CENTRAL NERVOUS SYSTEM INFECTIONS
= inflammatory impairments of CNS of infectious origin
Invasion of the CNS:
Blood-borne invasion
- across the blood-brain barrier…..encephalitis
- across the blood-cerebrospinal fluid (CSF) barrier.... meningitis
Direct spread from adjacent structures - sinuses, mastoids
Invasion via peripheral nerves
herpes simplex, varicella-zoster viruses, rabies virus
Naegleria sp. – via olfactory nerves
Pathogenesis:
Classifications:
extent of inflammation:
diffuse x focal
course of disease:
acute x subacute ....chronic
type of inflammation:
purulent x aseptic
pathogen:
bacterial x viral x fungal x parasitic
meningitis – encephalitis – myelitis
(radiculitis – neuritis)
Clinical symptoms:

meningeal syndrom - triad of symptoms:
1) constant and severe headache, aggravated by movement
2) nauzea, vomiting
3) positive meningeal signs:
neck stiffness, Brudzinski I
spine sign, Kernig I, Amos
Lassegue, Kernig II

fever

signs of cerebral dysfunction – declining level of consciousness (somnolence, sopor, coma),
confusion, seizures, palsies, tremor, ataxia, hypersensitivity (photophobia)

signs of increased intracranial pressure and brain stem impairment – coma, hypertension,
bradycardia, n III palsy

petechiae (purpura) in meningococcal disease
Clinical diferencies:
purulent meningitis
aseptic meningitis
symptoms duration:
1 – 2 days
several days, two-phase illness
history:
otitis, sinusitis, head trauma,
recent tick-bite
shunt, immunodeficiency
consciousness impaired:
common and severe, comma
less frequent,mild, somnolence
meningeal signs:
highly positive
mild to moderate, but tremor, ataxia,
nystagmus
brain edema
moderate to severe
mild to moderate
progress
rapid
slow
Cerebrospinal fluid changes during CNS infections
cells per mm3
protein g/L
glucose
mmol/L
0,1 – 0,4
2,2 – 4,2
Purulent
meningitis
0–5
lymphocytes
thousands
mainly neutrophils
Aseptic meningitis
(meningoencephalitis)
hundreds
< 1000 (2000)
mainly lymphocytes
Fungal meningitis
tens-hundreds mainly
mononuclears
Normal
↑↑↑  1
↓↓
pathogen
bacteria
amoebae
↑ 0,4 – 1
↔
viruses
spirochetae
↑↑
↓
fungi
(Cryptococcus)
PURULENT MENINGITIS
Etiology:
bacteria:
predisposing age:
Streptococcus pneumoniae -
any age except for neonates
Haemophilus influenzae type b - 3m – 5y
Neisseria meningitidis
-
1 – 4y, 15 – 19y, any age
Predisposing factors for specific pathogens:
neonatal age – Streptococcus agalactiae (group B), E.coli, other Enterobacteriacae (Klebsiella),
Listeria monocytogenes, Enterococcus sp.
otitis media, mastoiditis, sinusitis – S.pneumoniae, H. influenzae
penetrating head trauma or neurosurgery – S.aureus, S.epidermidis, gram-negative bacilli
closed head trauma (skull-base fr.) - S.pneumoniae
CSF shunt – S.epidermidis, S.aureus, gram-negative b. (Pseudomonas)
immunocompromised host – Listeria monocytogenes, fungi (Cryptococcus)
Mycobacterium tuberculosis
endocarditis, spondylodiscitis – S.aureus
Rare:
Mycobacterium tuberculosis
fungi: Cryptococcus neoformans
parasites: free-living amoebae – Naegleria fowleri, Acanthamoeba , Balamutia mandrilaris
Toxoplasma gondii
Pathogenetic classification:
1. primary meningitis – no preceding focus of purulent inflammation, organisms spread via blood
(N.m., H.i.) or along neural fibres (naegleriae) from mucosal surface, a viral infection may precede
2. secondary meningitis – bacteria spread from pre-existing focus (S.p., S.a., gramnegatives)
Diagnosis
history, clinical signs, neurological examination
CSF test:
cytology, biochemical tests
etiology:
CSF - Gram stain (microscopy), culture, PCR, latex agglutination
blood – culture, PCR, latex agglutination
inflammation markers: ESR, leukocytosis + left-shift, CRP
if papilloedema, focal neurological signs, focus in sinus or mastoid - CT, MRI
Treatment:

Antibiotics - bactericidal, well penetrating HLB:
ceftriaxon, cefotaxim
benzylpenicillin (penicillin G)
chloramphenicol

Corticosteroids – antiinflammatory and antiedema effects: dexamethason 0,15mg/kg q 6h or
0,4mg/kg q12h, for 2 or 4 days, confirmed benefit in haemophilus and pneumococcus meningitis

Treatment of brain edema:
- corticosteroids
- hyperosmolar agents (mannitol)
- strict bed rest, head elevation 30 degrees, sedation

