Meningitis

Inflammatory disease of the leptomeninges (tissues surrounding the brain and spinal cord)
à defined by an abn number of white blood cells in the CSF
• Bacterial meningitis reflects infection of the arachnoid mater + CSF in subarachnoid
space and the cerebral ventricles
• Dura mata involvement = pachymeningitis
• Disease course:
o Acute
o Subacute (development over days à few wks)
o Chronic (reactive CSF >4wks with no clinical improvement)
o Recurrent (Sx of CSF pleocytosis à Sx-free interval with normalisation of
CSF à recurrence after >2wks)

Pathways of infection: most colonise nasopharynx or upper airway à enter CNS via
1. Haematogenous spread
2. Contiguous spread of ear, nose or throat infection
3. Retrograde via or along peripheral / cranial nn. (rabies most common)

Aetiology
• Otitis media (drainage of pus from external ear canal)
• Sinusitis (eyelid swelling or fluid-level in sinuses)
• CSF leak after head trauma or neurosurgery
• Maternal group B streptococcal infection during birth
• Sepsis (pneumonia, lung abscess, BEct, UTI)

Risk factors
• Immunocompromise (HIV, asplenia, heavy alcohol use disorder, chronic illness,
cancer, sickle cell anaemia, old age, pregnancy)
• Crowded occupational or living conditions
• Close contact with an infected person

S pneumoniae predisposing conditions:

• Pneumonia
• Sinusitis
• Endocarditis
• Old or recent head trauma
• CSF leak
• Splenectomy
• Alcoholism

1
Other causes
Viral meningitis: often associated with encephalitis (meningoencephalitis)
• Enteroviruses (especially coxackievirus and echovirus)
• Herpesviruses: HSV (limbic meningitis = HSV2 and encephalitis
by HSV1), CMV, EBV, VZV

Fungal meningitis
• Coccidioides
• Candida spp.
• Aspergillus spp.

Parasitic meningitis
• Helminths (e.g., Echinococcus spp.)
• Protozoa (e.g., Naegleria fowleri)

Non-infectious meningitis (Aseptic)

• Infectious – recurrent lymphocytic meningitis (Mollaret’s meningitis)
• Malignancy – paraneoplastic snd, meningeal leukaemia
• Autoimmune inflammatory – sarcoidosis, SLE
• Medication (NSAIDs, MTX, lamotrigine)

Causes of meningitis in immunocompromised individuals

• Bacterial – Deficiency in various immune functions can predispose to certain types
of meningitis (↑ risk of recurrent bacterial meningitis)
o Defects in humoral immunity (including splenectomy): encapsulated
bacteria (N. meningitidis, S. pneumoniae, H. influenzae, etc.)
o Defects in cell-mediated immunity (e.g., in HIV, drug-
induced immunosuppression): M. tuberculosis, L. monocytogenes
• Viral – ↑ with cell-mediated immune deficiencies (HIV infection)
o Herpesviruses: CMV, EBV, VZV, and HSV-6
o HIV
• Fungal: ↑ with cell-mediated immune deficiencies
o Cryptococcus spp.
o Candida spp.
o Histoplasma capsulatum
o Aspergillus spp.
• Protozoal: Toxoplasma gondii

Clinical Presentation
Classic triad: fever, headache, and neck stiffness (only seen in 40%)
Other signs and Sx:
• Altered mental status
• Photophobia
• Nausea, vomiting
• Malaise
• Seizures, delirium
• Possibly cranial nerve palsies
• In the case of N. meningitidis
o Myalgia, petechial or purpuric rash (non-blanchable – do Tumbler test)
o Possibly Waterhouse-Friderichsen syndrome
• Common symptoms of viral meningitis
o Prodrome with flu-like symptoms (low-grade fever, malaise, fatigue, myalgia,
URTI symptoms, pharyngitis, herpangina, and/or rash)

2
Physical Examination
• Signs of meningeal irritation
o Neck stiffness
o Kernig sign
o Brudzinski sign
• Systemic signs of inflammation
o Fever
o Hypotension
o Tachycardia
• Signs of increased intracranial pressure: papilledema (< 5% of cases)
• Signs of underlying infections
o Bulging and redness of tympanic membrane: acute otitis media
o Skin manifestations
§ Cutaneous petechiae in meningococcal meningitis: suggestive
of meningococcaemia
§ Maculopapular rash in some viral meningitis (West Nile
virus, enterovirus)
§ Non-blanching rash: should raise suspicion for meningococcal
meningitis or Rocky Mountain spotted fever

Diagnosis
1. Initial workup:
• Blood cultures before ABx
• Bloods: peripheral WCC + diff, s-glu, CRP or PCT
• u-MCS

2. Neuroimaging – CTB
Not usually necessary for dx – only considered when at risk of Cx (FAILS)
- FND
- Altered mental status
- Immunocompromised, raised ICP
- Lesions in brain (SOL) or on skin at site
- Seizures

CT findings that contraindicate LP: crowding of cisterns, herniation, obstructive

hydrocephalus, post. fossa mass, focal lesion

3. LP for CSF

Additional tests
- Microbiological stains:
§ Acid-fast (TB
§ India ink (crypto)
§ Giemsa (toxo)
- PCR (viral suptypes, TB = GeneXp)
- Capsulated Ag (crypto)

3
Treatment
• Empiric ABx – Ceftriaxone (Rocephine) 2g IV bd (alternatives = vanco, imipenem,
meropenem, ampicillin for Listeria)

