation source: radiation exposure is proportion al to th e
inverse squa re of th e distan ce. Conven t ion al w isdom is to t r y to keep 6 feet aw ay. In a AANS
publication , 3 m (10 ft) w as recom m en ded 44
Lead apron s/sh ields m ay or m ay n ot w ork. Distan ce ALW AYS w orks 45 (inverse square law – double th e distan ce an d get 1/4 th e radiation ).
2. sh ieldin g: sh ieldin g is less e ect ive at h igh er kV (used w ith larger patien ts). Por table lead
“doors” are m ore e ective th an apron s. Wrap -aroun d 2-piece apron s are better th an fron t side
apron s. W ith fron t apron s th e w earer m ust always face th e x-ray source, oth erw ise th e apron
can act ually reflect som e radiation back on to th e w earer. Non -lead apron s m ay n ot provide th e
rated protect ion at levels > 100 keV46
3. don’t overuse m agn ification : m ost fluoro system s in crease th e radiation em itted × ≈ 4 to com pen sate for th e associated reduct ion in im age brigh t n ess
4. “boost” m ode can double th e radiation output. Use sh ould be kept to a m in im um
5. use live fluoro on ly w h en absolutely n ecessary
6. for lateral im aging, w h en possible stan d on th e “dow n stream ” (im age in ten sifier (Im I)) side of
th e C-arm : scatter is th e m ost sign ifican t cause of exposure h ere an d is h igh er on th e source
side47 (th is asym m et r y is n ot as sign ifican t for C-spin e 48 )
7. keep th e Im I as close to th e pat ien t as possible (reduces patien t & sta exposure an d im proves
im age qualit y)
8. on AP im ages (w ith th e patien t pron e or supin e): position th e x-ray tube under th e table w ith
th e Im I over th e patien t (low ers scatter exposure to sta )49
9. collima te th e beam as m uch as possible: reduces radiation to patien t an d to sta , an d results in
less im age degradation
10. keep h an ds, arm s, etc. out of th e prim ar y beam at all t im es (con sider usin g leaded gloves if
h an ds n eed to be w ith in th e beam or n earby for an exten ded tim e)
11. m in im ize n um ber of im ages: plan your sh ot, avoid frequen t “ch ecks” or peeks
12. use im age guided n avigation w h en possible an d pract ical
13. leaded glasses are recom m en ded on ly for person n el w ith ver y h igh fluoro tim es: cataracts can
be in duced by sin gle doses of 200 rads (ver y h igh ), cum ulat ive doses of 750 rads h ave n ot been
associated w ith cataracts
Plain Radiology and Cont rast Agent s
225
Table 12.5 Radiation exposure with fluoroscopy39a
Distance from beam
feet
Typical t eam m em ber
Deep exposure
m et ers
Direct beam
Superficial
exposure
(m rem /m in)
patient
4000
1
0.3
surgeon
20
29
2
0.6
assistant
6
10
3
0.9
scrub tech
0
≤2
5
1.5
anesthesiologist
0b
0b
a in a m ock OR set up for maxim al scatter
b after 10 minutes of exposure
Table 12.6 Annual occupational radiation dose limits
Target organ
Recom m ended MAXIMAL dose (rem /yr)
whole body
5
lens of eye
15
skin, hands, feet
50
other organs (including thyroid)
15
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Im aging and Angiography
227
13 Im aging and Angiography
13.1 CATscan (AKA CTscan)
13.1.1 General inform at ion
CAT scan s em ploy ion izin g radiation (x-rays) w ith th e atten dan t risks; see Radiation safety for n eurosurgeon s (p.223).
Atten uation of th e x-ray beam on a CT scan is defin ed in Houn sfield un its. Th ese un its are n ot
absolute, an d var y bet w een CT scan n er m odels. Som e sam ple values are sh ow n in Table 13.1.
13.1.2 Noncont rast vs. IV cont rast enhanced CTscan (CECT)
Non con trast CT scan s are often em ployed in em ergency sit uat ion s (to quickly rule-out m ost acute
abn orm alit ies), to evaluate bon e in great detail, or as a screen ing test . It excels in dem on stratin g
acute blood (EDH, SDH, IPH, SAH), fract ures, foreign bodies, pn eum oceph alus an d hydroceph alus. It
is w eak in dem on stratin g acute stroke (DW I MRI is preferred), an d often h as poor sign al qualit y in
th e posterior fossa (due to bon e art ifact).
IV en h an ced CT scan s are used prim arily for im aging n eoplasm s or vascular m alform ation s, especially in patien ts w ith con train dication s to MRI. All CT con trast agen ts con tain iodin e.
Typical IV dose of con trast: 60–65 m l of e.g. Isovue 300® (p.220) w h ich delivers 18–19.5 gram s
of iodin e.
13.1.3 CT angiography (CTA)
Em ploys rapid inject ion of iodin ated con trast at 3–4 cc/sec, t ypically 65–75 m l of e.g. Isovue 300®.
Optim al results in patien ts w h o can h old th eir breath for 30–40 secon ds (for spiral CT).
Table 13.1 Hounsfield units for a sam ple CTscanner
Definit ions
Hounsfield unit s
Com m ent
no attenuation (air)
–1000
definition
water
0
definition
dense bone
+ 1000
definition
Cranial CT
brain (grey m atter)
30 to 40
brain (white m atter)
20 to 35
cerebral edem a
10 to 14
CSF
+5
bone
+ 600
blood clot a
75 to 80
fat
–35 to –40
calcium
100 to 300
enhanced vessels
90–100
acute SDH or EDH, fresh SAH
Spine CT
disc m aterial
55–70
disc densit y is ≈ 2 × thecal sac
thecal sac
20–30
a Hct < 23% will cause an acute SDH to be isodense with brain
13
228
Im aging and Diagnostics
Various m eth ods m ay be used to determ in e tim in g of CT after inject ion : m ay be based on t im e to
peak in aorta after a sm all test inject ion , or can be based em pirically on tim e, or give injection an d
look for peak in th e region of in terest.
Accuracy is dim in ish ed for vessels th at are perpen dicular to th e axial CT plan e. Also in th e vicin ity
of den se clot, CTA h as trouble resolving th e adjacen t vessels.
13.1.4 CT perfusion (CTP)
Requires use of iodin ated con trast. Areas of in terest are selected from an un en h an ced CT scan in th e
3 supraten torial vascular territories. Con trast is given at a stan dard rate (e.g. 40 m l IV at 5 m l/sec).
Scan s th rough th e region s of in terest are repeated at in tervals, e.g. ever y 2 secon ds for 1 m in ute.
Acetazolam ide (ACZ) (Diam ox®) ch allenge: after th e above, a bolus of 1000 m g of IV ACZ is given ,
an d scan s are repeated at in tervals for approxim ately 10 m in utes, w ith a fin al scan usually at
15 m in utes.
Param eters th en calculated from th e im ages: cerebral blood volum e (CBV), CBF, m ean t t ran sit
t im es (MTT), an d t im e to peak (TTP). In isch em ic st roke, MTT is alm ost alw ays in creased an d CBF is
decreased.
Abn orm alities th at can be dem on strated:
1. flow sign ifican t sten osis: decreased CBV & CBF, in creased MTT an d TTP
2. steal: after ACZ ch allen ge (see above), CBV & CBF decrease, often w ith in creases in th e correspon din g con tralateral territor y; MTT in creases
In com parison to perfusion w eigh ted MRI (PW I) (p.232):
1. PW I acquires m ultiple slices of th e w h ole brain over an d over. CTP is lim ited to a given slice or
several slices (usually 10–20 m m th ick), an d on e h as to ch oose w h ere to place th at slice
2. PW I h as m ore art ifact th an CTP
13.2 Magnet ic resonance im aging (MRI)
13.2.1 General inform at ion
13
Defin ition s 1
Abbreviation s:
● TR: tim e to repet it ion
● TE: t im e to ech o
● TI: tim e to inversion
● T1 : spin -lattice relaxat ion tim e (“tim e to m agn etize”) (regrow th )
● T2 : spin -spin relaxation tim e (“t im e to dem agn etize”) (decay)
13.2.2 T1 w eight ed im age (T1WI)
Sh ort T1 → h igh sign al (brigh t). “An atom ic im age”, som ew hat resem bles CT. Sh orter acquisition t im e
th an T2WI. Proton rich t issue (e.g. H2 O) h as lon g T1.
Table 13.2 Range of acquisition data
short TE
(t e < 50)
long TE
(t e > 80)
short TR
(TR< 1000)
T1WI
long TR
(TR> 2000)
proton density or spin densit y
T2WI
Table 13.3 T1WI, MRI intensit y change
fat (including bone m arrow),
blood > 48 hrs old, m elanin
whit e m at t er
grey m at ter
calcium
(note: grey-bar illustrates direction of intensit y change and does not show actual grey on MRI)
CSF,
bone
Im aging and Angiography
229
Clues to recogn izin g T1W I: CSF is black, subcutan eous fat is w h ite, TR an d TE are sh ort (h un dreds
an d double digits, respectively).
Th e on ly objects th at appear w h ite on T1W I are: fat, m elan in , On yx® (p.1589), an d subacute
blood (> 48 h rs old). W h ite m atter is h igh er sign al th an grey m atter (m yelin h as a h igh fat con ten t).
Most path ology is low sign al on T1W I.
13.2.3 T2 w eight ed im age (T2WI)
Lon g T2 → h igh sign al (brigh t). “Path ological im age.” Most path ology sh ow s up as h igh sign al, in cludin g surroun ding edem a.
Clues to recogn izin g T2WI: CSF is w h ite, TR & TE are lon g (th ousan ds an d h un dreds, respect ively).
13.2.4 Spin densit y im age
AKA balan ced im age, AKA proton den sit y im age. Part w ay bet w een T1W I an d T2W I. CSF = grey,
approxim ately isoden se w ith brain . Becom in g less com m on ly used.
13.2.5 FLAIR
Acronym : FLuid-Atten uated Inversion Recover y. Long TR an d TE. Resem bles a T2W I except th e CSF is
n ulled out (appears dark). Th e grey/w hite in ten sit y pattern is reversed from T1W I an d is m ore
prom in en t. Most abn orm alit ies in cluding MS plaques, oth er w h ite m atter lesion s, t um ors, edem a,
en ceph alom alacia, gliosis an d acute in farcts appear brigh t. Periven tricular lesion s such as MS
plaques becom e m ore con spicuous. Also good for dem on stratin g abn orm alit ies in CSF.
Di eren tial diagn osis of in creased sign al in subarachn oid spaces on FLAIR:
1. subarach noid h em orrh age (SAH): th e best sequen ce for detect in g acute SAH on MRI
2. m en in gitis: occurs in som e cases
3. m en in geal carcin om atosis
4. superior sagittal sin us th rom bosis
5. st roke
6. adjacen t tum or: ? if related to h igh er protein
7. previous adm in istration of gadolin ium
8. h igh levels of FIO2 especially at levels n earin g 100%as m ay be used in patien ts gett in g MRI un der
gen eral an esth esia.2 Sh ow s up in basal cistern s an d in sulci over th e convexity, but n ot in
ven tricles
13.2.6 Echo t rain (AKA fast spin echo (FSE))
t r is h eld con stan t, te is progressively in creased utilizing m ultiple ech oes (8–16) rath er th an on e.
Im age approach es T2W I but w ith substan t ially reduced acquisition t im e (fat is brigh ter on FSE,
w h ich m ay be rect ified by fat suppression tech n iques).
13.2.7 Gradient echo
AKA T2* (called T2-star), an d som e m an ufact urers h ave t radem arked n am es for th is, e.g. “GRASS” (a
GE t radem arked acronym for Gradien t Recalled Acquisition in a Steady State) or FISP. A “fast” T2W I
utilizing a par t ial flip an gle. CSF an d flow in g vessels appear w h ite. Bon e, calcium an d h eavy m etals
are da rk. Typical acquisition data: TR = 22, TE = 11, an gle 8°. Used e.g. in cer vical spin e to produce a
“m yelograph ic” im age, im proves MRI’s abilit y to delin eate bony spurs. Also sh ow s sm all old cerebral
h em orrh ages (seen in 60% of patien ts presen t ing w ith h em orrh agic in farct ion , an d in 18% w ith
isch em ic in farcts 3 ); th ese pat ien ts m ay be at in creased risk of h em orrh age from an ticoagulation .
Gra dient-echo T2WI MRI is th e 3–4 × m ore sen sitive test th an FLAIR for dem on stratin g in t raparen chym al blood (w h ich appears da rk) due to h igh sen sitivit y to param agn etic ar tifact. It is n ot as sen sit ive as th e m ore recen tly in t roduced SW I.
Table 13.4 T1WI, MRI intensity change
brain edem a/wat er
CSF grey m at t er
white
m at t er
bone, fat
(note: grey-bar illustrates direction of intensit y change and does not show actual grey level on MRI)
13
230
Im aging and Diagnostics
13.2.8 “STIR” im age
Acronym for “Sh ort Tau Inversion Recover y.” Sum m ates T1 & T2 sign als. Causes fat to drop out –
som etim es also called fat suppression or “fat sat” (for fat saturation ), allow s gadolin ium en h an cem en t to sh ow up better in areas of fat. Useful prim arily in spin e an d orbit. Ver y good for sh ow in g
bon e edem a (can h elp in dat in g spin e fract ures). Th e dorsal root ganglion m ay en h an ce on fat sup pression im ages.
13.2.9 Cont raindicat ions t o MRI
General inform at ion
An exten sive referen ce 4 details safety issues. Web sites for MRI safety in clude: ww w.MRIsa fety.com
an d www.IMRSER.org . Som e issues th at com e up frequen tly in n eurosurgical patien ts follow s.
Pregnancy and MRI
Durin g th e first trim ester, MRI can cause reabsorpt ion of products of con ception (m iscarriage). Th ere
are n o st udies to determ in e th e lon g term e ect s of MRI on a fetus after th e first trim ester (th e low
risk of MRI in th is situation is probably preferable to th e kn ow n dan gers of ion izin g radiation of xrays (in cludin g CT)5 ). Gadolin ium con trast is con train dicated durin g all of pregn an cy, an d is n ot
approved for use in age < 2 years. Breast-feeding m ust be in terrupted for 2 days after adm in istration
of gadolin ium to th e m oth er.
Com m on contraindicat ions t o MRI
13
1. cardiac pacem akers/defibrillator, im plan ted n eurostim ulators, coch lear im plan ts, in fusion
pum ps: m ay cause tem porar y or perm an en t m alfun ction
2. ferrom agn et ic an eur ysm clips (see below ): som e cen ters exclude all patien ts w ith any t ype of
an eur ysm clip
3. m etallic im plan ts or foreign bodies w ith large com pon en t of iron or cobalt (m ay m ove in field, or
m ay h eat up)
4. Sw an n -Gan z cath eter (pulm on ar y arter y cath eter)
5. m etallic fragm en ts w ith in th e eye
6. placem en t of a vascular sten t, coil or filter w ith in th e past 6 w eeks
7. sh rapn el: BB’s (som e bullets are OK)
8. rela tive con train dication s:
a) claustroph obic pat ien ts: m ay be able to sedate adequately to perform study
b) crit ically ill patien ts: abilit y to m on itor an d access to pat ien t are im paired. Specially design ed
n on -m agn etic ven t ilator m ay be required. Can n ot use m ost bran ds of elect ron ic IV pum ps/
regulators
c) obese patien ts: m ay n ot physically fit in to m any closed bore MRI scan n ers. Open bore scan n ers m ay circum ven t th is but m any utilize low er field stren gth m agn ets an d gen erally produce in ferior qualit y im ages in large patien ts
d) n on -MRI com patible m etal im plan ts in th e region of in terest (or previous surgery w ith h igh
speed drills w h ich m ay leave m etal filin gs): m ay produce suscept ibilit y art ifact w h ich can distort th e im age in th at area
e) program m able sh un t valve (p. 418): m ost w ill tolerate up to a 3 T MRI w ith out perm an en t
dam age, h ow ever, th e pressure sett in g m ay be altered an d th erefore sh ould be rech ecked
after h avin g an MRI for any reason
Aneurysm clips and MRI
MRI con cern s in patien ts w ith a cerebral an eur ysm clip:
1. th e dan ger of th e MRI m agn etic field causin g th e an eur ysm clip to be pulled or torqued o of th e
an eur ysm or to tear th e n eck
2. th e art ifact produced by th e m etal of th e clip in th e m agn et ic field
3. h eat gen erated in th e region of th e clip: n ot clin ically sign ifican t
Th e m ore ferrom agnetic th e clip, th e larger th e force exerted on it by th e m agn etic field an d th e
greater th e im age distor t ion n ear th e clip.
Stain less steel (SS) is classified as m ar tensitic (ferrom agn etic) or austen it ic (n on -ferrom agn etic).
Cobalt-based superalloys are n on -ferrom agn et ic an d in clude Elgiloy (Sugita clips), Phyn ox (Yasargil),
Im aging and Angiography
231
Table 13.5 Magnetic rem anence of aneurysm clips6
Clip
Type of st eel
Magnet ic rem anence (no
unit s)
Drake DR 12
martensitic SS
100
Heifet z
17–7PH
44
Mayfield
martensitic SS
74
Scoville
EN-58J
64
MRI com patible: no
MRI com patible: yes
Olivecrona
0
Sugita
Elgiloy
0
Sugita with loop
gold plated
1
McFadden
Vari-Angle
0
Yasargil
316
0
Yasargil
Phynox
0
Yasargil (old)
1
silver clip
0
an d Vari-An gle (McFadden ). Essen tially all m odern an eur ysm clips are MRI com patible, but pat ien ts
clipped before th e 1990s m ay h ave ferrom agn etic clips.
Table 13.5 sh ow s th e m agn et ic rem an en ce of various clips w h ich is related to th eir ferrom agn etic propert ies. If in doubt at th e tim e of an eur ysm surger y, apply th e follow in g sim ple test: n on ferrom agn et ic clips can n ot be lifted or dragged w ith a sm all m agn et.
13.2.10 Hem orrhage on MRI
Because its sign al ch aracteristics ch ange w ith tim e (an d locat ion ), blood is on e of th e m ost com plex
en tit ies to in terpret on MRI. A m n em on ic for th e ch anges in appearan ce of blood on MRI w ith t im e
is sh ow n in Table 13.6. See also in t racerebral h em orrh age (p. 1330). Blood, h em osiderin an d calcium are dark on GRASS im ages. FLAIR (p. 229) is th e best sequen ce for detect in g SAH on MRI (p.229).
13.2.11 MRI cont rast
Curren t agen ts are m ostly based on gadolin ium (a rare earth m etal w h ich is param agn etic in solut ion s) in clude: gadopen tatate dim eglum in e (Magnevist®), gadodiam ide (Om n iscan ®), gadoversetam ide (OptiMARK®), gadoben ate dim eglum in e (MultiHan ce®) an d gadoteridol (ProHan ce®).
Adverse react ion s:
1. an aphylact ic react ion s: rare (prevalen ce: 0.03–0.1%)
2. n eph rotoxicit y: in ciden ce is low er th an w ith iodin ated agen ts used w ith an giogram s or CT an d xray con trast
3. n eph rogen ic system ic fibrosis (NSF): a rare, but serious illn ess ch aracterized by fibrosis of skin ,
join ts an d oth er organ s, w h ich is associated w ith cer tain gadolin ium con tain in g agen ts given to
patien ts w ith severe ren al failure (m ost w ere on dialysis). Gadolin ium is n ow relatively con train dicated w ith a GFR of 30–60 m l/m in , an d is con train dicated w ith GFR < 30.7 Safest agen ts: Dotarem , Gadovist an d ProHan ce.8 Con trast agen ts w ith a lin ear st ructure appear to be associated
w ith a h igh er risk of NSF an d in clude: Om n iscan , Mult ih an ce, Magn evist an d OptiMARK. In
patien ts w ith en d-stage ren al disease, th e risk is ≈ 2.4% per gadolin ium study 9
4. gadolin ium allergy: use th e sam e allergy prep as for iodin e allergy (p. 221)
5. as of th e t im e of publication of th is book, th e FDA is investigat in g th e risk of accum ulation of
gadolin ium in brain t issue after repeated MRI scan s using gadolin ium based con trast agen ts
(GBCAs).10 In th e m ean tim e, th e FDA is recom m en din g th at h ealth -care profession als con sider
13
232
Im aging and Diagnostics
Table 13.6 Variation of brain MRI signal characteristics of intraparenchym al blood over time
Phase
Approxim at e t im e aft er onset
T1 MRI
T2 MRI
Mnem onica
Hyperacute
0-6 hrsb
I
B
I be
Acute
6-72 hrs
I
D
iddy
Early subacute
3-7 d
B
D
biddy
Late subacute
7-14 d
B
B
baby
Chronic
> 2 weeks
D
D
doodoo
a Mnem onic: B (bright or hyperintense com pared to brain), D (dark or hypointense), I (isointense)
b Som e authors consider up to about 24 hrs as hyperacute
lim itin g th e use of GBCAs to sit uation s w h ere th e addit ion al in form ation provided by th e con trast is absolutely n ecessar y
6. see also issues related to pregn an cy (p. 230)
13.2.12 Magnet ic resonance angiography (MRA)
Th ere are 2 w ays to obtain an MRA
● Gadolin ium en h an ced: usually for extracran ial vessels (e.g. carotids)
● Non con trast im ages usin g flow related en h an cem en t tech n iques (m ost com m on : 2D tim e of fligh t
(2D TOF)). Usually for in tracran ial vessels. Anyth in g th at appears brigh t on T1W I w ill also sh ow up
on MRA, but doesn’t n ecessarily represent blood flow. Th is in cludes fat an d fat-laden m acroph ages
in an area of old stroke. Usin g fat-sat T1W I can m itigate th is. Has som e utilit y in screen ing for
an eur ysm s (p. 1161), an d for an giograph ically occult vascular m alform at ion s (p.1246). High -flow
AVMs are h ard to resolve because arterialized vein s can appear sim ilar to arteries.
13.2.13 Di usion-w eight ed im aging (DWI) and perfusion-im aging
(PWI)
13
Di usion-w eighted im aging
Prim ar y uses: early detect ion of isch em ia (stroke) an d di eren tiatin g act ive MS plaques from old
on es. DW I is sen sitive to ran dom Brow n ian m otion of w ater m olecules.
Tw o im ages are gen erated, an apparen t di usion coe cien t (ADC) m ap (based on a n um ber of
variables (tim e, slice orien tation…)), an d a t race im age (th e actual DW I).11 Freely di using w ater (e.
g. in CSF) appears dark on DWI.
Th e DWI is based on a T2W I, an d anyth in g th at is brigh t on T2W I can also be brigh t on DWI (socalled “sh in e-th rough”). Sin ce brigh t areas on DW I can represen t eith er restricted d usion or T2
“sh in e-th rough .” ch eck th e ADC m ap: if th e area is black on th e ADC m ap, th en th is likely represen ts t rue restricted di usion (recen t in farct is th e m ost com m on etiology).
In traparen chym al areas of brigh t sign al on DW I th at are n ot brigh t on th e ADC m ap are abn orm al an d represen t region s of restricted di usion such as acute stroke.
Di eren tial diagn osis of areas of in creased sign al (brigh t) on DW I:
1. isch em ic brain : a cute st roke an d areas w ith hypoperfusion (pen um bra). W h ile restricted di usion usually in dicates irreversible cell injur y (death ), it can som et im es indicate t issue th at is just
n ear cell death (pen um bra). Acute brain isch em ia can ligh t up w ith in m inutes.12,11 Th e DW I
abn orm alit y w ill persist for ≈ 1 m on th . Th e ADC m ap usually n orm alizes after ≈ 1 w eek
2. cerebral abscess (p. 323): DW I = brigh t , ADC = dark
3. a ct ive MS plaque (old plaques w ill n ot be brigh t)
4. som e t um ors: m ost t um ors are dark on DWI, but h igh ly cellular t um ors m ay h ave decreased diffusion (brigh t on DWI) (e.g. epiderm oids, som e m en in giom as…)
Oth er possible uses of DWI:
TIAs: som e, but n ot all,13 are associated w ith DWI abn orm alit ies. How ever, factors oth er th an focal
isch em ia (e.g. global isch em ia, hypoglycem ia, status epilepticus…) can produce ADC declin e an d th e
DWI im ages m ust th erefore be in terpreted in relation to th e clin ical sett in g.11
DWI m ay also be able to distin guish cytotoxic from vasogen ic edem a (p. 90).14,15
Im aging and Angiography
233
Perfusion-w eight ed MRI
Provides in form at ion related to th e perfusion status of th e m icrocirculation . PW I is th e m ost sen sitvie study for isch em ia of th e brain (m ore sen sitive th an DW I an d FLAIR w h ich prim ar ily sh ow
infa rcted t issue). Th ere are several m eth ods curren tly in use; th e bolus-con trast approach is th e m ost
w idely em ployed.11 Ultrafast gradien t im agin g is used to follow th e gradual reduct ion to n orm al follow in g adm in istration of con trast (usually gadolin ium ). A sign al w ash -out cur ve is derived an d is
com pared to con trast in an arter y. In pract ical term s, PW I is n ot w idely used because of tech n ical
ch allenges. Tim e-to-peak an d m ean -tran sit-tim e are 2 com m on param eters th at are displayed (h igh er sign al = lon ger t im es beyon d n orm al).
DWI and PWI m ism at ch
DW I an d PW I m ay be com bined to locate areas of di usion -perfusion m ism atch (deficit on PW I th at
exceeds th e zon e of di usion deficit on DW I), th us iden tifyin g salvageable brain tissue at risk of
in farction – “pen um bra” (p. 1202) – e.g. to screen for poten tial can didates for th rom bolyt ic
th erapy.16
13.2.14 Magnet ic resonance spect roscopy (MRS)
General inform at ion
Th is sect ion specifically covers proton (H +) MRS w h ich can be perform ed on alm ost any MRI scan n er
(especially un its ≥ 1.5 T) w ith th e appropriate soft w are. Spect roscopy of oth er n uclei (e.g. ph osph orous) can be evaluated on ly w ith specialized equipm en t .
Single voxel MRS
General inform ation
A sm all area is selected on th e “scout” MRI an d th e spectroscopic peaks for th at region are displayed
in reson an ce as a fun ct ion of par ts-per-m illion (ppm ). Sin ce on ly sm all region s are selected, m ay be
subject to “sam plin g” error.
Clin ically im portan t ch aracteristic peaks are delin eated in Table 13.7.
13
Table 13.7 Im portant peaks on proton MRS
Moiet y
Resonance
(ppm )
Descript ion
lipid
0.5–1.5
slightly overlaps lactate peak at TE ≈ 35
lactate
1.3
a couplet peak. Not present in norm al brain. End product
of anaerobic glycolysis, a m arker of hypoxia. Present in:
ischem ia, infection, demyelinating disease, inborn errors
of m etabolism… At higher TE (e.g. TE= 144), the peak
inverts which can help distinguish it from the lipid peak
N-acetyl aspartate
(NAA)
2
a neuronal marker. Norm ally the tallest peak (higher than
Cr or Cho).
↓ in ≈ all focal and regional brain abnormalities (tum or,
MS, epilepsy, Alzheim er’s disease, abscess, brain injury…)
creatine
(Cr)
3a
useful primarily as a reference for choline. Higher in grey
matter than white matter
choline
(Cho)
3.2
marker of mem brane synthesis.
↑ in neoplasms and som e rare conditions of increased
cell growth & in the developing brain. Stroke is low in
choline
a Cr has another less im portant peak
234
Im aging and Diagnostics
choline
a
Cr
n
choline
o
80
n
c
e
NAA
e
s
Cr
NAA
R
60
la cta te
lipid
40
20
0
-20
-40
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
PPM
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
PPM
Fig. 13.1 Proton MRS of (A) norm al brain, and (B) high grade glioma
Illustrative pat terns
13
Norm al brain : See Fig. 13.1.
Tum or: See Fig. 13.1. ↓ NAA, ↑ lact ate, ↑ lipid, ↑ ch olin e (ru le of th um b: w ith gliom as, th e
h igh er th e ch olin e, th e h igh er th e grade up to grade 3, th ereafter n ecrosis reduces relative ch olin e
levels an d th e lipid peak m ay be utilized).
St roke:↑ lact ate peak predom in ates. Ch olin e is ch aracteristically low.
Abscess 17 : Reduced NAA, Cr & ch olin e peaks, an d “atypical peaks” (succin ate, acetate…) from bacterial syn th esis is path ogn om on ic for abscess (n ot alw ays present). Lactate m ay be elevated.
Mu lt ip le scler osis: Blan d pattern . NAA sligh tly reduced. Lactate an d lipid sligh tly elevated. Ch olin e n ot elevated.
Possible uses of MRS
1. di eren tiatin g abscess from n eoplasm
2. post-op en h an cem en t vs. recurren ce of tum or
3. distinguish in g t um or from MS plaques: occasion ally can n ot be di eren tiated
4. in AIDS: m ay be able to h elp di eren tiate toxo from lym ph om a from PML (PML: ↓ NAA, n o sign ifican t in crease in ch olin e, lactate or lipid)
5. th e prom ise of di eren tiatin g t um or in filtration from edem a h as n ot m aterialized
6. som e ut ilit y in dist in guish in g tum or from radiation n ecrosis (p. 1560)
7. large in ositol peak m ay dist in guish h em angiopericytom a from m en ingiom a 18 )
Mult i-voxel MRS
Color coded scan w ith selected overlay for NAA, ch olin e… on e at a t im e. May reduce risk of sam plin g
error.
13.2.15 Di usion t ensor im aging (DTI) MRI and w hit e m at t er t ract s
AKA di usion ten sor tractography (DTT) MRI. An MRI tech n ique th at dem on strates white ma tter
t ra cts by exploit in g th e di eren ce in di usion parallel to th e n er ve axon s th at com prise w h ite m atter
t racts from di usion perpen dicular to th eir course.
Available on ly w ith specialized soft w are for specific MRI scan n ers.
Con train dication s are sam e as for MRI in gen eral (p. 230).
Probably m ost useful to perm it plan n ing surgical approach es th at m in im ize disruption of critical
w h ite m atter t racts durin g in traparen chym al brain surger y for deep lesion s, especially w h en a lesion
(e.g. tum or, AVM, cerebral h em orrh age…) m ay displace th ese t racts from th eir expected position .
Th e m ajor division s of w h ite m atter t ract s dem on strable by DTT MRI are ( Fig. 13.2):
● Projection fibers: ten d to be orien ted rostro-caudally
○ Corticospin al tract coalesces as coron a radiata fun n els in to in tern al capsule an d form s pyram idal tract
Im aging and Angiography
Sh
o
r t U Fib e r
235
s
Su p e rio r Lo n g it u d in a l Fa scicu lu
s
u lu m
Cin g
p u s Ca llo su m
Co r
AC
PC
Un cin at e
lu s
s
ul
uci
cs
a
F
it u
r Lo n g
o
i
r
e
f
In
a scicu
d in a l F
Fig. 13.2 White m atter tracts (color conventions for DTI are not used in this anatom ic diagram)
Com m isural fibers: m edio-laterally orien ted, con n ecting th e cerebral h em isph eres
○ Corpus callosum
○ An terior com m isure
○ Posterior com m isure
● Association fibers: con n ect region s w ith in th e sam e h em isph ere
○ U-fibers: con n ect adjacen t gyri
○ Lon g association fibers: con n ect m ore distan t areas
– Optic radiation s: con n ect lateral gen iculate bodies to visual cortex. Pass lateral to th e body of
th e lateral ven tr icles.
– Un cin ate fasciculus: con n ects th e an terior tem poral lobe to th e in ferior fron tal gyrus. Dam age
can cause lan guage deficits.
– Superior lon git udin al fasciculus (SLF): con n ects region s of fron tal lobe to tem poral an d occipital lobes. Injur y can cause lan guage deficits.
– Arcuate fasciculus: part of SLF. Classic n euroan atom y teach ing: con n ects th e superior an d
m iddle fron tal gyri (Broca’s area (m otor speech )) to th e superior tem poral gyrus (Wern icke’s
area (lan guage com preh en sion )). DTI h as suggested broader con n ection s, in cludin g prem otor
cortex. Injur y causes con duction aph asia
– In ferior lon gitudin al fasciculus (ILF): con n ects tem poral an d occipital lobes at th e level of th e
optic radiation . Injur y can cause deficits in object recogn ition , visual agn osias, prosopagn osia
(face blin dn ess)
– Cin gulum : project from cin gulate gyrus to th e en torh in al cortex as part of th e lim bic system
Th e conven tion for color coding tracts on DTI im ages 19 :
● Blue: superior-in ferior t ract s
● Red: m ediolateral (h orizon tal) t ract s
● Green : an terior-posterior t racts
●
Ow in g to a n um ber of tech n ical con sideration s, DTI is som ew hat m ore operator- depen den t th an
conven tion al MRI.
For surgical plan n in g, th e goal is to keep th e surgical t rajector y rough ly parallel (at < 30°angle) to
th e lon g axis of th e w h ite m atter tract th at on e is t r yin g to preser ve (un proven hypoth esis 20 ).
Surgical “corridors” h ave been described takin g in to con sideration preser vation of w h ite m atter
t racts:
● An terior corridor: parallel to association fibers, betw een th e SLF an d th e cin gulum
● Posterior corridor: en ters at th e parieto-occipital sulcus, passes adjacen t to th e opt ic radiation s
● Lateral corridor
13
236
Im aging and Diagnostics
13.3 Angiography
See En dovascular Neurosurgery sect ion (p. 1575).
13.4 Myelography
Con train dication s:
1. an ticoagulat ion
2. allergy to iodin ated con trast: requires iodin e allergy prep (p. 221). NB: risk of adverse reaction
st ill persists
3. in fect ion at th e desired pun ct ure site
4. exten sive m idlin e lum bar spinal fusion m ay preclude n eedle access to th e subarach noid space
Lu m bar m yelogr am
Usin g ioh exol (Om n ipaque® 140 or 180) as sh ow n in Table 12.4.
Cer vical m yelogram w it h w ater solu ble con t r ast via LP
Use ioh exol (Om n ipaque® 300 or 240) as sh ow n in Table 12.4. In ser t spin al n eedle in to lum bar
subarach noid space, t ilt th e h ead of th e m yelogram table dow n w ith th e pat ien t’s n eck exten ded an d
th en inject dye. If a com plete cer vical block is seen , h ave patien t flex n eck. If th e block can n ot be
t raversed, patien t m ay n eed C1–2 pun ct ure or MRI (first obtain a CT w h ich m ay sh ow dye above th e
block th at can n ot be appreciated on m yelography alon e).
Post m yelogra p h ic CT
In creases sen sitivit y an d specificit y of m yelography (p.1031). In cases of com plete block on m yelogram , CT w ill often sh ow dye distal to th e apparen t site of th e block.
13.5 Radionuclide scanning
13.5.1 Three phase bone scan
13
Techn etium -99 (99m Tc) pertech n etate is a radioisotope th at m ay be attach ed to various substrates
for use in bon e scan n ing. It m ay be used to label polyph osph ate (rarely used today), diph osph on ate 21
(MDP), or ph osph orous (HDP) (th e m ost w idely agen t used curren tly). Accum ulates in areas of
osteoblastic act ivity.
W ith tech n etium 99m -HDP, im ages are obtain ed im m ediately after inject ion (flow ph ase), at
15 m in (blood poolin g) an d in 4 h ours (bon e im aging). Cellulitis sh ow s up as in creased activity in th e
first 2 ph ases, an d th ere is litt le or di use in creased act ivit y in th e 3rd. Osteom yelitis causes
in creased uptake in all 3 ph ases.
Used in evaluation of acute osteom yelitis w ith sen sitivit y an d specificit y of ≈ 95%each , an d is usually positive w ith in 2–3 days. False positives can occur in con dition s involving in creased bon e t urn over, e.g. fract ure, septic arth rit is, tum ors. False n egative can occur in cases w ith associated bon e
in farction .
Applicat ion s for bon e scan s in clude:
1. in fect ion
a) osteom yelit is of th e spine – vertebral osteom yelitis (p. 355) – or sku ll
b) discitis (p.356)
2. tum or
a) spine m etastases (p. 818)
b) prim ar y bon e tum ors of th e spin e (p. 792)
c) skull tum ors (p.775)
3. diseases involving abn orm al bon e m etabolism
a) Paget’s disease: of th e skull or spin e (p.1120)
b) hyperostosis fron talis in tern a (p. 780)
4. cran iosyn ostosis (p. 252)
5. fract ures: spin e or sku ll
6. “low back problem s” (p. 1032): to h elp iden tify som e of th e above con dit ion s
13.5.2 Gallium scan
Nuclear m edicin e scan w ith 67Ga citrate w h ich accum ulates in areas of in flam m ation an d som e
m align an cies. Ut ilit y in n eurosurger y for: sarcoidosis (p.189), ch ron ic vertebral osteom yelitis; see
alsocom parison to bon e scan (p. 355).
Im aging and Angiography
237
References
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of MRI Pulse Sequen ces an d Tech n iqu es in Neu roim agin g. Surg Neurol. 1997; 47:185–199
[2] An zai Y, Ish ikawa M, Sh aw DW , Art ru A, Yarnykh V,
Maravilla KR. Param agn et ic e ect of supplem ental
oxygen on CSF hyperin ten sity on fluid-atten uated
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sp on tan eous brain h em orrh age: Correlation w ith
sign s of m icroan giopathy an d clin ical d ata. Radiology. 2006; 238:240–247
[4] Sh ellock FG. Referen ce Man u al for Magn etic Reson an ce Safet y. Salt Lake Cit y, Utah : Am irsys, Inc.;
2003
[5] Edelm an RR, Warach S. Magn et ic Reson an ce Im agin g (First of Tw o Parts). N En gl J Med . 1993;
328:708–716
[6] Rom n er B, Olsson M, Lju nggren B, et al. Magn etic
Reson an ce Im agin g an d An eur ysm Clip s: Magn etic
Prop erties an d Im age Art ifacts. J Neurosurg. 1989;
70:426–431
[7] Kan al E, Barkovich AJ, Bell C, et al. ACR guid an ce
docum en t for safe MR pract ices: 2007. Am J Roen tgen ol. 2007; 188:1447–1474
[8] Med icin es an d Health care Prod ucts Regu latory
Agen cy. 2007
[9] Deo A, Fogel M, Cow p er SE. Nep h rogen ic system ic
fibrosis: a popu lation stud y exam in ing th e relat ion sh ip of disease developm en t to gad olin iu m exposure. Clin J Am Soc Nep h rol. 2007; 2:264–267
[10] U.S. Food an d Drug Adm in istration (FDA). FDA Dru g
Safet y Com m un ication : FDA evalu atin g th e risk of
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[11] Fish er M, Albers GW . Ap plication s of di usion -perfusion m agn et ic reson an ce im agin g in acute ischem ic st roke. Neurology. 1999; 52:1750–1756
[12] Prichard JW , Grossm an RI. New reason s for early
use of MRI in st roke. Neurology. 1999; 52:1733–
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[13] Ay H, Buon an n o FS, Rordorf G, et al. Norm al di usion -w eigh ted MRI d u rin g stroke-like d eficits. Neurology. 1999; 52:1784–1792
[14] Ay H, Buon an no FS, Sch aefer PW , et al. Posterior
Leu koen cep h alopathy W ith ou t Severe Hyperten sion : Ut ilit y of Di usion -Weigh ted MRI. Neu rology.
1998; 51:1369–1376
[15] Schaefer PW , Buon ann o FS, Gon zalez RG, Sch w am m
LH. Di usion -Weigh ted Im agin g Discrim in ates
Bet w een Cytotoxic an d Vasogen ic Edem a in a Pat ien t w ith Eclam psia. St roke. 1997; 28:1082–1085
[16] Marks MP, Tong DC, Beaulieu C, et al. Evaluation of
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1999; 52:1792–1798
[17] Mar tin ez-Perez I, Moren o A, Alon so J, Aguas J, Con esa G, Capdevila A, Arus C. Diagn osis of brain
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[18] Barba I, Moren o A, Mar tin ez-Perez I, et al. Magn et ic
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[19] Douek P, Turn er R, Pekar J, Patronas N, Le Bih an D.
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[20] Kassam AB, Labib MA, Bafaquh M, et. al. Part I: Th e
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1974; 2:307–310
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Im aging and Diagnostics
14 Elect rodiagnost ics
14.1 Elect roencephalogram (EEG)
14.1.1 General inform at ion
Th e prim ar y use of EEG is in th e diagn osis an d m an agem en t of seizure disorders. Non -convulsive
use of EEG is essen tially lim ited to m on itoring for burst suppression (see below ) (e.g. in duced barbit urate com a) or for di eren tial diagn osis of di use en ceph alopathy, in cludin g:
1. di eren tiatin g psych ogen ic un respon siven ess from organ ic: a n orm al EEG in dicates eith er psych iatric un respon siven ess or locked-in syn drom e
2. n on -convulsive status epilepticus (seizures): absen ce or com plex part ial status
3. subclin ical focal abn orm alit ies: e.g. PLEDs (see below ), focal slow in g…
4. specific pattern s diagn ostic for certain path ologies: e.g.:
a) periodic lateralizin g epileptiform disch arges (PLEDs): m ay occur w ith any acute focal cerebral
in sult (e.g. h erpes sim plex en ceph alitis (HSE), abscess, t um or, em bolic in farct): seen in 85% of
cases of HSE (on set 2–5 d after presen tation ), if bilateral is ≈ diagn ostic of HSE
b) subacute sclerosing pan en ceph alitis (SSPE) (path ogn om on ic pattern ): periodic h igh voltage
w ith 4–15 secs separation w ith accom panying body jerks, n o ch ange w ith pain ful st im ulat ion
(di eren tial diagn osis in cludes PCP overdose)
c) Creutzfeldt-Jakob disease (p.367): m yoclonic jerks. EEG → bilateral sh arp w ave 1.5–2 per secon d (early → slow in g; later→ triph asic). May resem ble PLEDs, but are react ive to pain ful stim ulat ion (m ost PLEDs are n ot)
d) t riph asic w aves: n ot really specific. May be seen in h epatic en ceph alopathy, post-an oxia, an d
hypon atrem ia
5. object ive m easure of severit y of en ceph alopathy: usually used for an oxic en ceph alopathy (e.g.
periodic spikes w ith seizures in dicates < 5%ch an ce of n orm al n eurologic outcom e, w ith h igh
m ortalit y). Alph a com a, burst suppression , an d elect rocerebral silen ce are all poor
progn osticators
6. di eren tiatin g hydran en ceph aly (p. 288) from severe hydroceph alus
7. as a clin ical con firm ator y test in th e determ in at ion of brain death (p. 310)
14.1.2 Com m on EEG rhyt hm s.
Com m on EEG rhyth m s are sh ow n in
14
Table 14.1.
14.1.3 Burst suppression
Isoelectric in tervals in terrupted by bursts of 8–12 Hz electrical act ivit y th at dim in ish to 1–4 Hz prior
to electrical silen ce.1 Often used as an en dpoin t for t it ratin g n europrotect ive drugs such as barbiturates, propofol…
14.2 Evoked pot ent ials
14.2.1 General inform at ion
Evoked poten tials are averaged EEG w aveform s recorded follow in g repetitive stim ulat ion . Th e process of averaging n ulls-out EEG act ivity th at is n ot tim e -locked to th e st im ulus. Resultan t w aveform s
con tain peaks th at are n am ed N (n egative – upw ard deflection ) or P (positive – dow nw ard deflect ion ) follow ed by th e laten cy in m illisecon ds to th e on set of th e peak.
Table 14.1 Com mon EEG rhythms
Rhythm
Sym bol
Frequency
delta
Δ
0–3 Hz
theta
θ
4–7 Hz
alpha
α
8–13 Hz
beta
β
> 13 Hz
Elect rodiagnost ics
239
14.2.2 Sensory evoked pot ent ials (SEP)
General inform at ion
May use elect rical st im ulat ion of periph eral n er ves (som atosen sor y or (SSEP)), auditor y clicks
th rough earph on es (auditor y or AEP, AKA BAER (brain stem auditor y evoked respon se)) or flash in g
ligh ts th rough goggles (visual EP or VEP).
Evoked poten tials are m ost com m on ly used by n eurosurgeon s for in traoperative m on itoring purposes. SSEP (especially from m edian n er ve st im ulation ) also h as progn ostic sign ifican ce in cer vical
spon dylotic m yelopathy 2 alth ough use for th is purp ose is lim ited.
Typical w aveform s
Abbreviations
Abbreviation s used below : BAER = brain stem auditor y evoked respon se; UE/LE SSEP = upper/low er
extrem it y som atosen sor y evoked poten tial; PR VER = pat tern reversal visual evoked respon se w h ich
requires patien t cooperat ion an d visual atten t ion as opposed to flash VER w h ich m ay even be don e
th rough closed eyelids. See also referen ces.3,4
14.2.3 Int ra-operat ive evoked pot ent ials
General inform at ion
EPs m ay be used for intra-operative m onitoring (e.g. m onitoring hearing during resection of vestibular
schw ann om as, or m onitoring SSEPs during som e spine surgery), however, their delayed nature often
m akes them of lim ited usefulness in avoiding acute intra-operative injury. A 10% increased latency of
Table 14.2 Typical stim ulus values for intra-op evoked potentials
Test
St im ulus
Com m ent
Freq (Hz)
Durat ion
(m cS)
Magnit ude
BAER
23.5
150
85–100 dB
rarefaction usually better than compression
UE SSEP
(median nerve at wrist)
4.7
300–700
up to 50 mA
supram axim al stimulus (sensory
threshold + motor threshold)
LE SSEP
(posterior tibial at ankle)
4.7
300–700
up to 100 m A
supram aximal stimulus
PR VER
1.97
16 × 16 checks, 1.6 cm each, at 1
m eter (subtends 55" arc visual angle)
Table 14.3 Input characteristics for acquiring evoked potentials
Test
Analysis
Elect rode derivat ions
Input filt er
(Hz)
Sensit ive
(m cV)
Durat ion
(m S)
Reps
BAER
150–3000
25
15
1500
M1 a -CZZ, M2 *-CZ, ground = FZ
UE SSEP
30–3000
50
55–60
600
FZ-Erb’s point, CV7 -FPZ, C3 -FPZ, C3 ’-NC
(non-cephalic, e.g. shoulder)
LE SSEP
30–3000
50
60
600
popliteal fossa (front to back), CZ-FPZ,
back (L5 -T12 ) (difficult in obese or
elderly), CI-CC (optional: som atosensory ipsilateral to contralateral)
PR VER
5–100
50
500
100
O1-A1 , OZ-A1 , O2 -A1 , OZ-CZ
a M= mastoid (“i” is ipsilateral to stim ulus, and “c” is contralateral)
14
240
Im aging and Diagnostics
a m ajor EP peak, or a drop in am plitude of ≥ 50% is significan t and should cause the surgeon to assess
all variables (retractors, instrum ents, blood pressure…). Intra-operative SSEPs m ay also be used to
localize prim ary sensory cortex in anesth etized patients (as opposed to using brain m apping techniques in awake patients) by looking for phase reversal potentialsacross the central sulcus.5,6
Brainst em audit ory evoked responses (BAER)
AKA auditory brainstem response (ABR), AKA auditory evoked poten tial (AEP). Auditory clicks are
delivered to the patient by earphones. Peaks Table 14.4). Once used for assistance in diagnosing vestibular schwann om as, their use for intraoperative m onitoring is lim ited and has been largely replaced
by direct eighth cranial n erve m onitoring w hich provides m ore rapid inform ation for th e surgeon .
