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Created Jan 2009 by Charles Gomersall
Cryptococcal meningitis
Epidemiology
- common in AIDS patients particularly in SE Asia and Africa
- in areas with high prevalence of AIDS cryptococcus may be the most
common cause of community acquired meningitis
- associated with profound immunosuppression (CD4 <100 cells/μl)
- in non-HIV patients common predisposing factors are:
- steroids
- organ transplant
- chronic respiratory, renal or hepatic failure
- malignancy
- rheumatological disease
- no predisposing factor in 22% of non-HIV patients
- infection of apparently immunocompetent patients is a feature of
Cryptococcus gattii disease
Mycology
- Two important species:
- Cryptococcus neoformans
- Cryptococcus gattii (previously considered to be a variant of
C. neoformans)
Pathogenesis
- Primary pulmonary infection (frequently asymptomatic) followed by
extrapulmonary dissemination
- Dissemination may occur acutely or after a period of latency. This may
happen after the patient is immunosuppressed.
Clinical features
- May be associated with features of pneumonia
- More appropriately termed meningoencephalitis as brain parenchyma is
also involved
- Onset over several weeks:
- headache
- fever
- malaise
- altered mental status
- Clinical signs often absent but may include:
- meningism
- papilloedema
- cranial nerve palsies
- other focal neurological deficits
- depressed consciousness
- Presentation tends to be more acute in AIDS patients
Complications
- Common
- ICP in the absence of hydrocephalus may
cause profound hearing or visual loss
- Cognitive impairment and gait ataxia due to obstructive hydrocephalus
(less common)
Investigations
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AIDS patients |
Non-HIV patients |
| CXR |
Alveolar and interstitial infiltrates most common |
Single or multiple pulmonary nodules most common |
| CT brain |
May be normal or reveal meningeal enhancement, single or
multiple nodules, cerebral oedema or hydrocephalus. Often cortical
atrophy in AIDS patients |
| MRI |
May be multiple enhancing nodules within brain
parenchyma, meninges, basal ganglia and midbrain |
| CSF microscopy |
Organisms seen on India ink stain in 70-90% but WCC may be normal |
May be negative for organisms in 50% but WCC raised (predominantly
lymphocytes) |
| CSF biochemistry |
Protein usually raised. Glucose may be low |
| CSF or serum cryptococcal
antigen |
High sensitivity (>90%) and specificity |
Less sensitive |
Treatment
- 1st 2 weeks (4-6 weeks for C. gattii meningitis): amphotericin B
0.7-1 mg/kg/day plus flucytosine 100 mg/kg/day PO or IV
- Next 8 weeks: fluconazole 400 mg/day
- Thereafter until administration of anti-retroviral therapy (AIDS
patients): fluconazole 200 mg/day
- discontinuation of anti-fungal therapy before initiation of
anti-retroviral therapy associated with a worse outcome
Complications
intracranial pressure
- may result from obstruction to CSF outflow via arachnoid villi or
classical obstructive hydrocephalus
- if hydrocephalus, marked cerebral oedema and space-occupying lesion have
been excluded daily lumbar punctures should be performed to achieve a
closing pressure ≤20 cmH2O or ≤50%
of opening pressure. If this fails to control intracranial pressure consider
temporary lumbar drain
- mannitol, acetazolamide and steroids
ineffective
- external ventricular drain for hydrocephalus
Further reading
Bicanic T,
Harrison TS. Cryptococcal meningitis. Br Med Bull, 2005; 72(1):99-118
© Charles Gomersall, Jan 2009
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