• Definitive ABx
o Pneumococcal – ceftriaxone 2g IVI bd for 10d
o Meningococcal – ceftriaxone 2g IVI bd for 7d
§ Close-contact prophylaxis: cipro 500mg po single dose
o H. influenzae – ampicillin + ceftriaxone
o Gram negatives – cefepime, ceftazidime (community acquired) or
meropenem (health-care associated) 2g IVI for 21d
o Listeria – ampicillin 3g IVI qid for 21d + gentamycin

• Corticosteroids for suspected or proven S. pneumoniae, H. influenzae meningitis

o Dexamethasone use before ABx decreases local + systemic inflammation
associated with meningitis
o Discontinue if other causative agent identified

Chronic Meningitis
Most commonly TB, cryptococcal, mucormycosis, norcardia

Characteristics
• Subacute course over days, to a week or longer
• Febrile illness
• Neck stiffness (nuchal rigidity)
• Headache
• ± delirium, cognitive impairment, personality change
• Focal neurological deficits (CN fallout, hemiplegia, stroke-like snds d/t meningitic
endarteritis or vasculitis)
• CSF findings:
o Polymorphs <500/mm3
o Protein >1g/L
o Glucose <2.4mmol/L (or CSF:s-glu <50%)
o Raised pressure
• Peripheral WCC <10 000/mm3
• Suspicion of associated cause: crypto in HIV pts, TB, malignant meningitis

4
Tuberculous Meningitis (Mycobacterium tuberculosis)
Incubation period: approximately 2–8 weeks

Clinical course
• Subacute course over several weeks or months with miliary TB or subpial tubercle
rupture
• Gradual manifestation with intermittent fever

Clinical features
• Focal neurological deficits (e.g. hemiparesis) due to haematogenous dissemination
of cranial arteritis
• Cranial nerve deficits
o Most commonly seen in basal meningitis
o Predominantly involves the facial nerve and oculomotor nerve

Diagnostics
• CSF: acid-fast bacilli with gram stain, geneXp PCR, ADA >6units/L
• CSF Culture is gold standard for diagnosis but may take weeks
• CT/MRI findings: possible hydrocephalus, basilar meningeal
thickening, tuberculomas, oedema, infarcts

Complications
• Communicating (malabsorptive) hydrocephalus (deposition of exudate in membranes
of basal cistern and ventricles)
• Pituitary gland insufficiency

Treatment
• 4 drug regimen: Isoniazid (INH), Rifampicin (RIF), pyrazinamide and ethambutol or
streptomycin (SM) à if clinical improvement after 2mo = INH + RIF only for 10mo
• Pyridoxine 25-50mg po dly with INH use (prevent neuropathy)
• Monitor vision with ethambutol use (toxic optic neuropathy)
• Liver enzyme monitoring with INH, RIF, pyrazinamide (hepatotoxicity)

Further management
• CSF re-examined to assess Rx efficacy + drug levels
• Neuroimaging 2-3mo after Rx initiation, then at 3-6mo intervals thereafter to verify
lesion improvement
• Tuberculomas = may need 2yr Rx course

5
Cryptococcal Meningitis Cryptococcus neoformans (encapsulated yeast)
Risk factors
• HIV esp. CD4 <200 (oral thrush, widespread LAD)
• Previous HZV
• Steroid Rx, underlying lymphoma, sarcoidosis

Clinical course: subacute onset with (low) fever, fatigue, and headaches

Diagnostics
• Cryptococcal antigen testing of CSF and serum
o Highly specific and sensitive
o Typically performed via latex agglutination or enzyme immunoassay
• CSF culture (Sabouraud agar) – gold standard
• CSF gram staining: India Ink (clear halo), mucicarmine (red inner capsule)

• CT/MRI: gelatinous pseudocysts (soap bubble appearance)

o Crypto complications:
§ Hydrocephalus
§ Virchow Robin space (region of basal ganglia) collections
§ Basal ganglia infarctions
§ Cryptococcomas (granuloma)
§ Early cerebral atrophy with longstanding HIV

Treatment
• Test dose Amphotericin B 1mg IVI stat
• Induction phase (2 weeks):
o Amphotericin B 1mg/kg in 1L 5% dextrose water IV over 4hrs daily
o Fluconazole 1200mg po dly
o Electrolyte Mx
+
§ Slow K 2tab po bd (if s-K <3.3mmol/L à 40mmol/L KCl in 200mL NS
IVI at 50mL/hr)
§ Slow Mag 2tab po dly
• Consolidation phase (2 months):
o Fluconazole 800mg po daily
• Maintenance (lifelong):
o Fluconazole 200mg po dly
**guidelines advise stopping after 1yr with CD4 >200 measured 6mo apart
• Fluid management
o Prehydration before Amphotericin B dose à 1L NS + 2ommol/L KCl IVI over
2hrs
o Maintenance fluid 1L crystalloid IVI 6hrly
• Routine management:
o CMP, UKE every 2d (daily UKE if abn)
o Baseline + wkly Hb, LFT
o Monitor fluid input + output
o ART therapy should be delayed for at least 2 weeks after initiation
of antifungal therapy

Treatment S/E
• Amphotericin B: phlebitis, nephrotoxic, hypoK, anaphylaxis, BM suppression (↓ Hb)
• Fluconazole: hepatitis

6
Complications of Meningitis
• H: hydrocephalus
• A: abscess / arteritis
• C: cerebritis / cranial nerve lesion
• T: thrombosis
• I: infarct
• V: ventriculitis / vasculopathy
• E: extra-axial collection: empyema and hygroma
• S: SIADH (fluid restrict to Rx) / Sensorineural hearing loss / Spasticity