SSEP m onit oring during spine surgery
Paralytics act ually im prove SSEP recordings by reducin g m uscle art ifact, but w ill abolish th e visible
t w itch th at con firm s th at th e st im ulus is bein g received.
Typical stim ulus sites: m edian , uln ar, an d t ibial n er ves. Im pulses ascen d in th e ipsila tera l posterior
colum n . UE SSEPs travel prim arily in th e dorsal colum n s, but LE SSEPs are carried m ostly in th e dorsolateral fasciculus (p. 72) w h ich is supplied by th e a nter ior spin al artery. Th us, UE an d LE SSEPs are
m ore sen sitive to direct m ech an ical e ect s prim arily on th e posterior spin al cord (sen sor y) an d m ay
rem ain un ch anged w ith som e injuries to th e an terior cord (m otor), h ow ever, LE SSEPs can detect
isch em ic e ect s on th e an terior cord by vir t ue of involvem en t of th e an terior spin al artery.
In a person al series of 809 pat ien ts,7 17 h ad SSEP degradation , 14 of th ese (82%) respon ded to
in t ra-op in ter ven tion s (see below ), an d in 13 of th ese 14 (93%) th ere w ere n o n ew deficits. In th e 3
th at did n ot respon d, 2 h ad sign ifican t n ew n eurologic deficits.
Table 14.4 Evoked potential waveform s (note: values may di er from lab to lab)
Test
Figure
Possible generators
BAER
CM
P1 P2
Mi-CZ
P3 P4 P5
P7
P6
0.25 uV
CM cochlear m icrophonic
P1 1distal VIII nerve,
P2 2 proxim al VIII or cochlear nucleus,
P3 3 lower pons (? superior olivary com plex),
P4 4mid-upper pons,
P5 5upper pons or inferior colliculus
10 mS
14
UE SSEP
C3'-FPz
Cv7-FPz
N9 9(on FZ-EPP where EP is Erb’s point) AKA EP:
entry of volley into distal brachial plexus,
N11 11(on CV7 -FPZ): root entry zone (cervical
region),
N13 13cervicom edullary junction (recorded from
C2),
N19 19prim ary sensory cortex,
P22 22(early) m otor cortex,
P22 22(late) IPSP “reaction” to N18 18
P22
P22 early
N19
N13/P13
N11
EP
2 uV
Fz-Ep
10 mS
LE SSEP
Cv7-FPz
N25
N27
Cz-FPz
P22
L5-T12
0.25 uV
P40
N30
P22 2(on L5-T12 ): lum bo-sacral plexus,
P40 4(on CZ-FPZ): sensory cortex (analogous to N18
in UE SSEP, reversed in polarity for ? reason),
N27 2(on CV7 -FPZ): ? dorsal colum n nucleus
N30 30
N50
50 mS
PR VER
P100 striate & pre-striate occipital cortex, with
contributions from thalamocortical volleys
P100
Oz-Cz
5 uV
500 mS
Elect rodiagnost ics
241
Table 14.5 Norm al values for evoked potentialsa (note: values m ay di er from lab to lab)
Test
BAER
Param eters m easured
– – Norm al values – –
Mean
+ 2.5 std dev
I-V peak latency
4.01 mS
4.63 m S
I-III peak latency
2.15 mS
2.66 m S
V absolute latency
5.7 m S
6.27 m S
III-V peak latency
N99-N1818 peak
latency
9.38 mS
11.35 m S
LE SSEP
P2222-P40 40 peak
latency
15.62 mS
20.82 m S
P4040 absolute
latency
37.20 m S
44.16 mS
P100 10 absolute
latency
P100 inter-eye difference
prolongation suggests lesion bet ween
pons & colliculus, often vestibular
schwannom a
prolongation suggests lesion bet ween
lower pons & m idbrain, may be seen in
M.S.
UE SSEP
PR VER
Com m ent
+ 3 S.D.
8–10 mS
Inter-eye difference is more sensitive
with full field stimulation. Monocular
defect suggests conduction defect in
that optic nerve anterior to chiasm
(e.g. M.S., glaucoma, com pression
retinal degeneration). Bilateral defect
does not localize.
a normal values in boldface are critical values used as cutoff for abnorm al results
Transcranial m ot or evoked pot ent ials (TCMEPs)
An est h et ic requ ir em en t s: In addition to EP an esth etic requirem en ts, n eurom uscular blockade m ust
be m in im ized to perm it ≥ 2 out of 4 t w itch es.
AKA m otor evoked poten tials (MEP): tran scran ial elect rical or m agn etic st im ulation of m otor cortex an d descen din g m otor axon s w ith recordin g of m otor poten tials from distal spinal cord or m uscle
groups. Usin g direct elect rical st im ulation is lim ited in aw ake patien ts by local pain . Due to th e large
poten tials, th e acquisition t im e is sh orter an d feedback to th e surgeon is alm ost im m ediate. How ever, due to patien t m ovem en t from th e m uscle con tract ion s, con tin uous recording is usually n ot
possible (except w ith m on itoring th e respon se over th e spin al cord). Useful for surger y involving th e
spinal cord (cervical or th oracic), n o ut ilit y for lum bar spin e surgery.Seizures occur rarely, usually in
patien ts w ith in creased seizure risk an d w ith h igh -rate stim ulat ion frequen cy.
Con train dication s to MEP:
1. h istor y of epilepsy/seizures
2. past surgical skull defects
3. m etal in h ead or n eck
4. use special care w ith im plan ted elect ron ic devices
Descending evoked pot entials (DEP)
(Form erly referred to by th e m isleading term “n eurogen ic m otor evoked poten tials”). Rost ral stim ulation of th e spin al cord w ith recording of a caudal n eurogen ic respon se from th e spinal cord or
periph eral n er ve, or a m yogen ic respon se from a distal m uscle. DEPs can be m ediated prim arily by
sen sor y n er ves an d th erefore do n ot represen t t rue m otor poten tials. How ever, sh ow n to be sen sit ive to spinal cord ch anges an d m ay be useful w h en TCMEPs can n ot be obtain ed.
14
242
Im aging and Diagnostics
14.2.4 Elect rophysiologic m onit oring crit eria t o t rigger not ificat ion of
surgeon
Any of th e follow in g:
1. SSEP:
a) 50% decrease in peak sign al am plitu de from baselin e
b) in crease in peak laten cy > 10%
c) com plete loss of a w aveform
2. TCMEP: sustain ed 50%decrease in sign al am plitude
3. DEP: decrease in sign al of > 60%
Int ervent ions for loss or degradat ion of m onit oring signal during spine surgery
W h en com pression is th e culprit , th e progn osis m ay be good. Vascular injuries gen erally do n ot fare
as w ell.
Option s/suggest ion s in clude (adapted/excerpted from th e “Vitale ch eklist”8 ):
1. verify th at th e ch ange is real (check con n ection s, equipm en t…)
2. place OR on alert status
a) an n oun ce in traoperative pause an d stop th e case
b) elim in ate possible dist ract ion s (m usic, un n ecessar y conversation s…)
c) “m uster th e t roops”: th e attendin g an esth esiologist, sen ior n eurologist or n europhysiologist
an d experien ced n urse are called to th e room . Con sult a surgical colleague if n ecessar y
3. an esth etic/m etabolic con siderat ion s
a) optim ize m ean arterial pressure (MAP usually > 85 m m Hg preferred)
b) ch eck h em atocrit for an em ia (could con tribute to cord isch em ia)
c) optim ize blood pH (ru le out acidem ia) an d pCO2
d) n orm alize patien t body tem perature
e) ch eck an esth et ic tech n ical factors: assess exten t of paralytics
f) discuss possibilit y of “Stagn ara w ake up test” (see below ) w ith atten din g an esthesiologist an d
scrub n urse
4. tech n ical/n europhysiologic con sideration s
a) rule-out 60 Hz. in terferen ce from oth er equipm en t (OR table, C-arm , m icroscope… anyth in g
w ith a plug)
b) verify th at st im ulating electrodes recordin g leads are m akin g good con tact
14.3 NCS/EMG
14
14.3.1 General inform at ion
Elect rodiagn ostic studies of periph eral n er ves con sist of t w o parts:
1. con duction m easurem en ts: t ypically referred to as “NCV” (n er ve con duction velocit y) but tech n ically sh ould be called NCS (n er ve con duction st udies) sin ce am plitu de, laten cy an d duration of
m otor & sen sor y n er ves are also evaluated
2. elect rom yogram (EMG) AKA “n eedle exam ” (see below )
14.3.2 Elect rom yography
General inform at ion
Th ere are 3 ph ases of an EMG exam :
Ph ase 1 – in sertion al act ivity: th e elect ric respon se of th e m uscle to m ech anical irritation caused
by sm all m ovem en ts of th e n eedle
Ph ase 2 – spontan eous act ivity: in m uscle at rest
1. n orm al: silen t w ith station ar y n eedle on ce in sertion al activit y h as subsided
2. spon tan eous act ivity: in depen den tly produced electrical act ivity. Usually abn orm al (alth ough
som etim es seen in n orm al volun teers).
a) after den er vation (secon dar y to a n er ve injur y) or m uscle injur y:
● positive sh arp w aves (PSW )
● fibrillation poten tials (AKA fibrillat ion s or fibs): act ion poten tials arisin g from single m uscle
fibers. Detect able on EMG; n ot visible to th e n aked eye, c.f. fasciculat ion s (p. 505). Earliest
on set 7–10 days after den er vation , som etim es n ot for 3–4 w eeks. If th e n er ve recovers, it
Elect rodiagnost ics
243
m ay rein n er vate th e m uscle, but w ith larger m otor un its resultin g in lon ger durat ion an d
decreased n um bers
b) m yoton ic disch arges (“dive bom ber” soun d on speaker m on itor)
c) com plex repetit ive disch arge (CRD): eph aptic con duction of groups of adjacen t m uscle fibers.
Occurs in n europath ic or m yopath ic disorders
d) fasciculation poten tials: n on specific, but t ypically associated w ith m otor n euron disease (ALS)
(p.183)
e) other less com m on spon tan eous act ivity in cludes: m yokym ic, n eurom yton ic an d cram p
disch arges
Ph ase 3 – volit ion al act ivit y: evaluated w ith m in im al volit ion al e ort an d m axim al e ort
1. m otor un it action poten tial (MUAP) an alysis: in cludes evaluation of m otor un it am plitu de, duration , polyph asia an d stabilit y. Gen erally in crease am plitude an d duration suggest a disorder of
th e LMN, an d reduct ion of am plitude an d duration suggests a prim ar y m yopath ic disorder
2. w ith m in im al volition al e ort . Tw o possible abn orm al fin din gs
a) reduced recruit m en t (or fast firing) is always in dicative of a n europath ic process
b) early or in creased recruit m en t: in dicat ive of a m yopath ic process
3. w ith m axim al e ort
Definit ions
SNAP: sen sor y n er ve act ion poten tial. Key con cept: sin ce th e ganglion of th e sen sor y n er ves lies
w ith in th e n eural foram en , pregan glion ic lesion s (injur y to th e n er ve root proxima l to th e n eural
foram en , e.g. root com pression by h ern iated disc or root avulsion ) does n ot a ect th e cell body, an d
th erefore th e distal SNAP is un a ected.9 Postganglion ic lesion s (distal to th e n eural foram en , e.g.
periph eral n er ve injur y) reduces SNAP am plitu des an d/or slow s th e sen sor y con duction velocit y.
F-wave: st im ulation of a n er ve causes orth odrom ic an d an tidrom ic con duct ion . Som e an terior
h orn cells th at are stim ulated an tidrom ically w ill fire orth odrom ically producin g th e F-wave. F-w ave
laten cy m ay be prolonged in m ultilevel radiculopathy (n ot sen sitive). Most h elpfu l in evaluatin g
proxim al root slow in g, e.g. GBS (p. 184).
H-reflex: pract ical ≈ on ly in S1 n er ve root, sim ilar in form ation to th e an kle jerk. St im ulation of Ia
a eren t fibers passes th rough a m on osyn apt ic con n ection causin g an orth odrom ic alph a-m otor
act ion poten tial th at can be m easured in the t riceps surae.
Volition al act ivity: th e m otor un it action poten tial (MUAP) can be assessed on ly w ith volun tar y
m uscle con tract ion by th e patien t. Com pon en ts of th e MUAP m easured in clude: am plitu de, rise
t im e, duration , an d n um ber of ph ases (crossin gs of th e baselin e).
Polyph asic poten tials: MUAPs w ith > 4 ph ases. Norm ally com prise < 15% of MUAPs. Follow in g a
n er ve injur y, abn orm ally in creased polyphasic poten tials can be seen 6–8 w eeks after rein n er vation
begin s, gradually in crease over several m on th s, an d th en begin to w an e (as firin g becom es m ore
syn ch ron ous).
Myoton ia: th ere are a n um ber of m yoton ic con dition s, in cluding m yoton ic dyst rophy in w h ich
th ere is sustain ed con tract ion of th e m uscle. Classic EMG fin din g: “dive bom ber” soun d due to m yoton ic discharges.
EMG for radiculopat hy
EMG pearls for the neurosurgeon
Gen eral prin ciples:
● EMG – if a reliable m otor exam can be don e, th e EMG w ill n ot likely add any in form ation . A n orm al
m otor exam w ill usually be associated w ith a n orm al EMG
● EMG is n ot extrem ely sen sitive for radiculopathy (e.g. irritative radiculopathy m igh t n ot be picked
up), th is is m ore likely in th e cer vical region th an lum bar. How ever, w h en abn orm al, EMG is ver y
specific
● EMG is best reser ved for cases w ith docum en ted w eakn ess w h ere addition al localizing/progn ostic
in form ation is n eeded, or w h en th e pat ien t’s st ren gth can n ot be reliably assessed (in abilit y to
cooperate, fun ct ion al overlay…)
● Tim in g
○ It takes about 3 w eeks after on set of radiculopathy for th e EMG to reliably sh ow any fin din gs
○ “Acute ch anges” begin at about 3 w eeks an d can last up to about 6 m on th s
○ Ch ron ic ch anges can be seen startin g at about 6 m on th s, an d m ay persist in defin itely
14
244
Im aging and Diagnostics
Cer vical EMG:
● EMG is m ost h elpfu l for n er ve roots C5-T1. Th ere are n o good m uscles to reliably test C3-4, an d
com pression h ere m ay cause fin din gs in low er n er ve roots
Lum bar EMG:
If lum bar MRI is n orm al in a pat ien t w ith eviden ce of m otor w eakn ess (e.g. foot drop), do an EMG
to look for periph eral n europathy (again , a good m otor exam can give th e sam e in fo). If th e EMG is
n egative for periph eral n europathy (e.g. peron eal n er ve palsy) th en do an MRI (or CT) of abdom en
an d pelvis to look for pelvic floor t um or
●
Findings
In clude spon tan eous act ivity (fibs & PSW s, see above).
Th e earliest possible fin din g (w ith in 2–3 d) is reduced recruitm en t w ith volition al act ivity, but
th is occurs on ly w ith sign ifican t com pression of m otor fibers.
EMG is useful if th ere is a con cern about possible overlappin g periph eral n europathy (e.g. carpal
t un n el syn drom e vs. C6 radiculopathy).
EMG criteria for radiculopathy
1. fibrillation s an d/or positive sh arp w aves in at least 2 m uscles in n er vated by a sin gle n er ve root in
question , but by 2 di eren t per iphera l n er ves
2. abn orm al paraspin als: th is supports th e diagn osis, but is n ot required sin ce paraspin als w ill be
n orm al in ≈ 50%
14
Lum bar radiculopathy from h ern iated disc
W ith radiculopathy, SNAP is usually n orm al (see above). Paraspin al m uscle fibrillation s m ay occur.
Accuracy in predicting level of involvem en t 10 is ≈ 84%.
Foot drop: th e sh ort h ead of th e biceps fem oris in th e LE is th e first m uscle in n er vated by th e
peron eal division of th e sciatic n er ve at or just above th e popliteal fossa just after th e n er ve splits o
from th e sciatic n er ve. In cases e.g. of foot drop it is a good m uscle to test to determ in e if th ere is a
peron eal n europathy vs. a m ore proxim al lesion (i.e. above th e popliteal fossa).
Fin din gs w ith h ealin g radiculopathy (e.g. follow in g discectomy or spon tan eous h ealing):
● m otor poten tials return first (if n er ve injur y w ere “com plete”, it w ould take a m on th to return )
● if lost, sen sor y poten tials return last or m ay n ot return
● follow in g lam in ectom y, paraspin al poten tials m ay n o lon ger be useful for EMG because cutt in g
th e m uscles during surger y alters th eir elect rical sign als result in g in e ect ive den er vation due to
m uscle injur y. Fibs an d PSW s decrease in am plit ude over t im e but m ay rem ain present
in defin itely
EMG in plexopathy
Reduct ion of SNAP w ith no pa ra spina l m uscle fibrillation s (th e dorsal ram i exit proxim ally to in n ervate th e paraspin als, an d are involved ≈ only w ith root lesion s).
EMG in nerve root avulsion
Produces m uscles w eakn ess an d sen sor y loss w ith n orm al SNAP sin ce th e lesion is proxim al to th e
dorsal root gan glion (w h ere th e cell bodies for th e sen sor y n er ves are located).
References
[1] Don n egan JH, Blit t CD. In : Th e Elect roen cep h alogram . Mon itoring in Anesth esia an d Crit ical Care
Med icin e. New York: Ch urch ill Livin gston e;
1985:323–343
[2] Holly LT, Matz PG, An d erson PA, Gro MW , Hear y
RF, Kaiser MG, Mum m anen i PV, Ryken TC, Ch oudh ri
TF, Vresilovic EJ, Resn ick DK. Clin ical progn ostic
in dicators of surgical outcom e in cer vical spon dylotic m yelopathy. J Neurosurg: Spine. 2009;
11:112–118
[3] Ch iap p a KH. Evoked Poten t ials in Clin ical Medicin e
(First of Tw o Parts). N Engl J Med. 1982; 306:1140–
1150
[4] Ch iap pa KH. Evoked Poten t ials in Clin ical Med icin e
(Secon d of Tw o Parts). N En gl J Med . 1982;
306:1205–1211
[5] Gregori EM, Goldrin g S. Localization of Fu n ct ion in
th e Excision of Lesion s from th e Sen sorim otor Region . J Neu rosu rg. 1984; 61:1047–1054
[6] Woolsey CN, Erickson TC, Gibson W E. Localization
in Som atic Sen sor y an d Motor Areas of Hum an Cerebral Cortex as Determ in ed by Direct Recording of
Evoked Poten t ials an d Elect rical Stim ulat ion . J Neu rosurg. 1979; 51:476–506
[7] Roh M, W ilson -Hold en T, Padberg A. Th e u tilit y of
SSEP m on itorin g durin g cervical spin e surgery:
How often does it prom pt in tervent ion an d a ect
outcom e. 2002
Elect rodiagnost ics
[8] Vitale MG, Skaggs DL, Pace GI, Wrigh t ML, Matsu m oto H, An derson RCE, Brockm eyer DL, Dorm an s JP,
Em an s JB, Erickson MA, Flyn n JM, Glotzbecker MP,
Ibrah im KN, Lew is SJ, Luh m an n SJ, Men diratta A,
Rich ards BS, III, San ders JO, Sh ah SA, Sm ith JT, Song
KM, Spon seller PD, Sucato DJ, Roye DP, Len ke LG.
Best Pract ices in In traoperative Neu rom on itorin g in
Spine Deform it y Surgery: Developm en t of an In t raoperative Ch ecklist to Op tim ize Respon se. Sp in e
Deform it y. 2014; 2:333–339
245
[9] Benecke R, Conrad B. Th e distal sen sor y n er ve
act ion p oten t ial as a diagn ostic tool for th e di eren t iation of lesion s in dorsal roots an d perip h eral
n er ves. J Neurol. 1980; 223:231–239
[10] Youn g A, Gett y J, Jackson A, et al. Variat ions in th e
Pattern of Mu scle In n ervation by th e L5 an d S1
Nerve Roots. Sp in e. 1983; 8:616–624
14
Part IV
Developm ent al Anom alies
IV
15 Prim ary
Intracranial
Anom alies
248
16 Prim ary Spinal
Anom alies
265
17 Prim ary
Craniospinal
Anom alies
277
248
Developm ent al Anom alies
15 Prim ary Int racranial Anom alies
15.1 Arachnoid cyst s, int racranial
15.1.1 General inform at ion
Key concept s
a congenital abnormality, m ost common in middle fossa, cerebellopontine angle (CPA), suprasellar
region, and posterior fossa
● most are asym ptomatic (i.e. an incidental finding) except in the suprasellar region
● im aging often shows rem odeling of bone; imaging characteristics exactly mimic CSF on CT or MRI
in m ost cases
● recomm endation for incidentally discovered arachnoid cyst in adults: a single follow-up imaging
study in 6–8 months is usually adequate to rule-out any increase in size. Subsequent studies only if
concerning symptoms develop
●
AKA leptom en in geal cysts, dist in ct from postt raum atic leptom en in geal cysts (AKA grow in g skull
fract ures) (p. 915), an d un related to in fect ion . Arach n oid cysts (AC) are congen ital lesion s th at arise
during developm en t from splitt in g of arach noid m em bran e (th us th ey are tech n ically in t ra-arachn oid cysts) an d con tain fluid th at is usually iden tical to CSF. Th ey do n ot com m un icate w ith th e ven t ricles or subarach n oid space. May be un loculated or m ay h ave septat ion s. Typically lin ed w ith
m en in goth elial cells positive for epith elial m em bran e an tigen (EMA) an d n egative for carcin oem br yonic an tigen (CEA). AC m ay also occur in th e spin al can al.
“Tem poral lobe agen esis syn drom e” is a label th at h ad been used to describe th e fin din gs w ith
m iddle cran ial fossa ACs. Th is term is n ow obsolete sin ce brain volum es on each side are act ually th e
sam e,1 bon e expan sion an d sh ift of brain m atter accoun t for th e paren chym a th at appears to be
replaced by th e AC.
Tw o t ypes of h istological fin din gs 2 :
1. “sim ple arach n oid cysts”: arachn oid lin in g w ith cells th at appear to be capable of active CSF
secretion . Middle fossa cysts seem to be exclusively of th is t ype
2. cysts w ith m ore com plex lin in g w h ich m ay also con tain n euroglia, epen dym a, an d oth er tissue
t ypes
15.1.2 Epidem iology of int racranial arachnoid cyst s
15
In ciden ce: 5 per 1000 in autopsy series. Com prise ≈ 1% of in t racran ial m asses.
Male:fem ale ratio is 4:1. More com m on on th e left side.
Bilateral arach n oid cysts m ay occur in Hurler syn drom e (a m ucopolysacch aridosis).
15.1.3 Dist ribut ion
Alm ost all occur in relation to an arach n oid cistern (exception : in trasellar, th e on ly on e th at is extradural, Table 15.1).
Epiderm oid cysts in th e cerebellopon tin e an gle (CPA) m ay m im ic an arach n oid cyst, but are h igh
sign al on DWI MRI.
See also di eren tial diagn osis of m idlin e posterior fossa arach noid cysts (p.256).
15.1.4 Present at ion
Most ACs are asym ptom at ic. Th ose th at becom e sym ptom atic usually do so in early ch ildh ood.4 Th e
presen tation varies w ith location of th e cyst, an d often tim es appear m ild con siderin g th e large size
of som e.
Typical presen tation s are sh ow n in Table 15.2 4 an d in clude:
1. sym ptom s of in t racran ial hyper ten sion (elevated ICP): H/A, N/V, leth argy
2. seizures
3. sudden deterioration :
Prim ary Int racranial Anom alies
249
Table 15.1 Distribution of arachnoid cysts3
Locat ion
%
sylvian fissure
49%
CPA
11%
supracollicular
10%
vermian
9%
sellar & suprasellar
9%
interhemispheric
5%
cerebral convexit y
4%
clival
3%
Table 15.2 Typical presentations of arachnoid cysts
Middle fossa cyst s
Suprasellar cyst s wit h hydrocephalus
Diffuse supra- or infratentorial cyst s
wit h hydrocephalus
seizures
headache
hem iparesis
intracranial hypertension
craniom egaly
developmental delay
visual loss
precocious pubert y
bobble-head doll syndrom e
intracranial hypertension
craniomegaly
developm ental delay
4.
5.
6.
7.
a) due to h em orrh age (in to cyst or subdural com par tm en t): m iddle fossa cysts are n otorious for
h em orrh age due to tearin g of bridgin g vein s. Som e sports organ izat ion s do n ot allow participation in con tact sports for th ese pat ien ts
b) due to rupture of th e cyst
as a focal protrusion of th e sku ll
w ith focal sign s/sym ptom s of a space occupyin g lesion
in ciden tal fin ding discovered durin g evaluation for un related con dit ion
suprasellar cysts m ay addition ally presen t w ith 5 :
a) hydrocephalus (probably due to com pression of th e th ird ven tricle)
b) en docrin e sym ptom s: occurs in up to 60%. In cludes precocious pubert y
c) h ead bobbin g (th e so-called “bobble-h ead doll syn drom e”6 ): con sidered suggest ive of suprasellar cysts, but occurs in as few as 10%
d) visual im pairm en t
15.1.5 Evaluat ion
General inform at ion
Routin e evaluation w ith CT or MRI is usually satisfactory. Furt h er evaluation w ith CSF con trast or
flow studies (cistern ogram s, ven triculogram s…) are on ly occasion ally n ecessar y for th e diagn osis of
m idlin e suprasellar an d posterior fossa lesion s 4 ; for Di eren tial diagn osis, see In tracran ial cysts
(p.1374); see Fig. 15.1 for th e classification sch em e of Galassi et al for m iddle fossa cysts.
CTscan
Sm ooth bordered n on -calcified extraparen chym al cystic m ass w ith den sit y sim ilar to CSF an d n o en h an cem en t w ith IV con trast. Expan sion of n earby bon e by rem odellin g is usually seen , con firm ing
th eir ch ron ic n at ure. Often associated w ith ven t riculom egaly (in 64% of supraten torial an d 80% of
in fraten torial cysts).
Convexit y or m iddle fossa cysts exert m ass e ect on adjacen t brain an d m ay com press ipsilateral
lateral ven tr icle an d cause m idlin e sh ift . Suprasellar, quadrigem in al plate, an d m idlin e posterior-fossa cysts m ay com press th e th ird an d fourth ven t ricle an d cause hydrocephalus by obstruct in g th e
foram in a of Mon ro or th e Sylvian aqueduct .
15
250
Developm ent al Anom alies
Fig. 15.1 CT Classification of Sylvian fissure arachnoid cysts.7
Type I: small, biconvex, located in anterior temporal tip. No mass e ect. Comm unicates with subarachnoid space
on water-soluble contrast CT cisternogram (WS-CTC).
Type II: involves proximal and interm ediate segments of Sylvian fissure. Completely open insula gives rectangular
shape. Partial com munication on WS-CTC.
Type III: involves entire Sylvian fissure. Marked midline shift. Bony expansion of m iddle fossa (elevation of lesser
wing of sphenoid, out ward expansion of squam ous tem poral bone). Minim al com munication on WS-CTC. Surgical
treatm ent usually does not result in total reexpansion of brain (may approach t ype II lesion).
MRI
Better th an CT in di eren tiating th e CSF con tain ed in arach noid cysts from th e fluid of n eoplastic
cysts. May also sh ow cyst w alls.
Cist ernogram s and/or vent riculogram s
Usin g eith er iodin ated con trast or radion uclide tracers. Variable rate of opacificat ion h as resulted in
di cult y correlatin g results w ith operative fin din gs. Som e cysts are act ually divert icula, an d m ay fill
w ith radiot racer or con trast.
15.1.6 Treat m ent
General inform at ion
15
Many (but n ot all) auth ors recom m en d n ot t reat in g arach n oid cysts th at do n ot cause m ass e ect or
sym ptom s, regardless of th eir size an d location . For in ciden tally discovered arach n oid cyst in an
adult n ot con sidered for surger y: a sin gle follow -up im agin g study in 6–8 m on th s is usually adequate
to rule-out any ch anges (sin ce th ey m ay grow in size). Subsequen t st udies m ay be don e if con cern in g
sym ptom s develop. Pediatric patien ts m ay n eed to be follow ed un til adulth ood.
Treat m ent considerat ions for cyst s (excluding suprasellar cyst s)
Surgical treatm en t opt ion s are sum m arized in
Table 15.3.
Cyst shunt ing
Probably th e best overall t reatm en t. For sh un ting in to periton eum , use a low pressure valve. If th ere
is con curren t ven triculom egaly, on e m ay sim ultan eously place a ven tricular sh un t (e.g. th rough a
“Y” con n ector). Ult rasoun d, ven triculoscope, or im age guidan ce m ay assist in locat in g suprasellar
cysts. Sh unt in g of m iddle fossa ACs m ay also be accom plish ed th rough th e lateral ven tr icle, th us
sh un tin g both com partm en ts.9
NB: in run n ing th e distal sh un t t ubin g from th e m iddle fossa, it sh ould be routed beh in d th e
ear (do n ot t un n el in fron t of ear to avoid injur y to facial n er ve – if th is an terior route is un avoidable,
it m ay h elp to solicit th e ser vices of a plastic surgeon to h elp avoid th e facial n er ve).
Treat m ent of Suprasellar cyst s
Th ese cysts presen t w ith som e un ique treatm en ts option s w h ich in clude:
● t ran scallosal cystectom y 10
Prim ary Int racranial Anom alies
251
Table 15.3 Surgical treatment options for arachnoid cysts
Procedure
Advant ages
drainage by needle aspiration or burr hole evacuation
●
craniotomy, excising cyst
wall and fenestrating it into
basal cisterns
●
●
●
●
●
Disadvant ages
sim ple
quick
●
high rate of recurrence of cyst and
neurologic deficit
permits direct inspection of cyst (m ay
help with diagnosis)
loculated cysts (rare) treated m ore
effectively
avoids perm anent shunt (in some
cases)
allows visualization of bridging vessels
(small advantage)
●
subsequent scarring may block
fenestration allowing reaccum ulation of cyst
flow through subarachnoid space
m ay be deficient; many patients
develop shunt dependency post-op
significant morbidit y and m ortalit y
(m ay be due to abrupt decom pression)
●
●
endoscopic cyst fenestration
through a burr hole 8
●
as above
●
as above
shunting of cyst into peritoneum or into vascular system
●
definitive treatment
low m orbidit y/m ortalit y
low rate of recurrence
●
patient becom es “shunt dependent”
risk of infection of foreign body
(shunt)
●
●
●
percutan eous ven triculo-cystostom y: procedure of ch oice of Pierre-Kah n et al.5 Perform ed via a
param edian coron al burr h ole th rough th e lateral ven t ricle an d foram en of Mon ro (m ay be facilitated by using a ven triculoscope 8 )
● subfron tal approach (for fen estrat ion or rem oval): dan gerous an d in e ect ive 5
●
ven tricular drain age is in e ect ive (act ually prom otes cyst en largem en t) an d sh ould n ot be rout in ely con sidered
15.1.7 Out com e
Even follow in g successful treatm en t a port ion of th e cyst m ay rem ain due to th e rem odelin g of th e
bon e an d ch ronic sh ift of brain con ten ts. Hydroceph alus m ay develop follow in g t reatm en t. En docrin opath ies ten d to persist even after successful t reatm en t of suprasellar cysts.
15.2 Craniofacial developm ent
15.2.1 Norm al developm ent
Fontanelles
Anterior fonta nelle: th e largest fon tan elle. Diam on d sh aped, 4 cm (AP) × 2.5 cm (tran sverse) at birth .
Norm ally closes by age 2.5 yrs.
Poster ior fonta nelle :trian gular. Norm ally closes by age 2–3 m os.
Sphenoid an d ma stoid fonta nelles: sm all, irregular. Norm ally, form er closes by age 2–3 m os, latter
by age 1 yr.
Cranial vault
Grow th : largely determ in ed by grow th of brain . 90% of adult h ead size is ach ieved by age 1 yr; 95%
by age 6 yrs. Grow th essen tially ceases at age 7 yrs. By en d of 2n d yr, bon es h ave in terlocked at
sutures an d furth er grow th occurs by accret ion an d absorption .
Skull is un ilam in ar at birth . Diplöe appear by 4th yr an d reach a m axim um by age 35 yrs (w h en
diploic vein s form ).
Mastoid process: form at ion com m en ces by age 2 yrs, air cell form ation occurs durin g 6th yr.
15
252
Developm ent al Anom alies
15.2.2 Craniosynost osis
General
Origin ally called cran iosten osis. In ciden ce: ≈ 0.6/1000 live bir th s.
Prim arily a pren atal deform it y, postn atal cran iosyn ostosis (CSO) occurs un com m on ly (post n atal
causes con sist prim arily of position al alteration s w h ich m ay n ot represen t true syn ostosis). CSO is
rarely associated w ith hydroceph alus (HCP).11 Th e assert ion th at CSO m ay follow CSF sh un tin g for
HCP is un proven . Oth er causes for failure of n orm al skull grow th in clude lack of brain grow th due to
any of th e causes of arrested developm en t of the cerebral h em isph eres (lissen ceph aly, m icropolygyria, som e cases of hydran en ceph aly…).
Treatm en t is usually surgical. In m ost in stances, th e in dicat ion for surger y is for cosm esis an d to
preven t th e severe psych ological e ects of h avin g a disfigurin g deform it y. How ever, w ith m ultiple
CSO, brain grow th m ay be im peded by th e unyieldin g sku ll. Also, ICP m ay be path ologically elevated,
an d alth ough th is is m ore com m on in m ultiple CSO,12 elevated ICP occurs in ≈ 11% of cases w ith a
sin gle stenotic suture. Coron al syn ostosis can cause am blyopia. Most cases of sin gle suture involvem en t can be t reated w ith lin ear excision of th e suture. Involvem en t of m ult iple sutures or th e skull
base usually requires th e com bin ed e orts of a n eurosurgeon an d cran iofacial surgeon , an d m ay
n eed to be staged in som e cases. Risks of surgery in clude: blood loss, seizures, stroke.
Diagnosis
15
Many cases of “syn ostosis” are really due to position al flatten ing (e.g. “lazy lam bdoid”, see below ). If
th is is suspected, in st ruct paren ts to keep h ead o of flatten ed area an d rech eck pat ien t in 6–8
w eeks: if it w as position al, it sh ould be im proved, if it w as CSO th en it usually declares itself. Th e
diagn osis of CSO m ay be aided by:
1. palpation of a bony prom in ence over th e suspected syn ostotic suture (except ion : lam bdoidal
syn ostosis, see below )
2. gen tle firm pressure w ith th e th um bs fails to cause relative m ovem en t of th e bon es on eith er side
of th e suture
3. plain sku ll x-rays:
a) lack of n orm al lucency in center of suture. Som e cases w ith n orm al x-ray appearan ce of th e
suture (even on CT) m ay be due to focal bony spicule form ation 13
b) beaten copper calvaria (p. 254), sut ural diastasis an d erosion of th e sella m ay be seen in cases
of in creased ICP14
4. CT scan :
a) h elps dem on strate cran ial con tour
b) m ay sh ow th icken in g an d/or ridgin g at th e site of syn ostosis
c) w ill dem on strate hydrocephalus if presen t
d) m ay sh ow expan sion of th e fron tal subarach n oid space 15
e) th ree-dim en sional CT m ay h elp better visualize abn orm alit ies
5. in question able cases, a tech n etium bon e scan can be perform ed 16 :
a) th ere is little isotope uptake by any of th e cran ial sutures in th e first w eeks of life
b) in prem aturely closin g sutures, in creased act ivity com pared to th e oth er (n orm al) sut ures w ill
be dem on strated
c) in com pletely closed sutures, n o uptake w ill be dem on st rated
6. MRI: usually reser ved for cases w ith associated in t racran ial abn orm alit ies. Often n ot as h elpful as
CT
7. m easurem en ts, such as occipito-fron tal-circum feren ce m ay n ot be abn orm al even in th e face of a
deform ed sku ll sh ape
Increased ICP
Eviden ce of in creased ICP in th e n ew born w ith cran iosyn ostosis in clude:
1. radiograph ic sign s (on plain skull x-ray or CT, see above)
2. failure of calvarial grow th (un like th e n on -synostotic sku ll w h ere in creased ICP causes m acrocran ia in th e n ew born , h ere it is th e syn ostosis th at causes th e in creased ICP an d lack of skull
grow th )
3. papilledem a
4. developm en tal delay
Prim ary Int racranial Anom alies
253
Types of craniosynost osis
Sagit tal synostosis
General inform ation
Th e m ost com m on CSO a ect in g a single suture; 80% m ale. Results in dolich oceph aly or scaph oceph aly (boat sh aped skull) w ith fron tal bossing, prom in en t occiput , palpable keel-like sagittal ridge.
OFC rem ain s close to n orm al, but th e biparietal diam eter is m arkedly reduced. As m any as 44% of
patien ts w ith n on syn drom ic sagittal syn ostosis h ave elevated ICP.17
Surgical t reat m ent
Skin in cision m ay be lon git udin al or tran sverse. A lin ear “strip” cran iectom y is perform ed, excising
th e sagittal suture from th e coron al to th e lam bdoid suture, preferably w ith in th e first 3–6 m on th s
of life. Th e w idth of th e strip sh ould be at least 3 cm , n o proof exists th at in terposing artificial substan ces (e.g. silast ic sh eetin g over th e exposed edges of th e parietal bon e) retards th e recurren ce of
syn ostosis. Great care is taken to avoid dural laceration w ith poten tial injur y to th e un derlying superior sagit tal sin us. Th e ch ild is follow ed an d reoperated if fusion recurs before 6 m on th s age. After ≈
1 yr age, m ore exten sive cran ial rem odellin g is usually required.
Coronal synostosis
General inform ation
Accoun ts for 18% of CSO, m ore com m on in fem ales. In Crouzon’s syn drom e th is is accom pan ied by
abn orm alit ies of sph en oid, orbital an d facial bon es (hypoplasia of m idface), an d in Apert’s syn drom e
is accom pan ied by syn dact yly.18 Un ilateral coron al CSO → plagioceph aly w ith foreh ead on a ected
side flatten ed or con cave above eye (n orm al side falsely appears to bulge abn orm ally), supra-orbital
m argin h igh er th an n orm al side (on skull x-ray → h arlequin eye sign ). Th e orbit rotates out on th e
abn orm al side, an d can produce am blyopia. W ith out t reatm en t, flattened ch eeks develop an d th e
n ose deviates to th e n orm al side (root of n ose ten ds to rotate tow ards deform ity).
Bilateral coron al CSO (usually in cran iofacial dysm orph ism w ith m ult iple suture CSO, e.g. Apert’s)
→ brachyceph aly w ith broad, flatten ed foreh ead (acroceph aly). W h en com bin ed w ith prem ature closure of fron tosph en oidal an d frontoeth m oidal sutures, results in foresh orten ed an terior fossa w ith
m axillar y hypoplasia, sh allow orbits, progressive proptosis.
Surgical t reat m ent
Sim ple st rip cran iectom y of th e involved sut ure h as been used, often w ith excellen t cosm etic result .
How ever, som e argum en t th at th is m ay n ot be adequate h as been presen ted. Th erefore, a m ore curren t recom m en dation is to do fron tal cran iotom y (un i- or bi-lateral) w ith lateral can th al advan cem en t by takin g o orbital bar.
Metopic synostosis
At birth , th e fron tal bon e con sists of t w o h alves separated by th e fron tal or m etopic sut ure. Abn orm al closure results in a poin ted foreh ead w ith a m idlin e ridge (tr igon oceph aly). Many of th ese h ave
a 19p ch rom osom e abn orm alit y an d are retarded.
Lam bdoid synostosis
Epidem iology
Lon g con sidered a clin ical rarit y w ith a reported in ciden ce ran ge 1–9% of CSO,19 recen t reports suggest a h igh er in ciden ce of 10–20%20 w h ich m ay be due to an act ual in creased in ciden ce, or sim ply to
in creased aw aren ess or ch anging diagn ostic criteria. More com m on in m ales (m ale:fem ale = 4:1),
an d th e righ t side is involved in 70% of cases. Usually presen ts bet w een 3–18 m on th s of age, but m ay
be seen as early as 1–2 m on th s of age.
Con troversy exists regarding th e act ual criteria for th is con dition , an d som e auth ors di eren tiate
betw een th ose cases w h ich appear to h ave a prim ar y abn orm alit y of th e lam bdoid suture from th ose
w h ich m ay be due to position al flatten ing, th e so-called “lazy lam bdoid.” Oth ers do n ot m ake th is
dist in ct ion , an d som etim es refer to th e con dition as occipital plagioceph aly to avoid th e n eed to
im plicate abn orm alit ies of th e lam bdoid sut ure.
Position al flatten ing (or m olding) m ay be produced by:
1. decreased m obilit y: pat ien ts w h o con stan tly lie supin e w ith th e h ead to th e sam e side, e.g. cerebral palsy, m en tal retardat ion , prem aturit y, ch ron ic illn ess
2. abn orm al post ures: congenita l torticollis ,21 congen ital disorders of th e cer vical spin e
15
254
Developm ent al Anom alies
3. in ten tion al position in g: t ren d sin ce 1992 to place n ew born s in a supin e sleeping position to
reduce th e risk of sudden in fan t death syn drom e (SIDS),22 som etim es w ith a foam w edge to t ilt
th e ch ild to on e side to reduce th e risk of aspiration
4. in t rauterin e etiologies23 : in t rauterin e crow din g (e.g. from m ultiparous birth s or large fetal size),
uterin e an om alies
Clinical findings
Flatten in g of th e occiput . May be un ilateral or bilateral. If un ilateral, it is som etim es term ed lam bdoid plagioceph aly w h ich w h en severe also produces bulgin g of th e ipsilateral foreh ead resultin g in
a “rh om boid” skull w ith th e ipsilateral ear located an terior an d in ferior to th e con tralateral ear. Th e
con tralateral orbit an d foreh ead m ay also be flattened. Th is m ay be con fused w ith h em ifacial m icrosom ia or w ith plagioceph aly seen in un ilateral coron al cran iosyn ostosis. Bilateral lam bdoid syn ostosis produces brachyceph aly w ith both ears displaced an teriorly an d in feriorly.19 Unlike th e palpable
ridge of sagit tal or coron al syn ostosis, an indenta tion m ay be palpated alon g th e syn ostot ic lam bdoid
suture (alth ough a perisut ural ridge m ay be foun d in som e).
Diagnostic evaluation
Th e physical exam is th e m ost im por tan t aspect of diagn osis. Skull x-ray m ay h elp di eren tiate (see
below ). If th e skull x-ray is equivocal, preven t th e in fan t from layin g on th e a ected side for several
w eeks. A bon e scan sh ould be obtain ed if n o im provem en t occurs (see below ). In defin ite cases of
syn ostosis, an d for som e cases of refractory position al flatten ing (w h ich usually corrects w ith tim e,
but m ay take up to 2 years) surgical t reatm en t m ay be in dicated.
Sku ll x-ray: Show s a sclerotic m argin along one edge of the lam bdoid suture in 70% of cases. Local
“beaten copper cranium ” (BCC) occasionally m ay be seen due to inden tation s in the bone from underlying gyri w hich m ay be due to locally increased ICP. BCC produces a ch aracteristic m ottled appearance of the bon e w ith lucencies of varying depth h aving round an d poorly m arginated edges. BCC
correlates w ith generalized ↑ ICP only w hen it is seen w ith sellar erosion and sutural diastasis.14
CT scan : Bon e w in dow s m ay sh ow eroded or th in n ed in n er table in th e occipital region in 15–
20% of cases,20 > 95% are on th e side of th e involvem en t. Th e sut ure m ay appear closed. Brain w in dow s sh ow paren chym al brain abn orm alit ies in < 2%: h eterotopias, hydroceph alus, agen esis of th e
corpus callosum ; but ≈ 70% w ill h ave sign ifican t expan sion of th e fron tal subarach n oid space (m ay
be seen in syn ostosis of oth er sutures, see above).
Bon e scan : Isotope uptake in th e lam bdoid suture in creases during th e first year, w ith a peak at 3
m on th s of age 24 (follow in g th e usual in act ivity of th e first w eeks of life). Th e fin dings w ith syn ostosis
are th ose t ypical for CSO (p. 252).
15
Treat m ent
Early surgical t reatm en t is in dicated in cases w ith severe cran iofacial disfigurem en t or th ose w ith
evidence of in creased ICP. Oth erw ise, ch ildren m ay be m an aged n on surgically for 3–6 m on th s. Th e
m ajorit y of cases w ill rem ain static or w ill im prove w ith t im e an d sim ple n on surgical in ter ven t ion .
Approxim ately 15%w ill con tin ue to develop a sign ifican t cosm et ic deform it y.
Non surgical m an agem en t 25 :
Alth ough im provem en t can usually be attain ed, som e degree of perm an en t disfigurem en t is
frequen t.
Reposition in g w ill be e ective in ≈ 85% of cases. Patien ts are placed on th e un a ected side or on
th e abdom en . In fan ts w ith occipital flatten ing from tort icollis sh ould h ave aggressive ph ysical th erapy an d resolut ion sh ould be obser ved w ith in 3–6 m on th s.
More severe involvem en t m ay be treated w ith a t rial of m olding h elm ets 26 (h ow ever, n o con t rolled st udy h as proven th e e cacy).
Surgical treatm en t:
Required in on ly ≈ 20% of cases. Th e ideal age for surgery is betw een 6 an d 18 m on th s. Th e pat ien t
is position ed pron e on a w ell-padded cerebellar h eadrest (th e face sh ould be lifted an d gen tly m assaged ever y ≈ 30 m in utes by th e an esth esiologist to preven t pressure injuries).
Surgical option s ran ge from sim ple un ilateral cran iectom y of th e suture to elaborate recon struct ion by a cran iofacial team .
Lin ear cran iectom y exten ds from th e sagittal suture to th e asterion is often adequate for patien ts ≤
12 w eeks of age w ith out severe disfigurem en t. Great care is taken to avoid dural laceration n ear th e
asterion w h ich is in th e region of th e tran sverse sin us. Th e excised suture dem on strates an inter na l
ridge. Better results are obtain ed w ith earlier surger y, m ore radical surger y m ay be n ecessar y after
th e age of 6 m on th s.
Average blood loss for un com plicated cases is 100–200 m l an d th erefore tran sfusion is often
required.
Prim ary Int racranial Anom alies
255
Multiple synostoses
Fusion of m any or all cran ial sutures → oxyceph aly (tow er skull w ith un developed sin uses an d sh allow orbits). Th ese patien ts h ave elevated ICP.
Craniofacial dysm orphic syndrom es
Over 50 syn drom es h ave been described, Table 15.4, sh ow s a few selected on es.
A n um ber of cran iosyn ostosis syn drom es are due to m utation s in th e FGFR (fibroblast grow th factor receptor) gen es. FGFR gen e-related cran iosyn ostosis syn drom es in clude som e classic syn drom es
(Apert , Crouzon , Pfei er…) as w ell as several n ew er en tit ies (Beare-Steven son , Muen ke, Jackson Weiss syn drom es). All exh ibit autosom al dom in an t in h eritan ce.
