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Fungal meningitis

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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

  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


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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