Supportive care: adequate oxygenation, adequate blood pressure (crystaloids, colloids,
catecholamines) to keep sufficient cerebral perfusion pressure and brain O 2 supply
(if severe intracranial hypertension, ICPmonitoring recommended )

Symptomatic therapy: sedatives, anticonvulsants, analgesics, antiemetics, antipyretics

Focus sanation – mastoidectomy, sinus surgery
Complications:
subdural effusion
thrombophlebitis of cerebral vessels and venous sinuses
brain abscess
symptoms: focal neurological signs, fever, impaired consciousness, persisting/worsening CSF
inflammation
Sequelae:
hear imparment - partial or total deafness
cranial nerve paresis
encephalopathy – sleep and memory disturbancies, concentration and learning disabilities
Our strategy:
Clinics: meningeal syndrom + fever = suspected meningitis
Aseptic or purulent meningitis?
History: recent tick-bite, recurrent otitis media, head trauma, immunosupression, physical overload…
Symptoms duration:
hours = primary purulent meningitis
days = aseptic meningitis/meningoencephalitis
secondary purulent meningitis
If history, clinical signs (and elevated inflammatory markers) evoke suspicion of purulent meningitis, it
is necessary to confirm or exclude this dg., as the treatment has to start within 30 minutes after
admission!!!
Emergent:
fundoscopy
lumbar puncture + CSF tests:
leukocytes, protein, glucose, lactate
Gram-stain immediately, if available
latexagglutination
culture + PCR
blood culture
Treatment:
1. Dexamethason i.v. 16mg first dose, continue 8mg q6h, next dosage depends on the course
2. Antibiotic – start empirically, consider the most likely pathogens:
ceftriaxon 100mg/kg/24h up to 6g in 1-2doses, cefotaxim 200mg/kg/24h up to 12-16g in 4doses,
chloramphenicol 12g/24h in 3doses, meningococcus – benzylpenicillin 20milU/24h in 4doses
(neonate – different clinics, different pathogens, different treatment!!)
3. Manitol 20% 100-150ml q6h for 10-15min (not immediately after ATB)
+ necessary supportive care and symptomatic treatment
BRAIN ABSCESS
Diagnosis:

if abscess suspected, LP is contraindicated (CSF test rarely helpful)

CT – ring-enhancing lesion with surrounding edema

blood culture, other sites cultures
Treatment:

small abscess – conservative, large – surgery

CEF III + MET or CMP, guided by microbiological results

anticonvulsants, mannitol, (corticosteroids decrease edema, but may delay resolution)