15.2.3 Encephalocele
General inform at ion
Cran ium bifidum is a defect in th e fusion of th e cran ial bon e, it occurs in th e m idlin e, an d is m ost
com m on in th e occipital region . If m en in ges an d CSF h ern iate th rough th e defect , it is called a
m en in gocele. If m en in ges an d cerebral t issue protrude, it is called an en cephalocele.
En ceph alocele AKA ceph alocele is an exten sion of in tracran ial struct ures outside of th e n orm al
con fin es of th e skull. On e case w as seen for ever y five cases of spin al m yelom en ingoceles.28 A n asal
polypoid m ass in a newbor n sh ould be con sidered an en cephalocele un til proven oth erw ise. See also
Di eren tial diagn osis (p.1388).
Classificat ion
System based on Suw anw ela an d Suw anw ela 29 :
1. occipital: often involves vascular st ruct ures
2. cran ial vault: com prises ≈ 80%of en ceph aloceles in Western h em isph ere
a) in terfron tal
b) an terior fon tan elle
c) in terparietal: often involves vascular st ructures
d) tem poral
e) posterior fon tan elle
3. fron to-eth m oidal: AKA sin cipital; 15% of enceph aloceles; extern al open in g in to face in on e of th e
follow in g 3 region s:
a) n asofron tal: extern al defect in th e n asion
b) n aso-eth m oidal: defect bet w een n asal bon e an d n asal cartilage
c) n aso-orbital: defect in th e an tero-in ferior por t ion of m edial orbital w all
4. basal: 1.5%of en ceph aloceles; (see below )
a) tran seth m oidal: protrudes in to n asal cavit y th rough defect in cribriform plate
b) sph eno-eth m oidal: prot rudes in to posterior n asal cavit y
Table 15.4 Selected craniofacial dysm orphic syndrom es (modified 27 (p 123–4))
Syndrom e
Genetics
Craniofacial findings
Associat ed findings
Sporadic
Inherit ed
Crouzon (craniofacial dysostosis)
yes (25%)
FGFR AD
CSO of coronal & basal
skull sutures, m axillary
hypoplasia, shallow orbits, proptosis
HCP rare
Apert (acrocephalosyndact yly)
yes (95%)
FGFR AD
sam e as Crouzon
syndact yly of digits
2,3,4; shortened UE,
HCP common
Kleeblat tschadel
yes
AD
CSO with trilobular skull
isolated, or with
Apert’s or thanatophoric dwarfism
a Abbreviations: AD = autosom al dom inant; FGFR= fibroblast growth factor receptor gene-related; CSO = cranio-
synostosis; HCP = hydrocephalus; UE= upper extrem ities
15
256
Developm ent al Anom alies
c) t ran ssph en oidal: protrudes in to sph en oid sin us or n asoph ar yn x th rough paten t cran ioph aryn geal can al (foram en cecum )
d) fron to-sph en oidal or sph en o-orbital: protrudes in to orbit th rough superior orbital fissure
5. posterior fossa: usually con tain s cerebellar tissue an d ven tr icular com pon en t
Basal encephalocele
Th e on ly group th at does n ot produce a visible soft t issue m ass. May presen t as CSF leak or recurren t
m en in gitis. May be associated w ith oth er cran iofacial deform ities, in cludin g: cleft lip, bifid n ose,
optic-n er ve dysplasia, colobom a an d m icroph th alm ia, hypoth alam ic-pitu itary dysfun ct ion .
In ien ceph aly is ch aracterized by defects aroun d th e foram en m agn um , rach isch isis an d retrocollis.
Most are st illborn , som e sur vive up to age 17.
Et iology
Tw o m ain th eories:
1. arrested closure of n orm al con fin in g t issue allow s h ern iation th rough persisten t defect
2. early outgrow th of n eural tissue preven ts n orm al closure of cran ial coverin gs
Treat m ent
Occipit al encephalocele
Surgical excision of th e sac an d its con ten ts w ith w ater-tigh t dural closure. It m ust be kept in m in d
th at vascular struct ures are often in cluded in th e sac. Hydroceph alus is often presen t an d m ay n eed
to be t reated separately.
Basal encephalocele
Caution : a t ran sn asal approach to a basal en ceph alocele (even for biopsy alon e) m ay be fraugh t w ith
in tracran ial h em orrh age, m en in gitis, or persisten t CSF leak. Usually a com bin ed in tracran ial
approach (w ith am putation of th e extracran ial m ass) an d tran sn asal approach is used.
Out com e
Occipit al encephalocele
Th e progn osis is better in occipital m en in gocele th an in en ceph alocele. Th e progn osis is w orse if a
sign ifican t am oun t cerebral tissue is presen t in th e sac, if th e ven tricles exten d in to th e sac, or if
th ere is hydroceph alus. Less th an ≈ 5% of in fan ts w ith en ceph alocele develop n orm ally.
15.3 Dandy Walker m alform at ion
15
15.3.1 General inform at ion
Defin ition : an en larged posterior fossa w ith com plete or part ial agen esis of th e cerebellar verm is
an d cystic dilatation of th e fourth ven tricle w h ich is distorted an d en cased in a m em bran e. Th e
an om aly w as first described by Dan dy & Blackfan in 1914, an d w as n am ed Dan dy Walker m alform at ion for t y years later by Ben da to ackn ow ledge Taggart an d Walker’s con tribution s in 1942.30
15.3.2 Di erent ial diagnosis
Disorders w ith posterior fossa CSF collection s in clude 31 :
1. Dan dy Walker m alform ation (DW M)
2. Dan dy Walker varian t (DW V): verm ian hypoplasia an d cystic dilatation of th e fourth ven tricle,
w ith out en largem en t of th e posterior fossa
3. persisten t Blake’s pouch cyst (BPC): tetraven t ricular hydroceph alus, com m un icatin g 4th ven tricle
an d posterior fossa cyst, w ith or w ith out hypoplasia of both th e cerebellar verm is an d th e m edial
aspects of th e cerebellar h em isph eres
4. retrocerebellar arach n oid cyst: an teriorly displaces th e 4th ven tricle an d cerebellum , w h ich can
produce sign ifican t m ass e ect
5. Joubert’s syn drom e: absence or un derdevelopm en t of th e cerebellar verm is
6. m ega cistern a m agn a: en larged posterior fossa secon dar y to an en larged cistern a m agn a w ith a
n orm al verm is an d fourth ven tr icle)
Prim ary Int racranial Anom alies
257
Di eren t iat in g feat u res: DW M an d DW V are di cult to dist in guish , an d m ay represent a con tin uum of developm en tal an om alies th at are grouped togeth er as Dandy Walker com plex.32
Retrocerebellar arach n oid cysts an d BPCs m ay m im ic DW M, but th ese do not h ave verm ian agen esis an d th e cyst does n ot open in to th e 4th ven t ricle. Th e position of th e ch oroid plexus of th e
four th ven tricle is n orm al in arach n oid cysts, absen t in Dan dy Walker m alform at ion s, an d displaced
in to th e superior cyst w all in BPC. An in trath ecal en h an ced CT scan (perform ed after in stillin g iodin ated con trast in to a ven t ricular cath eter) w ould iden tify a m ega cistern a m agn a w h ich com m un icates w ith th e ven tricles, w h ile DW M an d m ost but n ot all arachn oid cysts do n ot.
15.3.3 Pat hophysiology
Th e etiology of DW M is un kn ow n . Multiple un sat isfactory th eories h ave been aban don ed. DW M is
likely due to dysem br yogen esis, secon dary to in sults of var ying severit y to th e cerebellum an d 4th
ven tr icle. Th is results in agen esis of th e cerebellar verm is w ith a large posterior fossa cyst com m un icatin g w ith an en larged 4th ven tr icle.32,30
Hydroceph alus occurs in 70–90% of cases, an d Dandy Walker m alform ation is presen t in 2–4% of
all cases of hydroceph alus.
15.3.4 Risk fact ors and epidem iology
Gestat ion al exposure to rubella, CMV, toxoplasm osis, w arfarin , alcoh ol, an d isotret in oin are th ough t
to be predisposin g factors. Autosom al recessive in h eritan ce h as been iden tified in a few cases, but a
gen et ic basis is lacking in m ost . In ciden ce: 1 per 25,000–35,000 live birth s.30 Male:fem ale=1:3.
15.3.5 Associat ed abnorm alit ies
CNS abn orm alit ies in clude agen esis of th e corpus callosum in 17%,33 an d occipital en ceph alocele in
7%. Oth er fin din gs in clude h eterotopias, spin a bifida, syrin gom yelia, m icroceph aly, derm oid cysts,
poren ceph aly, an d Klippel-Feil deform it y. Most h ave an en larged posterior fossa w ith elevation of
th e torcular h eroph ili. Atresia of th e foram in a of Magen die an d Luschka m ay occur.34
System ic abn orm alit ies in clude 33 : facial abn orm alit ies (e.g. an giom as, cleft palates, m acroglossia,
facial dysm orph ia), ocular abn orm alit ies (e.g. colobom a, retin al dysgen esis, m icroph th alm ia), an d
cardiovascular an om alies (e.g. septal defects, paten t duct us arteriosus, aortic coarctation , dextrocardia). Note: be aw are of th e possibilit y of a cardiac abn orm alit y w h en con siderin g surger y on th ese
patien ts.
15.3.6 Treat m ent
Early decom pression of ven t riculom egaly is recom m en ded to ach ieve m axim um cogn itive develop m en t. In th e absen ce of hydroceph alus, DW M m ay be follow ed. W h en t reatm en t is n ecessary, th e
posterior fossa cyst m ust be sh un ted. Sh un tin g th e lateral ven tricles alon e is con train dicated because
of th e risk of upw ard h ern iation .35 How ever, it is im portan t to con firm paten cy of th e cerebral aqueduct , oth erw ise th e supraten torial ven tricles n eed to be sh un ted con com itan tly. Var yin g reports
exist regardin g rates of associated aqueductal sten osis, alth ough it is w idely believed to be rare.
An oth er option on ce used com m on ly is excision of th e obstruct ing m em bran e. Th is h as fallen out
of favor due to its associated risks of m orbidit y an d m ortalit y. How ever, it rem ain s an opt ion for
patien ts w ith frequen t sh un t m alfun ction s.
New er treat m en ts in clude en doscopic th ird ven triculostom y in cases w h ere th e aqueduct is paten t, h ow ever fur th er st udy is n ecessar y.36,37
15.3.7 Prognosis
Progn osis ran ges w idely as th ere are various levels of severit y of th e m alform at ion . Som e pediatric
n eurosurgical literature quotes 12–50% m or talit y rates, alth ough th is is im proving w ith m odern
sh un tin g tech n iques. On ly 50% h ave n orm al IQ. Ataxia, spasticit y, an d poor fin e m otor con trol are
com m on . Seizures occur in 15%.
15
258
Developm ent al Anom alies
15.4 Aqueduct al st enosis
15.4.1 General inform at ion
Aqueductal sten osis (AqS) produces w h at is som etim es called t riven tricular hydroceph alus, ch aracterized by a n orm al sized 4th ven tricle an d en larged th ird an d lateral ven tricles on MRI or CT. Most
cases occur in ch ildren , h ow ever som e presen t for th e first tim e in adulth ood.
15.4.2 Et iologies
1. a congen ital m alform ation : m ay be associated w ith Ch iari m alform at ion or n eurofibrom atosis
2. acquired
a) due to in flam m ation (follow in g h em orrh age or in fect ion , e.g. syph ilis, T.B.)
b) n eoplasm : especially brain stem astrocytom as – in cludin g tectal gliom as (p. 634), lipom as
c) quadrigem in al plate arachn oid cysts
15.4.3 Aqueduct al st enosis in infancy
AqS is a frequen t cause of congen ital hydroceph alus (HCP) (up to 70% of cases 27 ), but occasionally
m ay be th e result of HCP. Pat ien ts w ith congen ital AqS usually h ave HCP at birth or develop it w ith in
≈ 2–3 m os. Congen ital AqS m ay be due to an X-lin ked recessive gene.28 Four t ypes of congen ital AqS
described by Russell (sum m arized 38 ):
1. forkin g: m ultiple ch an n els (often n arrowed) w ith n orm al epith elial lin in g th at do n ot m eet, separated by n orm al n er vous t issue. Usually associated w ith oth er congen ital abn orm alities (spin a
bifida, m yelom en ingocele)
2. periaqueductal gliosis: lum in al narrow in g due to subepen dym al ast rocyt ic proliferation
3. true sten osis: aqueduct h istologically n orm al
4. septum
15.4.4 Aqueduct al st enosis in adult hood
General inform at ion
AqS m ay be an overlooked cause of “n orm al pressure hydroceph alus” in th e adult .39 It is un kn ow n
w hy som e cases of AqS w ould rem ain occult, an d m an ifest on ly in adulth ood. In one series of 55
cases,40 35% h ad duration of sym ptom s < 1 year, 47% for 1–5 years; th e lon gest w as 40 yrs. Alth ough
m ost follow th is lon gstan ding ben ign course, th ere are reports of elevated ICP an d sudden death .
Sym pt om s
15
See Table 15.5. Headach e w as th e m ost com m on sym ptom , an d h ad ch aracteristics of H/A associated w ith elevated ICP. Visual ch anges w ere n ext, an d usually con sisted of blurring or loss of acuit y.
En docrin e ch anges in cluded m en st rual irregularit ies, hypothyroidism , an d h irsutism .
Signs
Papilledem a w as th e m ost com m on fin din g (53%). Visual fields w ere n orm al in 78%, th e rem ain der
h aving reduced periph eral vision , in creased blin d spots, quadran tic or h em ian opic field cuts, or scotom ata. In tellectual im pairm en t w as presen t in at least 36%. Oth er sign s in cluded: ataxia (29%), “pyram idal t ract sign s” in 44% (m ild h em i- or para-paresis (22%), spasticit y (22%), or Babin ski’s (20%)),
an osm ia (9%).
Evaluat ion
MRI is th e test of ch oice. MRI w ill sh ow th e absen ce of th e n orm al flow void in th e Sylvian aqueduct .
Con trast sh ould be given to rule-out t um or.
Treat m ent (of non-t um oral AqS)
Alth ough treatm en ts of th e prim ar y lesion h ave been attem pted (e.g. lysis of aqueductal sept um ),
th is h as fallen in to disfavor w ith th e im proved e cacy of CSF sh un ting an d en doscopic th ird ven triculostom y (ETV).
Prim ary Int racranial Anom alies
259
Table 15.5 Symptoms of aqueductal stenosis presenting in adulthood (55 patients > 16 years age 40 )
Sym pt om
No.
%
H/A
32
58%
visual disturbances
22
40%
m ental deterioration
17
31%
gait disturbance
16
29%
frequent falling
13
24%
endocrine disturbance
10
18%
nausea/vom iting
9
16%
seizures
8
15%
incontinence
7
13%
vertigo
6
11%
LE weakness
4
7%
hem iparesis or hem ianesthesia
4
7%
diplopia
3
5%
dysarthria
1
deafness
1
1. sh un tin g: CSF is usually sh un ted to th e periton eum or th e vascular system , h ow ever sh un tin g to
subarach noid space is also feasible (on ce obstruct ion at th e level of th e arachn oid gran ulation s
h as been ruled out)
2. a Torkildsen sh un t (sh un tin g a lateral ven tricle to th e cistern a m agn a 41 ) m ay w ork in adult
cases,38 h ow ever pediatric pat ien ts w ith obstructive hydroceph alus m ay n ot h ave an adequately
developed subarachn oid space for th is to fun ct ion properly
3. en doscopic th ird ven t riculostom y (p. 415)
Follow -up of at least t w o years to rule out t um or is recom m en ded.
15.5 Agenesis of t he corpus callosum
15.5.1 General inform at ion
A failure of com m issurat ion occurrin g ≈ 2 w eeks after con ception . Results in expan sion of th e th ird
ven tr icle an d separat ion of th e lateral ven tr icles (w h ich develop dilated occipital h orn s an d atria,
an d con cave m edial borders).
Th e corpus callosum (CC) form s from rostr um (gen u) to splen ium ,42 in agen esis th ere m ay be an
an terior portion w ith absen ce of th e posterior segm en t (th e converse occurs in frequen tly). Absen ce
of th e an terior CC w ith presen ce of som e posterior CC is in dicative of som e form of
h oloprosen ceph aly.
15.5.2 Incidence
1 in 2,000–3,000 n euroradiological exam in ation s.
15.5.3 Associat ed neuropat hologic findings
See referen ce.43
● poren ceph aly
15
260
Developm ent al Anom alies
m icrogyria
● in terh em isph eric lipoma s an d lipom as of th e corpus callosum (p. 260)
● arh in en ceph aly
● optic atrophy
● colobom as
● hypoplasia of th e lim bic system
● bun dles of Probst: abor ted begin n ings of corpus callosum , bulge in to lateral ven t ricles
● loss of h orizon tal orien tation of cin gulate gyrus
● sch izen ceph aly (p. 288)
● an terior an d h ippocam pal com m issures m ay be totally or part ially absen t 44
● hydrocephalus
● cysts in th e region of th e corpus callosum
● spina bifida w ith or w ith out m yelom en ingocele
● absence of th e septum pellucidum (p. 260)
●
15.5.4 Possible present at ion
hydrocephalus
m icroceph aly
● seizures (rare)
● precocious puber t y
● discon n ect ion syn drom e: m ore likely w ith a cquired CC defect th an in congen ital
●
●
May be an in ciden tal fin din g, an d by itself m ay h ave n o clin ical sign ifican ce. How ever, m ay be occur
as part of a m ore com plex clin ical syn drom e or ch rom osom al abn orm alit y (e.g. Aicardi syn drom e:
agen esis of CC, seizures, retardation , patch es of retin al pigm en tation ).
15.6 Absence of t he sept um pellucidum
Etiologies45 (p 178)
1. h oloprosen ceph aly (p. 289)
2. sch izen ceph aly (p. 288)
3. agen esis of th e corpus callosum (p. 259)
4. Ch iari t ype 2 m alform at ion (p. 284)
5. basal en ceph alocele
6. poren ceph aly/hydran en ceph aly
7. m ay occur in severe hydroceph alus: th ough t to be due to n ecrosis w ith resorption of th e septum
8. septo-optic dysplasia: see below
15
Septo-optic dysplasia 46,45 (p 175–8)
AKA de Morsier syn drom e. In com plete early m orph ogen esis of an terior m idlin e struct ures produces hypoplasia of th e opt ic n er ves an d possibly optic ch iasm (a ected patien ts are blin d) an d pituitar y in fun dibulum . Th e sept um pellucidum is absen t in about h alf th e cases. About h alf th e cases
also h ave sch izen ceph aly (p. 288).
Pr esen t at ion m ay b e d u e t o se con d ar y h yp op it u it ar ism m a n ife st in g as d w a r fism , isolat e d
gr ow t h h or m on e d eficie n cy, or p an h yp op it u it ar ism . Occasion a lly h yp e r se cr et ion of gr ow t h
h or m on e, cor t icot rop in or p r olact in m ay occu r, an d p r e cociou s p u b e r t y m ay occu r. Most
p at ie n t s ar e of n or m al in t ellige n ce alt h ou gh r et ard at ion m ay occu r. Se p t o - op t ic d ysp lasia m ay
b e a le ss seve r e for m of h olop r ose n ce p h aly (p . 28 9 ), an d occasion ally m ay occu r as p ar t of t h is
an om aly (w it h it s at t e n d an t p oor e r p r ogn osis for fu n ct ion or su r vival ). Th e ve n t r icles m ay b e
n or m al or d ilat e d . May b e se e n by t h e n e u r osu r ge on b e cau se of con ce r n s of p ossib le
h yd r oce p h alu s.
15.7 Int racranial lipom as
15.7.1 General inform at ion
In tracran ial an d in traspin al lipom as are felt to be of m aldevelopm en tal origin 47 (p 706) an d m ay arise
from failure of involution of th e prim itive m en in ges.48
Prim ary Int racranial Anom alies
261
15.7.2 Epidem iology of int racranial lipom as
In ciden ce: 8 in 10,000 autopsies. Usually foun d in or n ear th e m idsagit tal plan e, particularly over th e
corpus callosum ; lipom as in th is region are frequen tly associated w ith agen esis of th e corpus callosum (p. 259). Th e tuber cin ereum an d quadrigem in al plate are less frequen tly a ected.43 Rarely, th e
CP an gle or cerebellar verm is m ay be involved. May occur in isolat ion , but also h as been described in
association w ith a n um ber of congen ital an om alies, in cluding: trisom y 21, Pai’s syn drom e, fron tal
en ceph alocele, facial an om alies…. Oth er m idlin e abn orm alit ies m ay also be foun d: agen esis of th e
corpus callosum , m yelom en ingocele, an d spin a bifida.48
15.7.3 Evaluat ion
May be diagn osed by CT, MRI (study of ch oice), an d by ult rasoun d in in fan ts.
CT: Low den sit y, m ay h ave periph eral calcification (di cult to appreciate on MRI).48 Di eren tial
diagn osis on CT: prim arily bet w een derm oid cyst, teratom a 49 an d germ in om a.48
MRI: ch aracteristic fin din g is a m idlin e lesion w ith sign al ch aracteristics of fat (h igh in ten sit y on
T1WI, low in tensit y on T2W I).
15.7.4 Present at ion
Often discovered in ciden tally. Large lipom as m ay be associated w ith seizures, hypothalam ic dysfun ct ion , or hydroceph alus (possibly from com pression of th e aqueduct). Associated fin din gs th at m ay or
m ay n ot be directly related: m en tal retardation , beh avioral disorders an d h eadach e.
15.7.5 Treat m ent
Direct surgical approach is seldom n ecessar y for in t racran ial lipom as.49 Sh un tin g m ay be required
for cases w h ere hydroceph alus results from obstruction of CSF circulat ion .49
15.8 Hypot halam ic ham art om as
15.8.1 General inform at ion
Key concept s
rare, non-neoplastic congenital malformation, usually occurs in tuber cinereum
● m ay be parahypothalamic (pedunculated) or intrahypothalamic (sessile)
● presentation: precocious pubert y, seizures (usually starting with gelastic seizures (brief unprovoked
laughter)), developmental delay
● treatment: GnRH analogs for precocious pubert y. Latero-basal craniotomy for pedunculated
lesions, transcallosal interforniceal approach for intrahypothalam ic lesions, option of endoscopic
approach for lesions ≤ 1.5 cm dia, stereotactic radiosurgery may be an alternative
●
Hypoth alam ic h am artom as (HH; h am artom a: an abn orm al conglom erat ion of cells n orm ally foun d
in the sam e area) AKA dien ceph alic h am artom as or h am ar tom as of th e t uber cin ereum . Rare, n on n eoplastic congen ital m alform at ion s arisin g from in ferior hypoth alam us or t uber cin ereum (floor of
th e third ven tricle bet w een th e in fun dibular stalk an d th e m am m illary bodies). May occur as part of
Pallister-Hall syn drom e (gen et ics: AD in h erited defect in GL13 gene resultin g in abn orm ally sh ort
GL13 protein w h ich participates in n orm al sh apin g of m any organ s).
15.8.2 Clinical findings
1. specific t ypes of seizures:
a) gelastic seizures (brief episodes of un provoked laugh ter 50 ) are th e m ost ch aracteristic t ype
an d are th e earliest seizure m an ifestation . Presen t in up to 92%of patien ts.51 Th ey are resistan t to m edical m an agem en t an d can lead to cogn itive an d beh avioral deficits.52 Not path ogn om on ic. A n eocort ical origin h as been described 53
15
262
Developm ent al Anom alies
b) epileptic en ceph alopathy: gelastic fits gradually in crease in frequen cy an d oth er seizure t ypes
accrue: com plex part ial seizures, drop attacks, ton ic seizures, ton ic-clon ic seizures, an d secon darily gen eralized seizures. Th is ph ase is associated w ith m arked deterioration of cogn itive
an d behavioral abilities. Develops in 52%by a m ean age of 7 years 51
2. precocious pubert y: believed to be due to release of gonadotropin -releasing h orm on e (Gn RH)
foun d w ith in h am artom a cells.54 HH are th e m ost com m on CNS t um or to cause precocious pubert y, oth er causes in clude: oth er CNS t um ors – astrocytom a, epen dym om a, pin eal t um ors
(p.658), optic/hypoth alam ic gliom as (especially in NFT patien ts) -, CNS XRT, hydroceph alus, CNS
in flam m ation , septo-optic dysplasia (p. 260), an d ch ron ic hypothyroidism
3. developm en tal delay: prim arily in patien ts w ith seizure disorder (severit y correlates w ith duration of seizures). 46%of patien ts have borderlin e in tellectual fun ct ion (m en tal retardation )
4. beh avioral dist urban ces 55 : aggressive beh avior, rage attacks…
15.8.3 Im aging
MRI: n on en h an cin g, isoin ten se on T1W I, sligh tly hyperin tense or isoin ten se on T2W I.56
15.8.4 Pat hology
Tw o subt ypes of hypoth alam ic h am artom as 56,51 :
1. pedun culated or parahypoth alam ic: n arrow er base attach ed to th e floor of th e hypoth alam us
(n ot arisin g w ith in hypoth alam us). No distort ion of 3rd ven tr icle. Gen erally associated w ith precocious pubert y m ore th an seizures
2. in t rath alam ic or sessile: w ith in hypothalam us (distor tin g th e 3rd ven tricle) or broad attach m en t
to hypoth alam us. More often associated w ith seizures. 66% h ave developm en tal delay, 50% h ave
precocious pubert y
Microscop ic p at h ology: Clusters of disorgan ized sm all n euron s surroun ded by large pyram idal like
n euron s in an astrocyte-rich n europil57 (in con trast to th e usual gan glion cells surroun ded by oligoden drocytes foun d in th e hypothalam us).
15.8.5 Treat m ent
Precocious pubert y usually respon ds w ell to Gn RH an alogs.58
15
In d icat ion s for su rger y:
1. precocious pubert y th at fails to respon d to m edical th erapy (Gn RH an alogs)
2. seizures th at can n ot be adequately con trolled m edically. Post-op seizure con trol is related to
com pleten ess of resection
3. n eurologic deficit from m ass e ect of th e t um or
Op t ion s:
1. surgical resection
a) pedun culated lesion s: approach es in clude 59 subtem poral, subfron tal, pterion al, orbitozygom at ic (m ost com m on ly recom m en ded). Risks: cran ial n europath y, st roke 59
b) sessile lesion s w ith in t raven tr icular com pon en t: t ran scallosal an terior in terforn iceal
approach .60,61,62 Risks: m em or y im pairm en t (forn iceal injur y), en docrin e disturban ces, w eigh t
gain 60,62
c) n euroen doscopic approach : con sidered for HH ≤ 1.5 cm diam eter.63 Risks: 25% in ciden ce of
th alam ic cerebrovascular injur y
2. stereotactic radiosurger y: especially for sm all sessile lesion s, subtotal resection , or patien ts refusin g or n ot can didates for surgery. In sm all series, 3-year outcom e sh ow ed im provem en t sim ilar to
surgical resection w ith less n eurologic an d en docrin ologic m orbidit y64,65
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[49] Kazner E, Stoch dorph O, Wen de S, Grum m e T. In tracran ial Lipom a. Diagn ost ic an d Th erapeut ic Con sideration s. J Neurosurg. 1980; 52:234–245
[50] Daly D, Mulder D. Gelast ic epilepsy. Neurology.
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[55] Prigatan o GP. Cogn it ive an d behavioral d ysfu n ct ion
in ch ildren w ith h ypoth alam ic h am artom a and epilepsy. Sem in Pediatr Neurol. 2007; 14:65–72
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14:73–79
Math ieu D, Kon d ziolka D, Niran jan A, Flickin ger J,
Lun sford LD. Gam m a kn ife radiosurger y for refractory epilepsy caused by hypoth alam ic h am ar tom as.
Stereotact Fun ct Neurosurg. 2006; 84:82–87
Prim ary Spinal Anom alies
265
16 Prim ary Spinal Anom alies
16.1 Spinal arachnoid cyst s
16.1.1 General inform at ion
Alm ost always dorsal, m ost com m on in th oracic spin e. W ith a ven tral cyst, con sider a n euren teric
cyst (see below ). Most are act ually extradural an d th ese are som etim es referred to as arach n oid
divert icula – th ese m ay be associated w ith kyph oscoliosis in juven iles or w ith spin al dysraph ism .
In tradural arach n oid cysts m ay be congen ital or m ay follow in fect ion or traum a.
Usually asym ptom atic, even if large.
16.1.2 Treat m ent
W h en in dicated, treat m en t option s in clude:
1. percutan eous procedures: m ay be don e un der MRI1 or CT guidan ce. CT guidan ce usually requires
use of in trath ecal con trast to delin eate th e cyst
a) n eedle aspiration
b) n eedle fen estration 1
2. open surgical resection or fen estration
16.2 Spinal dysraphism (spina bifida)
16.2.1 Definit ions
See referen ce.2
Sp in a bifid a occu lt a. Congen ital absen ce of a spin ous process an d variable am oun ts of lam in a. No
visible exposure of m en inges or n eural tissue.
Th e follow in g t w o en tit ies are grouped togeth er un der th e term spina bifida apert a (aperta from
th e Latin for “open”) or spin a bifida cystica.
Men in gocele. Congen ital defect in ver tebral arch es w ith cystic disten sion of m en in ges, but n o
abn orm alit y of n eural tissue. On e th ird h ave som e n eurologic deficit .
Myelom en in gocele. Con gen ital defect in vertebral arch es w ith cystic dilatat ion of m en in ges an d
st ruct ural or fun ct ion al abn orm alit y of spin al cord or cauda equin a.
16.2.2 Spina bifida occult a (SBO)
Reported prevalen ce ran ge of SBO: 5–30% of North Am erican s (5–10% is probably m ore realistic).
Th e defect m ay be palpable, an d th ere m ay be overlyin g cutan eous m an ifestat ion s (in Table 16.3.
Often an in ciden tal fin din g, usually of n o clin ical im por tan ce when it occurs a lone. Num erous
review s h ave sh ow n n o statistical association of SBO w ith n on specific LBP.3,4 An in creased in ciden ce
of disc h ern iation w as sh ow n in on e st udy.5
SBO m ay occasion ally be associated w ith diastem atomyelia, teth ered cord, lipom a, or derm oid
t um or. W h en sym ptom at ic from on e of th ese associated con dition s, th e presen tation is usually th at
of teth ered cord; gait disturban ce, leg w eakn ess an d atrophy, urin ar y dist urban ce, foot deform ities…, see Teth ered cord syn drom e (p. 272).
16.2.3 Myelom eningocele
Em bryology
Th e an terior n europore closes at gestation day 25. Th e caudal n europore closes at day 28.
Epidem iology/genet ics
In ciden ce of spin a bifida w ith m en in gocele or m yelom en ingocele (MM) is 1–2/1000 live birth s (0.1–
0.2%). Risk in creases to 2–3% if th ere is on e previous birth w ith MM, an d 6–8% after t w o a ected
ch ildren . Th e risk is also in creased in fam ilies w h ere close relatives (e.g. siblin gs) h ave given bir th to
16
266
Developm ent al Anom alies
MM ch ildren , especially w h en on th e m oth er’s side of th e fam ily. In ciden ce m ay in crease in tim es of
w ar, fam in e or econ om ic disasters, but it m ay be gradually declin ing overall.6 Tran sm ission follow s
n on -Men delian gen etics, an d is probably m ultifactorial. Pren atal folate (in th e form of folic acid) low ers th e in ciden ce of MM (p. 290).
Hydrocephalus in m yelom eningocele
Hydroceph alus (HCP) develops in 65–85% of patien ts w ith MM, an d 5–10% of MM patien ts h ave clin ically overt HCP at bir th .7 Over 80% of MM pat ien ts w h o w ill develop HCP do so before age 6 m os.
Most MM patien ts w ill h ave an associated Ch iari t ype 2 m alform at ion (p. 284). Closure of th e MM
defect m ay convert a laten t HCP to act ive HCP by elim in atin g a route of egress of CSF.
Latex allergy in m yelom eningocele
Up to 73%of MM patien ts are allergic to protein s present in latex (th e m ilky sap from th e rubber t ree
Hevea brasilien sis), foun d on ly in n aturally occurring rubber products (an d w h ich are n ot presen t in
syn th etics such as: silicon e, vinyl, plastic, n eopren e, n itrile…). Th e allergy is th ough t to arise from
early an d frequen t exposure to latex products durin g m edical care for th ese patien ts, an d th ere is a
suggestion th at latex-free surgery on th ese in fan ts m ay reduce th e risk of th e developm en t of latex
allergy.8
Prenat al diagnosis
See Pren atal detect ion of n eural t ube defect s (p.290).
Intrauterine closure of MM defect
Con troversial. Does reduce in ciden ce of Ch iari II defect , but it h as n ot been determ in ed if th is is clin ically sign ifican t. Argued w h eth er th is reduces in ciden ce of hydroceph alus. Does n ot im prove distal
n eurologic fun ct ion .
General m anagem ent
Assessm ent and m anagem ent of lesion
m easure size of defect
● assess w h eth er lesion is ruptured or un ruptured
○ ruptured: start an tibiotics (e.g. n afcillin an d gen tam icin ; D/C 6 h rs after MM closure, or con tin ue if sh un t an ticipated in n ext 5 or 6 days)
○ un ruptured: n o an t ibiotics n ecessar y
● cover lesion w ith telfa, th en spon ges soaked in lact ated rin gers or n orm al salin e (form a sterile
gauze rin g aroun d th e lesion if it is cystic an d protrudin g) to preven t desiccation
● Tren delen burg position , patien t on stom ach (keeps pressure o lesion )
● perform surgical closure w ith in 36 h rs un less th ere is a con train dicat ion to surgery (sim ultan eous
sh un t is n ot usually don e except if overt hydroceph alus (HCP) at birth ): see below
●
16
Neurological assessm ent and m anagem ent
item s related to spin al lesion
○ w atch for spon taneous m ovem en t of th e LEs (good spontan eous m ovem en t correlates w ith better later fun ction al outcom e 9 )
○ assess low est level of n eurologic fun ct ion
Table 16.1) by ch eckin g respon se of LEs to pain ful
st im ulus: alth ough som e in fan ts w ill h ave a clear dem arcation betw een n orm al an d abn orm al
levels, at least 50% sh ow som e m ixture of n orm al, reflex, an d auton om ous activity (arisin g from
un in h ibited an terior h orn m otor n euron s)9
– di eren tiatin g reflex m ovem en t from volun tar y m ay be di cult. In gen eral, volun tar y m ovem en t is n ot stereotyped w ith repetitive stim ulus an d reflex m ovem en t usually on ly persists
as lon g as th e n oxious stim ulus is applied
● item s related to th e com m on ly associated Ch iari t ype 2 m alform at ion :
○ m easure OFC: risk of developin g hydroceph alus (see above). Use OFC graph s (p.395), an d also
look for abn orm al rate of grow th (e.g. > 1 cm /day)
○ h ead U/S w ith in ≈ 24 h rs
○ ch eck for in spirator y st ridor, apn eic episodes
●
Prim ary Spinal Anom alies
267
Table 16.1 Findings in various levels of MM lesion 10
Paralysis
below
Findings
T12
com plete paralysis of all muscles in LEs
L1
weak to m oderate hip flexion, palpable contraction in sartorius
L2
strong hip flexion and m oderate hip adduction
L3
normal hip adduction & alm ost norm al knee extension
L4
normal hip adduction, knee extension & dorsiflexion/inversion of foot; some hip abduction in flexion
L5
normal adduction, flexion &lateral rotation of hip; moderate abduction; normal knee extension, moderate
flexion; normal foot dorsiflexion; hip extension absent; • produces dorsiflexed foot and flexed thigh
S1
normal hip flexion & abduction/adduction, m oderate extension and lateral rotation; strong knee flexion
& inversion/eversion of foot; m oderate plantarflexion of foot; extension of all toes, but flexion only of
term inal phalanx of great toe; normal m edial & lateral hip rotation; com plete paralysis of foot intrinsic
(except abductor and flexor hallicus brevis); • produces clawing of toes and flattening of sole of foot
S2
difficult to detect abnorm alit y clinically; • with growth this produces clawing of the toes due to
weakness of intrinsic muscles of sole of foot (innervated by S3)
Ancillary assessm ent and m anagem ent
evaluation by n eon atologist to assess for oth er abn orm alities, especially th ose th at m ay preclude
surger y (e.g. pulm on ar y im m at urit y). Th ere is an average in ciden ce of 2–2.5 addit ion al an om alies
in MM pat ien ts
● bladder: star t patien t on regular urin ar y cath eterizat ion s, obtain urological con sultation (n on em ergen t)
● AP & lat spin e film s: assess scoliosis (baselin e)
● orthopedic consultation for severe kyphotic or scoliotic spine deform ities and for hip or knee deform ities
●
Surgical m anagem ent
Tim ing of MM closure
Early closure of MM defect is not associated w ith im provem en t of n eurologic fun ction , but evidence
supports low er in fect ion rate w ith early closure. MM sh ould be closed w ith in 24 h rs w h eth er or n ot
m em bran e is in tact (after ≈ 36 h rs th e back lesion is colon ized an d th ere is in creased risk of postoperative in fect ion ).
Sim ultaneous MM defect closure and VP shunting
In patien ts w ith out hydrocephalus, m ost surgeon s w ait at least ≈ 3 days after MM repair before
sh un tin g. In MM patien ts w ith clin ically overt HCP at birth (ven triculom egaly w ith en larged OFC
an d/or sym ptom s), MM repair an d sh un tin g m ay be perform ed in th e sam e sit ting w ith out in creased
in ciden ce of in fect ion , an d w ith sh orter h ospitalization .11,12 It m ay also reduce th e risk of MM repair
breakdow n previously seen durin g th e in ter val before sh untin g. Pat ien t is position ed pron e, h ead
t urn ed to r ight (to expose th e righ t occiput), righ t kn ee an d th igh flexed to expose righ t flan k (con sider usin g left flan k to preven t con fusion w ith appen dectom y scar later in life).
Surgical technique of m yelom eningocele repair
Key concept s
critical goals: 1) free placode from dura (to avoid tethering), 2) water-tight dural closure, 3) skin closure (can be accomplished in essentially all cases). Closure does not restore any neurologic function
● timing goal: surgical closure with latex-free setup ideally ≤ 36 hours after birth
● helpful tips: start at normal dura, open as wide as the defect, trim placode if necessary to close
dura, undermine skin to achieve closure (avoid trapping skin → derm oid tumor)
● post-op CSF leak usually means a shunt is required
●
16
268
Developm ent al Anom alies
Gen eral prin ciples 13 : preven t desiccation – keep th e exposed n eural tissue m oist. Use latex-free
environ m en t (reduces developm en t of latex allergy, as w ell as attack by m atern al an t ibodies th at
m ay h ave crossed th rough th e placen ta). Do n ot allow scrub solution s or ch em ical an t im icrobials to
con tact n eural placode. Do n ot use m on opolar cauter y. At ever y poin t durin g th e closure, avoid placin g ten sion on th e n eural placode.
Multiple layer closure is advocated, 5 layers sh ould be attem pted, alth ough occasion ally on ly 2 or
so layers m ay be closed. Th ere is n o evidence th at m ultiple layer closure eith er im proves n eurologic
fun ct ion or preven ts later teth erin g, but th ere is a suggestion th at w h en teth erin g does occur, it m ay
be easier to release w h en a previous m ultilayered closure w as perform ed. Silastic does n ot preven t
adh eren ce in series w ith lon g follow -up (> 6 yrs), an d m ay even ren der un teth erin g procedures m ore
di cult.
Begin by dividing th e abn orm al epith elial coverin g from th e n orm al skin . Th e pia-arach n oid m ay
be separated from the n eural t issue. Th e placode is folded in to a tube an d th e pia-arach n oid is th en
approxim ated around it w ith 7–0 suture (absorbable suture, e.g. PDS, m ay m ake fut ure re-operat ion
easier). It often h elps to start w ith n orm al dura above, an d th en w ork dow n . Th e dura can th en be
isolated aroun d th e periph er y an d follow ed deep to th e spin al can al superiorly. Th e dura is th en also
form ed in to a tube an d approxim ated in a w ater-t igh t closure. If th e dura can n ot be closed, th e placode m ay be judiciously trim m ed. Th e filum term in ale sh ould be divided if it can be located. Th e skin
is th en m obilized an d closed. Derm oid t um ors m ay result from retain ed skin durin g th e closure, but
altern atively derm oids m ay also be presen t congen itally.14
If th ere is a kyph otic deform it y, it is repaired at th e sam e sit tin g as th e MM defect closure. Th e
kyph otic bon e is ron geured, an d 2–0 Vicr yl is used to suture th e adjacen t bon es. Som e surgeon s use
a brace post-op, som e do n ot.
Post-op m anagem ent of MM repair
1.
2.
3.
4.
keep pat ien t o all in cision s
bladder cath eterizat ion regim en
daily OFC m easurem en ts
a void na rcotics (m idbrain m alform ation ren ders th ese pat ien t m ore sen sitive to respirator y
depression from n arcotics)
5. if n ot sh un ted
a) regular h ead U/S (t w ice w eekly to w eekly)
b) keep patien t flat to ↓ CSF pressure on in cision
6. if a kyph ectomy w as don e, use of a brace is option al (surgeon preferen ce)
Lat e problem s/issues
16
In clude:
1. hydrocephalus: m ay m im ic ≈ anyth in g listed below. ALWAYS RULE OUT SHUNT MALFUNCTION
w h en a MM pat ien t deteriorates
2. syrin gom yelia (an d/or syringobulbia) (p.1144):
3. Teth ered cord syn drom e (p. 272) as m any as 70% of MM pat ien ts h ave a teth ered cord radiograph ically (som e quote 10–20%), but on ly a m in orit y are sym ptom atic. Un fort un ately th ere is n o
good test to ch eck for sym ptom atic retetherin g (SSEPs m ay deteriorate,15 m yelography m ay h elp)
a) scoliosis: early un teth erin g of cord m ay im prove scoliosis; seeScoliosis in teth ered cord
(p. 272)
b) sym ptom at ic teth ering m ay m an ifest as delayed n eurological deterioration 16
4. derm oid tum or at th e MM site (p. 784) 17 : in ciden ce ≈ 16%
5. m edullar y com pression at foram en m agn um , see sym ptom atic Ch iari II m alform at ion (p.284)
6. use of grow th h orm on e to in crease stature is con troversial
Out com e
W ith out any treatm en t, on ly 14–30% of MM in fan ts sur vive in fan cy; th ese usually represen t th e
least severely involved; 70% w ill h ave n orm al IQ’s. 50% are am bulator y.
W ith m odern t reatm en t, ≈ 85% of MM in fan ts sur vive. Th e m ost com m on cause of early m ortalit y
are com plication s from th e Ch iari m alform ation (respirator y arrest, aspiration …), w h ere late m or talit y is usually due to sh un t m alfun ction . 80% w ill h ave n orm al IQ. Men tal retardation is m ost closely
lin ked to sh un t in fect ion . 40–85% are am bulator y w ith bracing, h ow ever, m ost ch oose to use w h eelch airs for ease. 3–10% h ave n orm al urin ar y con tin en ce, but m ost m ay be able to rem ain dr y w ith
in term itten t cath eterization .
Prim ary Spinal Anom alies
269
16.2.4 Lipom yeloschisis
General inform at ion
Dorsal spinal dysraph ism w ith lipom a. Six form s are described,18 th e follow in g 3 are clin ically im portan t as possible causes of progressive n eurologic dysfun ct ion via teth erin g (p. 272) an d/or
com pression :
1. (in t ra)dural lipom a
2. lipom yelom en ingocele (see below )
3. fibrolipom a of th e filum term in ale
Lipom yelom eningocele
General inform ation
A subcutan eous lipom a th at passes th rough a m idlin e defect in th e lum bodorsal fascia, vertebral
n eural arch , an d dura, an d m erges w ith an abn orm ally low teth ered cord.18 Th ese m ay be term in al,
dorsal, or tran sition al (betw een th e t w o).
Th e in t radural fatt y t um or m ay also be kn ow n as lipom a of th e cauda equin a. In addition to being
abn orm ally low, th e con us m edullaris is split in th e m idlin e dorsally usually at th e sam e level as th e
bifid spin e, an d th is dorsal m yelosch isis m ay exten d superiorly un der in tact spin al arch es.19 Th ere is
a th ick fibrovascular ban d th at join s th e lam in a of th e m ost ceph alic vertebrae w ith th e bifid lam in a.
Th is ban d con stricts th e m en ingocele sac an d n eural tissue, causin g a kin k in th e superior surface of
th e m en in gocele. Asym ptom at ic lipom as of th e filum term in ale occur in 0.2–4%20,21 of MRIs.
Th e dura is deh iscen t at th e level of th e dorsal m yelosch isis, an d reflects on to th e placode. Th e
lipom a passes th rough th is deh iscen ce to becom e attached to th e dorsal surface of th e placode, an d
m ay con tin ue ceph alad un der in tact arch es w ith th e possibilit y of exten sion in to th e cen t ral can al
superiorly to levels w ith out dorsal m yelosch isis. Th e lipom a is dist in ct from th e n orm al epidural fat
w h ich is looser an d m ore areolar. Th e subarach noid space t ypically bulges to th e side con tralateral
to th e lipom a. Th ese lipom as accoun t for 20% of covered lum bosacral m asses.
Presentation
In a pediatric series, 56% presen ted w ith a back m ass, 32% w ith bladder problem s, an d 10% because
of foot deform ities, paralysis or leg pain .22
Physical exam ination
Alm ost all patien ts h ave cutan eous stigm ata of th e associated spina bifida: fatt y subcutan eous pads
(located over th e m idlin e an d usually exten ds asym m et rically to on e side) w ith or w ith out dim ples,
port-w in e stain s, abn orm al h air, derm al sin us open in g, or skin appen dages.23 Clubbing of th e feet
(talipes equin ovarus) m ay occur.
Th e n eurologic exam m ay be n orm al in up to 50% of patien ts (m ost presen tin g w ith skin lesion
on ly). Th e m ost com m on n eurologic abn orm alit y w as sen sor y loss in th e sacral derm atom es.
Evaluat ion
Plain LS spin e x-rays w ill sh ow spina bifida in m ost cases. Presen t in alm ost all by defin ition , but
som e m ay h ave segm en tat ion an om alies in stead such as but terfly vertebra (p. 216). Abn orm alities of
fusion an d sacral defect s m ay also be seen .
Th e abn orm ally low con us can be dem on strated on m yelogram /CT or on MRI. MRI also dem on st rates th e lipom atous m ass (h igh sign al on T1W I, low sign al on T2WI).
All patien ts sh ould h ave pre-op urological evaluation to docum en t any deficit .
Treatm ent
Sin ce sym ptom s are due to (1) teth erin g of th e spin al cord, especially durin g grow th spurts, an d
(2) com pression due to progressive deposition of fat, especially durin g periods of rapid w eigh t gain ;
th e goals of surgery are to release th e teth erin g an d reduce th e bulk of fat t y t um or. Sim ple cosm etic
t reat m en t of th e subcutan eous fat pad does n ot preven t n eurologic deficit, an d m ay m ake later
defin itive repair m ore di cult or im possible.
