Older male with
headaches and
confusion
History
• Middle-aged, right handed Caucasian male no home medications,
no PMH
• Three week history of low grade fever and frontal headache
• Diagnosed by PCP as sinus infection and given antibiotics
• With no improvement admitted to OSH
– LP: 73 WBC (73% L), 11 RBC, 44 protein. Viral testing and cultures were
negative. Discharged home one day later ama as he felt better
• Readmitted 5 days later for somnolence and confusion.
• CT head: two new low density lesions. MRI: multiple acute
infarcts in various distributions
• Remote hx of pilonidal cyst removal, smokes 1ppd, no sick
contacts
Further work up at KU
•
Infectious
– West Nile CSF IgM/IgG,
Cryptococcal antigen, Influenza,
Monospot, Enterovirus PCR,
Hepatitis screen, HIV, VZV, HSV
1/2, Syphilis antibody, bacterial,
fungal, viral cultures, T spot
•
Autoimmune
– Rheumatoid factor, C3/C4, ACE, CANCA, P-ANCA, anti-double
strand, myeloperoxidase, Serine
protease, anti SSA, SSB, ANA screen
•
Hypercoagable
–
–
Factor V Leiden in one allele
(heterozygous)
Cardiolipin, protein C & S, antithrombin
III, factor 2 mutation
• LdL 89, A1C 5.6%
• Sed Rate 15, CRP 0.05
• Two LPs with WBC 21-29,
protein 41-49
• Paraneoplastic panel
negative
• No oligoclonal bands, CSF
ACE <4, CSF IgG was
normal
• CSF flow cytometry was
negative x2
Imaging
• Radiology
– IR Arteriogram
• Smooth vessels, no evidence of vasculitis
– MRI Brain w/wo gadolinium
• Patchy areas of subacute ischemia
– PET scan
• Normal
– Transesophageal echocardiogram
• unremarkable
– CT chest
• RLL pulmonary artery clot
• Factor V Leiden heterozygous positive 5-10 fold
increase in venous thrombosis
• Ophthalmology found right eye papilledema but no
known cause
• Discharged home after five days on coumadin, strokes
thought likely to be due to FVL, smoking,
athereosclerosis
Re-admission
• Re-admitted 2 weeks later with new onset imbalance and
left arm and leg weakness
• Found to have new acute infarcts
• Mental status detoriated and transient episodes of
hemiplegia upon awakening
• Episodes of unresponsiveness, rigid, hypertension,
tachycardia and fever. Transferred to ICU and intubated
• Started on AEDs and VEEG monitoring. No epileptiform
discharges. Thought to have autonomic storming
• Eventually had tracheostomy and percutaneous enteral
feeding tube placed
• Repeat Imaging
• Where?
• What?
• Brain biopsy
“Although the changes are not specific or diagnostic of a particular disorder, and
while the current biopsy does not contain an infarct, the vascular changes observed
would be compatible with a vascular-ischemic disorder, such as vasculitis, a leading
clinicoradiological impression. A neoplastic process is not recognized."
•
•
•
•
Pt started on high dose IV steroids, cytoxan
Propanolol for storming
Mental status plateaued
Discharged to L-TACH 6 weeks after admission
CNS VASCULITIS
CNS Vasculitis aka Primary Angiitis of the CNS
(PACNS)
• Inflammation of small and medium sized arteries only
in CNS causing CNS dysfunction
– Unexplained neurologic or psychiatric deficit
– Classic angiographic or histopathologic features
– No evidence of systemic vasculitis
• Difficult to diagnose and study
– Rarity – about 500 cases reported since 1959
– Nonspecific and various presentations
– No useful animal models
Pathology
• Pathologic findings include Langerhans or foreign body
giant cells, necrotizing vasculitis or lymphocytic
vasculitis
• Inflammation causes vessels to become narrowed,
occluded and thrombosed
• More likely to affect blood vessels in cerebral cortex
and leptomeninges more than subcortical regions
• Cause is unknown
– Infection Mycoplasma gallisepticum, VZV, WNV, HIV have
been proposed
Clinical Manifestations
• Suspected when in patients with recurrent strokes with
no identifiable cause or other CNS dysfunction with no
cause
• Male 2:1 predominance
• Mean age is 42 but can occur at any age
• Series of 116 patients presented with
– 83% had decreased cognition, 56% headache, 30% seizure,
14% stroke, 12% cerebral hemorrhage
• Strokes/TIAs occur in 30-50% of patients
Differential
•
•
Reversible cerebral vasoconstriction syndrome (Call-Fleming)
Systemic vasculitis involving the brain
– Behcet’s, polyarteritis nodosa, Wegener’s, Churg-Strauss, cryoglobulinemic vasculitis
•
Connective tissue diseases
– SLE, NAIM, rheumatoid vasculitis, antiphospholipid syndrome
•
Infections
– Varicella zoster, HIV, hepatitis C, CMV,
•
Atherosclerotic disease –
– Premature intracranial, Chronic hypertension
•
•
Demyelinating- MS, ADEM, PML
Embolic disease
– cardiogenic
•
Malignancy
– Intravascular lymphoma
•
Miscellanous
– PRES, sarcoidosis, Susac, CADASIL, MELAS, moyamoya
Testing
•
•
•
•
ESR and CRP- usually normal
Complete infectious and rheumatologic work up
Drugs of abuse screen- cocaine
CSF- abnormal in 80-90% of patients but no specific
abnormalities
– Elevated protein and wbc
– important to rule out other diseases
Imaging
• MRI – used frequently in work up to assess for stroke,
leptomeningeal enchancement, follow progress of
lesions
• Angiography: ectasia and stenosis “beading” usually in
small arteries with involvement of several sites.
– Also has multiple occlusions with sharp cutoffs and
circumferential or eccentric vessel irregularities
– Two series of patients found sensitivity of 60%. Cannot use
negative exam to rule out
• Vessels usually beyond resolution of exam
Differential Diagnosis of
vascular constriction and
ectasia/beading
Vasospasm
Infection
Emboli
Athereosclerosis
Hypercoaguable state
Biopsy
•
•
•
•
Gold standard
Sampling of leptomeninges and underlying cortex
One case series found 25% false negative
Positive – still need to stain for organisms
Treatment
• Initial- with infection excluded
– Glucocorticoids- no trials on route, dose or length of
treatment
• Biopsy confirmed
– Glucocorticoids
– Cyclophosphamide- 600-750mg/m2 qmonth for three to
sixth months
– Once in remission for 3-6 months switch to alternative agents
MMF, Azathioprine and MTX
– Serial MRIs
Conclusion
• PACNS is a difficult disease to identify and treat
• Should be entertained in patients who have new onset
neurologic deficits and multifocal strokes with no other
apparent cause
• Diagnosis is arrived at by exclusion of other causes and
a combination of clinical history, CSF findings,
radiologic and pathologic findings