surgery – aspiration or open drainage
MENINGITIS IN NEONATES
Etiology: group B streptococci, E.coli, other aerobic gram-negative bacilli (Klebsiella), Listeria
monocytogenes, Enterococcus sp.
Clinical signs – nonspecific:
poor feeding
lethargy or irritability, strange cry (high-pitched voice)
hypothermia rather than fever
hypotonus
vomiting
convulsions
bulging fontanelle
neck stiffness, opisthotonus
Treatment:
cefotaxim 200mg/kg/24h + ampicillin 400mg/kg/24h
alternative: ampicillin + gentamicin 5mg/kg/24h
Sequelae:
hydrocephalus
mental and motoric retardation
deafness, blindness
convulsions (epilepsy)
Neisseria meningitidis INFECTION
13 serogroups, A,B,C,Y, W135 – 95% of cases
Clinical forms:
1. superficial infection: pharyngitis, conjunctivitis
2. invasive disease:
meningitis, sepsis, mixed form
Meningococcal invasive disease:
History:
physical overload, sudden onset, nonspecific flu-like symptoms – fever, malaise, in meningitis inreasing
headache, vomiting and altered consciousness, in sepsis general dyscomfort, myalgia, diarhea, in both
rash - early maculopapular, later haemorhagic – petechiae, ecchymoses
Clinics:
sepsis – fever, haemorhagic rash, septic shock (tachycardia, hypotension, tachypnea, cold acra,
cyanosis, oliguria), altered mental status (restlessness, confusion)
meningitis – fever, meningeal syndrom,decreased consciousness
mixed form – more or less like sepsis plus signs of meningitis
Diagnosis:
blood tests:
blood count + differential leuko
acid-base balance, G, Na ,K ,Cl , urea, creatinine, lactate, protein, albumin, bilirubin, AST, ALT, CRP
coagulation – aPTT, PT (Quick), AT III, DD, fibrinogen
blood culture, PCR
CSF tests (if LP indicated):
WBC, biochemical – P, G, L, Cl –
microscopy, culture, (latexagglutination), PCR
Treatment:
1. treatment of sepsis and septic shock
2. treament of meningitis
ATB: cefotaxim, ceftriaxon
benzylpenicillin
chloramphenicol
Complications:
aseptic arthritis
serositis – pericarditis (perimyocarditis), pleuritis
neurological sequelae – deafness, other cranial nerve lesions
peripheral gangrene (purpura fulminans), loss of digits, extremities
fulminating sepsis with septic shock and MODS (multiple organ system failure = DIC, ARDS, cardiac
and circulatory failure, ARF, GIT, liver, encefalopathy)
autopsy dg.: Waterhouse-Friedrichsen syndrome – haemorhagic necrosis of adrenal glands
Prevention:
vaccination - indicated for persons at particular risk: military recruits, local epidemic, asplenic
patients, complement deficiences esp. C5-C9, travellers to the African meningitis belt and pilgrims
visiting Mecca
- polysacharide group A,C,Y,W135 vaccines
- conjugate C vaccines – capsular polysacharide conjugated with immunogenic proteins such as
diphtheria or tetanus toxoids
chemoprophylaxis - household and kissing-contacts in 10 days preceding disease: oral penicilin or cef
I, macrolide, rifampicin, ciprofloxacin
ASEPTIC MENINGITIS, MENINGOENCEPHALITIS
Etiology:
viruses:
enteroviruses: Coxsackie, ECHO
arboviruses: alphaviruses, flaviviruses - tick-borne Central European encephalitis, Russian SpringSummer encephalitis, louping-ill in Scotland, Eastern and Western equine, St.Louis encephalitis,
Japanese B encephalitis
respiratory viruses: parainfluenza, influenza, adenoviruses, RSV
herpesviruses: HSV 1,2, VZV, CMV, EBV, HHV6
viruses occuring very rarely due to vaccination: polio, mumps, measles, rubella, rabies virus
lymphocytic choriomeningitis virus
bacteria: spirochetae: Borrelia (Lyme borreliosis), Leptospira: all species, Treponema pallidum (lues)
Mycoplasma pneumoniae
rickettsiae: Coxiella burneti (Q-fever)
Diagnosis:
history, clinical symptoms
CSF test: cytology, biochem tests
etiology:
serology - TBE, LB, leptospirosis, respiratory viruses
PCR - HSV DNA in CSF, LB DNA in blood, CSF
virus isolation – CSF, nasopharynx, stool (enteroviruses)
other screening tests (blood count, CRP, ions, kidney and liver tests)
Treatment:
symptomatic therapy:
bed rest
antipyretics, analgesics, antiemetics
treatment of brain edema
supportive care
causative therapy: HSV encephalitis, Lyme borreliosis
Herpes Simplex Virus Encephalitis
Etiology:
HSV 1, 2
Pathology: focal necrotizing inflammation of brain tissue, often haemorrhagic, uni/bilateral, temporal
and frontal lobes
Clinics:
the onset abrupt or insidious
symptoms: fever, headache
focal signs – speech disturbancies (aphasia, dysphasia), paresthesia, convulsions, behaviour
abnormalities, personality changes
progressive loss of consciousness…coma
Diagnosis:
emergent CT or MRI !!! normal CT scan does not exclude dg!!!
EEG
CSF test – aseptic inflammation, erythrocytes
PCR - HSV DNA in CSF
(brain biopsy for histology and viral culture)
serology – not sufficiently sensitive, late dg.
Treatment:
acyclovir 10 mg/kg q 8h i.v. 21-28days
symptomatic
supportive care
Fungal meningitis
Cryptococcus neoformans
An ubiquitous agent, infection by inhalation.
Disseminated infection in patients with lymphoma, AIDS or on steroid therapy.
Clinics: insidious development of symptoms
headache, irritability, memory and behavior disturbances
focal neurological signs
fever and meningeal signs may be missing
Laboratory:
CSF – lymphocytes,  protein,  glucose
CSF stained with India ink for cryptococcus capsule
cryptococcus antigen in CSF and blood
culture - CSF, blood, sputum, urine
Treatment: amphotericin B + 5-fluorocytosin 6-10 weeks
AIDS pts – prophylaxis with amfo B o.w. + fluconazol daily
Amoebic meningoencephalitis
Free-living amoebae – Naegleria fowleri
By 1997 totally 180 cases, 7 survived. Distributed worldwide, most often in swimming-pool water.
Clinics and CSF signs similar to purulent meningitis
Laboratory:
microscopical detection of amoebae in fresh CSF
culture
Treatment: Amphotericin B + Rifampicin + Miconazol i.v.+i.th.
Granulomatous encephalitis - Acanthamoeba, Balamutia mandrilaris
Polyradiculoneuritis – Guillan-Barré syndrome
Acute demyelinating disease.
Etiology not clear, immunopathological response to infection, some evidence for: Campylobacter
jejuni, Mycoplasma pn., Borrelia burg., CMV, EBV, HIV, rare complication of chickenpox, measles,
influenza A vaccine.
Clinics: 1-2 weeks after upper resp. tract or diarheal illness
symmetrical sensory and motor loss beginning on distal parts of the limbs (“glove and stocking”)
ranging from weakness to plegia, slowly ascends to trunk and respiratory muscles, bulbar palsy
Dif.dg.: poliomyelitis, diphtheric polyneuritis, transversal myelitis
Dg.:
CSF - proteocytological dissociation – protein, normal leukocyte count and glucose
Treatment:
plasmapheresis or high-dose intravenous immunoglobulins
supportive care
long-term rehabilitation