Surgical treatm en t is in dicated w h en th e patien t reach es 2 m on th s of age, or at th e t im e of diagn osis if th e pat ien t presen ts later in life. Adjun cts to surgical treatm en t in clude evoked poten tial
m on itorin g an d laser. Overall, w ith surger y, 19% w ill im prove, 75% w ill be un ch an ged, an d 6% w ill
w orsen . Foot deform ities often progress regardless.
16
270
Developm ent al Anom alies
Surgical technique (m odified)
See referen ce.19
1. m obilize th e subcutan eous m ass, it fun n els dow n th rough th e deep fascia
2. open last in tact ver tebral arch (w ork from n orm al dura)
3. iden tify th e fibrovascular ban d th at crosses th e m ost ceph alic w idely bifid lam in a
4. sect ion in g th e fibrovascular ban d frees th e dural tube an d releases th e sh arp kin k in th e superior surface of th e m en in gocele
5. takin g care to preser ve dorsal n er ve roots, th e dura is in cised an terior to th e dura-lipom a
jun ction
6. sim ilar procedure is carried out w ith arach n oid m em bran e
7. dural/arach n oid in cision s are con tin ued aroun d en tire exten t of teth ered con us
8. cord an d placode are un teth ered; m on itorin g tech n iques described in Teth ered cord syn drom e
(p. 272) are an option
9.
subtotal rem oval of lipom a: lipom a is th en trim m ed as com pletely as possible, in ten t ion ally
leavin g som e fat beh in d to avoid injur y to dorsal surface of placode. Superior exten sion alon g
dorsal surface of cord or in to cen tral can al is debulked as m uch as is safely possible
10. th e placode is reform ed in to a closed n eural tube
11. close th e pial m argin s
12. th e dura is closed (prim arily if possible, or using fascia lata graft if too m uch ten sion is placed on
folded placode)
16.2.5 Derm al sinus
General inform at ion
A t ract begin n ing at th e skin surface, lin ed w ith epith elium . Usually located at eith er en d of n eural
t ube: ceph alic or caudal. Most com m on location is lum bosacral. Probably results from failure of th e
cutan eous ectoderm to separate from th e n euro-ectoderm at th e tim e of closure of th e n eural
groove.2
Spinal derm al sinus
General inform ation
16
May appear as a dim ple or as a sin us, w ith or w ith out h airs, usually ver y close to m idlin e, w ith an
open in g of on ly 1–2 m m . Surroun din g skin m ay be n orm al, pigm en ted (“port w in e” discolorat ion ),
or distorted by an un derlyin g m ass.
Th e sin us m ay term in ate superficially, m ay con n ect w ith th e coccyx, or m ay t raverse betw een
n orm al vertebrae or th rough bifid spines to th e dural tube. It m ay w iden at any poin t alon g its path
to form a cyst; called an epiderm oid cyst if lin ed w ith stratified squam ous epith elium an d con tain in g on ly keratin from desquam ated epith elium , or called a derm oid cyst if also lin ed w ith derm is
(con tain in g skin appen dages, such as h air follicles an d sebaceous glan ds) an d also con tain in g sebum
an d h air.
Alth ough in n ocuous in appearan ce, th ey are a poten tial path w ay for in tradural in fect ion w h ich
m ay result in m en in git is (som etim es recurren t) an d/or in trath ecal abscess. Less serious, a local in fect ion m ay occur. Th e lin in g derm is con tains n orm al skin appen dages w h ich m ay result in h air, sebum ,
desquam ated epith elium an d ch olesterol, w ith in th e t ract . As a result , th e con ten ts of th e sin us tract
are irritatin g an d can cause a sterile (ch em ical) m en in gitis w ith possible delayed a ra chnoiditis if it
en ters th e dural space.
In ciden ce of a presum ed sacral sin us (a dim ple w h ose bottom could n ot be seen on skin retract ion ): 1.2% of n eon ates.24
Derm al sin uses are sim ilar but dist in ct from p ilon id al cyst s w h ich m ay also be congen ital
(alth ough som e auth ors say th ey are acquired), con tain h air, are located superficial to th e postsacral
fascia, an d m ay becom e in fected.
If th e tract expan ds in trath ecally to form a cyst, th e m ass m ay presen t as a teth ered cord or as an
in t radural tum or. Bladder dysfun ct ion is usually th e first m an ifestation .
Th e tract from a spin al derm al sin us alw ays courses ceph alad as it dives inw ard from th e surface.
An occipital sin us m ay pen etrate th e skull an d can com m un icate w ith derm oid cysts as deep as th e
cerebellum or fourth ven tr icle.
Evaluation
Th ese t ract s are NOT to be probed or injected w ith con trast as th is can precipitate in fect ion or sterile
m en in gitis.
Prim ary Spinal Anom alies
271
Exam is directed tow ards detect in g abn orm alit ies in sph in cter fun ct ion (an al an d urin ary), lum bosacral reflexes, an d low er extrem it y sen sat ion an d fun ct ion .
Radiologic evaluation
W h en seen at birth , ultra sound is th e best m ean s to evaluate for spin a bifida an d a possible m ass
in side th e can al.
If seen in itially follow in g bir th , an MRI sh ould be obtain ed. Sagittal im ages m ay dem on strate th e
t ract an d its poin t of attach m en t. MRI also optim ally dem on strates m asses (lipom as, epiderm oids…)
w ith in th e can al.
Plain x-rays an d CT are un able to dem on strate th e fin e t ract w h ich m ay exist bet w een th e skin
an d th e dura.
Plain x-rays m ust be don e w h en em barking on surger y as part of operative plan n in g, as preparation for th e possibilit y of a com plete lam in ectom y.
Treatm ent
Sin uses above th e lum bosacral region sh ould be surgically rem oved. More caudally located sin uses
are sligh tly con troversial. Alth ough ≈ 25% of presum ed sacral sin uses seen at birth w ill regress to a
deep dim ple on follow -up (tim e n ot specified), it is recom m en ded th at all derm al sin uses sh ould be
surgically explored an d fully excised pr ior to th e developm en t of n eurologic deficit or sign s of in fect ion . Th e results follow in g in t radural in fect ion are n ever as good as w h en un der taken prior to in fect ion . Surgery w ith in th e w eek of diagn osis is appropriate. Sin uses th at term in ate on th e t ip of th e
coccyx rarely pen etrate th e dura, an d m ay n ot n eed to be treated un less local in fect ion occurs.
Surgical technique
An ellipse is cut aroun d th e open in g, an d th e sin us is follow ed deep un t il th e term in ation of th e tract
is en coun tered. Careful in sertion of a lacrim al duct probe un der direct vision m ay facilitate excision
w ith out violat in g th e tract . If th e tracts pen etrates th e spin e, lam in ectom y m ust be perform ed an d
th e t ract follow ed to its full exten t (even if n ecessar y to exten d th e lam in ectom y to T12). An extradural cyst m ay be presen t. If th e tract en ters th e dura, it usually does so in th e m idlin e, an d in th ese
cases th e dura sh ould be open ed an d in spected. Extrem e care is taken to preven t spillin g th e con ten ts in to th e subdural space.
Cranial derm al sinus
General inform ation
Stalk begin s w ith a dim ple in th e occipital or n asal region . Cutan eous st igm ata of h em angiom a, subcutan eous derm oid cyst, or abn orm al h air form ation m ay occur. Occipital sin uses exten d caudally,
an d if th ey en ter th e skull, th ey do so caudal to th e torcular h eroph ili. Presen tation m ay in clude
recurren t bacterial (usually S. aureus) or aseptic m en in gitis. Evaluation sh ould in clude MRI to look
for in tracran ial exten sion an d associated an om alies, in cluding an in tracran ial derm oid cyst.
Treatm ent
W h en operatin g on a cran ial derm al sin us, use a sagittally based in cision to perm it deep exploration .
Th e tract m ust be follow ed com pletely. Be prepared to en ter th e posterior fossa.
16.3 Klippel-Feil syndrom e
16.3.1 General inform at ion
Congen ital fusion of t w o or m ore cer vical vertebrae. Ran ges from fusion of on ly th e bodies (congen ital block vertebrae) to fusion of th e en tire vertebrae (in cludin g posterior elem en ts). Results from
failure of n orm al segm en tat ion of cer vical som ites betw een 3–8 w eeks gestation . Involved ver tebral
bodies are often flatten ed an d associated disc spaces are absen t or hypoplastic. Hem ivertebrae m ay
also occur. Neural foram in a are sm aller th an n orm al an d oval. Cer vical sten osis is rare. Com plete
absence of th e posterior elem en ts w ith an en larged foram en m agn um an d fixed hyperexten sion post ure is called in ien ceph aly an d is rare. In ciden ce of Klippel-Feil is un kn ow n due to its rarit y an d th e
fact th at it is frequen tly asym ptom atic.
May occur in conjun ct ion w ith oth er congen ital cer vical spin e an om alies such as basilar im pression an d atlan to-occipital fusion .
16
272
Developm ent al Anom alies
16.3.2 Present at ion
Classic clin ical triad (all 3 are presen t in < 50%):
1. low posterior h airlin e
2. sh or ten ed n eck (brevicollis)
3. lim itation of n eck m otion (m ay n ot be evident if < 3 ver tebrae are fused, if fusion is lim ited on ly
to th e low er cer vical levels,25 or if hyperm obilit y of n on fu sed segm en ts com pen sates). Lim itation
of m ovem en t is m ore com m on in rotation th an flexion -exten sion or lateral ben ding
Oth er clin ical association s in clude scoliosis in 60%, facial asym m et r y, tort icollis, w ebbing of th e n eck
(called pter ygium colli w h en severe), Sprengel’s deform it y in 25–35% (raised scapula due to failure
of th e scapula to properly descen d from its region of form ation h igh in th e n eck to its n orm al posit ion about th e sam e tim e as th e Klippel-Feil lesion occurs), syn kin esis (m irror m otion s, prim arily of
h an ds but occasion ally arm s also) an d less com m on ly facial n er ve palsy, ptosis, cleft or h igh arch ed
palate. System ic congenital abn orm alit ies m ay also occur in cludin g: gen itourin ar y (th e m ost frequen t being un ilateral absen ce of a kidn ey), cardiopulm on ar y, CNS, an d in ≈ 30% deafn ess 26 (due to
defect ive developm en t of th e osseous in n er ear).
No n eurologic sym ptom s h ave ever been directly attributed to th e fused vertebrae, h ow ever
sym ptom s m ay occur from n on fused segm en ts (less com m on in sh ort-segm en t fusion s) w h ich m ay
be hyperm obile possibly leading to in stabilit y or degen erat ive arth rit ic ch anges.
16.3.3 Treat m ent
Usually directed at detect in g an d m an agin g th e associated system ic an om alies. Pat ien ts sh ould h ave
cardiac evaluation (EKG), CXR, an d a ren al ult rasoun d. Serial exam in ation s w ith lateral flexion -exten sion lateral C-spin e x-rays to m on itor for in stabilit y. Occasion ally, judicious fusion of an un stable
n on fu sed segm en t m ay be n eeded at th e risk of furth er loss of m obilit y. See also recom m en dation s
regardin g ath letic com petition (p. 937).
16.4 Tet hered cord syndrom e
16.4.1 General inform at ion
Abn orm ally low con us m edullaris. Usually associated w ith a sh or t, th icken ed filum term in ale, or
w ith an in t radural lipom a (oth er lesion s, e.g. lipom a exten din g th rough dura, or diastem atom yelia
are con sidered as separate en tities). Most com m on in m yelom en ingocele (MM). Diagn osis m ust be
m ade clin ically in MM, as alm ost all of th ese patien ts w ill h ave teth erin g radiograph ically.
16.4.2 Present at ion
Presen ting sign s an d sym ptom s in patien ts w ith teth ered cord are sh ow n in
16
Table 16.2.
16.4.3 Myelom eningocele pat ient s
If a MM pat ien t h as in creasing scoliosis, in creasing spast icit y, w orsen ing gait (in th ose previously
am bulator y), or deteriorating urodyn am ics 28 :
● always m ake sure th at th ere is a w orkin g sh un t w ith n orm al ICP
● if pain ful, sh ould be con sidered teth ered cord un til proven oth erw ise
● if pain less, sh ould be con sidered syrin gom yelia un til proven oth erw ise
● m ay be due to brain stem com pression – see sym ptom atic Ch iari II m alform at ion (p. 284) – requirin g posterior fossa decom pression
16.4.4 Scoliosis in t et hered cord
Progressive scoliosis m ay be seen in conjun ction w ith teth ered cord. Early un teth erin g of th e cord
m ay result in im provem en t of scoliosis, h ow ever, un teth erin g m ust be don e w h en th e scoliosis is
m ild. W h en cases of ≤ 10° scoliosis w ere un teth ered, 68% h ad n eurologic im provem en t an d th e
rem ain ing 32%w ere stabilized, w h ereas w h en scoliosis is severe (≥ 50°) ≈ 16% deteriorated.
Prim ary Spinal Anom alies
273
Table 16.2 Presenting signs and sym ptom s27 (p 1331–2)
Finding
%
cutaneous findings
● hypertrichosis
● sub-Q lipom a (no intraspinal extension)
● miscellaneous (hem angiom atous discoloration, dermal sinus, m ultiple m anifestations)
54%
● 22%
● 15%
● 17%
gait difficult y with LE weakness
93%
visible muscle atrophy, short limb, or ankle deform it y
63%
sensory deficit
70%
bladder dysfunction
40%
bladder dysfunction as only deficit
4%
pain in back, leg, or foot arches
37%
scoliosis or kyphosisa
29%
posterior spina bifida (lum bar or sacral)
98%
a high incidence of scoliosis and kyphosis due to inclusion of series by Hoffm an
16.4.5 Tet hered cord in adult s
General inform at ion
Alth ough m ost cases of teth ered cord presen t in ch ildh ood, cases of adult teth ered cord also occur
(≈ 50 publish ed cases as of 1982). For com parison of adult an d ch ildh ood form s, Table 16.3
Evaluat ion
Radiograph ically: low con us m edullaris (below L2) an d th icken ed filum term in ale (defin ition of
th icken ed filum : n orm al diam eter < 1 m m ; diam eters > 2 m m are path ological). NB: apparen t filum
diam eter on CT-m yelogram m ay var y w ith con cen tration of con trast m aterial.
It is di cult to di eren tiate a teth ered cord from a con gen itally low lying con us (filum diam eter
is gen erally n orm al in th e latter).
16.4.6 Pre-op evaluat ion
Pre-operative cystomet rogra m is stron gly recom m en ded, especially if th e pat ien t seem s con tin en t
(postoperative ch anges in bladder fun ct ion are n ot un com m on , possibly due to stretch ing of th e low er fibers of th e cauda equin a).
Surgical t reat m ent
If th e on ly abn orm alit y is a th icken ed, sh orten ed filum , th en a lim ited lum bosacral lam in ectom y
m ay su ce, w ith division of th e filum on ce iden tified.
If a lipom a is foun d, it m ay be rem oved w ith th e filum if it separates easily from n eural t issues.
Dist inguishing feat ures of t he filum t erm inale int raoperat ively
Th e filum is di eren tiated from n er ve roots by presen ce of ch aracterist ic squiggly vessel on surface
of filum . Also, un der th e m icroscope, th e filum h as a distin ct ively w h iter appearan ce th an th e n er ve
roots, an d ligam en tous-like stran ds can be seen run n ing th rough it. NB: in tra-op electrical st im ulat ion an d recordin g of an al sph in cter EMG are m ore defin itive.
16
274
Developm ent al Anom alies
Table 16.3 Com parison of childhood and adult tethered cord syndrom e 29
Finding
Childhood tethered cord
Adult tethered cord
pain
uncomm on; usually in back and legs, not
peri-anal nor perineal
present in 86%, often peri-anal &
perineal; diffuse & bilateral; occasionally shock-like
foot deform ities
com mon early; usually progressive cavovarus deform it y (club foot)
not seen
progressive spinal deformity
com mon; usually progressive scoliosis
uncomm on (< 5%)
m otor deficits
com mon; usually gait abnorm alities & regression of gait training
usually presents as leg weakness
urological sym ptoms
common; usually continuous urinary dribbling, delayed toilet training, recurrent UTIs,
enuresis
com mon; usually urinary frequency,
urgency, sensation of incom plete
em pt ying, stress incontinence, overflow incontinence
trophic ulcerations
relatively common in LEs
rare
cutaneous stigm ata of
dysraphism
present in 80–100% (tuft of hair, dim ple,
capillary angiom a (naevus flamm eus)
present in < 50%
aggravating factors
growth spurts
traum a, maneuvers associated with
stretching conus, lum bar spondylosis,
disc herniation, spinal stenosis
From J Neurosurg, D. Pang and J.E. Wilberger, Vol. 57, pp. 40, 1982, with perm ission.
Out com e
In MM, it is usually im possible to perm an en tly un teth er a cord, h ow ever, in a grow in g MM ch ild, it
m ay be th at after 2–4 un teth erings th at th e ch ild w ill be fin ish ed grow in g an d teth erin g m ay cease
to be a problem . Cases th at are un teth ered early in ch ildh ood m ay recur later, especially durin g th e
adolescen t grow th -spurt. In ciden ce of post-op CSF leak: 15%.
Adult form : surgical release is usually good for pain relief. How ever, it is poor for return of bladder
fun ct ion .
16.5 Split cord m alform at ion
16.5.1 General inform at ion
16
Th ere is n o un iform ly accepted n om en clature for m alform ation s ch aracterized by duplicate or split
spinal cords. Pang et al.30 h ave proposed th e follow in g.
Th e term split cord m alform ation (SCM) sh ould be used for all double spinal cords, all of w h ich
appear to h ave a com m on em br yologic etiology.
16.5.2 Type I SCM
Defin ed as t w o h em icords, each w ith its ow n cen tral can al an d surroun din g pia, each w ith in a separate dural t ube separated by a dural-sh eath ed rigid osseocart ilagin ous (bony) m edian sept um . Th is
h as often (but n ot con sisten tly) been referred to as diastem atom yelia. Th ere are abn orm alit ies of th e
spine at th e level of th e split (absen t disc, dorsal hypert roph ic bon e w h ere th e m edian “spike”
attach es).31 Tw o-th irds h ave overlyin g skin abn orm alit ies in cludin g: n evi, hypertrich osis (tuft of
h air), lipom as, dim ples or h em angiom as. Th ese patien ts often h ave an d an orth opedic foot deform it y
(n eurogen ic h igh arch es).
Treatm ent: sym ptom s are m ost com m on ly due to teth ering of th e cord; an d are usually im proved
by un teth ering. In addit ion to un teth erin g, th e bony sept um m ust be rem oved an d th e dura recon stit uted as a sin gle tube (th ese spin es are often ver y distor ted an d rotated, th erefore start at n orm al
an atom y an d w ork tow ards defect ). DO NOT cut th e teth ered filum un t il a fter th e m edian septum
is rem oved to avoid h avin g th e cord retract up again st sept um .
Prim ary Spinal Anom alies
275
16.5.3 Type II SCM
Con sists of tw o h em icords w ith in a single dural t ube, separated by a n on rigid fibrous m edian sep t um . Th is h as som etim es been referred to as diplom yelia. Each h em icord h as n er ve roots arisin g
from it. Th ere is usually n o spin e abn orm alit y at th e level of th e split, but th ere is usually spin a bifida
occulta in th e lum bosacral region .
Treatm en t: con sists of un teth ering th e cord at th e level of th e spin a bifida occulta, an d occasion ally at th e level of th e split.31
16.6 Lum bosacral nerve root anom alies
Congen ital an om alies of n er ve roots are rare. Th is possibilit y sh ould be con sidered in cases of failed
back surgery for h ern iated disc.
Classification system of Can n on et al.32
1. Type 1 an om alies: in clude conjoin ed n er ve root (2 n er ve roots arise from a com m on dural
sh eath ). Th ey separate at various distan ces from th e th ecal sac, an d exit th rough th e sam e or sep arate n eural foram in a. Neurosurgeon s n eed to be aw are of th is an om aly to avoid in adverten t
injur y e.g. durin g surgery for h ern iated disc
2. Type 2 an om alies: 2 n er ve roots exit th rough on e foram en . Varian ts 33 :
a) leaves an un occupied n eural foram en
b) all foram in a occupied, but on e foram en h as 2 n er ve roots
3. Type 3 an om alies: adjacen t n er ve roots are con n ected by an an astom osis
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[11] Epstein NE, Rosen th al RD, Zito J, et al. Sh u n t Placem en t an d Myelom en in gocele Rep air: Sim ultan eou s
versus Sequen tial Sh un tin g. Ch ilds Ner v Syst. 1985;
1:145–147
[12] Hu bballah MY, Ho m an HJ. Early Repair of Myelom en in gocele an d Sim u ltan eou s In sert ion of VP
Sh u n t: Tech n iqu e an d Resu lts. Neurosurgery. 1987;
20:21–23
[13] McLon e DG. Tech n iqu e for Closu re of Myelom en in gocele. Childs Brain . 1980; 6:65–73
[14] Ram os E, Marlin AE, Gaskill SJ. Con gen ital derm oid
tu m or in a ch ild at in itial m yelom en in gocele closure: an etiological discussion . J Neurosurg Ped iatrics. 2008; 2:414–415
[15] Larson SJ, San ces A, Ch risten son PC. Evoked Som atosen sory Poten tials in Man . Arch Neurol. 1966;
15:88–93
[16] Hein z ER, Rosen baum AE, Scar TB, Reigel DH, et al.
Teth ered Spin al Cord Follow in g Men ingom yelocele
Repair. Radiology. 1979; 131:153–160
[17] Scott RM, Wolper t SM, Bartoshesky LE, Zim bler S,
Klauber GT. Derm oid tum ors occurrin g at the site of
previous m yelom en in gocele repair. J Neu rosurg.
1986; 65:779–783
[18] Em er y JL, Len d on RG. Lip om as of th e Caud a Equin a
an d Oth er Fatt y Tum ors Related to Neu rosp in al Dysrap h ism . Dev Med Ch ild Neurol. 1969; 11:62–70
[19] Naid ich TP, McLon e DG, Mu tlu er S. A n ew u n d erstan din g of dorsal dysraphism w ith lipom a (lipom yelosch isis): radiologic evaluation an d surgical
correct ion . AJNR. 1983; 4:103–116
[20] Uch in o A, Mori T, Oh n o M. Th icken ed fatt y filu m
term in ale: MR im agin g. Neuroradiology. 1991;
33:331–333
[21] Brow n E, Matth es JC, Bazan C, III, Jin kin s JR. Prevalen ce of in ciden tal in traspin al lip om a of th e lum bosacral sp in e as d eterm in ed by MRI. Sp in e. 1994;
19:833–836
[22] Bruce DA, Sch ut L. Spin al Lipom as in In fan cy an d
Ch ild h ood . Ch ilds Brain . 1979; 5:192–203
[23] Sato K, Sh im oji T, Sum ie H, et al. Surgically Confirm ed Myelograp h ic Classification of Con gen ital
In traspin al Lipom a in th e Lum bosacral Region .
Ch ild s Nerv Syst. 1985; 1:2–11
[24] Powell KR, Ch err y JD, Horigan TJ, et al. A Prospect ive
Search for Con genital Derm al Abnorm alities of Cran iospin al Axis. J Pediatr. 1975; 87:744–750
[25] Gray SW, Rom ain e CB, Skan dalakis JE. Con gen ital
Fusion of th e Cer vical Ver tebrae. Surg Gynecol
Obstet. 1964; 118
[26] Hen singer RN, Lan g JR, MacEw en GD. Klip pel-Feil
Syn drom e: A Con stellation of Associated Anom alies.
J Bon e Join t Surg. 1974; 56A
[27] Youm an s JR. Neurological Surgery. Ph iladelphia
1982
[28] Park TS, Cail W S, Maggio W M, Mitch ell DC. Progressive Sp asticit y an d Scoliosis in Ch ild ren w ith Myelom enin gocele:
Radiological Invest igation
an d
Surgical Treatm en t . J Neurosurg. 1985; 62:367–375
16
276
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[29] Pang D, W ilberger JE. Teth ered Cord Syn d rom e in
Ad ults. J Neurosurg. 1982; 57:32–47
[30] Pang D, Dias MS, Ah ab -Barm ad a M. Sp lit Cord Malform ation : Part I: A Unified Th eor y of Em bryogen esis for Dou ble Sp in al Cord Malform ation s.
Neurosurger y. 1992; 31:451–480
[31] Ho m an HJ. Com m en t on Pang D, et al.: Split Cord
Malform ation : Part I: A Un ified Th eor y of Em br yogen esis for Double Spin al Cord Malform ations. Neurosu rgery. 1992; 31
16
[32] Can n on BW , Hu n ter SE, Picaza JA. Nerve-root
an om alies in lum bar-disc surger y. J Neurosurg.
1962; 19:208–214
[33] Neid re A, MacNab I. An om alies of th e lum bosacral
n er ve roots. Review of 16 cases an d classification .
Spin e. 1983; 8:294–299
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277
17 Prim ary Craniospinal Anom alies
17.1 Chiari m alform at ions
17.1.1 General inform at ion
Th e term “Ch iari m alform ation ” (after path ologist, Han s Ch iari) is preferred for t ype 1 m alform at ion s, w ith th e com m on ly used term “Arn old-Ch iari m alform ation” reserved for t ype 2
m alform at ion .
Th e Ch iari m alform ation s con sists of four t ypes of h in dbrain abn orm alit ies, probably un related to
each oth er. Th e m ajorit y of Ch iari m alform ation s are t ypes 1 or 2 Table 17.1), a ver y lim ited n um ber of cases com prise th e rem ain ing t ypes. Ch iari zero is a n ovel con dition (p. 286).
17.1.2 Type 1 Chiari m alform at ion
General inform at ion
Key concept s
a heterogeneous entit y with the common feature of im paired CSF circulation through the foramen
m agnum
● m ay be congenital or acquired
● evaluation: MRI of brain and cervical spine (to R/O syringomyelia). Cine MRI to evaluate CSF flow
through foramen m agnum in uncertain cases
● cerebellar tonsillar herniation on MRI: criteria vary, > 5 mm below the foramen magnum is often
cited, but is neither essential nor diagnostic of the condition
● treatment, when indicated, is surgical, but aspects of what that surgery should entail are controversial (enlargement of foram en magnum is usually involved)
● associated with syringomyelia in 30–70% which almost always improves with treatment of the
Chiari m alformation
●
AKA prim ar y cerebellar ectopia,2 AKA adult Ch iari m alform at ion (sin ce it ten ds to be diagn osed in
th e 2n d or 3rd decade of life). A h eterogen eous group of con dition s, w ith th e un derlying com m on alit y of disruption of n orm al CSF flow th rough th e foram en m agn um (FM). Som e cases are congen ital,
but oth ers are acquired (th is sect ion is kept h ere un der developm en tal for h istorical an d organ ization al reason s).
Table 17.1 Comparisons of Chiari t ype 1 and 2 anomalies (adapted 1)
Finding
Chiari t ype 1
(see below)
Chiari t ype 2 (p. 284)
caudal dislocation of medulla
unusual
yes
caudal dislocation into cervical canal
tonsils
inferior verm is, medulla, 4th
ventricle
spina bifida (myelomeningocele)
may be present
rarely absent
hydrocephalus
may be absent
rarely absent
medullary “kink”
absent
present in 55%
course of upper cervical nerves
usually norm al
usually cephalad
usual age of presentation
young adult
infancy
usual presentation
cervical pain, suboccipital H/A
progressive hydrocephalus,
respiratory distress
17
278
Developm ent al Anom alies
Classically d escr ibed as a rare abn or m alit y rest r icted to cau d al d isp lacem en t of cerebellu m
w ith ton sillar h ern iat ion below t h e foram en m agn u m (below for cr iter ia) an d “p e g-like elon gat ion of ton sils.” Un like Ch iari t yp e 2, t h e m ed u lla is n ot cau d ally d isp laced (som e au t h ors d isagree on t h is p oin t 3 ), t h e brain stem is n ot in volved , low er cran ial n e r ves are n ot elon gat ed , an d
u p p er ce r vical n er ves d o n ot cou r se cep h alad . Syrin gom yelia of th e sp in al cord is p rese n t in 30–
70%.4 Tru e h yd rom yelia p rob ab ly d oesn ’t occu r; CSF flow h as n ot been d ocu m en ted in m an , an d
it is gen erally n ot p ossible to fin d com m u n icat ion bet w een t h e syr in x an d t h e cen t ral can al in
Ch iar i 1 p at ien t s. Hyd rocep h alu s occu rs in 7–9% of p at ien t s w it h Ch iar i t yp e 1 m alfor m at ion an d
syr in gom yelia.4
Cerebellar ton sil descen t below FM w ith im paction , w h ile com m on , is n o lon ger a sin e qua n on of
diagn osis.
Associat ions
May be associated w ith
1. a sm all posterior fossa
a) un derdevelopm en t of th e occipital bon e due to a defect in th e occipital som ites origin atin g
from th e para-axial m esoderm
b) low lying ten torium (th e roof of th e p -fossa)
c) th icken ed or elevated occipital bon e (th e floor of th e p -fossa)
d) space occupyin g lesion in p -fossa: arach n oid cyst (retrocerebellar or supracerebellar 5 ), tum or
(e.g. FM m en in giom a or cerebellar ast rocytom a), hyper vascular dura
2. h as been described w ith just about anyth in g th at takes up in t racran ial space
a) ch ronic subdural h em atom as
b) hydrocephalus
3. follow in g lum boperiton eal sh un t (p.418) or m ult iple (traum atic) LPs 6 : acquired Ch iari 1 m alform at ion (m ay be asym ptom atic)
4. arach n oid w eb or scar or fibrosis aroun d brain stem an d ton sils n ear FM
5. abn orm alit ies of th e upper cer vical spin e
a) hyperm obilit y of th e cran iovertebral jun ct ion
b) Klippel-Feil syn drom e
c) occipitalization of th e atlas
d) an terior in den tat ion at foram en m agn um : e.g. basilar invagin at ion or retroversion of th e
odon toid process
6. Eh lers-Dan los syn drom e
7. cran iosyn ostosis: especially cases involving all sutures
8. retain ed rh om boid roof: rare
Epidem iology
Average age at presentation is 41 years (ran ge: 12–73 yrs). Sligh t fem ale prepon deran ce (fem ale:
m ale = 1.3:1). Average durat ion of sym ptom s clearly related to Ch iari m alform at ion is 3.1 yrs (range:
1 m on th -20 yrs); if n on specific com plain ts, e.g. H/A, are in cluded, th is becom es 7.3 years.7 Th is
laten cy is probably low er in th e MRI era.
Clinical
17
Clinical correlates
Pat ien ts w ith Ch iari t ype 1 m alform at ion m ay presen t due to any or all of th e follow in g:
1. com pression of brain stem at th e level of th e foram en m agn um
2. hydrocephalus
3. syrin gom yelia
4. isolat ion of th e in tracran ial pressure com par t m en t from th e spin al com part m en t causin g tran sien t elevation s of ICP in tracran ial pressure
5. 15–30%of pat ien ts w ith adult Ch iari m alform at ion are asym ptom atic8
Sym ptom s
Th e m ost com m on sym ptom is pain (69%), especially h eadach e w h ich is usually felt in th e suboccipital region Table 17.2). H/A are often brough t on by n eck exten sion or valsalva m an euver. Weakn ess
is also prom in en t, especially un ilateral grasp. Lh erm it te’s sign m ay also occur. Low er extrem it y
involvem en t usually con sists of bilateral spasticit y.
Prim ary Craniospinal Anom alies
279
Table 17.2 Presenting symptoms in Chiari 1 m alformation (71 cases3 )
Sym pt om
%
pain
69%
H/A
34%
neck (suboccipital, cervical)
13%
girdle
11%
arm
8%
leg
3%
weakness (1 or m ore lim bs)
56%
num bness (1 or m ore lim bs)
52%
loss of t em perature sensat ion
40%
painless burns
15%
unst eadiness
40%
diplopia
13%
dysphasia
8%
tinnit us
7%
vom iting
5%
dysart hria
4%
m iscellaneous
dizziness
3%
deafness
3%
fainting
3%
facial numbness
3%
hiccough
1%
facial hyperhidrosis
1%
Signs
Dow n beat nystagm us is con sidered a ch aracterist ic of th is con dition . 10% w ill h ave a n orm al n eurologic exam w ith occipital H/A as th eir on ly com plain t. Som e patien ts m ay presen t prim arily w ith
spasticit y.
See Table 17.3. Th ree m ain pattern s of clusterin g of sign s 3 :
1. fora men ma gnum compression syndrome (22%): ataxia, corticospin al an d sen sor y deficits, cerebellar sign s, low er cran ial n er ve palsies. 37% h ave severe H/A
2. centra l cord syndrome (65%): dissociated sen sor y loss (loss of pain & tem perature sen sation w ith
preser ved touch & JPS), occasion al segm en tal w eakn ess, an d lon g tract sign s (syrin gom yelic syn drom e 9 ). 11% h ave low er cran ial n er ve palsies
3. cerebellar syndrome (11%): t run cal an d lim b ataxia, nystagm us, dysarth ria
Nat ural hist ory
Th e n atural h istor y is n ot kn ow n w ith certain t y (on ly 2 reports on “n atural h istor y”). A patien t m ay
rem ain stable for years, w ith in term itten t periods of deteriorat ion . Rarely, spon tan eous im provem en t m ay occur (debated).
17
280
Developm ent al Anom alies
Table 17.3 Presenting signs in Chiari I malform ation (127 patients7 )
Sign
%
hyperactive lower extrem it y reflexes
52%
nystagmusa
47%
gait disturbance
43%
hand atrophy
35%
upper extremit y weakness
33%
“cape” sensory loss
31%
cerebellar signs
27%
hyperactive upper extremit y reflexes
26%
lower cranial nerve dysfunction
26%
Babinski sign
24%
lower extrem it y weakness
17%
dysesthesia
17%
fasciculation
11%
Horner’s sign
6%
a classically: downbeat nystagmus on vertical m ovem ent, and rotatory nystagmus on horizontal movem ent; also
includes oscillopsia 10
Evaluat ion
Plain x-rays
Of 70 sku ll x-rays, on ly 36%w ere abn orm al (26% sh ow ed basilar im pression , 7% platybasia, an d 1 pat ien t each w ith Paget’s an d con cave clivus); in 60 C-spin e x-rays, 35% w ere abn orm al (in cludin g
assim ilation of atlas, w iden ed can al, cervical fusion s, agen esis of posterior arch of atlas).
MRI
17
MRI of brain an d C-spin e is th e diagn ostic test of ch oice. Easily sh ow s m any of th e classic abn orm alities described earlier, in cludin g ton sillar h ern iation , as w ell as hydrosyrin gom yelia w h ich occurs in
20–30% of cases. Also dem on st rates ven tral brain stem com pression w h en presen t. Oth er fin dings
in clude: hydroceph alus, em pt y sella.
Ton sillar h ern iation : Criteria for th e descen t of th e ton sillar tips below th e foram en m agn um
(FM) to diagn ose Ch iari t ype 1 m alform ation h ave gon e th rough a n um ber of recon sideration s.
Σ
Tonsillar herniation identified radiographically is of limited prognostic value in diagnosing Chiari I m alform ation, and requires clinical correlation.
In itially, > 5 m m w as defin ed as clearly path ologic11 (w ith 3–5 m m bein g borderlin e). Barkovich 12
foun d ton sillar position s as sh ow n in Table 17.4, an d Table 17.5 sh ow s th e e ect of utilizing 2 vs.
3 m m as th e low est n orm al position .
Th e ton sils n orm ally ascen d w ith age 13 as sh ow n in Table 17.6
Prim ary Craniospinal Anom alies
281
Table 17.4 Location of cerebellar tonsils below foramen magnum 12
Group
Mean a
Range
normal
1 m m above
8 mm above to 5 m m below
Chiari I
13 m m below
3–29 m m below
a based on m easurements in 200 normals and 25 Chiari I patients taken in relation to the lower part of the
foramen magnum
Table 17.5 Criteria for Chiari I12
Criteria for lowest ext ent of
t onsils accept ed as norm al
Sensit ivit y for Chiari I
Specificit y for Chiari I
2 m m below FM
100%
98.5%
3 m m below FM
96%
99.5%
Table 17.6 Tonsillar position relative to FM at various ages13
Age
(years)
Norm al
(m m )a
2 S.D.b
(m m )
0–9
–1.5
–6
10–19
–0.4
–5
20–29
–1.1
30–39
0.0
40–49
0.1
50–59
0.2
60–69
0.2
70–79
0.6
80–89
1.3
–4
–3
a negative num ber indicates distance below FM
b S.D. = standard deviation. Descent > 2 S.D. beyond norm al is suggested as a criteria for tonsillar ectopia
Pat ien ts w ith syrin gohydrom yelia w ith out h in dbrain h ern iation th at respon ded to p -fossa
decom pression h ave been described 14 (so-called “Ch iari zero m alform ation ”). Conversely, 14% of
patien ts w ith ton sillar h ern iation > 5 m m are asym ptom atic15 (average exten t of ectopia in th is group
w as 11.4 ± 4.86 m m ).
Poten tially m ore sign ifican t th an th e absolute ton sillar descen t is th e am oun t of com pression of
th e brain stem at th e FM, best appreciated on axial T2W I MRI th rough th e FM. Com plete obliteration
of CSF sign al an d com pression of th e brain stem at th e FM by im pacted ton sils is a com m on sign ifican t fin din g.
Cine MRI
AKA CSF flow study. May dem on strate blockage of CSF flow at FM. Not w idely available. Accuracy is
n ot h igh , th erefore usually does n ot alter m an agem en t.
17
282
Developm ent al Anom alies
Myelography
Gen erally used on ly w h en MRI can n ot be obtain ed. On ly 6% false n egative. It is critical to run th e
in trath ecal con trast (dye) all th e w ay up to th e foram en m agn um . Usually com bin ed w ith CT scan .
CT
Un en h an ced CT is poor for evaluating th e foram en m agn um region due to bony art ifact. It is ver y
good at dem on stratin g hydroceph alus (as is MRI). W h en com bined w ith in t rath ecal iodin ated con t rast (m yelogram ), reliabilit y im proves. Fin dings: ton sillar descen t w ith possible com plete blockage
of dye at foram en m agn um .
Treat m ent
Indications for surgery
Sin ce patien ts respon d best w h en operated on w ith in 2 years of th e on set of sym ptom s (below ),
early surger y is recom m en ded for sym ptom at ic patien ts. Asym ptom at ic patien ts m ay be follow ed
an d operated upon if an d w h en th ey becom e sym ptom atic. Patien ts w h o h ave been sym ptom at ic
an d stable for years m ay be con sidered for obser vation , w ith surger y in dicated for sign s of
deterioration .
Surgical techniques
17
Th e m ost frequen tly perform ed operation is posterior fossa decom pression (suboccipital cran iectom y), w ith or w ith out oth er procedures (usually com bin ed w ith dural patch graft in g an d cer vical
lam in ectom y of C1, som etim es to C2 or C3). Option s for grafts: sam e in cision (pericran ium ), separate
in cision (e.g. or fascia lata), an d allograft (avoided by m any auth ors because of dissat isfaction w ith
abilit y to provide w ater-t igh t closure an d because of in fect ious risks).
Goals of surger y: decom press th e brain stem an d reestablish n orm al flow of CSF at th e cran iocervical jun ct ion .
Th e patien t is position ed pron e on ch est rolls w ith th e h ead in a Mayfield h ead-h older or in a
h orsesh oe h eadrest. Flex th e n eck to open th e in terspace betw een th e occiput an d posterior arch of
C1. Th e sh oulders are retracted in feriorly w ith adh esive tape. If a fascia lata graft is to be taken , elevate on e th igh on a san dbag. A m idlin e in cision from in ion to ≈ C2 spin ous process is m ade. Th e
rem oval of bon e above th e foram en m agn um sh ould be ≈ 3 cm h igh by ≈ 3 cm w ide (keep th e posterior-fossa part of th ese operation s sma ll, th e m ain th rust is to open th e foram en m agn um to decom press th e ton sils an d an upper cer vical lam in ectom y; th e com pression is not in th e p -fossa).
Excessive rem oval of occipital bon e m ay allow th e cerebellar h em isph eres to h ern iate th rough th e
open in g ("cerebellar ptosis”), an d create addit ion al problem s. If a pericran ial graft is to be taken , it
sh ould be h ar vested at th is t im e to reduce th e am oun t of blood en terin g th e subsequen t dural open in g.16 Pericran ial graft can be procured w ith out exten din g th e in cision about th e in ion using th e
tech n ique of Dr. Rober t Ojem an n 16 w ith subgaleal dissection an d using a m on opolar cautery w ith a
ben t tip to in cise th e periosteum an d th en a Pen field # 1 dissector to free it from th e bon e surface.
Open th e dura in a “Y” sh aped in cision , an d excise th e t riangular top flap. CAUTION: th e t ran sverse sin uses are usually abn orm ally low in Ch iari m alform at ion s. Sut ure th e patch graft to provide
m ore room for th e con ten ts (ton sils + m edulla).
An opt ion th at is som et im es used in pediatrics is to n ot in itially open th e dura but to lyse con st rictin g ban ds over th e dura at th e foram en m agn um an d th en an d use in traoperative ult rasoun d to
determ in e if th ere is adequate room for CSF flow, th e dura is th en open ed on ly if th ere is n ot.
Historical procedures th at h ave been appen ded to th e above: pluggin g th e obex (w ith m uscle or
teflon ), drain age of syrin x if present (fen estration , usually th rough dorsal root en tr y zon e, w ith or
w ith out stent or sh un t), 4th ven t ricular sh un tin g, term in al ven triculostom y, an d open ing foram en of
Magen die if obstructed (see referen ce for illustration s 9 ). Curren t recom m en dat ion s are th at th ese or
oth er addition al procedures beyon d dural patch graft ing are usually n ot w arran ted.
Som e auth ors repeatedly adm on ish not to attem pt to rem ove adh esion s bin din g th e ton sils
togeth er (to avoid injurin g vital st ructures, in cludin g PICAs). Oth ers recom m en d cautiously separatin g th e ton sils an d even sh rin kin g th em dow n w ith bipolar cauter y.
In cases w ith ven tral brain -stem com pression , som e auth ors advocate perform ing a t ran soral clivus-odon toid resection as th ey feel th ese patien ts m ay poten tially deteriorate w ith posterior fossa
decom pression alon e.17 Sin ce th is deterioration w as reversible w ith odon toidectom y, it m ay be reason able to perform th is procedure on pat ien ts w h o sh ow sign s of deterioration or progression of
basilar im pression on serial MRIs after posterior fossa decom pression .
Prim ary Craniospinal Anom alies
283
Booking t he case : Chiari m alform at ion
Also see defaults & disclaim ers (p. 27).
1. position: prone
2. equipment:
a) optional microscope
b) intra-op Doppler, if used
3. consent:
a) procedure: surgery through the back of the neck to open the bone at the base of the skull and
to insert a “patch” to make m ore room for the brainstem
b) alternatives: non-surgical management is usually not e ective
c) com plications: CSF leak, brainstem injury/stroke, apnea, failure to improve syrinx (if present)
Operative findings
See Table 17.7.
Ton sillar h ern iation is presen t in all cases (by defin it ion ); th e m ost com m on position being at C1
(62%). Fibrous adh esion s bet w een dura, arachn oid an d ton sils w ith occlusion of foram in a of Lusch ka
an d Magen die in 41%. Th e ton sils separated easily in 40%.
Surgical com plicat ions
After suboccipital cran iectom y plus C1–3 lam in ectom y in 71 patien ts, w ith dural patch grafting in
69, on e death due to sleep apn ea occurred 36 h rs post-op. Respirator y depression w as th e m ost com m on post-op com plication (in 10 patien ts), usually w ith in 5 days, m ostly at n igh t. Close respirator y
Table 17.7 Operative findings in Chiari I (71 patients3 )
Finding
%
t onsillar descent
100%
below foramen magnum
4%
C1
62%
C2
25%
C3
3%
unspecified level
6%
adhesions
41%
syringom yelia
32%
dural band (at foram en m agnum or C1 arch)
30%
vascular abnorm alit iesa
20%
skeletal abnorm alities
inverted foram en m agnum
10%
keel of bone
3%
C1 arch atresia
3%
occipitalization of C1 arch
1%
cervicom edullary “hum p”
12%
a vascular abnorm alities: PICA dilated or abnormal course in 8 patients (PICA often descends to lower margin of
tonsils9 ); large dural venous lakes in 3
17
284
Developm ent al Anom alies
Table 17.8 Long-term follow-up after surgery for Chiari I malform ation (69 patients, 4 years m ean F/U3)
early im provem ent of pre-op sym ptom s
82%
percent of above that relapsed a
21%
early im provem ent of pre-op signs
70%
no change from pre-op status
16%
worse t han pre-op
0
a these patients deteriorated to pre-op status (none deteriorated further) within 2–3 years of surgery; relapse
occurred in 30% with foramen magnum com pression syndrome, and in 21% with central cord syndrom e
m on itorin g is th erefore recom m en ded.3 Oth er risks of th e procedure in clude: CSF leak, h ern iation of
cerebellar h em isph eres, vascular injuries (to PICA…).
Operat ive result s
See Table 17.8.
Pat ien ts w ith pre-op com plain ts of pain generally respon d w ell to surgery. Weakn ess is less
respon sive to surgery, especially w h en m uscle atrophy is presen t .17 Sen sat ion m ay im prove w h en
th e posterior colum n s are un a ected an d th e deficit is due to spin oth alam ic involvem en t alon e.
Rh oton feels th at th e m ain ben efit of operat ion is to arrest progression .
Th e m ost favorable results occurred in patien ts w ith cerebellar syn drom e (87% sh ow in g im provem en t, n o late deterioration ). Factors th at correlate w ith a w orse outcom e are th e presen ce of atrophy, ataxia, scoliosis, an d sym ptom s lastin g lon ger th an 2 years.17
17.1.3 Type 2 (Arnold)-Chiari m alform at ion
General inform at ion
Key concept s
usually associated with myelomeningocele, often accom panied by hydrocephalus pathology
includes: caudally displaced cervicomedullary junction, small posterior fossa, tectal beaking. Is
probably not due to tethering
● major clinical findings: swallowing di culties, apnea, stridor, opisthotonos, downbeat nystagmus
● when sym ptomatic: always check the shunt first! Then, consider surgical decom pression (which
cannot correct intrinsic brainstem abnormalities)
● cranial and cervical MRI is the diagnostic test of choice.
●
17
Usually associated w ith m yelom en ingocele (MM), or rarely spina bifida occulta.
Pat hophysiology
Probably does not result from teth erin g of th e cord by th e associated MM. More likely due to prim ar y
dysgen esis of th e brain stem w ith m ult iple oth er developm en tal an om alies.18
Major findings
Caudally dislocated cer vicom edullar y jun ct ion , pon s, 4th ven tricle an d m edulla. Cerebellar ton sils
located at or below th e foram en m agn um . Replacem en t of n orm al cervicom edullar y jun ction flexure
w ith a “kin k-like deform it y.”
Oth er possible associated fin din gs:
1. beakin g of tectum
2. absence of th e septum pellucidum w ith en larged in terth alam ic adh esion : absen ce of th e septum
pellucidum is th ough t to be due to n ecrosis w ith resorption secon dar y to hydroceph alus, an d
n ot a congenital absen ce 19 (p 178)
Prim ary Craniospinal Anom alies
285
3.
4.
5.
6.
7.
8.
9.
poorly m yelin ated cerebellar folia
hydrocephalus: present in m ost
h eterotopias
hypoplasia of falx
m icrogyria
degen eration of low er cran ial n er ve n uclei
bony abn orm alit ies:
a) of cer vicom edullar y jun ction
b) assim ilation of atlas
c) platybasia
d) basilar im pression
e) Klippel-Feil deform it y (p. 271)
10. hydrom yelia
11. cran iolacun ia of th e skull (see below )
Present at ion
Fin din gs are due to brain stem an d low er cran ial n er ve dysfun ct ion . On set is rare in adulth ood. Th e
presen tation of n eon ates di ers substan t ially from older ch ildren , an d n eon ates w ere m ore likely to
develop rapid n eurological deterioration w ith profoun d brain stem dysfun ct ion over a period of several days th an w ere older ch ildren in w h om sym ptom s w ere m ore in sidious an d rarely as severe.20
Fin din gs in clude 21,20 :
1. sw allow in g di cult ies (n eurogen ic dysph agia) (69%).22 Man ifests as poor feedin g, cyan osis durin g feedin g, n asal regurgitat ion , prolonged feedin g t im e, or poolin g of oral secretion s. Gag reflex
often decreased. More severe in n eon ates
2. apn eic spells (58%): due to im paired ven tilatory drive. More com m on in n eon ates
3. st ridor (56%): m ore com m on in n eon ates, usually w orse on in spiration (abductor an d occasion ally adductor vocal cord paralysis seen on lar yn goscopy) due to 10th n er ve paresis; usually tran sien t, but m ay progress to respirator y arrest
4. aspirat ion (40%)
5. arm w eakn ess (27%) th at m ay progress to quadriparesis 23
6. opisth oton os (18%)
7. nystagm us: especially dow n beat nystagm us
8. w eak or absen t cr y
9. facial w eakn ess
Diagnostic evaluat ion
Skull film s
May dem on strate ceph alofacial disproport ion from congen ital HCP. Cran iolacun ia (AKA lü cken sch ädel) in 85% (roun d defect s in th e skull w ith sh arp borders, separated by irregularly bran chin g ban ds
of bon e; not due to in creased ICP). Low lying in tern al occipital protuberan ce (foresh orten ed posterior fossa). En larged foram en m agn um in 70%; elon gation of upper cer vical lam in a.1
CT and/or MRI findings
Cran ial an d cer vical MRI is th e diagn ost ic test of ch oice.
● prim ar y fin dings
a) “Z” ben d deform it y of m edulla*
b) cerebellar peg
c) tectal fusion (“tectal beaking”)
d) en larged m assa in term edia (in terth alam ic adh esion )*
e) elon gation /cer vicallization of m edulla
f) low attach m en t of ten torium
● associated fin din gs
a) hydrocephalus
b) syrin gom yelia in th e area of th e cer vicom edullar y jun ct ion (reported in ciden ce in pre MRI
era 17 ran ges from 48–88%)
c) t rapped fourth ven tr icle
d) cerebellom edullar y com pression
e) agen esis/dysgen esis of corpus callosum *
* item s w ith an asterisk are best appreciated on MRI
17
286
Developm ent al Anom alies
Laryngoscopy
Perform ed in patien ts w ith stridor to rule out croup or oth er upper respirator y t ract in fect ion .
Treat m ent
General inform ation
in sert CSF sh un t for hydroceph alus (or ch eck fun ct ion of existin g sh un t)
● if n eurogen ic dysph agia, str idor, or apn eic spells occur, expedit ious posterior fossa decom pression
is recom m en ded (see below ) (required in 18.7% of MM patien ts 21 ); before recom m en ding decom pression , always m ake sure th e pat ien t h as a fun ct ion in g sh un t!
●
Surgical decom pression
NB: it h as been argued th at par t of th e explan ation for th e poor operative results in in fan ts is th at
m any of th e n eurological fin din gs m ay be due in part to in t rin sic (un correctable) abn orm alit ies
w h ich surgical decom pression can n ot im prove.24,25 A dissen tin g view is th at th e h istologic lesion s
are due to ch ron ic brain stem com pression an d concom itan t isch em ia, an d th at expedit ious brain
stem decom pression sh ould be carried out w h en any of th e follow in g critical w arn ing sign s develop:
neurogenic dyspha gia , str idor, a pneic spells.20
Surgical technique
Decom pression of cerebellar ton sils, usually w ith dural graft to decom press dura. Patien ts is placed
pron e, w ith th e n eck flexed. A suboccipital cran iectom y is com bin ed w ith a cer vical lam in ectom y
w h ich m ust be carried dow n to th e bottom of th e ton sillar t ip.23 A th ick con strict in g dural ban d is
usually foun d betw een th e C1 arch an d foram en m agn um . Th e dura is open ed in a “Y” sh aped in cision . Caution w h en open in g th e dura above th e level of th e foram en m agn um in in fan ts as th ey h ave
a w ell-developed occipital sin us an d m ay h ave large dural lakes.21 DO NOT attem pt to dissect ton sils
from un derlying m edulla. In cases w ith a sign ifican t syrin gom yelic cavit y, a syrin go-subarach n oid
sh un t is placed.20
Trach eostom y (usually tem porary) is recom m en ded if stridor an d abductor lar yn geal palsy w ere
presen t pre-op. Close post-op respirator y m on itoring is n eeded for obstruct ion a nd reduced ven tilatory drive (m ech an ical ven tilation is in dicated for hypoxia or hypercarbia).
Out com e
68% h ad com plete or n ear com plete resolut ion of sym ptom s, 12% h ad m ild to m oderate residual deficits, an d 20% h ad n o im provem en t (in gen eral, n eon ates fared w orse th an older ch ildren ).20
Respirator y arrest is th e m ost com m on cause of m or talit y (8 of 17 pat ien ts w h o died), w ith th e
rest due to m en ingit is/ven triculit is (6 patien ts), aspirat ion (2 patien ts), an d biliar y atresia (1
patien t).21
In follow -up ran ging 7 m os-6 yrs, 37.8% m ortalit y in operated pat ien ts.
Pre-op status an d th e rapidit y of n eurologic deterioration w ere th e m ost im por tan t progn osticators. Mortalit y rate is 71% in in fan ts h avin g cardiopulm on ar y arrest, vocal cord paralysis or arm
w eakn ess w ith in 2 w eeks of presen tat ion ; com pared to 23% m ortalit y in patien ts w ith a m ore gradual deterioration . Bilateral vocal cord paralysis w as a par ticularly poor progn osticator for respon se
to surger y.20
17
17.1.4 Ot her Chiari m alform at ions
Chiari t ype 0
Pat ien ts w ith syrin gohydrom yelia w ith out h in dbrain h ern iation th at respon d to p -fossa decom pression h ave been described 14 (so-called “Ch iari zero m alform ation ”).
Chiari t ype 1.5
Obex situated below foram en m agn um , does n ot respon d to suboccipital decom pression w ith or
w ith out duroplasty.
Chiari t ype 3
Rare. Both th e defin ition an d even th e existen ce are con troversial. Most description s are based on 1
or 2 cases. Origin al descript ion cited dislocation of th e cerebellum below th e foram en m agn um in to
Prim ary Craniospinal Anom alies
287
an occipital en ceph alocele.26 Som e h ave added h ern iation of th e m edulla, fourth ven tricle an d all of
th e cerebellum in to an occipital an d h igh cer vical en ceph alocele. Som e h ave sided w ith Raim on di
w h o in cluded occipital en ceph aloceles associated w ith caudal displacem en t of th e cerebellum an d
m edulla.27,28
Progn osis is poor for m ost, as it is usually in com pat ible w ith life.
Chiari t ype 4
Origin ally described as cerebellar hypoplasia w ith out cerebellar h ern iation .29 Existen ce as a distin ct
clin ical en tit y is debated.26
17.2 Neural t ube defect s
17.2.1 Classificat ion
General inform at ion
Th ere is n o un iversally accepted classification system . Tw o are presen ted below.
Lem ire classificat ion
A system adapted from Lem ire.30
1. n eurulation defects: n on -closure of th e n eural t ube results in open lesions
a) cran iorach isch isis: total dysraph ism . Many die as spon tan eous abor tion
b) an en cephaly: AKA exen ceph aly. Due to failure of fusion of th e an terior n europore. Neith er
cran ial vault n or scalp covers th e part ially dest royed brain . Un iform ly fatal. Risk of recurren ce
in future pregn an cies: 3%
c) m en in gom yelocele: m ost com m on in lum bar region
● m yelom en ingocele (MM) (p. 265)
● m yelocele
2. postn eurulation defect s: produces skin -covered (AKA closed) lesion s (som e m ay also be con sidered “m igration abn orm alit ies”, see below )
a) cran ial
● m icroceph aly: see below
● hydran en ceph aly: loss of m ost of cerebral h em isph eres, replaced by CSF (see below ). Must
R/O m axim al hydroceph alus (see below )
● h oloprosen ceph aly: see below
● lissen ceph aly: see below
● poren ceph aly: see below to dist in guish from sch izen ceph aly
● agen esis of corpus callosum : see below
● cerebellar hypoplasia/Dan dy Walker syn drom e (p. 256)
● m acroen ceph aly AKA m egalen ceph aly: see below
b) spinal
● diastem atom yelia, diplom yelia: see Split cord m alform ation (p. 274)
● hydrom yelia/syrin gom yelia (p. 1144)
Migrat ion abnorm alit ies
A sligh tly di eren t classification sch em e defin es th e follow in g as abn orm alit ies of n euron al m igrat ion (som e are con sidered post n eurulation defects, see above):
1. lissen ceph aly: Th e m ost severe n euron al m igration abn orm alit y. Maldevelopm en t of cerebral
convolution s (probably an arrest of cort ical developm en t at an early fetal age). In fan ts are
severely retarded an d usually don’t sur vive > 2 yrs
a) agyria: com pletely sm ooth surface
b) pachygyria: few broad & flat gyri w ith sh allow sulci
c) polym icrogyria: sm all gyri w ith sh allow sulci. May be di cult to diagn ose by CT/MRI, an d
m ay be con fused w ith pachygyria
2. h eterotopia: abn orm al foci of (n on en h an cing) gray m at ter w h ich m ay be located anyw h ere from
th e subcort ical w h ite m atter to (m ost com m on ly) th e subepen dym al lin in g of th e ven tricles. May
m an ifest as n odules or as a ban d of cortex. An early m igration defect th at results from arrest of
radial m igration . Alm ost always presen ts w ith seizures
3. cort ical dysplasia: a cleft th at does n ot com m un icate w ith th e ven t ricle. Heterotopias are com m on . A m igration abn orm alit y n ot quite as severe as sch izen ceph aly
17
288
Developm ent al Anom alies
4. sch izen cep h aly:
a) sin e qua n on : cleft th at com m un icates w ith th e ven t ricle (com m un ication m ay be con firm ed
w ith CT cistern ogram if n ecessar y)
b) cleft lin ed w ith cort ical grey m atter (often abn orm al, m ay h ave polym icrogyria). Th is dist in guish es it from p oren cep h aly, a cystic lesion lin ed w ith con n ective or glial tissue th at m ay
com m un icate w ith th e ven tricular system , often caused by vascular in farcts or follow in g
in tracerebral h em orrh age or pen etrat in g traum a (in cludin g repeated ven tricular pun ct ures)
c) t w o form s:
● open lipped: large cleft to ven tricle. Ver y severe form s m ay m im ic hydran en ceph aly (see
below )
● close lipped (w alls fused):
look for a dim ple in th e lateral w all of th e lateral ven tricle
im m ediately un der th e cort ical cleft (th e appearan ce of w h ich m ay m im ic an en larged
sulcus)
d) m ay be un ilateral or bilateral
e) pia an d arach n oid fuse
f) th ere m ay be an “abn orm al” vein th at represen ts a cort ical vein th at n ow looks m edullar y
because it follow s th e cortex in to th e cleft)
g) absence of septum pellucidum in 80–90%
h ) presen tation m ay ran ge from seizures to h em iparesis depen din g on size an d locat ion
17.2.2 Exam ples of neural t ube defect s
Hydranencephaly
General inform ation
A post-n eurulation defect . Total or n ear-total absen ce of th e cerebrum (sm all ban ds of cerebrum
m ay be con sisten t w ith th e diagn osis 31 ), w ith in tact cran ial vault an d m en in ges, th e in t racran ial cavit y being filled w ith CSF. Th ere is usually progressive m acrocran ia, but h ead size m ay be n orm al
(especially at bir th ), an d, occasion ally, m icroceph aly m ay occur. Facial dysm orph ism is rare.
May be due to a variety of causes, th e m ost com m on ly cited is bilateral ICA in farcts (w h ich results
in absence of brain tissue supplied by th e an terior an d m iddle cerebral ar teries w ith preser vation in
th e dist ribution of th e PCA). May also be due to in fect ion (congen ital or n eon atal h erpes, toxoplasm osis, equin e virus).
Less a ected in fan ts m ay appear n orm al at birth , but are often hyperirritable an d retain prim itive
reflexes (Moro, grasp, an d stepping reflex) beyon d 6 m o. Th ey rarely progress beyon d spon tan eous
vow el product ion an d social sm ilin g. Seizures are com m on .
Di erentiation from hydrocephalus
17
Progressive en largem en t of CSF spaces m ay occur w h ich can m im ic severe (“m axim al”) hydroceph alus (HCP). It is critical to di eren tiate th e t w o sin ce t rue HCP m ay be t reated by sh un tin g w h ich m ay
produce som e re-expan sion of th e cort ical m an tle. Many m ean s to distin guish hydran en ceph aly an d
HCP h ave been described, in cluding:
1. EEG: sh ow s n o cort ical act ivity in hydran en cephaly (m axim al HCP t ypically produces an abn orm al EEG, but backgroun d act ivity w ill be presen t th rough out th e brain 31 ) an d is on e of th e best
w ays to di eren tiate th e t w o
2. CT,32,31 MRI or ultrasoun d: m ajorit y of in t racran ial space is occupied by CSF. Usually do n ot see
fron tal lobes or fron tal h orn s of lateral ven tricles (th ere m ay be rem n an ts of tem poral, occipital
or subfron tal cortex). A str uct ure con sist in g of brain stem n odule (roun ded th alam ic m asses,
hypoth alam us) an d m edial occipital lobes sitt in g on th e ten torium occupies a m idlin e position
surrounded by CSF. Posterior fossa struct ures are grossly in tact. Th e falx is usually in tact (un like
alobar holoprosen ceph aly), an d is n ot th icken ed, but m ay be displaced laterally. In HCP, som e
cort ical m an tle is usually iden tifiable
3. t ran sillum in ation of th e skull: in a darken ed room , a brigh t ligh t is placed again st th e surface of
th e skull. To tran sillum in ate, th e patien t m ust be < 9 m os old an d th e cort ical m an tle un der th e
ligh t source m ust be < 1 cm th ick,33 (p 215) can also occur if fluid displaces th e cortex inw ard (e.g.
subdural e usion s). Too in sen sitive to be ver y h elpful
4. an giography: in “classic” cases result in g from bilateral ICA occlusion , n o flow th rough supraclin oid carotids an d a n orm al posterior circulat ion is expected
Prim ary Craniospinal Anom alies
289
Treatm ent
Sh un ting m ay be perform ed to con trol h ead size, but un like th e case w ith m axim al hydroceph alus,
th ere is n o restitut ion of th e cerebral m an tle.
Holoprosencephaly
AKA arhinencephaly. Failure of the telencephalic vesicle to cleave into two cerebral hemispheres. The
degree of cleavage failure ranges from the severe alobar (single ventricle, no interhem ispheric fissure) to
sem ilobar and lobar (less severe m alform ations). The olfactory bulbs are usually sm all and the cingulate
gyrus rem ains fused. Median faciocerebral dysplasia is com m on, and the degree of severity parallels the
extent of the cleavage failure Table 17.9). 80% are associated w ith trisomy (prim arily trisomy 13, and to
a lesser extent trisomy 18). Survival beyond infancy is uncom m on, m ost survivors are severely retarded,
a m inority are able to function in society. Som e develop shunt dependent hydrocephalus. The risk of holoprosencephaly is increased in subsequent pregnancies of the sam e couple.
Microcephaly
Defin ition : h ead circum feren ce m ore th an 2 stan dard deviation s below th e m ean for sex an d gestat ion al age. Term s th at are som etim es used syn onym ously: m icrocran ia, m icroceph alus. Not a sin gle
en tit y, m any of th e con dition s in Table 17.9 m ay be associated w ith m icroceph aly. It m ay also
result from m atern al cocain e abuse.35 It is im por tan t to di eren tiate m icroceph aly from a sm all skull
result in g from cran iosyn ostosis in w hich surgical treatm en t m ay provide opport un it y for im proved
cerebral developm en t.
Macroencephaly
Adapted.36 (p 109) AKA m acren ceph aly, AKA m egalen ceph aly. Not to be con fused w ith m acroceph aly
(p.1403), w h ich is en largem en t of th e skull. Not a sin gle path ologic en tity. An en larged brain w h ich
m ay be due to: hypert rophy of gray m atter alon e, gray an d w h ite m atter, presen ce of addition al
st ruct ures (glial overgrow th , di use gliom as, h eterotopias, m etabolic storage diseases…).
Con dition s in w h ich m acroceph aly m ay be seen in clude:
● n eurocutan eous syn drom es (especially n eurofibrom atosis)
● m egalen ceph aly-capillar y m alform at ion syn drom e (MCAP): an overgrow th syn drom e w ith m egalen ceph aly (often w ith hydroceph alus, Ch iari m alform ation , polym icrogyria an d seizures), an d
capillar y m alform ation s in th e skin (usually on th e face)
Brain s m ay w eigh up to 1600–2850 gram s. IQ m ay be n orm al, but developm en tal delay, retardation ,
spast icit y an d hypoton ia m ay occur. Head circum feren ce is 4–7 cm above m ean . Th e usual sign s of
hydrocephalus (fron tal bossing, bulgin g fon tan elle, “sett in g sun ” sign , scalp vein en gorgem en t) are
absent . Im aging studies (CT or MRI) sh ow n orm al sized ven t ricles an d can be used to rule out extraaxial fluid collection s.
Table 17.9 The five facies of severe holoprosencephaly34
Type of face
Facial feat ures
Cranium and brain findings
cyclopia
single eye or partially divided eye in
single orbit; arhinia with proboscis
microcephaly; alobar holoprosencephaly
ethm ocephaly
extrem e orbital hypotelorism; separate orbits; arhinia with proboscis
microcephaly; alobar holoprosencephaly
cebocephaly
orbital hypotelorism; proboscis-like
nose; no m edian cleft lip
microcephaly; usually has alobar holoprosencephaly
with median cleft lip
orbital hypotelorism; flat nose
microcephaly; sometimes has trigonocephaly; usually has alobar holoprosencephaly
with median philtrum -premaxilla anlage
orbital hypotelorism; bilateral lateral
cleft lip with m edian process representing philtrum -prem axillary anlage; flat nose
m icrocephaly; som etimes has trigonocephaly; semilobar or lobar holoprosencephaly
17
290
Developm ent al Anom alies
17.2.3 Risk fact ors
1. lack of pren atal folic acid: early adm in istration of folic acid 37,38,39 (0.4 m g/d if n o h istor y of n eural
tube defects; 4 m g/d in a carrier or w ith previous ch ild w ith NTD w as associated w ith a 71%
reduct ion in recurren ce of NTD40 ) (con firm th at vitam in B12 levels are n orm al)
2. folate an tagon ists (e.g. carbam azepin e) doubles th e in ciden ce of MM
3. m others w ith 5, 10-m ethylenetetrahydrofolate reductase (MTHFR) gene polym orphism . The com m on variant, C677 T, substitutes an alanine residue for valine at position 222 in the folate dependent MTHFR enzym e → decreased enzym e activity → reduced levels of tissue folate, and increased
levels of hom ocysteine in th e plasm a. This polym orphism m ay be h om ozygous (TT genotype) or
heterozygous (CT genotype); present in ≈10% and 38% of the population, respectively. The e ects
w ith the TT genotype are m ore pronounced than w ith th e heterozygous CT form , and there is an
in creased risk of neural tube defects, as w ell as a lesser in creased risk of cardiovascular disease 41
4. use of valproic acid (Depaken e®) durin g pregn an cy is associated w ith a 1–2% risk of NTD42
5. m atern al h eat exposure in th e form of h ot-t ubs, saun as or fever (but n ot elect ric blan kets) in th e
first t rim ester w as associated w ith an in creased risk of NTDs 43
6. obesit y (before an d durin g pregn an cy) in creases th e risk of NTD44,45
7. m atern al cocain e abuse m ay in crease th e risk of m icroceph aly, disorders of n euron al m igration ,
n euron al di eren tiation an d m yelin ation 35
17.2.4 Prenat al det ect ion of neural t ube defect s
Serum alpha-fet oprot ein (AFP)
See Alph a-fetoprotein (p.600) for backgroun d. A h igh m atern al serum AFP (≥ 2 m ultiples of th e
m edian for th e appropriate week of gestation) betw een 15–20 weeks gestation carries a relative risk
of 224 for n eural tube defects, an d an abnorm al value (h igh or low ) was associated w ith 34% of all
m ajor congen ital defects.46 The sen sitivity of m atern al serum AFP for spina bifida w as 91% (10 of
11 cases), it was 100% for 9 cases of anenceph aly. How ever, oth er series sh ow a lower sensitivity.
Closed lum bosacral spine defects, accounting for ≈ 20% of spina bifida patients,47 w ill probably be
m issed by serum AFP screen ing, and m ay also be m issed on ultrasound. Since m aternal serum AFP
rises during norm al pregnan cy, an overestim ate of gestational age m ay cause an elevated AFP to be
in terpreted as n orm al, and an underestim ate m ay cause a norm al level to be interpreted as elevated.48
Ult rasound
Pren atal ult rasoun d w ill detect 90–95% of cases of spin a bifida, an d th us in cases of elevated AFP, it
can h elp di eren tiate NTDs from n on -n eurologic causes of elevated AFP (e.g. om phalocele), an d can
h elp to m ore accurately estim ate gestation al age.
Am niocentesis
17
For pregn an cies subsequen t to a MM, if pren atal ultrasoun d does n ot sh ow spin al dysraph ism , th en
am n iocen tesis is recom m en ded (even if abort ion is n ot con sidered, it m ay allow for opt im al postpar tum care if MM is diagn osed). Amniotic fluid AFP levels are elevated w ith open n eural tube
defect s, w ith a peak betw een w eeks 13–15 of pregn an cy. Am n iocentesis also carr ies a ≈ 6% risk of
fetal loss in th is population .
17.3 Neurent eric cyst s
17.3.1 General inform at ion
No un iform ly accepted n om en clature. Working defin ition : CNS cyst lin ed by en doth elium prim arily
resem blin g th at of th e GI t ract , or less often , respirator y tract. Congen ital. Not t rue n eoplasm s. Most
com m on altern ate term : en terogen ous cyst. Less com m on term s in clude: teratom atous cyst, in testin om a, arch en teric cyst,49 en terogen e cyst, an d en doderm al cyst. Usually a ect th e upper th oracic
an d low er cervical spin e.50 Associated developm en tal vertebral an om alies (e.g. diastem atom yelia)
are com m on .51 Rarely in tracran ial (see below ). Spin al n euren teric cysts (NEC) m ay h ave a fistulous
or fibrous con n ect ion to th e GI tract (th rough a spin al dysraph ism ) an d som e call th ese en doderm al
Prim ary Craniospinal Anom alies
291
sin us cysts. Occurs as a result of persisten ce of th e n euren teric can al (tem porar y duct betw een th e
n otoch ord an d th e prim itive gut (am n iotic an d yolk sacs) form ed durin g w eek 3 of em br yogen esis
by breakdow n of th e floor of th e n otoch ordal can al).
17.3.2 Int racranial neurent eric cyst s
General inform at ion
Rare, m ost com m on in p -fossa. In it ially, m ay be di cult to rule-out m etastasis from an extrem ely
w ell-di eren tiated prim ar y aden ocarcin om a of un kn ow n origin (absen ce of progressive disease suggests NEC). Locat ion s:
1. posterior fossa
a) cerebellopon tin e an gle (CPA) 49 : usually in t radural, extraaxial (case report of extradural lesion
w ith bon e destruct ion 52 )
b) in m idlin e an terior to brain stem 50
c) cistern a m agn a 53
2. supraten torial: on ly 15 case reports as of 2004.54 Location s: suprasellar 55 (possible con fusion
w ith Rath ke’s cleft cyst), fron tal lobe in t raparen chym al,54 quadrigem in al plate region , duralbased extra-axial. Source of en doderm is con troversial sin ce th e prim it ive foregut exten ds cran ially on ly to th e m idbrain .56 Th eor y: colloid cysts, Rath ke cleft cysts, an d supraten torial NECs m ay
all arise from rem n an ts of Seesel’s pouch , a tran sien t en doderm ally derived divert iculum of th e
cran ial en d of th e em br yon ic foregut 57
Clinical
Most com m on ly presen t durin g th e first decade of life.51 Pain or m yelopathy from th e in traspin al
m ass are th e m ost com m on presentation s in older ch ildren an d adults. Neon ates an d young ch ildren
m ay present w ith cardiorespirator y com prom ise from an in trathoracic m ass, or w ith cer vical spin al
cord com pression .51 Men in gitis m ay occur from th e fistulous tract , especially in n ew born s an d
in fan ts.
Im aging
In tracran ial NEC:
● CT: usually low den sit y, n on en h an cing 58
● T1W I MRI: isoin ten se or sl hyperin ten se to CSF (m ay be hyperin ten se if th ere are blood products).
T2W I isoin ten se to CSF.58 Non en h an cing
Hist ology
Most are sim ple cysts lin ed by cuboidal-colum n ar epith elium an d m ucin secretin g goblet cells. Less
com m on t ypes of epith elium described in clude: stratified squam ous an d pseudostratified colum n ar,
an d ciliated epith elial cells. Mesoderm al com pon en ts m ay be presen t , in cluding sm ooth m uscle an d
adipose tissue, an d som e h ave called th ese teratom atous cysts 59,60 w h ich is n ot to be con fused w ith
teratom as w h ich are true germ in al cell n eoplasm s. May be h istologically iden tical to colloid cysts.
Treat m ent
Spinal NEC
Surgical rem oval usually reverses th e sym ptom s. Recurren ce is un com m on w ith com plete rem oval
of cyst w all.
Intracranial NEC
Capsule adh eren t to brain stem m ay preven t com plete resection , w h ich predisposes to delayed recurren ce. Apparen tly successful treatm en t by evacuation of con ten ts an d m arsupialization h as been
reported (5 cases, m ean follow -up: 5 yrs 61 ). In com plete rem oval requires lon g-term follow -up.
Hydroceph alus is sh un ted if in dicated.
17
292
Developm ent al Anom alies
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17
Part V
Com a and Brain Deat h
V
18 Com a
296
19 Brain Death and
Organ Donat ion
307
296
Com a and Brain Deat h
18 Com a
18.1 General inform at ion
Con sciousn ess h as t w o com pon en ts: arousal an d con ten t. Im pairm en t of arousal can var y from m ild
(drow sin ess or som n olen ce), to obtun dation , to st upor to com a. Com a is th e severest im pairm en t of
arousal, an d is defin ed as th e in abilit y to obey com m an ds, speak, or open th e eyes to pain .
Th e Glasgow Com a Scale (GCS) is a w idely used scoring system w ith good repeatabilit y an d is
sh ow n in Table 18.1 (n ote: th e scale is used to assess level of con sciousn ess an d is n ot design ed for
follow in g n eurologic deficits). Gen eral pract ice is to record a “T” (for “in tubated”) n ext to th e verbal
score an d th e total score for patien ts w h ose verbal axis can n ot be assessed because of in tubation .2
No sin gle GCS score defin es a cuto for com a, h ow ever, 90% of patien ts w ith GCS ≤ 8 an d n on e w ith
GCS ≥ 9 m eet th e above defin ition of com a. Th us, GCS ≤ 8 is a gen erally accepted operation al defin it ion of com a.
A n um ber of scales for use in ch ildren h ave been proposed. On e is sh ow n in Table 18.2.3
Com a results from on e or m ore of th e follow in g:
● dysfun ct ion of h igh brain stem (cen tral upper pon s) or m idbrain
● bilateral dien ceph alic dysfun ct ion
● di use lesion s in both cerebral h em isph eres (cort ical or subcort ical w h ite m atter)
Table 18.1 Glasgow com a a scale 1 (recom m ended for age ≥ 4 yrs)
Point sb
Best eye opening
Best verbal
Best m ot or
6
–
–
obeys
5
–
oriented
localizes pain
4
spontaneous
confused
withdraws to pain
3
to speech
inappropriate
flexion (decorticate)
2
to pain c
incomprehensible
extensor (decerebrate)
1
none
none
none d
a technically, this is a scale of im paired consciousness, whereas “com a” implies unresponsiveness
b range of total points: 3 (worst) to 15 (normal)
cwhen testing eye opening to pain, use peripheral stim ulus (the grimace associated with central pain m ay cause
eye closure)
d if no m otor response, im portant to exclude spinal cord transection
Table 18.2 Children’s com a scale a (for age < 4 yrs)
Point sb
Best eye
6
–
5
–
18
Best verbal
–
Best m otor
obeys
smiles, oriented to sound, follows objects,
interacts
Crying
Int eract ion
localizes pain
4
spontaneous
consolable
inappropriate
withdraws to
pain
3
to speech
inconsistently consolable
moaning
flexion (decorticate)
2
to pain
inconsolable
restless
extensor (decerebrate)
1
none
none
none
none
a sam e as adult Glasgow com a scale except for verbal response 3
b range of total points: 3 (worst) to 15 (normal)
Com a
297
18.2 Post uring
18.2.1 General inform at ion
Th e follow in g term s do n ot accurately localize th e site of th e lesion . Decort icate posturin g im plies a
m ore rostral lesion th an exten sor posturing, an d progn osis m ay be sligh tly better.
18.2.2 Decort icat e post uring
Classically attributed to disin h ibition by rem oval of cort icospin al path w ays above th e m idbrain .
Over view : abn orm al flexion in UE an d exten sion in LE.
Detail:
● UE: slow flexion of arm , w rist an d fin gers w ith adduct ion
● LE: exten sion , in tern al rotat ion , plan tarflexion
18.2.3 Decerebrat e post uring
Classically att ributed to disin h ibition of vestibulospin al tract (m ore caudal) an d pon tin e reticular
form ation (RF) by rem oving in h ibition of m edullar y RF (tran sect ion at in tercollicular level, betw een
vestibular an d red n uclei).
Over view : abn orm al exten sion in UE an d LE.
Detail:
● Head & t run k: opisth oton os (head an d trun k exten ded), teeth clen ch ed
● UE: arm s exten ded, adducted an d hyperpron ated (in tern ally rotated), w rists flexed, fin gers flexed
● LE: exten ded an d in tern ally rotated, feet plan tarflexed an d inver ted, toes plan tarflexed.
18.3 Et iologies of com a
18.3.1 Toxic/m et abolic causes of com a
1.
elect rolyte im balan ce: especially hypo- or hypern atrem ia, hypercalcem ia, ren al failure w ith elevated BUN & creatin in e, liver failure w ith elevated am m on ia
2. en docrin e: hypoglycem ia, n on ketotic hyperosm olar state, DKA (diabetic ketoacidosis, AKA diabetic com a), m yxedem a com a, Addison ian crisis (hypoadren alism )
3. vascular: vasculit is, DIC, hyper tensive en ceph alopathy (p. 194)
4. toxic: EtOH, drug overdose (in cludin g n arcotics, iatrogen ic polyph arm acy, barbiturates), lead
in toxication , carbon m on oxide (CO) poison in g, cyclosporin e (causes an en ceph alopathy th at
sh ow s w h ite-m atter ch anges on MRI th at is often reversible w ith discon tin uation of th e drug)
5. in fect ious/in flam m ator y: m en in gitis, en ceph alitis, sepsis, lupus cerebritis, n eurosarcoidosis
(p.189), toxic-sh ock syn drom e
6. n eoplastic: leptom en ingeal carcinom atosis, rupture of n eoplastic cyst
7. n utrition al: Wern icke’s en ceph alopathy, vitam in B12 deficien cy
8. in h erited m etabolic disorders: porphyria, lact ic acidosis
9. organ failure: urem ia, hypoxem ia, h epatic en ceph alopathy, Reye’s syn drom e, an oxic en ceph alopathy (e.g. post-resuscitation from cardiac arrest), CO2 n arcosis
10. epilept ic: status epilepticus (in cludin g n on -convulsive status), post-ictal state (especially w ith
un observed seizure)
18.3.2 St ruct ural causes of com a
1. vascular:
a) bilateral cort ical or subcort ical in farcts (e.g. w ith cardioem bolism due to SBE, m it ral sten osis,
A-fib, m ural th rom bus…)
b) occlusion of vessel supplyin g both cerebral h em ispheres (e.g. severe bilateral carotid sten osis)
c) bilateral dien ceph alic in farcts: w ell described syn drom e. May be due to occlusion of a th alam o-perforator supplying both m edial th alam ic areas or w ith “top -of-th e-basilar” occlusion .
In itially resem bles m etabolic com a (in cludin g di use slow in g on EEG), patien t even tually
arouses w ith apathy, m em ory loss, vert ical gaze paresis
2. in fect ious: abscess w ith sign ifican t m ass e ect , subdural em pyem a, h erpes sim plex en ceph alit is
3. t raum a: h em orrh agic con tusion s, edem a, h em atom a (see below )
4. n eoplastic: prim ary or m etastatic
18
298
Com a and Brain Deat h
5. h ern iation from m ass e ect: presum ably brain stem com pression causes dysfun ct ion of reticular
activatin g system or m ass in on e h em isph ere causin g com pression of th e oth er results in bilateral
h em isph ere dysfun ct ion
6. in creased in tracran ial pressure: reduces CBF
7. acute lateral sh ift (m idlin e sh ift) of th e brain : e.g. due h em atom a (subdural or epidural)
Table 18.3)
18.3.3 Pseudocom a
Di eren tial diagn osis:
1. locked-in syn drom e: ven tral pon tin e in farction
2. psych iatric: cataton ia, conversion react ion
3. n eurom uscular w eakn ess: m yasth en ia gravis, Guillain -Barré
18.3.4 Approach t o t he com at ose pat ient
General inform at ion
Th is sect ion addresses n on traum atic com a. See Head t raum a (p. 824) for th at topic.
In itial evaluation : in cludes m easures to protect brain (by providin g CBF, O2 , an d glucose), assesses
upper brain stem (Cr. N. VIII), an d rapidly iden tifies surgical em ergen cies. Keep “pseudocom a” as a
possible etiology in back of m in d.
Out line of approach t o com at ose pat ient
1.
2.
3.
4.
5.
6.
18
cardiovascular stabilization : establish airw ay, ch eck circulation (h eartbeat, BP, carotid pulse),
CPR if n ecessar y
obtain blood for tests
a) STAT: elect rolytes (especially Na, glucose, BUN), CBC+ di , ABG
b) oth ers as appropriate: toxicology screen (serum & urin e), calcium , am m on ia, an tiepileptic
drug (AED) levels (if patien t is takin g AEDs)
adm in ister em ergency support ive m edicat ion s
a) glucose: at least 25 m l of D50 IVP. Due to poten tially h arm ful e ect of glucose in global isch em ia, if possible ch eck fin gerstick glucose first, oth erw ise glucose is given w ith out exception ,
un less it is kn ow n w ith cer tain t y th at serum glucose is n orm al
b) n aloxon e (Narcan®): in case of n arcotic overdose. 1 am p (0.4 m g) IVP
c) flum azen il (Rom azicon ®): in case of ben zodiazepin e overdose. Start w ith 0.2 m g IV over
30 secon ds, w ait 30 secs, th en give 0.3 m g over 30 secs at 1 m in ute in ter vals up to 3 m g or
un til patien t arouses
d) th iam in e: 50–100 m g IVP (3% of Wern icke’s presen t w ith com a)
core n euro exam (assesses m idbrain /upper pon s, allow s em ergen cy m easures to be in stit uted
rapidly, m ore th orough evaluation possible on ce stabilized): see Core n euro exam below
if h ern iation syn drom e or sign s of expan ding p -fossa lesion w ith brain stem com pression
Table 18.4): in itiate m easures to low er ICP – see Treatm en t m easures for elevated ICP (p.866)
-, th en get a CT scan if pat ien t begin s im proving, oth erw ise em ergen cy surger y. Do NOT do LP
if m en ingitis suspected (altered m en tal status + fever, m en in geal sign s…)
a) if n o in dication of h ern iation , p -fossa m ass ( Table 18.4), focal deficit in dicat in g m ass e ect
or papilledem a: perform LP, start an tibiotics im m ediately (do n ot w ait for CSF results); see
Men in gitis (p.318)
b) if evidence of possible m ass e ect , coagulopathy or h ern iation , CT to R/O m ass. If sign ifican t
delay an ticipated, con sider em piric an tibiotics or careful LP w ith sm all gauge n eedle (≤ 22
Table 18.3 E ect of lateral shift on level of consciousness4
Am ount of m idline shift
Level of consciousness
0–3 m m
alert
3–4 mm
drowsy
6–8.5 m m
stuporous
8–13 m m
comatose
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Table 18.4 Signs of herniation syndrome or posterior fossa lesion
Herniation syndrom es
Signs of P-fossa lesion
also see Herniation syndromes (p. 302)
also see Posterior fossa (infratentorial) tum ors (p. 592)
●
●
●
●
unilateral sensory or m otor deficit
progressive obtundation → com a
unilateral 3rd nerve palsy
decorticate or decerebrate posturing (especially if unilateral)
●
●
●
●
●
●
●
●
●
initial symptoms of diplopia, vertigo, bilateral lim b weakness, ataxia, occipital H/A
rapid onset of deterioration/coma
bilateral m otor signs at onset
m iosis
absent calorics to horizontal m ovem ent, possibly with
preserved vertical m ovem ents
ocular bobbing
ophthalmoplegia
m ultiple cranial nerve abnorm alities with long tract signs
apneustic, cluster or ataxic respirations
Ga.), m easure open in g pressure (OP), rem ove on ly a sm all am oun t of CSF if OP h igh , replace
CSF if patien t deteriorates; LP in th is settin g m ay be risky, see Lum bar pun ct ure (p.1504).
7. treat gen eralized seizures if presen t. If status epilept icus is suspected, t reat as in dicated (p. 470);
obtain em ergen cy EEG if available
8. treat m etabolic abn orm alit ies
a) restore acid-base balan ce
b) restore elect rolyte im balan ce
c) m ain tain body tem perature
9. obtain as com plete h istory as possible on ce stabilized
10. adm in ister specific th erapies
Core neuro exam for com a
Respiratory rate and pat tern
Th e m ost com m on disorder in im paired con sciousn ess (th is in form ation is often lackin g in pat ien ts
th at are in t ubated early in th eir course):
● Ch eyn e-Stokes ( Fig. 18.1 a): breath ing gradually crescen dos in am plitude an d th en t rails o , follow ed by an expiratory pause, an d th en th e pattern repeats. Hyperpn eic ph ase is usually lon ger
th an apn eic. Usually seen w ith dien ceph alic lesion s or bilateral cerebral h em isph ere dysfun ct ion
(n on -specific), e.g. early in creased ICP or m etabolic abn orm alit y. Results from an in creased ven tilator y respon se to CO2
● hyper ven tilation : usually in respon se to hypoxem ia, m etabolic acidosis, aspiration , or pulm on ar y
edem a. True cen tral n eurogenic hyper ven tilation is rare, an d usually results from dysfun ct ion
w ith in th e pon s. If n o oth er brain stem sign s are presen t , m ay suggest psych iatric disorder
● cluster breath in g ( Fig. 18.1 b): periods of rapid irregular breath in g separated by apn eic spells,
m ay appear sim ilar to Ch eyn e-Stokes, m ay m erge w ith various pat tern s of gaspin g respiration s.
High m edulla or low er pon s lesion . Often an om in ous sign
● apn eustic (rare;
Fig. 18.1 c): a pause at full in spirat ion . In dicates pon t in e lesion , e.g. w ith basilar
ar tery occlusion
● ataxic (Biot’s breath in g; ( Fig. 18.1 d): n o pattern in rate or depth of respiration s. Seen w ith
m edullar y lesion . Usually preterm in al
18
Pupil
Record size (in m m ) in am bien t ligh t , an d in react ion to direct/con sen sual ligh t
1.
equal an d react ive pupils in dicates toxic/m etabolic cause w ith few exception s (see below )
(m ay h ave h ippus). Th e ligh t reflex is th e m ost useful sign in dist in guish in g m etabolic from struct ural com a
a) th e only m etabolic causes of fixed/dilated pupil: gluteth im ide toxicit y, an oxic en ceph alopathy,
an tich olin ergics (in cludin g topically applied atropin e), occasion ally w ith botulism toxin
poison in g
b) n arcotics cause sm all pupils (miosis ) w ith a sm all ran ge of con striction an d sluggish reaction
to ligh t (in severe overdose, th e pupils m ay be so sm all th at a m agn ifying glass m ay be n eeded
to see reaction )
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Com a and Brain Deat h
Fig. 18.1 Respiratory rate and pattern.
a) Cheyne-Stokes respiratory pattern
b) Cluster breathing
c) Apneustic respiratory pattern
d) Ataxic respirations
2. un equal; n ote: an a eren t pupillar y defect does not produce an isocoria, see Alteration s in pupillar y diam eter (p.561)
a) fixed an d dilated pupil: usually due to oculom otor palsy. Possible h ern iation , especially if larger pupil associated w ith ipsilateral 3rd n er ve EOM palsy (eye deviated “dow n an d out”)
b) possible Horn er’s syn drom e: con sider carotid occlusion /dissect ion (NB: in Horn er’s syn drom e,
th e m iotic (sm aller) pupil is th e abn orm al on e)
3. bilateral pupil abn orm alit ies
a) pin poin t w ith m in ute reaction th at can be detected w ith m agn ifying glass 5 : pon t in e lesion
(sym path etic in put is lost; parasym path et ics em erge at Edinger-Westph al n ucleus an d are
un opposed)
b) bilateral fixed an d dilated (7–10 m m ): subtotal dam age to m edulla or im m ediate post-an oxia
or hypoth erm ia (core tem perat ure < 90° F (32.2° C))
c) m idposition (4–6 m m ) an d fixed: m ore exten sive m idbrain lesion , presum ably due to in terruption of sym path etics an d parasym path etics
Extraocular m uscle function
18
1. deviation s of ocular axes at rest
a) bilateral conjugate deviation :
● fron tal lobe lesion (fron tal cen ter for con tralateral gaze): looks tow ard side of destruct ive
lesion (aw ay from h em iparesis). Looks aw ay from side of seizure focus (looks at jerkin g
side), m ay be status epilepticus. Reflex eye m ovem en ts (see below ) are n orm al
● pon tin e lesion : eyes look a way from lesion an d tow ards h em iparesis; calorics im paired on
side of lesion
● ”w rong w ay gaze”: m edial th alam ic h em orrh age. Eyes look aw ay from lesion an d tow ards
h em iparesis (an exception to th e axiom th at th e eyes look towa rds a dest ructive supraten torial lesion ) 5
● dow nw ard deviation : m ay be associated w ith un react ive pupils, Parin aud’s syn drom e
(p.99). Etiologies: th alam ic or m idbrain pretect al lesion s, m etabolic com a (especially barbiturates), m ay follow a seizure
b) unilateral out w ard deviation on side of larger pupil (III palsy): un cal h ern iation
c) unilateral inw ard deviation : VI (abducen s) n er ve
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d) skew deviation
● III or IV n er ve/n ucleus lesion
● in fraten torial lesion (frequen tly dorsal m idbrain )
2. spon tan eous eye m ovem en ts
a) “w in dsh ield w iper eyes”: ran dom rovin g conjugate eye m ovem en ts. Non -localizing. In dicates
an in tact III n ucleus an d m edial lon gitudin al fasciculus
b) periodic altern at in g gaze, AKA “pin g-pon g gaze”: eyes deviate side to side w ith frequen cy of ≈
3–5 per secon d (pausin g 2–3 secs in each direction ). Usually in dicates bilateral cerebral
dysfun ct ion
c) ocu lar bobbin g (p. 570): repetitive rapid vert ical deviation dow nw ard w ith slow return to
n eut ral position .
3. in tern uclear oph th alm oplegia (INO) (p. 565): due to lesion in m edial lon gitudin al fasciculus
(MLF) (fibers crossin g to con tralateral III n ucleus are in terrupted). Eye ipsilateral to MLF lesion
does not adduct on spon tan eous eye m ovem en t or in respon se to reflex m an euvers (e.g. calorics)
4. reflex eye m ovem en ts (m an euvers to test brain stem )
a) oculovestibular reflex a , AKA ice w ater calorics: first rule-out TM perforation an d occlusion of
th e EAC by cerum en . Elevate th e HOB 30°, irrigate on e ear w ith 60–100 m l of ice w ater b . NB:
respon se is in h ibited by n eurom uscular blockin g agen ts (NMBA)
● a com atose patien t w ith an inta ct brain stem w ill h ave ton ic conjugate eye deviation to side
of cold st im ulus w h ich m ay be delayed up to on e m in ute or m ore. Th ere w ill be n o fast
com pon en t (nystagm us) (th e cortical com pon en t) even if th e brain stem is in tact. (NB: oculoceph alic reflexc (doll’s eyes) provides sim ilar in form ation as oculovestibular reflex d , but
poses a greater risk to th e spinal cord if C-spin e n ot cleared)
● n o respon se: sym m etrical, could be specific toxin (e.g. n eurom uscular block or barbiturates), m etabolic cause, brain death or possibly m assive in fraten torial lesion
● asym m et ric: in fraten torial lesion , especially if respon se in con sisten t w ith 3rd n er ve palsy
(h ern iation ). Usually m ain tain ed in toxic/m etabolic com a
● nystagm us w ith out ton ic deviation (i.e. eyes rem ain in prim ar y position ) virt ually diagnost ic of psych ogen ic com a
● con tralateral eye fails to adduct: INO (MLF lesion )
b) optokin etic nystagm us presen ce st ron gly suggests psych ogen iccom a
Not es:
a Ocu lovest ibu lar r eflexes (calorics): th e an ticipated respon se is com m on ly m isun derstood. In a
n orm al aw ake patien t t h ere is slow d eviat ion t ow ard s t h e sid e of t h e cold st im u lu s w it h n yst agm u s (w h ich is n am ed for th e rapid, cortical ph ase) in th e opposite direction (h en ce th e m n em on ic
“COWS” (cold-opposite, w arm -sam e)). Nystagm us w ill be absen t in th e com atose patien t.
b HOB at 30° places th e h orizon tal sem icircular can al (SCC) vertically for m axim al respon se.6 (p 56)
– Cold w ater → dow nw ard en dolym ph atic curren ts, aw ay from th e am pulla of th e h orizon tal SCC.6 (p
57)
c Ocu locep h alic reflex (“doll’s eyes” or “doll’s h ead”): do n ot perform if th ere is any un cer tain t y
about cer vical-spin e stabilit y. In an awake pat ien t, th e eyes w ill eith er m ove w ith th e h ead, or, if th e
m ovem en t is slow en ough an d th e patien t is fixatin g on an object , th ere w ill be con traversive conjugate eye m ovem en t 7 (c.f. oculovestibular reflex w h ich does n ot depen d on patien t’s level of cooperat ion ). In a com atose patien t w ith an in tact brain stem & cran ial n er ves, th ere w ill also be
con traversive conjugate eye m ovem en t (a positive doll’s eyes respon se).
d Oculovestibular reflexes are absent but oculoceph alic are m ain tain ed on ly w h en vestibular
in puts are in terrupted, e.g. st reptom ycin toxicit y of labyrin th s or bilateral vestibular sch wan n om as.
18
Motor
Record m uscle ton e an d reflexes, respon se to pain , plan tar reflex (Babin ski). Note asym m et ries
1. appropriate: im plies cort icospin al tracts an d cortex in tact
2. asym m etric: supraten torial lesion (ton e usually in creased), un likely in m etabolic
3. in con sisten t/variable: seizures, psych iatric
4. sym m etric: m etabolic (usually decreased). Asterixis, trem or, m yoclon us m ay be presen t in m etabolic com a
5. hyporeflexia: con sider m yxedem a com a, especially in patien t presen t in g w eeks after tran ssph en oidal surger y
6. pattern s
a) decor ticate posturin g: arm s flex, legs exten d: large cort ical or subcort ical lesion
b) decerebrate posturin g: arm s an d legs exten d: brain stem injur y at or below low er m idbrain
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Com a and Brain Deat h
c) arm s flexed, legs flaccid: pon tin e tegm en t um
d) arm s flaccid, legs appropriate (“m an -in -th e-barrel syn drom e”): an oxic injur y (poor
progn osis)
Ciliospinal reflex
Pupillar y dilatation to n oxious cutan eous st im uli: tests in tegrit y of sym path et ic path ways
1. bilaterally presen t: m etabolic
2. un ilaterally presen t: possible 3rd n er ve lesion (h ern iation ) if on side of larger pupil. Possible preexistin g Horn er’s syn drom e if on side of sm aller pupil
3. bilaterally absen t: usually n ot h elpful
18.4 Herniat ion syndrom es
18.4.1 General inform at ion
Classic teach in g h as been th at sh ifts in brain t issue (e.g. caused by m asses or in creased in tracran ial
pressure) th rough rigid open in gs in th e skull (hern iation ) com press oth er st ructures of th e CNS producin g th e observed sym ptom s. In act ualit y it m ay be th at h ern iation is an epiph en om en on th at
occurs late in th e process an d is n ot act ually th e cause of th e obser vation s.8 How ever, h ern iation
m odels still ser ve as useful m odels.
Th e five m ost com m on h ern iation syn drom es are:
● Supraten torial h ern iation
○ central (tran sten torial) h ern iation (p.303)
○ un cal h ern iation (p. 304)
● cin gulate h ern iation : cin gulate gyrus h ern iates un der falx (AKA subfalcin e h ern iation ). Usually
asym ptom atic un less ACA kin ks an d occludes causin g bifron tal in farction . Usually w arn s of
im pendin g tran sten torial h ern iation
● In fraten torial h ern iation
○ upw ard cerebellar (see below )
○ ton sillar h ern iation (see below )
18.4.2 Com a from suprat ent orial m ass
See referen ce.6
General inform at ion
Cen t ral an d un cal h ern iation each causes a di eren t form of rostral-caudal deterioration . Cen tral
h ern iation results in sequen tial failure of: dien ceph alon , m idbrain , pon s, m edulla (p. 303). See also
un cal h ern iation (p. 304). “Classic” sign s of in creased ICP (HTN, bradycardia, altered respirator y pattern ) usually seen w ith p -fossa lesion s m ay be absen t in slow ly developin g supraten torial m asses.
Dist in ct ion betw een cen tral an d un cal h ern iation is di cult w h en dysfun ct ion reach es th e m idbrain level or below. Predict in g th e location of th e lesion based on th e h ern iation syn drom e is
un reliable.
Clinical charact erist ics di erent iat ing uncal from cent ral herniat ion
●
●
18
decreased con sciousn ess occurs early in cen tral h ern iation , late in un cal
un cal h ern iation syn drom e ra rely gives rise to decorticate post urin g
Di erent ial diagnosis of suprat ent orial et iologies
1.
2.
3.
4.
vascular: stroke, in tracerebral h em orrh age, SAH
in flam m atory: cerebral abscess, subdural em pyem a, h erpes sim plex en ceph alit is
n eoplastic: prim ar y or m etastatic
traum atic: epidural or subdural h em atom a, depressed skull fract ure
18.4.3 Com a from infrat ent orial m ass
General inform at ion
NB: it is essen tial to iden tify patien ts w ith prim ar y posterior fossa lesion s ( Table 18.4) as th ey m ay
require em ergen t surgical in ter ven tion .
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Et iologies of infrat ent orial m asses:
1. vascular: brain stem in farct ion (in cluding basilar ar ter y occlusion ), cerebellar in farct ion or
h em atom a
2. in flam m ator y: cerebellar abscess, cen tral pon tin e m yelin olysis, brain stem en ceph alit is
3. n eoplasm s: prim ary or m etastat ic
4. t raum at ic: epidural or subdural h em atom a
Hydrocephalus
In fraten torial m asses can produce obstruct ive hydroceph alus by com pressin g th e Sylvian aqueduct
an d/or 4th ven tr icle.
Upw ard cerebellar herniat ion
Occasion ally seen w ith p -fossa m asses, m ay be exacerbated by ven tr iculostom y. Cerebellar verm is
ascen ds above ten torium , com pressin g th e m idbrain , an d possibly occludin g SCAs → cerebellar
in farction . May com press sylvian aqueduct → hydroceph alus.
Tonsillar herniat ion
Cerebellar ton sils “con e” th rough foram en m agn um , com pressin g m edulla → respirator y arrest. Usually rapidly fatal.
Occurs w ith eith er supra- or in fra-ten torial m asses or w ith elevated ICP. May be precipitated by
LP. In m any cases, th ere m ay sim ply be pressure on th e brain stem w ith out act ual h ern iation .9 Th ere
are also cases w ith sign ifican t cerebellar h ern iation th rough th e foram en m agn um w ith th e pat ien t
rem ain ing alert .8
18.4.4 Cent ral herniat ion
General inform at ion
AKA t ran sten torial h ern iation AKA tentorial h ern iation . Usually m ore ch ron ic th an un cal h ern iation ,
e.g. due to tum or, especially of fron tal, parietal or occipital lobes.
Th e dien ceph alon is gradually forced th rough th e ten torial in cisura. Th e pit uitar y stalk m ay be
sh eared, resultin g in diabetes in sipidus. PCAs m ay be trapped alon g th e open edge of th e in cisura,
an d m ay occlude producin g cort ical blin dn ess; see Blin dn ess from hydroceph alus (p. 396). Th e brain stem su ers isch em ia from com pression an d sh earin g of perforatin g arteries from basilar artery →
h em orrh ages w ith in th e brain stem (Duret h em orrh ages).
Im aging
MRI or CT: th e perim esen ceph alic cistern s m ay be com pressed.
Skull x-rays: dow nw ard displacem en t of th e pin eal glan d m ay be iden tified.10
St ages of cent ral herniat ion
Diencephalic stage
Early. May be due to di use bilateral h em isph ere dysfun ct ion (e.g. from decreased blood flow from
in creased ICP) or (m ore likely) from bilateral dien ceph alic dysfun ct ion due to dow nw ard displacem en t. Th is stage w arn s of im pen din g (irreversible) m idbrain dam age but is frequen tly reversible if
th e cause is treated.
Con sciou sn ess: Altered aler tn ess is first sign ; usually leth argy, agitat ion in som e. Later: st upor →
com a.
Resp ir at ion : Sigh s, yaw n s, occasion al pauses. Later: Ch eyn e-Stokes.
Pu p ils: Sm all (1 – 3 m m ), sm all ran ge of con traction .
Ocu lom ot or: Conjugate or sligh tly divergen t roving eyes; if conjugate th en brain stem in tact . Usually positive DOLL’S EYES an d conjugate ipsilateral respon se to cold water calorics (CW C). Im paired
upgaze due to com pression of superior colliculi an d dien ceph alic pretect um : Parin aud’s syn drom e
(p.99)
Motor: Early: appropriate respon se to n oxious st im uli, bilateral Babin ski, gegen h alten (paraton ic
resistan ce). If previously h em iparet ic con tralateral to lesion : m ay w orsen . Later: m otion lessn ess &
grasp reflexes, th en DECORTICATE (in itially con tralateral to lesion in m ost cases).
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Com a and Brain Deat h
Midbrain – upper pons stage
W h en m idbrain sign s fully developed (in adults), progn osis is ver y poor (extrem e isch em ia of m idbrain ). Few er th an 5% of cases w ill h ave a good recover y if treatm en t is successfully un dertaken at
th is stage.
Resp irat ion : Ch eyn e-Stokes → sustain ed tachypn ea.
Pu p ils: Moderately dilated m idposit ion (3–5 m m ), fixed. Note: in pon t in e h em orrh age pinpoin t
pupils appear because th e loss of sym path etics leaves th e parasym path et ics un opposed, w h ereas in
h ern iation , th e parasym path et ics are usually lost, too (3rd n er ve injur y).
Ocu lom ot or: Doll’s eyes & CW C im paired, m ay be dysconjugate. MLF lesion → in tern uclear oph th alm oplegia (w h en doll’s or CW C elicited an d dysconjugate, m edially m ovin g eye m oves less th an
laterally m ovin g eye).
Motor: Decorticate → bilaterally DECEREBRATE (occasion ally spon tan eously).
Lower pons – upper m edullary stage
Resp irat ion : Regular, sh allow an d rapid (20–40/m in ).
Pu p ils: Midposition (3–5 m m ), fixed.
Ocu lom ot or: Doll’s eyes an d CWC un elicitable.
Motor : Flaccid. Bilateral Babin ski. Occasion ally LE flexion to pain .
Medullary stage (term inal stage)
Resp irat ion : Slow, irregular rate an d depth , sigh s/gasps. Occasion ally hyperpn ea altern atin g w ith
apn ea
Pu p ils: Dilate w idely w ith hypoxia.
Out com e aft er cent ral herniat ion
In a series of 153 patien ts w ith sign s of cen tral h ern iation (altered level of con sciousn ess, an isocoria
or fixed pupils, abn orm al m otor fin din gs) 9% h ad good recover y, 18% h ad fun ct ion al outcom e, 10%
w ere severely disabled, an d 60% died.11
Fact or s associate d w it h a bet ter resu lt w ere you n g age (esp ecially age ≤ 17 yrs), an isocor ia
w ith d eter iorat in g Glasgow Com a Score an d n on flaccid m otor fu n ct ion . Factors associate d w it h
p oor ou tcom e w er e bilat erally fixed p u p ils, w it h on ly 3.5% of t h ese p at ien t s h avin g a fu n ct ion al
recover y.
18.4.5 Uncal herniat ion
General inform at ion
Usually occurs in rapidly expan din g t raum atic h em atom as, frequen tly in th e lateral m iddle-fossa or
tem poral lobe push in g m edial un cus an d h ippocam pal gyrus over edge of tentorium , en trapping
th ird n er ve an d directly com pressin g m idbrain . PCA m ay be occluded (as w ith cen t ral h ern iation ).
For CT criteria see below.
Im p aired con sciou sn ess is NOT a reliable early sign . Earliest con sisten t sign : u n ilat erally d ilat in g p u p il. How ever, it is u n likely t h at a p at ien t u n d ergoin g early u n cal h ern iat ion w ou ld be com p letely n eu rologically in t act excep t for an isocor ia (d o n ot d ism iss con fu sion , agit at ion , etc.).
On ce brain stem fin d in gs ap p ear, d ete r ior at ion m ay be rap id (d eep com a m ay occu r w it h in
h ou rs).
18
CT and/or MRI crit eria
See referen ce.12
Th e tentorial in cisura surroun ds th e in terpedun cular an d pre-pon tin e cistern s an d brain stem .
Th ere is great in terperson al variabilit y in th e am oun t of space in th e in cisura.
Im pen din g un cal or h ippocam pal h ern iation m ay be in dicated by en croach m en t on lateral aspect
of suprasellar cistern → flatten in g of n orm al pen tagon al sh ape. On ce h ern iation occurs CT m ay sh ow :
brain stem displacem en t an d flatten in g, com pression of con tralateral cerebral pedun cle, m idbrain
rotat ion w ith sligh t in crease of ipsilateral subarachn oid space. Also, con tralateral hydroceph alus
m ay occur.13
Obliteration of parasellar an d in terpedun cular cistern s occurs as un cus an d/or h ippocam pus are
forced th rough h iatus. Brain stem is elon gated in AP direction due to lateral com pression . Sin ce dural
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st ruct ures en h an ce w ith IV con trast, th is m ay be used to h elp delin eate ten torial m argin s w h en
n ecessar y.
St ages of uncal herniat ion
Early third nerve stage
Th is is not a brain stem fin ding, it is due to 3rd n er ve com pression .
Pu p ils: Approach to th e com atose patien t
Ocu lom ot or: Doll’s eyes (oculoceph alic reflex) = n orm al or dysconjugate. CWC (oculovestibular
reflex) = slow ipsilateral deviation , im paired nystagm us, m ay be dysconjugate if extern al oculom otor
oph th alm oplegia (EOO).
Resp irat ion s: Norm al.
Motor: Appropriate respon se to n ociceptive st im ulus. Con tralateral Babin ski.
Lat e third nerve stage
Midbrain dysfun ct ion occurs alm ost im m ediately after sym ptom s exten d beyon d th ose due to focal
cerebral lesion (i.e. m ay skip dien ceph alic stage, due to lateral pressure on m idbrain ). Treatm en t
delays m ay result in irreversible dam age.
Pu p ils: Pupil fully dilates.
Ocu lom ot or: On ce pupil blow n , th en extern al oculom otor oph th alm oplegia (EOO).
Con sciou sn ess: On ce EOO occurs: st upor→com a
Resp irat ion s: Sustain ed hyper ven tilation , rarely Ch eyn e-Stokes.
Motor: Usually produces con tralateral w eakn ess. How ever, th e con tralateral cerebral pedun cle
m ay be com pressed again st th e ten torial edge causin g ipsilateral h em iplegia (Ker noha n’s phenomenon, a false localizin g sign ). Th en bilateral decerebration (decort icat ion un usual).
Midbrain – upper pons stage
Con tralateral pupil fixes in m idposition or full dilation . Even tu ally, both m idposition (5–6 m m ) an d
fixed.
Ocu lom ot or: Im paired or absent.
Resp irat ion s: Sustain ed hyperpn ea.
Motor: Bilateral decerebrate rigidit y.
Following the m idbrain – upper pons stage
From th is poin t onw ard, th e un cal syn drom e is in distin guish able from cent ral h ern iation (see
above).
18.5 Hypoxic com a
An oxic en ceph alopathy m ay be due to an oxem ic an oxia (drop in pO2 ) or an em ic an oxia (follow in g
exsanguin at ion or cardiac arrest). Myoclon us is com m on .
Vuln erable cells:
1. cerebral grey m atter: lesion s predom in ate in 3rd cort ical layer (w h ite m at ter is usually better
preser ved due to low er O2 requirem en ts)
2. Am m on’s h orn is also vuln erable, especially th e Som m er sect ion
3. in th e basal ganglia (BG):
a) an oxem ic an oxia severely a ect s globus pallidus
b) an em ic an oxia a ect s the caudate n ucleus an d putam en
4. in th e cerebellum : Purkinje cells, den tate n uclei, an d in ferior olives are a ected
Multivariate an alysis yields outcom e progn osticators sh ow n in Table 18.5 an d Table 18.6. NB:
th is an alysis applies only to hypoxic-isch em ic com a; an d is based retrospectively on 210 patien ts,
m ost S/P cardiac arrest w ith m any m edical com plication s.14 More recen t studies con firm th e poor
progn osis of un react ive pupils an d lack of m otor respon se to pain 15 ; if eith er of th ese fin dings are
seen w ith in a few h ours after cardiac arrest th ere is an 80% risk of death or perm an en t vegetative
state, an d if presen t at 3 days th ese th is rate rose to 100%.
Glucocor ticoids (steroids) h ave been sh ow n to h ave n o ben eficial e ect on sur vival rate or n eurological recover y rate after cardiac arrest.16
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Table 18.5 Patients with BEST chance of regaining independence a
Tim e of exam
Finding
< 6 hrs from onset
(pupillary light reflex present)
AND (GCS-m otor > 1)
AND (spontaneous EOM WNL, i.e. orienting or conjugate roving)
1 day
(GCS-motor > 3)
AND (GCS-eye im proved ≥ 2 from initial)
3 days
(GCS-motor > 3)
AND (spontaneous EOM WNL)
1 week
GCS-motor = 6
2 weeks
oculocephalic WNL
a abbreviations: WNL= within normal limits, GCS = Glasgow Coma Scale (“GCS-motor” refers to the m otor
score…); EOM = extraocular muscle;
Table 18.6 Patients with virtually NO chance of regaining independence a
Tim e of exam
Finding
< 6 hrs
no pupillary light reflex
1 day
(GCS-m otor < 4)
AND (spontaneous eye m ovements not orienting nor conjugate roving)
3 days
GCS-motor < 4
1 week
(GCS-m otor < 6)
AND (at < 6 hrs spontaneous EOM not orienting nor conjugate roving)
AND (at 3 d GCS-eye < 4)
2 week
(oculocephalic not WNL)
AND (at 3 d GCS-m otor < 6)
AND (at 3 d GCS-eye < 4)
AND (at 2 wk GCS-eye not im proved at least 2 points from initial)
a abbreviations: WNL= within normal limits, GCS = Glasgow Com a Scale (“GCS-m otor” refers to the m otor score…);
EOM = extraocular m uscle;
References
18
[1] Teasdale G, Jen n ett B. Assessm en t of Com a an d
Im paired Con sciousn ess: a Pract ical Scale. Lancet.
1974; 2:81–84
[2] Valadka AB, Narayan RK, Narayan RK, W ilberger JE,
Povlishock JT. In : Em ergen cy Room Managem en t of
th e Head-In jured Patien t. Neurotraum a. New York:
McGraw -Hill; 1996:119–135
[3] Hah n YS, Ch yu n g C, Bar th el MJ, Bailes J, Flan n ery
AM, McLon e DG. Head Injuries in Ch ild ren Und er
36 Mon th s of Age: Dem ography an d Ou tcom e.
Ch ilds Nerv Syst. 1988; 4:34–40
[4] Ropper AH. Lateral Displacem en t of the Brain and
Level of Con sciousness in Patients w ith an Acute
Hem isph eral Mass. N Engl J Med. 1986; 314:953–958
[5] Fisher CM. Som e Neuro-Ophthalm ological Observations. J Neurol Neurosurg Psychiatry. 1967; 30:383–392
[6] Plum F, Posn er JB. Th e Diagn osis of Stupor an d
Com a. 3rd ed . Ph iladelph ia: F A Davis; 1980:87–130
[7] Buettn er UW , Zee DS. Vestibular Testing in Com atose Patients. Arch Neurol. 1989; 46:561–563
[8] Fisher CM. Acute Brain Hern iation : A Revised Con cept. Sem Neurology. 1984; 4:417–421
[9] Fisher CM, Picard EH, Polak A, Ojem ann RG, et al.
Acute Hyp erten sive Cerebellar Hem orrh age: Diagn osis and Surgical Treatm ent . J Nerv Men t Dis.
1965; 140:38–57
[10] Hah n F, Gu rn ey J. CT Sign s of Cen tral Descen d in g
Transten torial Hern iation. Am J Neuroradiol. 1985;
6:844–845
[11] An drew s BT, Pit ts LH. Fu n ct ion al Recover y After
Traum atic Tran sten torial Herniation . Neurosurger y.
1991; 29:227–231
[12] Osborn AG. Diagn osis of Descen d ing Tran sten torial
Herniation by Cranial CT. Radiology. 1977; 123:93–
96
[13] Stovrin g J. Descen d in g Ten torial Hern iation : Fin din gs on Com puterized Tom ography. Neuroradiology. 1977; 14:101–105
[14] Levy DE, Caron n a JJ, Singer BH, et al. Pred ictin g Ou tcom e from Hypoxic-Isch em ic Com a. JAMA. 1985;
253:1420–1426
[15] Zan d bergen EGJ, de Haan RJ, Stouten beek CP, et al.
System atic Review of Early Predict ion of Poor Outcom e in An oxic-Isch em ic Com a. Lan cet. 1998;
352:1808–1812
[16] Jastrem ski M, Sut ton -Tyrell K, Vaagen es P, et al. Glucocort icoid Treatm en t Does Not Im prove Neurological Recover y Follow in g Cardiac Arrest. JAMA. 1989;
262:3427–3430
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19 Brain Deat h and Organ Donat ion
19.1 Brain deat h in adult s
Th e Presiden t’s Com m ission for th e St udy of Eth ical Problem s in Medicin e first publish ed guidelin es
for th e determ in ation of death in 1981 1 w h ich con tributed to th e approval of th e Un iform Determ in ation of Death Act (UDDA; policy statem en t, see box).2
Uniform det erm inat ion of deat h act , 1980 (verbat im quot e)
“An individual who has sustained either
1. irreversible cessation of circulatory and respiratory functions, or
2. irreversible cessation of all functions of the entire brain, including the brain stem,
is dead.
A determination of death m ust be made with accepted m edical standards.”
Most states h ave adopted th e UDDA, alth ough som e h ave en acted am en dm en ts stipulating qualification s of th e determ in in g clin ician (s). In dividual h ospitals m ay also m an date th at certain protocols be
follow ed.
As rea rm ed in 2010,3 w h en th e clin ical determ in ation of brain death is m ade in accordan ce
w ith th e origin al publish ed guidelin es,4 th ere h as been n o report of recover y of n eurologic fun ct ion
in adults.
19.2 Brain deat h crit eria
19.2.1 General inform at ion
Th is sect ion deals w ith brain death in adults. For in dividuals < 5 years age, see Brain death in ch ildren
(p.312).
W h en th e cause of death is oth er th an n atural causes th e Medical Exam in er or Coron er (depen din g on th e auth orit y in your jurisdict ion ) w ill be con tacted per h ospital policy.
Key poin t: Criteria sh ow n below m ay be used to determ in e th e clin ical absen ce of brain an d
brain stem fun ction . Th en to en sure th at th e total cessation of brain fun ction is irreversible, th e clinician m ust take in to con sideration th e cause of th e absen ce, an d exclude con dition s th at can m im ic
th e clin ical appearan ce of brain death . Th is m ay require an cillar y con firm ator y tests an d observation
for a period of tim e.
Waitin g periods: Th ere is in su cien t evidence to support a specific obser vation period to en sure
th at th e cessation of n eurologic fun ct ion is irreversible.3 Th is requires th at th e determ in ation of
brain death take in to con sideration all of th e available in form at ion an d circum stan ces.
19.2.2 Est ablishing t he cause of cessat ion of brain act ivit y
Th e cause of th e cessat ion of brain activit y (CBA) can usually be determ in ed by a com bin ation of h istory, physical exam in at ion , laboratory tests an d im aging studies.
19.2.3 Clinical crit eria
See Table 19.1 for a sum m ar y of basic requirem en ts an d clin ical fin din gs th at m ay be used in
determ in in g brain death . Details follow below.
Recom m en dat ion s 1,5,3 :
1. Absen ce of brain stem reflexes:
a) ocular exam in ation :
● fixed pupils: n o respon se to brigh t ligh t (caution after resuscitation : see below ). Th e size of
th e pupils is un im portan t (th ey are usually m idposition (4–6 m m ) but m ay var y to dilated
ran ge (9 m m ): dilated pupils can be com patible w ith brain death because cer vical sym path etic path w ays m ay rem ain in tact)
● absent corn eal reflexes (corn eal reflex: eye closin g to corn eal, n ot scleral, st im ulation )
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Table 19.1 Sum m ary of findings in brain death (see text for details)3
Vit al signs & general crit eria
●
Core tem p > 36° C (96.8° F)
●
SBP ≥ 100 m m Hg
●
No drugs that could simulate brain death. Blood alcohol content (BAC) should be < 0.08%
Absence of brainst em reflexes
●
Fixed pupils
No pupillary reaction to light
●
Absent corneal reflexes
Touching cornea with a gauze does not cause eye
closure
●
Absent oculovestibular reflex (calorics)
No eye m ovement of any sort to ice water in ear with
HOB elevated to 30°
●
Absent oculocephalic reflex: “Doll’s eyes” (p. 301)
Turning the head does not cause contralateral eye
deviation (clear C-spine first)
●
Absent gag reflex
No gagging reaction to m ovement of ET tube
●
Absent cough reflex
No coughing in response to bronchial suctioning
No response t o deep cent ral pain
Stim ulate areas like supraorbit al ridge. No lim b
m ovem ent , no eye m ovem ent, no facial m ovem ent
Failed apnea challenge
No respirat ions wit h pCO2 > 60 m m Hg
absent oculoceph alic “doll’s eyes” reflex (p. 301), con train dicated if C-spin e n ot cleared
● absent oculovestibular reflex (cold w ater calorics): in still 60–100 m l ice w ater in to on e ear
( do n ot do if TM perforated) w ith HOB at 30°. Brain death is excluded if a ny eye m ovem en t. Wait at least 1 m in ute for respon se, an d ≥ 5 m in before testin g th e opposite side (to
preven t can cellation of opposing respon se)
b) absent oroph aryn geal reflex (gag) to stim ulation of posterior ph ar yn x
c) n o cough respon se to bron ch ial suction ing
2. apn ea test AKA apn ea ch allenge: n o spon tan eous respiration s after discon n ection from ven tilator
(assesses fun ction of m edulla). Respiration s are defin ed as abdom in al or ch est excursion s th at
produce adequate tidal volum es; if th ere is any question , a spirom eter m ay be con n ected to th e
patient.4 Sin ce elevatin g PaCO2 in creases ICP w h ich could precipitate h ern iation an d vasom otor
in stabilit y, th is test sh ould be reserved for last an d on ly used w h en th e diagnosis of brain death
is reason ably cer tain . Guidelin es 6,7 :
a) Apn ea for > 2 m in utes w ith PaCO2 > 60 m m Hg or PaCO2 > 20 m m Hg over baselin e or pH < 7.3
(CO2 is th e m ost poten t st im ulus for respiration s). If patien t does n ot breath e by th is poin t,
th ey won’t breath e at a h igh er PaCO2 . Not as valid w ith severe COPD
b) to preven t hypoxem ia durin g th e test (w ith th e danger of cardiac arrhyth m ia or m yocardial
in farction ):
● preoxygen ate for ≥ 10 m in utes before th e test w ith 100% FIO2 to PaO2 > 200 m m Hg
● prior to th e test , reduce th e ven tilator rate to brin g th e PaCO2 to 35-40 m m Hg (to sh orten
th e test tim e an d th us reduce th e risk of hypoxem ia)
● durin g th e test , h ave passive O2 flow adm in istered at 6 L/m in th rough eith er a pediatric
oxygen can n ula or a No. 14 French t rach eal suct ion cath eter (w ith th e side por t covered
w ith adh esive tape) passed to the estim ated level of th e carin a
c) startin g from n orm ocapn ea, th e average tim e to reach PaCO2 = 60 m m Hg is 6 m in u tes (classic
teach in g is th at PaCO2 rises 3 m m Hg/m in , but in act ualit y th is th e rate at w h ich PaCO2 rises
varies w idely, w ith an average 3.7 ± 2.3 6 ; or 5.1 m m Hg/m in if start ing at n orm ocarbia 7 ).
Som etim es as lon g as 12 m in utes m ay be n ecessary
d) th e test is aborted if:
● th e patien t breath es (ch est or abdom in al m ovem en t, gasps): in com patible w ith brain death
● SBP < 90 m m Hg (hypoten sion )
● if O2 saturation drops < 80% for > 30 secon ds (on pulse oxim eter)
● sign ifican t cardiac arrhyth m ias occur
●
19
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4.
5.
6.
309
e) if patien t does n ot breath e, sen d ABG at regular in tervals an d at th e com pletion of test regardless of reason for term in ation . If th e patien t does n ot breath e for at least 2 m in utes a fter a
PaCO2 > 60 m m Hg is docum en ted, th en th e test is valid an d is com patible w ith brain death (if
th e patien t is stable an d ABGs results are available w ith in a few m in utes, th e apn ea ch allenge
m ay be con tin ued w h ile w ait in g for results in case th e PaCO2 is < 60)
f) if PaCO2 stabilizes below 60 m m Hg an d th e pO2 rem ain s adequate, tr y reducing th e passive
O2 flow rate sligh tly (O2 flow m ay be w ash ing out CO2 from lun gs)
g) th e test is positive (i.e. com patible w ith brain death) if th ere are n o respiration s an d PaCO2 is ≥
60 m m Hg (or th ere is a 20 m m Hg rise in PaCO2 above baselin e)
n o m otor fun ction
a) n o respon se to deep centra l pain : th ere sh ould be n o m ovem en t of lim bs, n o eye open in g or
eye m ovem en t, n o facial m ovem en t
b) true decerebrate or decorticate post urin g or seizures are in com patible w ith th e diagn osis of
brain death
c) spinal cord m ediated reflex m ovem en ts (in cludin g flexor plan tar reflexes, flexor w ith draw al,
m uscle st retch reflexes,8 an d even abdom in al an d crem asteric reflexes) can be com pat ible
w ith brain death, an d m ay occasion ally con sist of com plex m ovem en ts,9 in cludin g brin ging
on e or both arm s up to th e face,10 or sitting up (th e “Lazarus” sign 11 ) especially w ith hypoxem ia (th ough t to be due to spin al cord isch em ia stim ulatin g sur viving m otor n euron s in th e
upper cervical cord). If com plex in tegrated m otor m ovem en ts occur, it is recom m en ded th at
con firm ator y test in g be perform ed prior to pron oun cem en t of brain death 12
absence of complica ting conditions (th at could sim ulate brain death on exam ):
a) hypoth erm ia: core tem p sh ould be > 36° C (96.8° F). Below th is tem p, pupils m ay be fixed an d
dilated,13 respiration s m ay be di cult to detect , an d recover y is possible 14
b) n o eviden ce of rem ediable exogen ous or en dogen ous in toxication , in cludin g drug or m etabolic (blood alcoh ol level sh ould be < 0.08%, barbiturates, ben zodiazepin es, m eprobam ate, m eth aqualon e, t rich loroethylen e, paralyt ics, h epatic en ceph alopathy, hyperosm olar com a…). If
th ere is doubt, depen ding on circum stan ces, lab tests in cludin g drug levels (serum an d urin e)
m ay be sen t. Pseudoch olin esterase deficien cy is present in 1/3000 patien ts w h ich can cause
succinych olin e to last up to 8 h ours (in stead of 5 m in s). A t w itch m on itor can rule-out NMB
(place th e elect rodes im m ediately beh in d th e eye or across th e zygom atic arch )
c) sh ock (n euro exam sh ould be reliable if SBP ≥ 100 m m Hg) an d an oxia. Loss of > 45% of circulatin g blood volum e can produce leth argy
d) im m ediately post-resuscitation : sh ock or an oxia m ay cause fixed an d dilated pupils. Atropin e
(p.311) m ay cause sligh t dilatation but not un react ivit y. Neurom uscular blockage (e.g. for in tubation ) does n ot a ect pupils because th e iris lacks n icotin ic receptors
e) patien ts com ing out of pen tobarbital com a (w ait un til level ≈ ≤ 10 m cg/m l)
con firm ation of brain death by use of An cillar y con firm atory tests (preferred tests 3 : EEG, CRAG or
an giography, see below ) is n ot required. May be used at th e discretion of th e physician , gen erally
if th ere is un certain t y about th e reliabilit y of oth er par ts of th e exam
recom m en ded obser vation periods: th ere is in su cien t evidence to determ in e a m in im al observation period to en sure th at n eurologic fun ct ion h as irreversibly ceased 3 :
a) in sit uation w h ere overw h elm ing brain dam age from an irreversible con dition is w ell establish ed (e.g. m assive in tracerebral h em orrh age, gun sh ot w oun d traversin g th e brain ...), an d n o
un certain t y in th e clin ical exam , an an cillar y con firm atory tests w ould usually n ot be
n ecessar y
b) in clear-cu t sit u at ion s as ou t lin e d above, if several h ou rs h ave p assed sin ce t h e on set of
t h e brain in su lt , a sin gle n eu rologic exam in at ion con sisten t w it h brain d eat h sh ou ld su ffice alt h ough m an y st ates requ ire t w o exam in at ion s by st at u te 3 (see st ate an d local law s
below )
c) in less clear-cut situation s (e.g. an oxic brain injur y, hypoth erm ia…) lon ger obser vation periods are appropriate an d an cillar y con firm atory tests m ay be con sidered (see below )
19
19.2.4 St at e and local law s
Most states h ave adopted th e Un iform Determ in ation of Death Act (UDDA) regarding brain death .
State am en dm en ts an d local regulat ion s or h ospital policies m ay dictate th at m ore th an 1 pract it ion er m ust con cur on th e diagn osis. It is in cum ben t th at th e pract it ion er kn ow th e applicable regulation s before m akin g th e diagnosis.
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19.2.5 Ancillary confirm at ory t est s
General inform at ion
Th ere is in su cien t evidence th at any an cillar y test can accurately determ in e brain death.3 Preferred
tests 3 : EEG, CRAG or an giography.
Cerebral angiography
Requires absen ce of cerebral blood flow, w h ich is in com patible w ith brain sur vival. Pros: h igh ly sen sit ive for determ in ing death of cerebral h em isph eres. Con s: costly, tim e-con sum ing, requires tran sport of th e patien t to x-ray departm en t , invasive, poten tially dam agin g to organ s th at m ay be used
for don ation , an d is n ot opt im al for detect in g sm all am oun t of blood blow to brain stem . Requires a
radiologist an d tech n ician . Criteria: absen ce of in t racran ial flow at th e level of th e carotid bifurcation
or circle of Willis 5 ). Fillin g of th e superior sagittal sin us m ay occur in a delayed fash ion an d is n ot
in com pat ible w ith brain death . In terobserver validit y h as n ot been st udied. Not routin ely used in
th e diagnosis of brain death , but m ay be em ployed in di cult situation s.
EEG
Can be don e at bedside. Requires experien ced in terpreter. Does n ot detect brain stem activity, an d
elect rocerebral silen ce (ECS) (i.e. isoelectric EEG) does n ot exclude th e possibilit y of reversible com a.
Use ECS as a clin ical con firm atory test on ly in patien ts w ith out drug in toxication , hypoth erm ia, or
sh ock, an d n ot in patien ts w h ere brain stem activit y m igh t be preser ved (i.e. situation s w h ere th e
clin ical brain stem exam can n ot be perform ed). Note: a pract ical problem w ith EEG for brain -death
determ in ation is th at it is often di cult to get a tracin g th at is totally free of elect rical sign al even in
patien ts w h o are brain dead by oth er criteria.
Defin ition of elect rocerebral silen ce on EEG: n o elect rical activit y > 2 m cV w ith th e follow in g
requirem en ts:
1. recordin g from scalp or referen tial elect rode pairs ≥ 10 cm apart
2. 8 scalp elect rodes an d ear lobe referen ce electrodes
3. in ter-electrode resistan ce < 10,000 Ω (or im pedan ce < 6,000 Ω) but over 100 Ω
4. sen sitivit y of 2 m cV/m m
5. t im e con stan ts 0.3–0.4 sec for par t of recordin g
6. n o respon se to st im uli (pain , n oise, ligh t)
7. record > 30 m in s
8. repeat EEG in doubtful cases
9. qualified tech n ologist an d elect roen ceph alograph er w ith ICU EEG experien ce
10. teleph on e t ran sm ission n ot perm issible
Cerebral radionuclide angiogram (CRAG)
General inform ation
19
Can be don e using a gam m a cam era, or m ore con tem porar y HMPAO SPECT (for 99m Techn etium
h exam ethylpropylen eam in e oxim e single-ph oton em ission CT). May n ot detect m in im al blood flow
to th e brain , especially brain stem . Necessitates t ran sport to th e radiology/n uclear m edicin e departm en t an d requires an experien ced in terpreter.
May be useful to con firm clin ical brain death in th e follow in g sett in gs:
1. w h ere com plicatin g con dition s are presen t , e.g. hypotherm ia, hypoten sion (sh ock), drug in toxication … (e.g. patien ts em erging from barbiturate com a), m etabolic abn orm alit ies
2. in patien ts w ith severe facial traum a w h ere evaluation of ocular fin dings m ay be di cult or
con fusin g
3. in patien ts w ith severe COPD or CHF w h ere apn ea testing m ay n ot be valid
4. to sh orten th e observat ion period
Technique
Usin g gallium cam era
1. scin tillation cam era is position ed for an AP h ead an d n eck view
2. inject 20–30 m Ci of 99m Tc-labeled serum album in or pertech n etate in a volum e of 0.5–1.5 m l
in to a proxim al IV por t, or a cen t ral lin e, follow ed by a 30 m l NS flush
3. perform serial dyn am ic im ages at 2 second in tervals for ≈ 60 secon ds
4. th en , obtain static im ages w ith 400,000 counts in AP an d th en lateral view s at 5, 15 & 30 m in utes
after inject ion
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5. if a st udy n eeds to be repeated because of a previous n on -diagn ost ic st udy or a previous exam
in com pat ible w ith brain death , a period of 12 h ours sh ould lapse to allow th e isotope to clear
from th e circulation
Findings
No uptake in brain paren chym a = “h ollow skull ph en om en on ” ( Fig. 19.1). Term in at ion of carotid
circulation at th e sku ll base, an d lack of uptake in th e ACA an d MCA dist ribut ion s (absen t “can delabra e ect ”). Th ere m ay be delayed or fain t visualizat ion of dural ven ous sin uses even w ith brain
death 15 due to con n ect ion s bet w een th e extracran ial circulat ion an d th e ven ous system .
MRI and MR angiography (MRA)
MRA is ver y sen sitive for detecting loss of blood flow in cavern ous ICA, h ow ever th e specificit y h as
n ot been accurately evaluated 3 (i.e. m igh t give false positives for brain death in com atose patien ts)
an d is n ot con sidered a valid confirm atory test.
CT angiography (CTA)
Blood flow on CTA (i.e. n ot con sisten t w ith brain death ) w as seen in patien ts w ith isoelect ric EEG.
False positive rate h ad n ot been determ in ed in com atose n on -brain dead patien ts. CTA is n ot con sidered to be a valid con firm ator y test for brain death.3
Transcranial doppler
See referen ce.4
Not w idely used.
1. sm all peaks in early systole w ith out diastolic flow or reverberating flow (in dicative of sign ifican tly in creased ICP)
2. in itial absen ce of doppler sign als can n ot be used as criteria for brain death sin ce 10% of patien ts
do n ot h ave tem poral in son ation w in dow s
SSEPs
On e protocol requires bilateral absen ce of N20-P22 respon se w ith m edian n er ve stim ulat ion . An
altern ative criteria is disappearan ce of th e P14 peak 16 (substrate: m edial lem n iscus an d n ucleus
cun eatus) on n asoph ar yn geal electrode recordin gs. St udies w ere judged as Class III data an d th at
P14 recordin gs could be a valuable con firm ator y test but th at th is test h as n ot been used routin ely
an d th at in terobserver variabilit y n eeded to be st udied.3
At ropine
In brain death , 1 am p of atropin e (1 m g) IV sh ould n ot a ect th e h eart rate due to th e absen ce of
vagal ton e (th e n orm al respon se to atropin e of in creased h eart rate rules out brain death , but
Fig. 19.1 “Hollow-skull” sign on CRAG radionuclide CBF
study (static AP view taken15 minutes after injection)
19
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Com a and Brain Deat h
absence of th e respon se is n ot h elpfu l sin ce som e con dition s such as Guillain -Barre m ay blun t th e
respon se).
System ic atropin e in usual doses causes sligh t pupillar y dilatation ,17,18 but does n ot elim in ate
react ion to ligh t (th erefore, to elim in ate un certain t y, it is pruden t to exam ine th e pupils before givin g th e atropin e).
19.2.6 Pit falls in brain deat h det erm inat ion
Th e follow in g pitfalls m ay com plicate th e determ in ation of brain death :
● Movem en t of body par ts after brain death . Movem en ts are som etim es com plex in n ature, an d
m ay occur as lon g as 32 h ours after brain death . Many are m ediated by spin al cord disch arges as it
un dergoes cell death . Docum en ted obser vation s in clude: facial m ovem en ts, fin ger trem or, repetit ive leg m ovem en ts, an d even sit t in g up. Th ese m ovem en ts are often repet itive, usually stereot yp ical, an d do n ot ch ange w ith ch angin g stim uli.
● Th e appearan ce of breath in g. Th is t ypically occurs w ith a ven tilator th at is set to t rigger on detect in g respirator y e or t. Ven tilators m ay be sen sin g air m ovem en t created by tran sm ission of arterial
pulses of th e great vessels to th e lung or action s of a ch est t ube.
19.3 Brain deat h in children
19.3.1 General inform at ion
Th e follow in g is based on 2011 guidelin es 19 th at are en dorsed by th e Societ y of Crit ical Care Medicin e, Th e Section for Crit ical Care an d Section of Neurology of th e Am erican Academ y of Pediatrics
an d th e Am erican College of Crit ical Care Medicin e.
Key poin ts 19 :
● Th e diagn osis of brain death in term n ew born s, in fan ts an d ch ildren is a clin ical diagn osis requirin g absen ce of n eurologic fun ct ion an d a kn ow n irreversible cause of loss of fun ction .
● Th ese guidelin es are n ot supported for in fan ts < 37 w eeks gestation al age because of in su
cien t
data
● An cillar y tests are n ot required an d are n ot a substitute for a correctly perform ed n eurologic exam
● Tw o exam in at ion s th at in clude apn ea test in g separated by an observat ion period is recom m en ded
● Treat an d correct con dition s th at can in terfere w ith th e n eurologic exam in cludin g: hypoth erm ia,
hypoten sion , in terferin g drugs (h igh levels of sedat ives, an algesics, paralyt ics, h igh doses of an t iconvulsan t drugs) an d m etabolic dist urban ces
19.3.2 Clinical exam inat ion
Tw o exam in at ion s each in cludin g apn ea test in g, each con sisten t w ith brain death, perform ed by differen t atten din g physician s separated by an obser vation period are required. Apn ea testing m ay be
perform ed by th e sam e physician .
Apn ea testin g requires docum en tation of arterial PaCO2 th at is 20 m m Hg above th e baselin e an d ≥
60 m m Hg w ith n o respirator y e ort . If apn ea testin g can not be safely com pleted, an an cillar y st udy
sh ould be don e.
Recom m en ded obser vation periods betw een exam s:
● For term n ew born s (37 w eeks gestation al age) th rough 30 days of age: 24 h ours
● For in fan ts an d ch ildren (> 30 days to 18 years): 12 h ours
● Follow in g cardiopulm on ar y resuscitation , th e diagn osis of brain death sh ould be deferred ≥ 24 h rs
if th ere are con cern s or in con sisten cies in th e exam in at ion
19
19.3.3 Ancillary st udies
Th ese tests are n ot required to m ake th e determ in at ion of brain death . Use m ay be con sidered:
● W h en apn ea test in g can n ot be safely com pleted e.g. due to un derlying m edical con dition s or desat uration to < 85% or in abilit y to ach ieve paCO2 ≥ 60 m m Hg
● If th ere is un cer tain ty about results of th e n eurologic exam in ation
● If drugs th at in terfere w ith th e n eurologic exam m ay be presen t
● To reduce th e in ter-exam in ation obser vation period
W h en an cillar y tests are em ployed, a secon d n eurologic exam in at ion an d apn ea test sh ould be perform ed to th e exten t possible, an d th ere sh ould n ot be any fin din g in con sisten t w ith brain death .
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19.4 Organ and t issue donat ion
19.4.1 General considerat ions
Th e Cen ter for Medicare Ser vices (CMS) con dition s of part icipat ion require all h ospitals th at receive
Medicare fun ds to refer all im m in en t death s to th e local Organ Procurem en t Organ izat ion (OPO).20
Th e OPO is respon sible for th e determ in ation of suitability an d for discussion of don at ion w ith th e
legal n ext of kin . Th e discussion m ust be by train ed person n el. Th e OPO is also respon sible for organ
don or m an agem en t, allocation an d facilitat in g recover y of organ s in th e OR.20
19.4.2 Referral of t he pot ent ial organ donor
Most OPO’s h ave developed a process for referral of th e poten tial organ don or by educatin g th e critical care n urses to referral by a set of “triggers.” Th e t riggers usually in clude patien ts w ith a n eurologic injur y (an oxia, h em orrh age, t raum a etc.), on a ven tilator an d eith er losin g brain stem reflexes,
GCS < 5 or for discussion of w ith draw al of support . Th is set of t riggers results in th e referral of m any
patien ts n ot suitable for don ation but allow s for th e early n otification of th e OPO an d reduces th e
risk of m issed referrals.
19.4.3 Medical m anagem ent of t he pot ent ial organ donor
Brain death results in several predictable physiologic aberration s. Many h ospitals h ave developed
“Catast roph ic Brain Injur y” order sets to address th ese predictable con sequen ces.
Hypot ension
W ith hypovolem ia due to diabetes in sipidus an d destruct ion of th e pon tin e an d m edullar y vasom otor cen ters m ost brain dead patien ts are hypoten sive. Treatm en t requires restoration of a euvolem ic
state an d support w ith vasopressors. Usually n orepin eph rin e to supply in otropic support an d n eosyn eph rin e to in crease periph eral vascular resistan ce is su cien t to support th e blood pressure.
Diabet es insipidus
W ith loss of hypoth alam ic fun ct ion brain dead in dividuals frequen tly h ave posterior pit uitar y dysfun ct ion an d diabetes in sipidus. Th is is m an ifest by large volum e dilute urin ar y out put, hypern atrem ia an d hyperosm olar serum . Man agem en t option s in clude DDAVP inject ion (1-2 m cg SC/IV q
12 h ours) or a vasopressin drip (0.01 – 0.04 un its/m in IV). Th e vasopressin drip m ay be preferable
because th e sh orter durat ion of act ion can h elp avoid oliguria due to overdosing.
Hypot herm ia
Loss of tem perat ure regulation frequen tly causes hypoth erm ia w h ich can w orsen coagulopathy an d
invalidate brain death test in g. Application of a w arm ing blan ket to support tem perature w ill h elp
restore n orm al physiology.
19.4.4 Organ Procurem ent Organizat ion (OPO) process
Aut horization
OPO sta w ill respon d to referrals an d after discussion w ith m edical sta an d n ursin g sta en gage
th e fam ily in a discussion involving auth orization for organ don ation . Un ited Net w ork for Organ
Sh arin g (UNOS) data h as dem on strated th at OPO train ed sta h ave h igh er auth orization rates th an
m edical sta . Th is is th ough t to be due to th e position of th e OPO sta on ly advocating for don ation
an d if th e treating sta advocates for don ation th ere m ay be a sen se of aban don m en t.
Donor evaluat ion
Th e OPO sta w ill evaluate don or suitability. Don ors w ill be ruled out if th ere is th ough t to be a h igh
poten tial for t ran sm ission of m align an cy. Th e OPO w ill screen for blood-born e path ogen s (HIV, HCV,
HBV). Each organ w ill be evaluated for suitabilit y.
● Heart: EF > 50%, n o LVH, n o CAD
● Lun gs: P/F Ratio > 300, n orm al bron ch oscopy
● Liver: ALT, AST, GGTP an d bilirubin W NL or return in g to n orm al an d n o kn ow n liver disease
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Com a and Brain Deat h
Kidn eys: BUN an d Creat in in e W NL
● Pan creas: n orm al lipase, am ylase an d HgbA1c
●
Allocat ion and recovery
On ce brain death occurs in a patien t auth orized or organ don at ion , th e OPO w ill allocate organ s
according to UNOS allocat ion policy an d UNOS gen erated allocation lists. W h en th e tran splan t cen ters h ave accepted organ s an OR t im e w ill be set an d th e team s w ill com e to th e don or h ospital for
organ recover y. Th e t im e fram e from auth orization un til organ recover y frequen tly takes 24 to 36
h ours or lon ger.
19.4.5 Organ donat ion aft er cardiac deat h
General inform at ion
Key concept s
candidates: ventilator dependent patients (t ypically with brain or spinal cord injury) where the fam ily has decided to withdraw support and the m edical team expects the patient would progress to
asystole less than 60 m inutes after withdrawal
● consent from legal next of kin for: organ donation, heparin, and fem oral lines
● clearance from medical exam iner when applicable (usually, cases of unnatural death)
● counsel the family that the procedure cannot be done in ≈ 20% of cases. They are to be notified
im mediately if this happens and end-of-life care continues
● the transplant team cannot participate in end-of-life care or declaration of death, and should not
be in O.R. until after cardiac death is declared
●
Can didates for organ don at ion after cardiac death are t ypically ven tilator depen den t patien ts w ith
brain or spin al cord injuries w h o are so n ear death th at furth er t reatm en t is futile, but w h o do n ot
m eet brain death criteria. Organ s typically recovered in th is m an n er: kidn eys, liver, pan creas, lungs,
an d rarely th e h eart.21
Eth ical con cern s related to DCD organ recover y h ave been raised.22 Th e In stit ute of Medicin e h as
review ed DCD t w ice (1997 an d 2000) an d determ in ed DCD to be eth ically soun d an d OPO’s h ave
been en couraged to pursue DCD don ation .23
Consent
Prior to any discussion of don ation , th e fam ily sh ould h ave m ade th eir decision to w ith draw support
an d allow th e patien t to progress to death . After th e fam ily h as h ad th is discussion w ith th e t reating
physician , th e OPO can discuss DCD w ith th e legal n ext of kin . Con sen t m ust also be obtain ed for any
don ation -related procedures prior to death (w h ich t ypically in cludes h eparin in fusion to prolong
organ viabilit y 24 an d th e possibilit y of fem oral cath eters). Th e discussion sh ould also in clude process
to return to ICU if th e patien t does n ot progress to asystole.
Clearan ce from th e m edical exam in er m ust be obtain ed in applicable cases (in cluding death s due
to acciden t, h om icide, suicide…).
Procedure
19
Life sustain ing m easures are discon tin ued (t ypically con sistin g of extubation ) usually in th e operatin g room . Death is pron oun ced t ypically ≈ 2 to 5 m in utes after cardiac activit y becom es in su cien t
to gen erate a pulse, because lim ited data in dicates th at circulation w ill n ot spon tan eously return 25
(NB: EKG act ivity does n ot n eed to cease). After declaration of death , cold perfusion of organ s is perform ed an d th ey are procured.
To avoid poten tial con flict s of in terest , n o m em ber of th e t ran splan t team can part icipate in en dof-life care n or th e declaration of death .21 About 20% of th e t im e, th e progression to cardiac death
does n ot occur in a tim efram e th at perm its organ retrieval. In th ese cases, organ don ation is can celled, th e fam ily m ust be im m ediately n ot ified, an d en d-of-life care con tin ues.
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References
[1] Gu id elin es for th e d eterm in ation of d eath . Report of
th e m edical con sultan ts on th e diagn osis of death
to th e Presiden t's Com m ission for th e Stu dy of Eth ical Problem s in Med icin e an d Biom ed ical an d
Behavioral Research . JAMA. 1981; 246:2184–2186
[2] Nation al Con feren ce of Com m ission ers on Uniform
State Law s. Uniform Determ in ation of Death Act .
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1980
[3] W ijd icks EF, Varelas PN, Gron seth GS, Greer DM.
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Neu rology. Neu rology. 2010; 74:1911–1918
[4] W ijd icks EF. Determ in in g Brain Death in Ad ults.
Neu rology. 1995; 45:1003–1011
[5] Qu alit y Stan dard s Subcom m ittee of th e Am erican
Academ y of Neurology. Pract ice Param eters for
Determ in in g Brain Death in Ad ults (Sum m ar y Statem en t). Neurology. 1995; 45:1012–1014
[6] Ben zel EC, Gross CD, Had den TA, et al. Th e Ap n ea
Test for th e Determ ination of Brain Death . J Neurosurg. 1989; 71:191–194
[7] Ben zel EC, Mash bu rn JP, Con rad S, Mod lin g D.
Apn ea Testin g for th e Determ in ation of Brain
Death: A Modified Protocol. J Neurosurg. 1992;
76:1029–1031
[8] Ivan LP. Sp in al Reflexes in Cerebral Death . Neurology. 1973; 23:650–652
[9] Tu rm el A, Rou x A, Bojan ow ski MW . Sp in al Man
After Declarat ion of Brain Death . Neurosurgery.
1991; 28:298–302
[10] Heyten s L, Verlooy J, Gh eu en s J, et al. Lazaru s Sign
an d Exten sor Post u rin g in a Brain -Dead Patien t. J
Neurosurg. 1989; 71:449–451
[11] Rop p er AH. Un u su al Sp on tan eou s Movem en ts in
Brain -Dead Patien ts. Neurology. 1984; 34:1089–
1092
[12] Jastrem ski MS, Pow n er D, Snyd er J, Sm ith J, Gren vik
A. Sp on tan eou s Decerebrate Movem en t After Declaration of Brain Death . Neurosurger y. 1991; 29:479–
480
[13] Treatm en t of Hypoth erm ia. Med Letter. 1994;
36:116–117
[14] An tret ter H, Dap u n t OE, Mu eller LC. Su r vival After
Prolonged Hypoth erm ia. N En gl J Med. 1994; 330
[15] Good m an JM, Heck LL, Moore BD. Con firm ation of
Brain Death w ith Por table Isotop e An giography: A
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[25]
Review of 204 Con secutive Cases. Neurosurgery.
1985; 16:492–497
Wagn er W . Scalp, earlobe an d n asop h ar yn geal
record in gs of th e m ed ian n erve som atosen sor y
evoked P14 poten t ial in com a an d brain death .
Detailed laten cy an d am plitu d e an alysis in 181
patien ts. Brain . 1996; 119 (Pt 5):1507–1521
Green an J, Prasad J. Com p arison of th e Ocu lar
E ects of Atropin e an d Glycopyrrolate w ith Tw o IV
Induct ion Agen ts. Br J An aesth . 1985; 57:180–183
Goett in g MG, Con treras E. System ic Atropin e
Ad m in istration Du rin g Card iac Arrest Does Not
Cau se Fixed an d Dilated Pu pils. An n Em erg Med .
1991; 20:55–57
Nakagawa TA, Ash w al S, Math u r M, Mysore MR,
Bruce D, Con way EE,Jr, Du th ie SE, Ham rick S, Harrison R, Klin e AM, Lebovitz DJ, Mad d en MA, Mon tgom ery VL, Perlm an JM, Rollin s N, Sh em ie SD,
Voh ra A, W illiam s-Ph illip s JA. Guid elin es for th e
d eterm in ation of brain death in infan ts and child ren : an u pd ate of th e 1987 Task Force recom m en d ation s. Crit Care Med. 2011; 39:2139–2155
U.S. Electron ic Cod e of Fed eral Regu lation s. Con d it ion of Part icipation for Hospitals. 1998
Stein brook R. Organ d on ation after card iac d eath . N
En gl J Med. 2007; 357:209–213
DuBois JM, DeVita M. Don ation after cardiac death
in th e United States: h ow to m ove forw ard. Crit Care
Med . 2006; 34:3045–3047
Com m it tee on Non -Heart-Beatin g Transplan tat ion
II, Division of Health Care Ser vices - In st itute of
Med icin e. Non -Heart-Beatin g Organ Tran sp lan tat ion : Pract ice an d Protocols. Wash in gton , D.C.:
Nation al Academ y Press; 2000
Bern at JL, D'Alessan dro AM, Port FK, Bleck TP, Heard
SO, Medina J, Rosen baum SH, Devita MA, Gaston RS,
Merion RM, Barr ML, Marks W H, Nath an H, O'Con n or K, Rudow DL, Leich tm an AB, Sch w ab P, Asch er
NL, Metzger RA, Mc Bride V, Grah am W , Wagn er D,
Warren J, Delm on ico FL. Rep ort of a Nation al Con ference on Don ation after cardiac death . Am J Tran sp lan t. 2006; 6:281–291
DeVita MA. Th e death w atch : cert ifying death using
card iac criteria. Prog Tran splan t. 2001; 11:58–66
19
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Part VI
Infect ion
20 Bact erial Infections
of the Parenchym a
and Meninges and
Com plex Infect ions
318
21 Skull, Spine, and
Post-Surgical
Infections
339
22 Other Nonbact erial
Infections
364
VI
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Infect ion
20 Bact erial Infect ions of t he Parenchym a and
Meninges and Com plex Infect ions
20.1 Meningit is
20.1.1 General inform at ion
Com m u n it y acqu ired m en in git is (CAM) is gen erally m ore fu lm in an t t h an m en in git is follow in g
n eu rosu rgical p roced u res or t rau m a (CAM ten d s to occu r w it h m or e vir u len t organ ism s or
in in d ivid u als w it h im p aired h ost d efen ses). Wat erh ou se-Frid er ich sp age en syn d rom e: occu rs in
10–20% of ch ild ren w ith m en in gococcal in fect ion (u su ally d issem in at ed in fect ion in
age < 10 yrs), p rod u ces large p ete ch ial h em or rh ages in th e skin an d m u cou s m em bran es, fever,
sept ic sh ock, ad ren al failu re (d u e to h em or rh age in to ad ren al glan d s) an d DIC. Focal n eu rologic
sign s are rare in acu te p u r u len t m en in git is. Com m u n it y acquired m e n in git is is a m ed ical em e rgen cy, an d sh ou ld be t reated im m ed iately. See Lu m bar p u n ct u re (p . 323) for a d iscu ssion abou t
w h en to p e rfor m an LP.
Th e rem ain der of th is ch apter discusses m en in git is th at is n ot com m un it y acquired.
20.1.2 Post -neurosurgical procedure m eningit is
1. usual organ ism s: coagulase-n egat ive staphylococci, S. aureus, En terobacteriaceae, Pseudom on as
sp., pn eum ococci usually w ith basilar sku ll fract ures an d otorh in ologic surger y
2. em piric an tibiotics: van com ycin (to cover MRSA), adult 15 m g/kg q 8-12 h ours to ach ieve
trough 15-20 m g/dl + cefipim e 2 gm IV q 8 h rs
3. if severe PCN allergy, use aztreon am 2gm IV q6-8 H or ciprofloxacin 400 m g IV q8h
4. if severe in fect ion , con sider in trath ecal th erapy delivered daily (use on ly preser vative free drug)
● van com ycin
● tobram ycin /gen tam icin
● am ikacin
● colistin
5. st ream lin e ABX based on sen sitivities, e.g. if organ ism t urn s out to be MSSA, ch ange van com ycin
oxacillin or n afcillin
For suspected CSF fistula
1. usual organ ism s: streptococci; see CSF fistula (cran ial) (p. 384)
2. treat m en t/w ork-up; see CSF fist ula (cran ial) (p.384)
3. im m un ocom prom ised h ost (e.g. AIDS)
a) usual organ ism s: as above PLUS Cr yptococcus n eoform an s, M. t uberculosis, HIV aseptic m en in gitis, L. m on ocytogen es
b) em piric an t ifun gal agen ts for cr yptococcal m en in gitis: In duction th erapy: Liposom al am ph otericin B 3-4 m g/kg IV daily + flucytosin e25 m g/kg PO QID for at least 2 w eeks follow ed by
c) Con solidation th erapy: flucon azole 400 m g PO daily for at least 8 w eeks follow ed by
d) Ch ron ic m ain tenan ce th erapy: flucon azole 200 m g PO daily
20.1.3 Post craniospinal t raum a m eningit is (post -t raum at ic m eningit is)
Epidem iology
Occurs in 1–20%of patien ts w ith m oderate to severe h ead injuries.1 Most cases occur w ith in 2 w eeks
of traum a, alth ough delayed cases h ave been described.2 75% of cases h ave dem on strable basal skull
fract ure (p. 884), an d 58%h ad obvious CSF rh in orrh ea.
20
Pat hogens
As expected from above, th ere is a h igh rate of in fect ion w ith organ ism s in digen ous to th e n asal cavit y. Th e m ost com m on organ ism s in a series from Greece w ere Gram -positive cocci (Staph . h em oliticus, S. w arn eri, S. coh n ii, S. epiderm idis, an d St rep. pn eum on ia) an d Gram -n egative bacilli (E. coli,
Klebsiella pn eum on ia, Acin etobacter an itratus).1
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Treat m ent
1. See also CSF Fistu la, Treatm en t (p. 388)
2. an tibiotics: appropriate an t ibiotics are selected based on CSF pen etration an d organ ism sen sitivities (adapted to th e path ogen s com m on in th e patien t’s locale; in th e above series, all Gram -n egative strain s appeared resistan t to am picillin an d th ird-gen erat ion ceph alosporin s, but w ere
sen sitive to im ipen em an d ciprofloxacin ; Gram -positive strain s w ere all sen sitive to van com ycin ).
For em piric an tibiotics: Van com ycin 15 m g/kg IV q8-12 h ours to ach ieve trough 15-20 m g/dl +
m eropen em 2gm IV q8h
3. surgical t reatm en t vs. “con ser vative t reat m en t”: con troversial. Som e feel th at any case of postt raum atic CSF rh in orrh ea sh ould be explored,3,4 an d th at cases of spon tan eous cessation often
represen t obscuration by in carcerated brain , so-called “sh am h ealing” w ith th e poten tial for later
CSF leak an d/or m en in gitis.2 Oth ers support th e n otion th at cessation (possibly w ith th e assistan ce of lum bar spinal drain age) is acceptable
4. con tin ue an tibiotics for 1 w eek after CSF is sterilized. If rh in orrh ea persists at th is t im e, surgical
repair is recom m en ded
20.1.4 Recurrent m eningit is
Pat ien ts w ith recurren t m en in gitis m ust be evaluated for th e presence of abn orm al com m un ication
w ith th e in traspin al/int racran ial com par t m en t. Etiologies in clude derm al sin us (p. 270) (eith er spin al
or cran ial), CSF fist ula (p.384), or n euren teric cyst (p. 290).
20.1.5 Chronic m eningit is
Usually due to on e of th e follow in g etiologies:
1. t uberculosis
2. fun gal in fect ion s
3. cysticercosis, n eurocysticercosis (p. 371)
Di eren tial diagn osis in cludes:
1. sarcoidosis
2. m en in geal carcin om atosis
20.1.6 Ant ibiot ics for specific organism s in m eningit is
Specific ant ibiot ics
See referen ce.5
Route is IV un less specified oth er w ise.
1. S. pn eum on iae: PCN G (2n d ch oice: ch loram phen icol)
a) if MIC≤ 0.06: PCN G or am picillin , altern ative: th ird generation ceph alosporin (ceftriaxon e)
b) if MIC≥ 0.12: th ird gen eration ceph alosporin (ceftriaxon e)
c) if ceph alosporin resistan ce: van com ycin
d) altern ative: m oxifloxacin
2. N. m en ingit idis: PCN G (2n d ch oice: ch loram ph en icol)
a) if MIC≤ 0.1 PCN G or am picillin
b) if MIC≥ 0.1: th ird gen eration ceph alosporin (ceft riaxon e)
c) altern ative: m oxifloxacin , m eropen em
3. H. in fluen za:
a) beta lactam ase n egative: am picillin
b) beta lactam ase positive
● th ird generation ceph alosporin (ceftriaxon e)
● altern ative: azt reon am , ciprofloxacin
4. Group B st rep
a) am picillin
b) altern ative: van com ycin
5. L. m on ocytogen es
a) am picillin ± IV gen tam icin
b) altern ative: IV sulfam eth oxazole/trim eth oprim
6. S. aureus
a) if m eth icillin susceptible
● oxacillin or n afcillin
● PCN allergy: van com ycin
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b) if m eth icillin resistan t
● van com ycin ± rifam pin
● altern ative: lin ezolid ± rifam pin
7. aerobic Gram n egative bacilli (GNB)
a) ceftriaxon e, or cefotaxim e, or m oxifloxacin (in order of preferen ce, m ake alteration s based on
sensitivities)
b) if am in oglycoside required, in traven t ricular th erapy m ay be in dicated after th e n ew born
period
8. P. aerugin osa
a) ceftazidim e or cefepim e
b) altern ative m eropen em or azt reon am
c) if ven triculit is: con sider IT gen tam icin or tobram ycin
9. Can dida spp: Liposom al am ph otericin B 3-4 m g/kg IV daily + flucytosin e25 m g/kg PO QID
Lengt h of t reat m ent for m eningit is
Gen erally con tin ue an t ibiotics for 10 – 14 days total. Duration is depen den t on organ ism an d clin ical
respon se. Treat m en t sh ould be 21 days for listeria, group B st rep an d som e GN bacilli.
20.2 Cerebral abscess
20.2.1 General inform at ion
Key concept s
may arise from hem atogenous spread, contiguous spread, or direct traum a
● risk factors: pulmonary abscess or AV fistulas, congenital cyanotic heart disease, immune compromise, chronic sinusitis/otitis, dental procedures
● symptoms are sim ilar to any other mass lesions but tend to progress rapidly
● peripheral WBC may be norm al or slightly ↑ , CRP usually ↑
● organism s: Streptococcus is m ost common, up to 60% are polymicrobial
● im aging: usually round with thin enhancing ring on CT or MRI. T2WI → high signal lesion with thin
rim of low intensit y surrounded by hi signal (edem a). Unlike with tum or, DWI often shows core of
restricted di usion (not reliable)
● treatment: IV antibiotics, needle drainage for som e, excision infrequently (for fungal or resistant
abscess)
●
20.2.2 Epidem iology
Approxim ately 1500–2500 cases per year in th e U.S. In ciden ce is h igh er in developin g coun tries.
Male:fem ale ratio is 1.5–3:1.
20.2.3 Risk fact ors
Risk factors in clude: pulm on ary abn orm alit ies (in fect ion , AV-fistulas…, see below ), congen ital cyan otic h ear t disease (see below ), bacterial en docarditis, pen etrating h ead t raum a (see below ), ch ron ic
sin usitis or otit is m edia, an d im m un ocom prom ised h ost (tran splan t recipien ts on im m un osuppressan ts, HIV/AIDS).
20
20.2.4 Vect ors
General inform at ion
Pr ior to 1980, t h e m ost com m on sou rce of cerebral abscess w as from con t igu ou s sp read . Now ,
h em at ogen ou s d issem in at ion is t h e m ost com m on vector. In 10–60% n o sou rce can be
id en t ified .6
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Hem at ogenous spread
Abscesses arisin g by th is m ean s are m ultiple in 10–50% of cases.7 No source can be foun d in up to
25%of cases. Th e ch est is th e m ost com m on origin :
1. in adults: lung abscess (th e m ost com m on ), bron ch iectasis an d em pyem a
2. in ch ildren : congen ital cyan ot ic h eart disease (CCHD) (est im ated risk of abscess is 4–7%, w h ich is
≈ 10-fold in crease over gen eral population ), especially tetralogy of Fallot (w h ich accoun ts for
≈ 50% of cases). Th e in creased Hct an d low PO2 in th ese patien ts provides an hypoxic environ m en t suitable for abscess proliferation . Th ose w ith righ t-to-left (ven o-atrial) sh un ts addition ally
lose th e filterin g e ect s of th e lungs (th e brain seem s to be a preferen tial target for th ese in fect ion s over oth er organ s). Streptococcal oral flora is frequen t, an d m ay follow den tal procedures.
Coexistin g coagulation defects often furth er complicate m an agem en t 8
3. pulm on ar y arterioven ous fist ulas: ≈ 50% of th ese patien ts h ave Osler-Weber-Ren du syn drom e
(AKA h ereditary h em orrh agic telan gect asia), an d in up to 5% of th ese patien ts a cerebral abscess
w ill even tu ally develop
4. bacterial en docarditis: on ly rarely gives rise to brain abscess.9 More likely to be associated w ith
acute en docarditis th an w ith subacute form
5. den tal abscess
6. GI in fect ion s: pelvic in fect ion s m ay gain access to th e brain via Batson’s plexus
In patien ts w ith septic em bolization , th e risk of cerebral abscess form ation is elevated in areas of previous in farct ion or isch em ia.10
Cont iguous spread
1. from puru len t sin usitis: spreads by local osteom yelitis or by ph lebit is of em issary vein s. Virt ually
always sin gular. Rare in in fan ts because th ey lack aerated paran asal an d m astoid air cells. Th is
route h as becom e a less com m on source of cerebral abscess due to im proved treatm en t of sin us
disease (w ith an t ibiotics an d, especially w ith surger y for ch ron ic otit is m edia an d m astoidit is)
a) m iddle-ear an d m astoid air sin us in fect ion s → tem poral lobe an d cerebellar abscess. Th e risk
of developin g a cerebral abscess in an adult w ith act ive ch ron ic otit is m edia is ≈ 1/10,000 per
year 11 (th is risk appears low, but in a 30 year-old w ith active ch ron ic otitis m edia th e lifetim e
risk becom es ≈ 1 in 200)
b) eth m oidal an d fron tal sin usitis → fron tal lobe abscess
c) sph enoid sin usitis: th e least com m on location for sin usitis, but w ith a h igh in ciden ce of in tracran ial com plication s due to ven ous exten sion to th e adjacen t cavern ous sin us → tem poral
lobe
2. odon togenic → fron tal lobe. Rare. Associated w ith a den tal procedure in th e past 4 w eeks in m ost
cases.12 May also spread h em atogen ously
Follow ing penet rat ing cranial t raum a or neurosurgical procedure
Follow in g pen etrating t raum a: Th e risk of abscess form at ion follow in g civilian gun sh ot w oun ds to
th e brain is probably ver y low w ith th e use of prophylactic an tibiotics, except in cases w ith CSF leak
n ot repaired surgically follow in g t raversal of an air sin us. An abscess follow in g pen etrating t raum a
can n ot be t reated by sim ple aspirat ion as w ith oth er abscesses, open surgical debridem en t to
rem ove foreign m atter an d devitalized tissue is required.
Post-n eurosurgical: especially w ith t raversal of an air sin us. Abscess h as been repor ted follow in g
use of in tracran ial pressure m on itors an d h alo tract ion .13
20.2.5 Pat hogens
1.
2.
3.
4.
5.
6.
7.
cultures from cerebral abscesses are sterile in up to 25%of cases
organ ism s recovered varies w ith th e prim ar y source of in fect ion
in gen eral: St reptococcus is th e m ost frequen t organ ism , 33–50% are an aerobic or m icroaeroph ilic. Mult iple organ ism s m ay be cultured to var ying degrees (depen ds on care of tech n ique),
usually in on ly 10–30%of cases, but can approach 60%,6 an d usually in cludes an aerobes (Bacteroides sp. com m on )
w h en secon dar y to fron to-eth m oidal sin usitis: St rep. m illeri an d St rep. angin osus m ay be seen
from otitis m edia, m astoidit is, or lun g abscess: usually m ultiple organ ism s, in cludin g an aerobic
st rep., Bacteroides, En terobacteriaceae (Proteus)
post traum atic: usually due to S. aureus or En terobacteriaceae
odon togen ic (den tal) source: m ay be associated w ith Actin om yces
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8.
9.
follow in g n eurosurgical procedures: Staph . epiderm idis an d aureus m ay be seen
im m un ocom prom ised h osts in cludin g t ran splan t patien ts (both bon e m arrow an d solid organ )
an d AIDS: fun gal in fect ion s are m ore com m on th an oth erw ise w ould be seen . Organ ism s
in clude:
a) Toxoplasm a gondii (p. 334); see also treatm en t (p. 333)
b) Nocardia asteroides (p. 336)
c) Can dida albican s
d) Listeria m on ocytogen es
e) m ycobacterium
f) Aspergillus fum igatus often from a prim ar y pulm on ar y in fect ion
10. in fan ts: Gram n egatives are com m on because IgM fract ion of an tibodies don’t cross th e placen ta
20.2.6 Present at ion
Adults: n o fin dings are specific for abscess, an d m any are due to edem a surroun din g th e lesion . Most
sym ptom s are due to in creased ICP (H/A, N/V, leth argy). Hem iparesis an d seizures develop in 30–
50% of cases. Sym ptom s ten d to progress m ore rapidly th an w ith n eoplasm s.
New born s: p aten t su t u res an d p oor abilit y of in fan t brain to w ard o in fect ion → cran ial
en largem en t . Pap illed em a is rare before 2 yrs of age. Com m on fin d in gs: seizu res, m en in git is,
irr it abilit y, in creasin g OFC, an d failu re to t h r ive. Most n ew bor n s w ith abscess are afebr ile. Progn osis is p oor.
20.2.7 St ages of cerebral abscess
Table 20.1 sh ow s th e four w ell recogn ized h istologic stages of cerebral abscess, an d correlates th is
w ith th e resistan ce to in sertion of an aspirating n eedle at th e tim e of surger y. It takes at least 2
w eeks to progress th rough th is m at uration process, an d steroids ten d to prolon g it .
20.2.8 Evaluat ion
Bloodw ork
Periph eral W BC: m ay be n orm al or on ly m ildly elevated in 60–70% of cases (usually > 10,000).
Blood cultures: sh ould be obtain ed w h en abscess is suspected, usually n egative.
ESR: m ay be n orm al (especially in con gen ital cyan otic h eart disease CCHD w h ere polycyth em ia
low ers th e ESR).
C-react ive protein (CRP): h epatic syn th esis in creases w ith in flam m ator y con dition s, h ow ever,
in fect ion anyw h ere in body (in cludin g brain abscess an d den tal abscess) can raise th e CRP level. May
also be elevated in n on in fect ious in flam m ator y con dition s an d brain tum or. Sen sitivity for abscess is
≈ 90%, specificit y is ≈ 77%.14 See also n orm al values (p.347).
Table 20.1 Histologic staging of cerebral abscess
20
St age
Hist ologic charact erist ics
(days shown are general est im at es)
Resistance to aspirating needle
1
early cerebritis: (days 1–3) early infection &
inflamm ation, poorly demarcated from surrounding brain, toxic changes in neurons, perivascular
infiltrates
interm ediate resistance
2
late cerebritis: (days 4–9) reticular matrix (collagen
precursor) & developing necrotic center
no resistance
3
early capsule: (days 10–13) neovascularit y, necrotic
center, reticular net work surrounds (less well
developed along side facing ventricles)
no resistance
4
late capsule: (> day 14) collagen capsule a , necrotic
center, gliosis around capsule
firm resistance, “pop” on entering
a abscess is ≈ the only process in the brain that leaves a collagen scar, all other scars are glial scars
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Lum bar punct ure (LP)
Th e role of LP is ver y dubious in abscess. Alth ough LP is abn orm al in > 90%, th ere is n o ch aracteristic
fin din g diagn ostic of abscess. Th e OP is usually in creased, an d th e W BC coun t an d protein m ay be
elevated. Th e o en din g organ ism can rarely be iden tified from CSF obtain ed by LP (un less abscess
ruptures in to ven tr icles) w ith positive cultures in ≈ 6–22%.15 Th ere is a risk of tran sten torial h ern iation , especially w ith large lesion s.
Σ
Due to the risk involved and the low yield of useful information, avoid the use of LP in evaluating
patients with suspected cerebral abscess if not already done.
Brain im aging
CT
Rin g en h an cin g. Sen sitivity ≈ 100%. For CT stagin g of abscess see below.
MRI
See Table 20.2 for fin dings. En h an ced T1W I → th in -w alled rin g en h an cem en t surroun ding low
in ten sity cen t ral region ( Fig. 89.1). Fluid-fluid levels m ay be seen . Occasion ally gas producin g
organ ism s m ay cause pn eum oceph alus.
Di usion MRI: DWI → brigh t, ADC → dark (restricted di usion suggestin g viscous fluid) 16
( Fig. 89.1). Un like m ost tum ors w h ich are da rk on DW I ( Fig. 89.2). More reliable w ith pyogen ic
abscess, less reliable e.g. w ith fun gal17 or TB abscess).
MR-spectroscopy: presen ce of am ino acids an d eith er acetate or lactate are diagn ostic for abscess.
Infrequently used im aging
Leukocyte scan w ith 99m Tc-HMPAO: patien t’s ow n WBCs are tagged an d reinjected. Close to 100%
sen sitivit y an d specificit y (sen sitivit y w ill be reduced if patien t is treated w ith steroids w ith in 48 h rs
prior to th e scan ).14
Staging cerebral abscess on im aging
CTstaging
Late cerebritis (stage 2) h as sim ilar features to early capsule (stage 3) on routin e con trast an d n on con trast CT. Th ere is som e th erapeutic im portan ce in di eren tiating th ese t w o stages; th e follow in g
aids in dist in guish in g 18 :
1. cerebritis: ten ds to be m ore ill-defin ed
a) ring-en h an cem en t: usually appears by late cerebrit is stage, usually thick
b) furth er di usion of con trast in to cen tral lum en , an d/or lack of decay of en h an cem en t on
delayed scan 30–60 m in after con trast in fusion
2. capsule:
a) fain t rim presen t on pre-con trast CT (n ecrot ic cen ter w ith edem atous surroun din g brain
cause collagen capsule to be seen )
b) thin ring en h an cem en t AND (m ore im portan tly) delayed scan s → decay of en h an cem en t
NB: Th in ring en h an cem en t but lack of delayed decay correlates better w ith cerebritis
NB: Steroids reduce degree of con trast en h an cem en t (especially in cerebritis)
Table 20.2 MRI findings with cerebral abscess
St age
T1 WI
T2 WI
cerebritis
hypointense
hi signal
capsular
lesion center → low signal,
capsule → m ildly hyperintense,
perilesional edem a → low signal
center → iso- or hyperintense,
capsule → dark (collagen),
perilesional edem a → hi signal
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MRI staging
Table 20.2 sh ow s MRI fin din gs in cerebral abscess. In th e cerebrit is stage, th e m argin s are ill
defin ed.
Addit ional evaluat ion
CXR an d ch est CT (if in dicated) to look for pulm on ar y source.
Cardiac ech o (in cludin g TEE, Doppler an d/or echo w ith agitated salin e injection (bubble study)):
for suspected h em atogen ous spread, to look for paten t foram en ovale or cardiac vegetation s.
20.2.9 Treat m ent
General inform at ion
Th ere is n o single best m eth od for t reat in g a brain abscess. Treatm en t usually involves:
● Surgical treatm en t: n eedle drain age or excision
● correct ion of th e prim ar y source
● lon g-term use of an tibiot ics: often IV x 6-8 w eeks an d possibly follow ed by oral route x 4-8 w eeks.
Duration sh ould be guided by clin ical an d radiograph ic respon se
Surgical vs. pure m edical m anagem ent
General inform ation
In a patien t w ith suspected cerebral abscess, tissue sh ould be obtain ed in alm ost ever y case to con firm diagn osis an d to isolate path ogen s (preferably before in itiation of an t ibiotics).
Medical treatm ent
In gen eral, surgical drain age or excision is em ployed in th e treat m en t. Purely m edical treatm en t of
ea rly abscess (cerebritis stage)19 is con troversial. NB: path ogen s w ere cultured from w ell en capsulated abscesses despite adequate levels of appropriate an tibiotics in 6 patien ts w h o failed m edical
th erapy.20 Failure m ay be due to poor blood supply an d acidic con dition s w ith in th e abscess (w h ich
m ay in act ivate an t ibiot ics in spite of con cen tration s exceedin g th e MIC).
Medical th erapy alon e is m ore successful if:
1. treat m en t is begun in cerebrit is stage (before com plete en capsulat ion ), even th ough m any of
th ese lesion s subsequen tly go on to becom e en capsulated
2. sm all lesion s: diam eter of abscesses successfully treated w ith an t ibiotics alon e w ere 0.8–2.5 cm
(1.7 m ean ). Th ose th at failed w ere 2–6 cm (4.2 m ean ).
3 cm is suggested as a cuto ,21 above th is diam eter surger y sh ould be in cluded
3. duration of sym ptom s ≤ 2 w ks (correlates w ith h igh er in ciden ce of cerebritis stage)
4. patien ts sh ow defin ite clin ical im provem en t w ith in th e first w eek
Medical m an agem en t alon e con sidered if:
1. poor surgical can didate (NB: w ith local an esth esia, stereotactic biopsy can be don e in alm ost any
patien t w ith n orm al blood clott ing)
2. m ultiple abscesses, especially if sm all
3. abscess in poorly accessible location : e.g. brain stem 22
4. con com itan t m en in gitis/epen dym itis
Indications for surgical treatm ent
20
In dication s for in it ial surgica l treatm en t in clude:
1. sign ifican t m ass e ect exerted by lesion (on CT or MRI)
2. di cult y in diagn osis (especially in adults)
3. proxim it y to ven tricle: in dicates likelih ood of in t raven tricular rupture w h ich is associated w ith
poor outcom e 23,8
4. evidence of sign ifican tly in creased in tracran ial pressure
5. poor n eurologic con dition (patien ts respon ds on ly to pain , or does n ot even respon se to pain )
6. t raum at ic abscess associated w ith foreign m aterial
7. fun gal abscess
8. m ultiloculated abscess
9. follow -up CT/MRI scan s can n ot be obtain ed ever y 1–2 w eeks
10. failure of m edical m an agem en t: n eurological deterioration , progression of abscess tow ards ven t ricles, or after 2 w ks if th e abscess is en larged. Also con sidered if n o decrease in size by 4 w ks.
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Managem ent
General outline
obtain blood cultures
in itiate an tibiotic th erapy (preferably after biopsy specim en obtain ed), regardless of w h ich m ode
of treatm en t (m edical vs. surgical) is ch osen (see below )
● LP (p. 323): avoid in m ost cases of cerebral abscess
● an ticonvulsan ts: in dicated for seizures, prophylactic use is opt ion al
● steroids: con troversial. Reduces edem a, but m ay im pede th erapy (see below )
●
●
Antibiotic selection
1. in itial an tibiot ics of ch oice w h en path ogen un kn ow n , an d especially if S. aureus suspected (if
th ere is n o h istory of traum a or n eurosurgical procedure, th en th e risk of MRSA is low ):
● van com ycin : covers MRSA. 15 m g/kg IV q8-12 h ours to ach ieve trough 15-20 m g/dl
PLUS
● a 3rd gen eration ceph alosporin (ceft riaxon e); utilize cefepim e if post surgical
PLUS
● m et r on id azole (Flagyl®). Adult: 500 m g q6-8 h ours
● altern ative to cefepim e + m etron idazole: m eropen em 2gm IV q8h
● m ake appropriate ch anges as sen sitivities becom e available
2. if culture sh ow s on ly st rep, m ay use PCN G (high dose) alon e or w ith ceftriaxon e
3. if cultures sh ow m eth icillin sen sitive staph aureus an d th e patien t does n ot h ave a beta lactam
allergy, can ch ange van com ycin to n afcillin (adult: 2 gm IV q 4 h rs. peds: 25 m g/kg IV q 6 h rs)
4. Cr yptococcus n eoform an s, Aspergillus sp., Can dida sp.: Liposom al am ph otericin B 3-4 m g/kg IV
daily + flucytosin e25 m g/kg PO QID.
5. in AIDS patien ts: Toxoplasm a gon dii is a com m on path ogen , an d in itial em piric treatm en t w ith
sulfadiazin e + pyrim eth am in e + leucovorin is often used (p. 332)
6. for suspected or con firm ed n ocardia asteroides, see details (p. 336)
Antibiotic duration
IV an t ibiotics for 6–8 w ks (m ost com m on ly 6), m ay th en D/C even if the CT a bnorma lit ies persist
(n eovascularit y rem ain s). NB: CT im provem en t m ay lag beh in d clin ical im provem en t. Durat ion of
t reat m en t m ay be reduced if abscess an d capsule en tirely excised surgically. Oral an tibiot ics m ay be
used follow in g IV course.
Glucocorticoids (steroids)
Reduces edem a an d decreases likelih ood of fibrous en capsulat ion of abscess. May reduce pen etrat ion
of an t ibiotics in to abscess.21 Im m un e suppression m ay also be deleterious.
Reser ved for patien ts w ith clin ical an d im aging eviden ce of deterioration from m arked m ass
e ect , an d duration of th erapy sh ould be m in im ized.
Follow-up im aging
If th erapy is successful, im agin g sh ould sh ow decrease in :
1. degree of ring en h an cem en t
2. edem a
3. m ass e ect
4. size of lesion : takes 1 to 4 w ks (2.5 m ean ). 95%of lesion s th at w ill resolve w ith an tibiotics alon e
decrease in size by 1 m on th
Surgical treatm ent
Options
See referen ce.24
1. n eedle aspiration : th e m ain stay of surgical t reatm en t. Especially w ell-suited for m ult iple or deep
lesion s (see below ) m ay also be used w ith th in w alled or im m ature lesion s
2. surgical excision : Sh orten s len gth of tim e on an t ibiotics an d reduces risk of recrudescen ce. Recom m en ded in t raum atic abscess to debride foreign m aterial (especially bon e), an d in fun gal
abscess because of relative an tibiotic resistan ce (see below )
3. extern al drain age: con troversial. Not frequen tly used
4. in stillat ion of an t ibiotics directly in to th e abscess: h as n ot been extrem ely e cacious, alth ough it
m ay be used as for refractor y Aspergillus abscesses
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Needle aspiration
Most often im plem en ted w ith stereotact ic localization especially for deep lesion s.25 May be perform ed un der local an esth esia if n ecessar y (e.g. in patien ts w h o are poor surgical can didates for gen eral an esth esia). May be com bin ed w ith irrigation w ith an tibiot ics or n orm al saline. Repeated
aspiration s are required in up to 70% of cases. May be th e on ly surgical in terven tion required (in
addit ion to an t ibiotics), but som et im es m ust be follow ed w ith excision (especially w ith m ultiloculated abscess).
Perform ed th rough a t rajectory ch osen to:
1. m in im ize th e path len gth th rough th e brain
2. avoid traversing th e ven tr icles or vital n eural or vascular struct ures
3. avoid traversing in fected st ructures outside th e in tracran ial com partm en t (in fected bon e, paran asal sin uses, an d scalp w oun ds)
4. in cases of m ultiples abscesses, target 7 :
a) w h en th e diagn osis is un kn ow n : the largest lesion or th e on e causin g th e m ost sym ptom s
b) on ce th e diagnosis of abscess is confirm ed
● any lesion ≥ 2.5 cm diam eter
● lesion s causin g sign ifican t m ass e ect
● en largin g lesion s
Cultures
Sen d aspirated m aterial for th e follow in g:
1. stain s
a) Gram stain
b) acid-fast stain for Mycobacterium (AFB stain , acid-fast resist decolorization w ith an acid-alcoh ol m ixture an d retain th e in itial dye carbolfu ch sin an d appear red. Th e gen us Mycobacterium an d th e gen us Nocardia are acid-fast, all oth er bacteria w ill be decolorized an d stain
blue, th e color of th e coun terstain m ethylen e blue)
c) m odified acid-fast stain (for Nocardia, see below ) lookin g for bran ch ing acid fast bacillus
d) special fun gal stain s (e.g., m eth en am in e silver, m ucicarm in e)
2. culture
a) routin e cultures: aerobic an d an aerobic
b) fun gal culture: th is is n ot on ly h elpful for iden tifyin g fun gal in fect ion s, but sin ce th ese cult ures are kept for lon ger period an d any grow th th at occurs w ill be fur th er ch aracterized, fast idious or in dolen t bacterial organ ism s m ay som etim es be iden tified
c) TB culture
d) m olecular testin g: PCR (m ycobacteria, EBV, JC virus)
Excision
Can on ly be perform ed durin g th e “ch ron ic” ph ase (late capsule stage). Abscess is rem oved as any
w ell en capsulated tum or. Th e len gth of tim e on an t ibiotics can be sh or ten ed to ≈ 3 days in som e
cases follow in g total excision of an accessible, m at ure abscess (e.g. located in pole of brain ). Recom m en ded for abscesses associated w ith foreign body an d m ost Nocardia abscesses (see below ). May
also be n eeded n ecessar y for: fun gal abscess, m ultiloculated or resistan t lesion s.
20.2.10 Out com e
In th e pre-CT era, m ortalit y ran ged from 40–60%. W ith advan ces in an tibiotics, surger y, an d th e
im proved abilit y to diagn ose an d follow respon se w ith CT an d/or MRI, m ortalit y rate h as been
reduced to ≈ 10%, but m orbidit y rem ain s h igh w ith perm an en t n eurologic deficit or seizures in up to
50% of cases. Curren t outcom es are sh ow n in Table 20.3. A w orse progn osis is associated w ith poor
n eurologic fun ct ion , in traven tr icular rupture of abscess, an d alm ost 100% m ortalit y w ith fun gal
abscesses in t ran splan t recipien ts.
20
Table 20.3 Outcomes with cerebral abscess
m ortalit y (CT era data)26,7
0–10%
neurologic disabilit y
45%
late focal or generalized seizures
27%
hem iparesis
29%
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20.3 Subdural em pyem a
20.3.1 General inform at ion
Referred to as subdural abscess prior to 1943.27 Subdural em pyem a (SDE) is a suppurative in fect ion
th at form s in th e subdural space, w h ich h as n o an atom ic barr ier to spread over th e convexit y an d
in to th e in terh em isph eric fissure 28 (an d occasion ally to th e opposite h em isph ere an d posterior fossa). An tibiot ic pen etration in to th is space is poor. Dist in guish ed from abscess w h ich form s w ith in
brain substan ce, surroun ded by t issue reaction w ith fibrin an d collagen capsule form ation . Hen ce,
SDE ten ds to be m ore em ergen t .
SDE m ay be com plicated by cerebral abscess (seen in 20–25% of im aging studies in patien ts w ith
SDE), cort ical ven ous th rom bosis w ith risk of ven ous in farct ion , or localized cerebrit is.
20.3.2 Epidem iology
Less com m on th an cerebral abscess (ratio of abscess:em pyem a is ≈ 5:1). Foun d in 32 cases in 10,000
autopsies. Male:fem ale ratio is 3:1.
Location : 70–80% are over th e convexity, 10–20%are parafalcin e.
20.3.3 Et iologies
See Table 20.4 for etiologies. Most often occurs as a result of direct exten sion of local in fect ion
(rarely follow in g sept icem ia). Spread of th e in fect ion to th e in tracran ial com par tm en t m ay occur
th rough th e valveless diploic vein s, often w ith associated th rom boph lebitis.29
Ch ron ic ot it is m ed ia w as t h e lead in g cau se of SDE in t h e p rean t ibiot ic era, bu t in t h e U.S. th is
h as n ow been su r p assed by p aran asal sin u s d isease esp ecially w it h fron t al sin u s in volvem en t 3 0
(m ay also follow m ast oid sin u sit is). SDE is a rare bu t som et im es fat al com p licat ion of cran ial
t ract ion d evices.3 1 ,3 0 In fect ion of p re exist in g su bd u ral h em atom as (bot h t reate d an d u n t reated ,
in in fan ts an d ad u lt s) h ave been rep or ted 30 (bacterem ic seed in g of an u n op erat ed SDH is ver y
rare).
Traum a in cludes com poun d skull fract ures an d pen etrating injuries. Oth er etiologies in clude:
osteom yelit is, pn eum on ia, un related in fect ion (e.g. foot cellulit is) in diabetics.
20.3.4 Organism s
Th e cau sat ive or gan ism var ies w it h t h e sp e cific sou rce of t h e in fe ct ion . SDE associat e d w it h
sin u sit is is oft e n cau se d by ae r ob ic an d an ae r ob ic st r e p t o cocci Tab le 20 .5 ). Follow in g t r au m a or n e u r osu r gical p r oce d u r es, st ap h ylococci an d Gr am - n e gat ive sp ecie s p r e d om in at e
(w h e r e as S. au r e u s w as n ot a com m on p at h oge n in sin u sit is r elat e d SDE). St e r ile cu lt u r es
occu r in u p t o 4 0 % (som e of w h ich m ay be d u e t o fast id iou s an aer ob es an d /or p r eviou s exp o su r e t o an t ib iot ics).
Table 20.4 Etiologies of SDE
Locat ion
%
paranasal sinusitis (especially frontal)a
67–75
otitis (usually chronic otitis media)b
14
post surgical (neuro or ENT)
4
trauma
3
m eningitis (more com mon in peds32 )
2
congenital heart disease
2
m isc. (including pulmonary suppuration)
4
undetermined
3
a more com m on in adults
b no cases from otitis in a recent series 30
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Table 20.5 Organism s in SDE associated with sinusitis
Organism s
%
Adult cases
aerobic streptococcus
30–50%
staphylococci
15–20%
m icroaerophilic and anaerobic strep
15–25%
aerobic Gram-negative rods
5–10%
other anaerobes
5–10%
Childhood
Organisms are sim ilar to m eningitis for the same age group. Antibiotics choice is the sam e as for m eningitis
Table 20.6 Findings on presentation with SDEa
Finding
%
fever
95
H/A
86
m eningism us (nuchal rigidit y…)
83
hem iparesis
80
altered m ental status
76
seizures
44
sinus tenderness, swelling or inflam mation
42
nausea and/or vom iting
27
hom onym ous hem ianopsia
18
speech difficult y
17
papilledem a
9
a from a review of multiple articles30
20.3.5 Present at ion
Neurologic fin dings are sh ow n in Table 20.6. Sym ptom s are due to m ass e ect , in flam m ator y
involvem en t of th e brain an d m en in ges, an d th rom boph lebitis of cerebral vein s an d/or ven ous
sin uses. SDE sh ould be suspected in th e presen ce of m en in gism us + un ilateral h em isph ere dysfun ct ion . Marked ten dern ess to percussion or pressure over a ected air sin uses is com m on .28 Foreh ead
or eye sw ellin g (from em issary vein th rom bosis) m ay occur.
Focal n eurologic deficit an d/or seizures usually occur late.
20.3.6 Evaluat ion
20
CT: IV con trast is usually h elpfu l. CT m ay m iss som e cases (related to early gen eration scan n ers,
failure to give IV con trast, poor scan qualit y…). If n orm al, repeat th e CT at a later tim e or do an
MRI if clin ical suspicion persists. Fin din gs: hypoden se (but den ser th an CSF) crescen tic or len ticular extracerebral lesion w ith den se en h an cem en t of m edial m em bran e; inw ard displacem en t of
gray-w h ite in terface; ven tricular distor tion an d e acem en t of basal cistern s are com m on
fin din gs 33
● MRI: low sign al on T1WI, h igh sign al on T2WI. Pial epen dym al lin e: a n on -specific MRI fin din g in
CNS in fect ion
●
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LP: poten tially h azardous (risk of h ern iation ). Organ ism s are usually presen t on ly in cases origin atin g from m en in gitis. If n o m en ingit is, usually see fin dings con sistent w ith a param en ingeal
in flam m atory process: m oderate sterile pleocytosis (150–600 WBC/m m 3 ) w ith PMNs predom in atin g; glucose n orm al; open in g pressure is usually h igh 28 ; protein is usually elevated (ran ge: 75–
150 m g/dl)
20.3.7 Treat m ent
1. su r gical d r ain age: in d icat e d in m ost cases (n on su r gical m an age m e n t h as b e e n r e p or t e d ,3 4
b u t sh ou ld on ly b e con sid e r e d w it h m in im al n e u r ologic in volve m e n t , lim it e d ext e n sion
a n d m ass e e ct o f SDE, an d ea r ly favorab le r esp on se t o a n t ib iot ics) u su a lly d on e r elat ively
e m e r ge n t ly
2. early in th e course, th e pus ten ds to be m ore fluid an d m ay be m ore am en able to burr h ole drain age; later, loculation s develop w h ich m ay n ecessitate cran iotom y
3. th ere h as been con troversy over th e optim al surgical treatm en t. Early studies in dicated a better
outcom e w ith cran iotom y th an w ith burr h oles. Recen t st udies sh ow less di eren ce
a) critically ill pat ien ts w ith localized SDE m ay be can didates for burr-h ole drain age (usually
in adequate if loculation s are presen t). Repeat procedures m ay be n eeded, an d up to 20% w ill
later require a cran iotom y
b) cran iotom y: to debride an d, if possible, drain . A w ide cran iotom y is often required because of
septat ion s. Th e dura appears w h ite because of pus un dern eath . Open an d w ash out subdural
space. Do n ot t r y to rem ove m aterial adh eren t to cortex (m ay cause in farct ion )
4. an tibiotics: sim ilar to t reat m en t for cerebral abscess
5. an ticonvulsan ts: usually used prophylact ically, m an dator y if seizures occur
20.3.8 Out com e
See Table 20.7. Mortalit y h as dropped from n ear 100% in th e per-an tibiotic era to ≈ 10%. Neurologic deficits tend to im prove follow in g treatm en t, but w ere presen t in 55% of patien ts at th e t im e of
disch arge from th e h ospital.30 Age ≥ 60 years, obtun dation or com a at presen tation , an d SDE related
to surger y or t raum a (rath er th an sin usitis) carr y a w orse progn osis.30 Burr-h ole drain age m ay be
associated w ith a w orse outcom e th an w ith cran iotom y, but th is m ay h ave been in fluen ced by th e
poorer con dition of th ese patien ts. Fatal cases m ay h ave associated ven ous in farct ion of th e brain .
20.4 Neurologic involvem ent in HIV/AIDS
20.4.1 Types of neurologic involvem ent
General inform at ion
40–60% of all patien ts w ith acquired im m un odeficien cy syn drom e (AIDS) w ill develop n eurologic
sym ptom s, w ith on e–th ird of th ese presen t in g in itially w ith th eir n eurologic com plain t.35,36 On ly ≈
5% of patien ts th at die w ith AIDS h ave a n orm al brain on autopsy. On e study foun d th e CNS com plication s of AIDS sh ow n in Table 20.8.
Th e m ost com m on con dition s producin g foca l CNS lesion s in AIDS38 :
1. toxoplasm osis
2. prim ar y CNS lym ph om a
3. progressive m ultifocal leukoen ceph alopathy (PML)
4. cr yptococcal abscess
5. TB (tuberculom a)
Table 20.7 Outcom e with SDE
Out com e
%
persistent seizures
34%
residual hem iparesis
17%
m ortalit y
10–20%
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Table 20.8 CNS com plications of AIDS (320 patients35 )
Com plication
%
viral syndrom es
subacute encephalitisa
17
atypical aseptic meningitis
6.5
herpes simplex encephalitis
2.8
progressive multifocal leukoencephalopathy (PML)
1.9 b
viral myelitis
0.93
varicella zoster encephalitis
0.31
non-viral infections
Toxoplasm a gondii
> 32
Cryptococcus neoformans
13
Candida albicans
1.9
coccidiomycosis
0.31
Treponem a pallidum (neurosyphilis)
0.62
atypical Mycobacteria
1.9
Mycobacterium tuberculosis
0.31
Aspergillus fumigatus
0.31
bacteria (E. coli)
0.31
neoplasm s
primary CNS lym phoma
4.7
systemic lymphom a with CNS involvem ent
3.8
Kaposi’s sarcoma (including brain mets)
0.93
stroke (stroke)
infarct
1.6
intracerebral hem orrhage
1.2
m iscellaneous/unknown
7.8
a CMV encephalitis occasionally occurs
b more recent estim ate 37 of the incidence of PML in AIDS: 4%
Prim ary e ect s of HIV infect ion
20
Aside from opportun istic in fect ion an d tum ors caused by th e im m un odeficien t state, in fect ion w ith
th e Hum an Im m un odeficien cy Virus (HIV) itself can cause direct n eurologic involvem en t in cludin g:
1. AIDS en ceph alopathy: th e m ost com m on n eurologic involvem en t, occurs in ≈ 66% of patien ts
w ith AIDS involving th e CNS
2. AIDS dem en tia AKA HIV dem en tia com plex
3. aseptic m en in gitis
4. cran ial n europath ies: in cludin g “Bell’s palsy” (occasion ally bilateral)
5. AIDS related m yelopathy: vacuolizat ion of spin al cord; see Myelopathy (p. 1407)
6. periph eral n europath ies
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CNS t oxoplasm osis in AIDS
May presen t as:
1. m ass lesion (toxoplasm osis abscess): th e m ost com m on lesion causin g m ass e ect in AIDS
patien ts (70–80% of cerebral m ass lesion s in AIDS39 ) (see below for CT/MRI fin dings)
2. m en in goen ceph alitis
3. en ceph alopathy
CNS toxoplasm osis occurs late in th e course of HIV in fection , usually w h en CD4 coun ts are < 200
cells/m m 3 .
PML in HIV/AIDS
Progressive m ultifocal leukoecn eph alopathy (PML):
1. Is caused by a ubiquitous polyom avirus (a subgroup of papova virus, sm all nonenveloped viruses
w ith a closed circular double DNA-stranded genom e) called “JC virus” (JCV, nam ed after the initials
of the patient in w hom it was first discovered, not to be confused w ith Jakob-Creutzfeldt – a prion
disease – nor w ith Jam estow n Canyon virus, also con fusingly called JC virus, a single-stranded RNA
virus that occasionally causes encephalitis in hum ans). 60–80% of adults have antibodies to JCV40
2. frequen tly m an ifests in patien ts w ith suppressed im m un e system s, in cludin g
a) AIDS: curren tly th e m ost com m on un derlying disease associated w ith PML
b) prior to AIDS, th e m ost com m on associated diseases w ere ch ron ic lym ph ocytic leukem ia &
lym ph om a
c) allograft recipien ts: due to im m un osuppression 41
d) ch ronic steroid th erapy
e) PML also occurs w ith oth er m align an cies, an d w ith autoim m un e disorders (e.g. SLE)
3. path ologic fin din gs: focal m yelin loss (dem yelin ation , e ect s w h ite m at ter) w ith sparin g of
axon cylin ders, surroun ded by en larged ast rocytes an d bizarre oligoden droglial cells w ith eosin oph ilic in tran uclear in clusion bodies. EM can detect th e virus. Som etim es occurs in brain stem an d
cerebellum
4. clin ical fin dings: m en tal status ch anges, blin dn ess, aph asia, progressive cran ial n er ve, m otor, or
sen sor y deficits an d ult im ately com a. Seizures are rare
5. im agin g fin din gs: see below
6. clin ical course: usually rapidly progressive to death w ith in a few m on th s, occasion ally lon ger survival occurs in explicably.42 Th ere is n o e ect ive treatm en t. Som e prom ise in itially w ith an ti-retroviral th erapy 43
7. defin itive diagn osis requires brain biopsy (sen sitivity: 40–96%) alth ough it is in frequen tly
em ployed. JCV h as been isolated from brain an d urin e. Polym erase ch ain reaction (PCR) of JCV
DNA from CSF h as been reported, an d is specific but n ot sen sitive for PML
Prim ary CNS lym phom a (PCNSL) in AIDS
Occurs in ≈ 10% of patien ts w ith AIDS.44 PCNSL is associated w ith th e Epstein -Barr virus (p. 711).
Neurosyphilis
1. AIDS patien ts can develop n eurosyph ilis in as little as 4 m os from in fect ion 45 (un like th e 15–20
yrs usually required in n on -im m un ocom prom ised patien ts)
2. n eurosyph ilis can develop in spite of w h at w ould oth erw ise be adequate treatm en t for early
syph ilis w ith ben zath in e PCN45,46
3. CDC recom m endations 47 : treat patients having sym ptom atic or asymptom atic neurosyphilis w ith :
● pen icillin G 3-4-m illion un its IV q 4 h rs (total of 24-m illion un its/d) for 10-14 days or
● pen icillin G procain e 2.4 m illion un its IM daily + proben ecid 500 m g QID orally, both for 10-14
days
● alternative: Rocephin 2gm IV once daily for 10-14 days for patients with a m ild beta-lactam allergy
● for severe beta-lactam allergy: PCN desen sitizat ion
20.4.2 Neuroradiologic findings in AIDS
Overview
MR w ith gadolin ium is recom m en ded as th e in itial screen ing procedure of ch oice for AIDS pat ien ts
w ith CNS sym ptom s (low er false n egative rate th an CT38 ).
See Table 20.9 for a com parison of n euroradiologic fin din gs in toxoplasm osis, PCNSL an d PML.
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Infect ion
Table 20.9 Comparison of neuroradiologic lesions in AIDSa
Feature
Toxo
PCNSL
PML
Multiplicity
usually > 5 lesions
m ultiple but < 5 lesions
may be multiple
Enhancem ent
ring
hom ogeneous
none
Location
basal ganglia and grey-white junction
subependym al
usually limited to
white mat ter
Mass effect
mild-m oderate
m ild
none-m inimal
Miscellaneous
lesions surrounded by edem a
m ay extend across corpus
callosum
high signal on
T2WI, low on T1WI
a abbreviations: Toxo = toxoplasmosis, PCNSL= primary CNS lym phoma, PML= progressive m ultifocal leukoence-
phalopathy
CT/MRI findings in t oxoplasm a abscess
See Table 20.9.
1. m ost com m on fin dings: large area (low den sit y on CT) w ith m ild to m oderate edem a, ring en h an cem en t w ith IV con trast in 68%com pat ible w ith abscess (of th ose th at did n ot rin g en h an ce,
m any sh ow ed hypoden se areas w ith less m ass e ect w ith sligh t en h an cem en t adjacen t to lesion ),
w ell circum scribed m argin s 48
2. m ost com m on ly located in ba sa l ga nglia , are also often subcort ical
3. often m ultiple (t ypically > 5 lesion s 49 ) an d bilateral
4. usually w ith little to m oderate m ass e ect 38 (in BG, m ay com press th ird ven tricle an d sylvian
aqueduct causin g obstruct ive hydroceph alus)
5. m ost pat ien ts w ith toxoplasm osis h ad evidence of cerebral atrophy
CT/MRI findings in PML
See Table 20.9. Note: th e appearan ce of PML m ay di er in AIDS patien ts from its appearan ce in
n on -AIDS patien ts.
1. CT: di use areas of low den sity. MRI: h igh in ten sity on T2W I
2. n orm ally involves on ly w h ite m atter (spares cortex), h ow ever in AIDS pat ien ts gray m atter
involvem en t h as been reported
3. n o en h an cem en t (on eith er CT or MRI), un like m ost toxoplasm osis lesion s
4. n o m ass e ect
5. n o edem a
6. lesion s m ay be solitar y on 36%of CTs an d on 13% of MRIs
7. borders are usually m ore ill-defin ed th an in toxoplasm osis 48
CT/MRI findings in prim ary CNS lym phom a (PCNSL)
See Table 20.9. NB: th e appearan ce of PCNSL m ay di er in AIDS patien ts from n on -AIDS patien ts.
1. m ultiple lesion s w ith m ild m ass e ect an d edem a th at tend to rin g-en h an ce on CT, or appear as
areas of hypoin ten sity surroun din g cen t ral area of h igh in ten sity (target lesion s) on T2WI MRI
(un like n on -AIDS cases w h ich ten d to en h an ce h om ogen eously 50 )
2. th ere is a greater ten den cy to m ulticen tricit y in AIDS patien ts th an in th e n on im m un osuppressed
populat ion 51
20
20.4.3 Managem ent of int racerebral lesions
Neurosurgical con sultat ion is often requested for biopsy in an AIDS patien t w ith question able lesion
(s). Th e diagn ostic dilem m a is usually for low den sit y lesion s on CT, an d in th e Un ited States is prim arily betw een th e follow in g:
● toxoplasm osis: t reated w ith pyrim eth am in e an d sulfadiazin e + leucovorin (see below )
● PML: n o proven e ect ive treatm en t (in itiate or optim ize an t iretroviral th erapy m ay h elp 43 )
● CNS lym ph om a: usually treated w ith RTX; see CNS lym ph om a (p. 710)
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n ote: cr yptococcus is m ore com m on th an PML or lym ph om a, but usually m an ifests as cr yptococcal m en in gitis (p. 376), an d not as a r ing enha ncing lesion
Recom m endat ions
PML can usually be iden tified radiograph ically. How ever, radiograph ic im agin g alon e can n ot reliably
di eren tiate toxoplasm osis from lym ph om a or from som e oth er con curren t con dition s (patien ts
w ith toxoplasm osis m ay h ave oth er sim ultan eous diseases). Th erefore, th e follow in g recom m en dat ion s are m ade:
1. obtain baselin e toxoplasm osis serology (IgG) on all kn ow n AIDS pat ien ts (NB: 50% of th e gen eral
populat ion h ave been in fected by toxo an d h ave positive t iter by age 6 years, 80–90%w ill be positive by m iddle adulth ood).
2. m ultiple en h an cin g lesion s w ith basal ganglion involvem en t in a patien t w h ose toxo titer is positive h ave a h igh probability of bein g toxo
3. prim ar y CNS lym ph om a (PCNSL): w ith a single lesion s, lym ph om a is m ore likely th an toxo. If th e
possibilit y of PCNSL is st ron g
a) con sider LP (con train dicated in presen ce of m ass e ect)
● high volum e LP for cytology: PCNSL can be diagnosed in ≈ 10–25% of cases using ≈ 10 m l of CSF
● or sen d CSF for polym erase ch ain reaction (PCR) am plification of viral DNA of Epstein -Barr
virus or JC-virus 52 (th e agen ts respon sible for AIDS-related PCNSL an d PML, respectively)
b) som e cen ters recom m en d early biopsy to iden tify PCNSL cases to avoid delayin g RTX for 3
w eeks w h ile assessing respon se to an tibiotics 38 ; in stead of biopsy, a few cen ters advocate
em piric radiation t reat m en t (for possible lym phom a)
4. in patien t w ith possible toxoplasm osis (i.e. positive toxo serology an d im aging fin din gs t ypical
for toxo) even if oth er con dition s h ave n ot been excluded:
a) in itial th erapy: sulfadiazin e 1000 m g four tim es daily for pat ien ts < 60 kg or 1500 m g four tim e
daily for patien ts ≥ 60 kg + pyrim eth am in e 200 m g loading dose, th en 50 m g daily for
patien ts < 60 kg or 75 m g daily for patien ts ≥ 60 kg + folin ic acid 10-25 m g daily to preven t pyrim eth am in e in duced h em atologic toxicit y
b) for patien ts w h o can n ot take sulfadiazin e (in cludin g th ose w h o develop sulfa allergy), ch ange
sulfadiazin e to clindam icin 600 m g IV or PO q 6 h rs
c) altern ative regim en s:
● atovaquon e 1500 m g PO BID + pyrim eth am in e 200 m g loading dose, th en 50 m g daily for
patien ts < 60 kg or 75 m g daily for pat ien ts ≥ 60 kg + folin ic acid 10-25 m g daily
● atovaquon e 1500 m g PO BID + sulfadiazin e 1000 m g four t im es daily for patien ts < 60 kg or
1500 m g four t im e daily for pat ien ts ≥ 60 kg
d) th ere sh ould be a clinical an d radiograph ic respon se w ith in 2-3 w eeks 53
e) if n o respon se to th erapy after 3 w eeks (som e recom m en d 7-10 days 54 ), th en con sider altern ative diagn osis (brain biopsy sh ould be con sidered)
f) if respon se is good, reduce dosage of sulfadiazin e after 6to 50% of th e above dose for ch ron ic
m ain tenan ce th erapy: sulfadiazin e 1000 m g t w ice daily for patien ts < 60 kg or 1500 m g four
t w ice daily for patien ts ≥ 60 kg + pyrim eth am in e 25-50 m g daily + folin ic acid 10-25 m g daily
g) ch ronic m ain ten an ce th erapy can be discon tin ued in asym ptom at ic patien ts w h o h ave com pleted in itial th erapy if th ey are receivin g an tiretroviral th erapy (ART), h ave a suppressed HIV
viral load, an d h ave m ain tain ed a CD4 coun t > 200 cells/m cl for at least six m on th s
5. perform biopsy in th e follow in g sett in gs:
a) in patien t w ith a n egative toxo t iter (n ote: patien ts occasion ally h ave negative titer because of
an ergy)
b) accessible lesion (s) at ypical for toxo (i.e. n on -en h an cin g, sparin g basal gan glia, periven tricular
location )
c) in th e presen ce of extran eural in fect ion s or m align an cies th at m ay involve th e CNS
d) lesion th at could be eith er lym ph om a or toxo (e.g. sin gle lesion , see 3. A.)
e) in patien ts w h o h ave lesion s n ot in con sisten t w ith toxo but fail to respon d to appropriate
an ti-toxo m edication s in th e recom m en ded tim e (see above)
f) th e role of biopsy for non-enha ncing lesion s is less w ell defin ed as th e diagn osis does n ot
in fluen ce th erapy (m ost are PML or biopsies are n on -diagn ostic), it m ay be useful on ly for
progn ostic purposes 54
g) n ote: th e risk of open biopsy in AIDS patien ts m ay be h igh er th an n on im m un ocom prom ised
patien ts. Stereotactic biopsy m ay be especially w ell suited, w ith up to 96% e cacy, fairly low
m orbidit y (m ajor risk: sign ifican t h em orrh age, ≈ 8%in ciden ce) an d low m ortalit y 55,56
6. stereotactic biopsy guidelin es:
a) if m ultiple lesion s are presen t, ch oose th e m ost accessible lesion in th e least eloquen t brain
area, or th e lesion n ot respon din g to t reat m en t
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Infect ion
b) biopsy th e cen ter of n on -en h an cing lesion s, or th e en h an cin g portion of rin g-en h an cing
lesion s
c) recom m en ded studies on biopsy: h istology; im m un operoxidase stain for Toxoplasm a gon dii;
stain s for TB an d fun gus; culture for TB, fun gi, pyogen s
20.4.4 Prognosis
Pat ien ts w ith CNS toxo h ave a m edian sur vival of 446 days, w h ich is sim ilar to th at w ith PML but
lon ger th an AIDS-related PCNSL.49
Pat ien ts w ith CNS lym ph om a in AIDS sur vive on average a sh orter t im e th an sim ilarly t reated
CNS lym ph om a in n on im m un osuppressed patien ts (3 m on th s vs. 13.5 m os). Median sur vival is < 1
m on th w ith n o t reatm en t. CNS lym ph om a in AIDS ten ds to occur late in th e disease, an d pat ien ts
often die of un related causes (e.g. Pn eum ocystis carin ii pn eum on ia).54
20.5 Lym e disease – neurologic m anifest at ions
20.5.1 General inform at ion
Lym e disease (LD) is a com plex m ultisystem disease caused by various species of Borrelia spiroch etes
(in Nor th Am erica: Borrelia burgdorferi) tran sm itted to h um an s by th e Ixodes scapularis or pacificus
t icks (th e Am erican dog tick is n ot involved). It w as first recognized in Lym e, Con n ect icut in 1975,
an d is n ow th e m ost com m on arth ropod-born e in fect ion in th e U.S.57
20.5.2 Clinical findings
Th ere are 3 clin ical stages w h ich can overlap or occur separately.
St age 1 (early localized d isease, er yt h em a m igr an s an d flu -like illn ess). System ic sign s of in fect ion usually begin w ith a flu-like illn ess w ith in days to w eeks of in fect ion , sym ptom s in clude: fever,
ch ills, m alaise, fatigue or leth argy, backach e, h eadach e, arth ralgia, an d m yalgia. Region al or gen eralized lym ph adenopathy m ay occur.
Th e h allm ark of LD is er yt h em a ch ron icu m m igr an s (ECM) (classically a “bu lls-eye rash ”)
w h ich begin s 3–30 d ays after t h e t ick bit e, an d occu rs in 60–75% of p at ien ts. ECM u su ally begin s
in t h e t h igh , in gu in al region , or axilla, an d con sist s of an exp an d in g m acu lar rash w it h br igh t
red bord ers an d cen t ral clearin g an d in d u rat ion t h at u su ally fad es w it h ou t scar r in g in 3–4
w eeks. In ad d it ion to ECM, ot h e r d er m atologic fin d in gs in clu d e: m alar rash (13%), d i u se er yt h em a, an d u r t icar ia. W ith in 30 d ays of t h e t ick bite, sp iroch etes m ay be d em on st rated in acellu lar
sp in al flu id .
St age 2 (ear ly d issem in at ed d isease). Several w eeks to m on th s after in fect ion , un treated pat ien ts
develop sign s of m ore serious organ involvem en t. Cardiac an d n eurologic involvem en t m ay occur.
Man ifestat ion s in clude:
1. cardiac: occurs in 8%. Con duct ion defect s (usually A-V block, gen erally brief an d m ild) an d
m yopericarditis
2. ocular: pan oph th alm it is, isch em ic optic atrophy, an d in terstitial keratit is occur rarely
3. n eurologic: occurs in 10–15%of patien ts w ith stage 2 disease
a) th e clin ical triad of n eurologic m an ifestat ion s of Lym e disease is 58 :
● cran ial n eurit is (especially th at m im ickin g Bell’s palsy: Lym e disease is th e m ost com m on
cause of bilateral “Bell’s palsy” (facial diplegia) in en dem ic areas)
● m en in git is
● radiculopathy
b) other possible n eurologic involvem en t in cludes: en ceph alit is, m yelit is, periph eral n euritis
20
Neurologic fin din gs are frequen tly m igrator y, an d ≈ 60% of patien ts h ave m ultiple n eurologic fin din gs sim ultan eously. In Europe, Ban nw arth’s syn drom e (ch ron ic lym ph ocyt ic m en ingit is, periph eral
n europathy, an d radiculopathy) is th e m ost com m on m an ifestation , an d prim arily a ect s th e periph eral n er vous system .59 Neurologic sym ptom s usually resolve gradually.
St age 3 (late d isease). Arth rit is an d ch ron ic n eurologic syn drom es m ay occur in th is stage.
Arth ralgias are com m on in stage 1, but t rue ar th rit is usually does n ot begin for m on th s to years after
in fect ion , an d is seen in ≈ 60% of cases.60 W h en arth ritis occurs, it m ay a ect th e kn ee (89%), h ip
(9%), sh oulder (9%), an kle (7%) an d/or elbow (2%).61 Neurologic involvem en t in cludes 62 :
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Bacterial Infections of the Parenchym a and Meninges and Com plex Infections
1.
2.
3.
4.
5.
6.
7.
335
en ceph alopathy (ch ron ic, m an ifestat ion m ay be subtle)
en ceph alom yelit is (ch ron ic, m an ifestation m ay be subtle)
periph eral n europathy (ch ron ic, m an ifestation m ay be subtle)
ataxia
dem en tia
sleep disorder
n europsych iatric disease an d fatigue syn drom es
20.5.3 Diagnosis
Diagnostic crit eria
Th ere is n o test in dicat ive of active in fect ion . Th e spiroch ete is di cult to culture from in fected
h um an s. Diagnosis is easy if a h istor y of t ravel to en dem ic areas, t ick bite, an d ECM are iden tified.
Table 20.10 sh ow s th e CDC criteria for diagn osis.
Serology
It takes 7–10 days from in itial in fect ion to develop an tibodies to B. burgdorferi, but it takes ≈ 2–3
w ks before an tibodies can reliably be detected in un treated pat ien ts (an tibiot ics can reduce th e
im m un e respon se).64 If th e first serum test is n egative, it sh ould be repeated in 4–6 w eeks if th e clin ical suspicion of LD is st ron g (seroconversion from n egative to positive is support ive of B. burgdorferi
in fect ion ). False positives can occur w ith oth er borrelial an d t repon em al in fect ion s (e.g. syph ilis,
h ow ever, VDRL test w ill di eren tiate th e t w o).
En zym e-lin ked im m un osorben t assay (ELISA) detects IgM or IgG. An tibodies to B. burgdorferi is
th e usual test m eth od. IgM is elevated acutely, an d IgG gradually rises an d is elevated in alm ost all
patien ts at 4–6 w eeks an d is usually h igh est in patien ts w ith ar th ritis.57 Western blot m ay h elp iden t ify false-positive ELISA results (m ore sen sitive an d specific th an ELISA, h ow ever, results m ay var y
betw een labs). Am plificat ion of B. burgdorferi DNA by polym erase ch ain react ion (PCR) yields a m ore
ver y sen sitive test th at m ay h ave sign ifican t false positives, an d can be positive even if th e DNA is
from dead organ ism s.
CSF
Elevated CSF IgG an tibody t iter to B. burgdorferi m ay occur w ith n eurologic involvem en t.65 CSF fin din gs in late disease are usually com patible w ith aseptic m en ingitis. Oligoclon al ban ds an d in creased
ratio of IgG to album in m ay occur.66
20.5.4 Treat m ent
See referen ces.67,68,62
An tibiot ic th erapy is m ore e ect ive early in th e illn ess.
20.6 Nocardia brain abscess
20.6.1 General inform at ion
Nocardia in fect ion s m ay involve th e CNS in m ultiple w ays.
Table 20.10 CDC criteria for diagnosis of Lym e disease 63
Area
Criteria
In endem ic area
●
●
In non-endemic area
●
●
●
erythem a chronicum migrans (ECM)
antibody titer ≥ 1:256 by IFAa and involvem ent of ≥ 1 organ system b
ECM with antibody titer ≥ 1:256
ECM with involvem ent of ≥ 2 organ system sb
antibody titer ≥ 1:256 by IFAa and involvem ent of ≥ 1 organ system b
a IFA= imm unofluorescence antibody
b either m usculoskeletal, neurologic or cardiac
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Nocardiosis is caused prim arily by Nocardia asteroides (oth er Nocardia species such as N. brasiliensis are less com m on ), a soil-born aerobic act in om ycete (a bacteria, n ot a fun gus) th at is usually
in oculated th rough th e respirator y t ract an d produces a localized or dissem in ated in fect ion . Hem atogen ous spread frequen tly results in cutan eous lesion s an d CNS involvem en t. Nocardia is respon sible for 2%of all brain abscesses, th e m ajorit y of th ese are N. asteroides.
Nocardiosis occurs prim arily in patien ts w ith ch ron ic debilitatin g illn esses in cludin g:
1. n eoplasm s: leukem ia, lym ph om a…
2. con dition s requirin g lon g-term cort icosteroid t reatm en t
3. Cush in g’s disease
4. Paget’s disease of bon e
5. AIDS
6. ren al or cardiac organ t ran splan t recipien ts
Th e diagn osis is suspected in h igh -risk pat ien ts presen ting w ith soft -tissue abscesses an d CNS
lesion s. CNS involvem en t occurs in about on e-th ird an d in cludes:
1. cerebral abscess: often m ultiloculated
2. m en in git is
3. ven tr iculitis in pat ien ts w ith CSF sh un t 69
4. epidural spinal cord com pression from ver tebral osteom yelitis 70
20.6.2 Diagnosis
Brain biopsy m ay n ot be n eeded in h igh -risk pat ien ts w ith con firm ed n ocardia in fect ion in oth er
sites,69 except possibly in AIDS pat ien ts w h ere th e risk of m ult iple organ ism in fect ion s or in fect ion
plus t um or (particularly lym ph om a) is con siderable.
20.6.3 Treat m ent
General inform at ion
Surgical in dicat ion s (p.324) are th e sam e as for oth er abscesses.
Ant ibiot ics
See referen ces.71,72
● Prim ar y ch oice: trim eth oprim -sulfam eth oxazole (TMP-SMZ 15 m g/kg IV of trim eth oprim com pon en t per day in t w o to four divided doses PLUS im ipen em 500 m g IV q6h ± am ikacin 7.5 m g/kg IV
q12h (if CNS disease w ith m ultiorgan involvem en t)
● Altern at ive if sulfa allergy: im ipen em 500 m g IV q6h PLUS am ikacin 7.5 m g/kg IV q12h
Antim icrobial suscept ibilit y testing sh ould be con ducted on all isolates.
Duration : because of risks of relapse or h em atogen ous spread, treat m en t is recom m en ded forat
least on e year w ith CNS involvem en t, possibly in defin itely in for im m un ocom prom ised h osts.
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[59] Pach ner AR, Du ray P, Steere. Cen tral Ner vou s System Man ifestation s of Lym e Disease. Arch Neurol.
1990; 46:790–795
[60] Steere AC, Sch oen RT, Taylor E. Th e Clin ical Evolu tion of Lym e Arth ritis. An n In tern Med . 1987;
107:735–731
[61] Cen ters for Disease Con t rol. Lym e Disease - Con n ect icut. MMW R. 1988; 37:1–3
[62] Sigal LH. Lym e Disease Overd iagn osis: Cau se an d
Cu re. Hosp Pract. 1996; 31:13–15
[63] Wein stein A, Bu jak DI. Lym e Disease: A Review of
its Clin ical Featu res. NY State J Med . 1989; 89:566–
571
[64] Magn arelli LA. Cu rren t Statu s of Laborator y Diagn osis for Lym e Disease. Am J Med . 1995; 98 (S4A):10–
2S
[65] W ilkse B, Sch eirz G, Preac-Mursic V, et al. In trath ecal Product ion of Specific An tibodies Again st Borrelia burgd orferi in Patien ts w ith Lym ph ocyt ic
Men in gorad icu litis (Ban nw arth 's Syn drom e). J
In fect Dis. 1986; 153:304–314
[66] Hen riksson A, Lin k H, Cruz M, et al. Im m un oglobulin Abn orm alities in Cerebrospin al Fluid an d Blood
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Over th e Cou rse of Lym ph ocyt ic Men in gorad iculitis
(Ban nw arth 's Syn drom e). An n Neurol. 1986;
20:337–345
Treatm en t of Lym e Disease. Med Letter. 1988;
30:65–66
Steere AC. Lym e Disease. N En gl J Med. 1989;
321:586–596
Byrn e E, Brop hy BP, Pettett LV. Nocard ia Cerebral
Abscess: New Con cepts in Diagn osis, Man agem en t ,
an d Progn osis. J Neu rol Neurosurg Psych iat r y. 1979;
42:1038–1045
Aw ad I, Bay JW , Petersen JM. Nocardial Osteom yelit is of th e Sp in e w ith Epidural Spin al Cord Com pression - A Case Report . Neurosurgery. 1984; 15:254–
256
Sorrell TC, Iredell JR, Mandell GL, Ben n ett JE, Dolin
R. Prin ciples an d Practice of In fect ious Diseases. 6th
ed. Ph iladelph ia: Elsevier; 2005
Lern er PI. Nocardiosis. Clin Infect Dis. 1996;
22:891–903; quiz 904-5
Skull, Spine, and Post -Surgical Infect ions
21 Skull, Spine, and Post -Surgical Infect ions
21.1 Shunt infect ion
21.1.1 Epidem iology
Acceptable sh un t in fect ion rate 1 : < 5–7% (alth ough m any publish ed series h ave a rate n ear 20%,2 possibly due to di eren t patien t populat ion ).
Risk of early in fect ion after sh un t surger y: reported ran ge is 3–20% per procedure (t ypically ≈ 7%).
Over 50% of staph in fect ion s occur w ith in 2 w eeks post-sh un t, 70% w ith in 2 m os. Source is often
th e patien t’s ow n skin .1 It is estim ated th at in ≈ 3% of operation s for sh un t in sertion th e CSF is
already in fected (th erefore CSF durin g sh un t in sert ion is recom m en ded).
21.1.2 Morbidit y of shunt infect ions in children
Ch ildren w ith sh un t in fect ion s h ave an in creased m ortalit y rate an d risk of seizure th an th ose w ith out sh un t in fect ion . Th ose w ith m yelom en ingocele w h o develop ven triculitis after sh un tin g h ave a
low er IQ com pared to th ose w ith out in fect ion .3 Mor talit y ran ges from 10–15%.
21.1.3 Risk fact ors for shunt infect ion
Many factors h ave been blam ed. Som e th at seem to be better docum en ted in clude:
● youn g age of patien t 2 : in m yelom en ingocele (MM) patien ts, w aiting un til th e ch ild is 2 w eeks old
m ay sign ifican tly low er th e in fect ion rate
● len gth of procedure
● open n eural tube defect
21.1.4 Pat hogens
Early infect ion
Most com m on ly:
● Staph . epiderm idis (coagulase-n egative staph ): 60–75% of in fect ion s (m ost com m on )
● S. aureus
● Gram -n egat ive bacilli (GNB): 6–20% (m ay com e from in test in al perforation )
In n eon ates E. coli an d St rep. h em oliticus dom in ate.
Lat e infect ion (> 6 m ont hs aft er procedure)
Risk: 2.7–31% per patien t (t ypically 6%). Alm ost all are S. epiderm idis. 3.5% of patien ts accoun t for
27%of in fect ion s.4
“Late” sh un t in fect ion s m ay be due to:
● an in dolen t in fect ion due to Staph . epiderm idis
● seeding of a vascular sh un t durin g episode of septicem ia (probably ver y rare)
● colon ization from an episode of m en in gitis
Fungal infect ions
Candida spp. infections
Can dida spp. are respon sible for th e m ajorit y of fun gal ven t ricular sh un t in fect ion s. Usually occurs in
ch ildren < 1 year age. In ciden ce: 1–7%.5 Th e 4th leading path ogen causin g m en in gitis in n eurosurgical patien ts in 1 study,6 possibly related to th e use of prophylactic an tibiotics used for ICP m on itorin g
an d CSF drain age. High er in ciden ce in VP sh un t patien ts w ith abdom in al in fect ion s an d sh un ts
placed in pat ien ts w ith previous bacterial m en in gitis.7 CSF t ypically sh ow s: elevated W BCs an d protein , n orm al glucose. Man agem en t recom m en dation s:
1. com pletely rem ove th e con tam in ated sh un t (m ay be m ore im por tan t th an w ith bacterial
in fection s)
2. place a fresh extern al ven tricular drain (if patien t is sh un t depen den t)
3. t reat w ith an tifun gal th erapy
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4. place a fresh sh un t after ≥ 5–7 days of th erapy an d clin ical respon se is apparen t
5. con tin ue an tifun gal agen ts for 6–8 w eeks
21.1.5 Present at ion
Signs and sym pt om s
Non -specific syn drom e: fever, N/V, H/A, leth argy, an orexia, irritabilit y. May also presen t as sh un t
m alfun ct ion ; 29% of patien ts presentin g w ith sh un t m alfun ct ion h ad positive cultures.
Er yth em a an d ten dern ess alon g sh un t t ubin g m ay occur.
Distal in fect ion of ven triculoperiton eal sh un ts m ay m im ic acute abdom en .
In n eon ates m ay m an ifest as apn eic episodes, an em ia, h epatosplen om egaly, an d sti n eck.8 S. epiderm idis in fect ion s ten d to be in dolen t (sm olderin g). GNB in fect ion s usually cause m ore severe illn ess; abdom in al fin dings are m ore com m on ; m ain clin ical m an ifestat ion is fever, usually
in term itten t an d low grade.
Sh un t n eph rit is 9 : m ay occur w ith ch ron ic low level in fect ion of a ven triculovascular sh un t causin g
im m un e com plex deposition in ren al glom eruli, ch aracterized by protein uria an d h em aturia.
Blood t est s
WBC: < 10K in on e fourth of sh un t in fect ion s. It is > 20K in on e–th ird.
ESR: rarely n orm al in sh un t in fect ion s.
Blood cult ures: positive in less th an on e–th ird of cases.
CSF: W BC is usually n ot > 100 cells/m m 3 . Gram stain s m ay be positive ≈ 50% (yield w ith S. epiderm idis is m uch low er). Protein is often elevated, glucose m ay be low or n orm al. Rapid an tigen tests
used for com m un it y acquired m en ingitis are usually n ot h elpful for th e organ ism s th at ten d to cause
sh un t in fect ion s. CSF cultures are n egative in 40% of cases (h igh er cult ure yield if CSF W BC coun t
is > 20K).
Evaluat ion of shunt for infect ion
1. h istor y an d physical directed at determ in in g presen ce of above sign s an d sym ptom s w ith em ph asis on
a) h istor y suggestive of in fect ion at an oth er site
● exposure to oth ers w ith viral syn drom es, in cludin g sick siblin gs
● GI source (e.g. acute gast roen terit is). Often associated w ith diarrh ea.
● otit is m edia (ch eck t ym pan ic m em bran es)
● ton sillit is/ph ar yn git is
● appen dicitis (periton eal in flam m ation m ay im pede VP sh un t outflow )
● URI
● UTI
● pn eum on ia
b) physical exam to R/O m en in gism us (sti n eck, ph otoph obia…)
2. bloodwork
a) serum WBC coun t w ith di eren tial
b) acute ph ase reactan ts: ESR & CRP
c) blood cultures
3. sh un t tap: sh ould be don e in cases of suspected sh un t in fect ion . Clip h air (do n to sh ave) an d prep
carefully to avoid in troducing in fect ion . GNB requires di eren t th erapy an d h as h igh er m orbidit y
th an staph , th us it is desirable to iden tify th ese rare patien ts: > 90% of th ese h ad positive Gram stain ed CSF sm ear (on ly a few Gram -positive in fect ion s h ave positive results). GNB h ave h igh er
protein an d low er glucose, an d n eutroph ils predom in ate in di eren tial (un publish ed data 1 )
4. im agin g
a) CT: usually n ot h elpfu l for diagn osin g in fect ion . Epen dym al en h an cem en t w h en it occurs is
diagn ostic of ven t riculit is. CT m ay dem on strate sh un t m alfun ct ion
b) abdom in al U/S or CT: th e presen ce of an abdom in al pseudocyst is suggest ive of in fect ion
5. LP: u su ally NOT recom m en d e d . May be h azard ou s in obst r u ct ive h yd rocep h alu s (HCP) w it h
a n on fu n ct ion in g sh u n t . Often d oes n ot yield t h e p at h ogen even in com m u n icat in g HCP,
esp ecially if t h e in fe ct ion is lim ite d to a ven t ricu lit is. If p osit ive, m ay obviate a sh u n t t ap
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Skull, Spine, and Post -Surgical Infect ions
21.1.6 Treat m ent
Ant ibiot ics alone (w it hout rem oval of shunt hardw are)
Alt h ou gh e r ad icat ion of sh u n t in fe ct ion s w it h ou t r e m oval of h ard w ar e h as b e en r e p or t e d ,1 0 (
p 5 9 5 – 7 ),1 1 t h is h as a low e r su ccess r at e t h an w it h sh u n t r e m oval,1 2 m ay r e qu ir e p r ot r act e d
t r e at m e n t (u p t o 4 5 d ays in som e ), r isks p r oble m s associat e d w it h d r ain in g in fe ct e d CSF in t o
t h e p e r it on e u m (r e d u ce d CSF a bsor p t ion , a b d om in al sign s/ sym p t om s in clu d in g t e n d e r n e ss t o
fu ll- b low n p e r it on it is 1 0 (p 2 3 5 ) ) or va scu lar syste m – sh u n t n e p h r it is (p . 3 4 0 ), se p sis… – an d
oft e n r e qu ire s at le ast p ar t ial sh u n t r evision at som e p oin t in m ost ca ses. Tr e at m e n t w it h
an t ib iot ics w it h o u t sh u n t r e m oval is t h e r efor e r e com m e n d e d on ly in cases w h e r e t h e p at ie n t :
is t e r m in ally ill, is a p oor an e st h e t ic r isk, or h as slit ve n t r icles t h at m igh t b e d i cu lt t o
cat h e te r ize.
Rem oval of shunt hardw are
In m ost in st an ces, d u r in g t h e in it ia l t r e at m e n t w it h an t ibiot ics t h e sh u n t is eit h er e xte r n alize d (i.e. t u b in g is d ive r t e d at som e p oin t d ist al t o t h e ve n t r icu la r cat h et e r an d con n e ct e d t o a
closed d r ain age syst e m ), or som et im es t h e e n t ir e sh u n t m ay b e r e m ove d . In t h e lat t e r case,
som e m e an s of CSF d r ain age m u st be p r ovid e d in sh u n t d e p e n d e n t cases; e it h e r by in se r t ion
of an ext e r n al ve n t r icu la r d r ain (EVD), or by in t e r m it t e n t ve n t r icu lar t ap s (r ar ely e m p loye d)
or LPs (w it h com m u n icat in g HCP). EVD allow s e asy m on it or in g of CSF flow , con t r ol of ICP, a n d
r e p e at e d sam p lin g for sign s of r esolu t ion of in fe ct ion (n or m alizat ion of W BC cou n t an d su r ve illan ce cu lt u r es). In ad d it ion , EVD allow s for p ossib le ad m in ist rat ion of in t r at h e cal a n t ibiot ics. In sym p t om at ic p at ie n t s or t h ose w it h a p osit ive CSF cu lt u r e,1 3 an y h ar d w ar e r e m ove d
sh ou ld b e cu lt u r e d as on ly ≈ 8% ar e st e r ile in sh u n t in fe ct ion s. Skin or gan ism s ar e fast id iou s
an d m ay t a ke seve r al d ays t o gr ow .
If th ere is an abdom in al pseudocyst, th e fluid sh ould be drain ed th rough th e periton eal cath eter
before rem ovin g it .
Ant ibiot ics
Em piric antibiotics
See referen ce.14
1. Van com ycin (adult) 15 m g/kg IV q8-12 h ours to ach ieve trough 15-20 m g/dl for MRSA coverage +
cefepim e 2gm IV q8h or m eropen em 2gm q8h to cover gram n egative path ogen s. St ream lin e
th erapy based on culture an d sen sitivit y results
2. in t raven tricular injection of preser vative-free an tibiotics m ay be used in addition to IV th erapy.
Clam p EVD for on e h our after injection
Treatm ent for specific organism s
Positive cultures from sh un t h ardw are rem oved at th e tim e of sh un t revision in th e absen ce of clin ical sym ptom s or a positive CSF culture m ay be due to con tam in at ion an d do n ot always require
t reat m en t .13
1. S. aureus an d S. epiderm idis
a) if m eth icillin sen sitive: n afcillin or oxacillin ± IT van com ycin
b) if m eth icillin resistan t: con tin ue IV van com ycin + PO rifam pin ± IT van com ycin
2. En terococcus: IV am picillin ± IT gen t
3. oth er streptococci: eith er an t ist reptococcal or above en terococcal regim en
4. aerobic GNR: base on susceptibilities. Both IV beta-lact am & IT am in oglycoside in dicated
5. Serratia m arcescen s: a rare cause of VP sh un t in fect ion 15 but th e h igh m orbidit y m ay w arran t
aggressive an tibiotic th erapy (IV ceft riaxon e + IT am in oglycoside) an d surgical th erapy
6. Cor yn ebacterium spp. & Proprion ibacterium spp. (diph theroids)
a) if PCN sen sitive: use en terococcal regim en above
b) if PCN resistan t: IV + IT van com ycin
7. Can dida spp.: see protocol an d drugs (p. 320). System ic ant ifun gal th erapy an d rem oval of sh un t
is w arran ted. Avoid ech in ocan din s (an t ifun gal drugs th at in h ibit syn th esis of glucan in th e fun gal
cell w all) as th ey h ave poor CNS pen etrat ion
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Subsequent m anagem ent
On ce th e CSF is sterile × 3 days, conver t th e EVD to a sh un t (if an EVD w as n ot used, it is still recom m en ded th at th e sh un t be replace w ith n ew h ardw are). Con t in ue an t ibiot ics an addit ion al 10–14
days.
Managing vent riculoperit oneal shunt s in pat ient s w it h perit onit is
Periton itis m ay occur as a result of:
1. perforation of a viscus (som et im es as a result of pen etrat ion by th e periton eal cath eter tip,16
m ore com m on w ith obsolete Raim on di w ire-rein forced t ubin g)
2. spon tan eous bacterial periton itis (SBP): absen ce of an iden tifiable in t ra-abdom in al source. Most
com m on ly diagn osed in patien ts w ith cirrh otic ascites 17
3. or as a result of seeding th rough a VP sh un t in a patien t w ith a sh un t in fect ion : predom in antly
gram -positive, cutan eous organ ism s 18
Con cern s follow in g an episode of periton it is in a patien t w ith VP sh un t:
1. ascen din g in fect ion in to th e CNS: un com m on , especially in th e acute sett in g w h ile on appropriate
an tibiotics w ith sh un ts con tain in g a 1-w ay valve (as m ost do). CSF grow s predom in an tly m ixed,
gram -n egat ive in testin al flora 18
2. con tam in ation of th e distal sh un t: preven ts perm an en t eradicat ion of in fect ion (appen dicitis in
th e absen ce of periton itis does n ot produce sh un t in fect ion 18 )
3. sh un t m alfun ction due to distal sh un t obstruct ion : often as a result of w alling o of th e cath eter
tip, usually by om en tu m in react ion to th e in fect ion
Man agem en t recom m en dation s follow in g an episode of periton itis (m any viable option s):
1. im m ediate appropriate treatm en t of periton itis, usually m an aged by gen eral surgeon (e.g. for
ruptured appen dix: appen dectom y an d appropriate an tibiotics), w ith in itial attem pt to address
sh un t n ot bein g m an dator y
2. an ecdotally, cases h ave been m an aged successfully by clean ing o th e periton eal cath eter w ith
bacitracin solution , an d th en w rapping th e cath eter in a bacitracin soaked lap spon ge un t il th e
tim e to close th e abdom en
3. if th e periton itis w as di use or if th e sh un t cath eter is believed to h ave been con tam in ated, an
option is to extern alize th e distal cath eter, preferably on ce th e pat ien t h as stabilized from th e
periton it is (afebrile, stable vital sign s, n orm al W BC)
a) extern alization is don e in a m an n er to avoid pulling con tam in ated cath eter up tow ards h opefully sterile port ion s