Cryptococcal Meningitis

Aka: Cryptococcal Meningitis, Cryptococcal Meningoencephalitis

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II. Etiology

  1. Cryptococcus neoformans (fungal infection)

III. Epidemiology

  1. Incidence
    1. United States: 2-7 cases per 1000 AIDS patients
    2. Worldwide: 1 Million cases annually (especially sub-Sahara Africa)

IV. Risk Factors

  1. Consider in all at risk and known HIV patients with Headache
  2. Advanced HIV (AIDS)
    1. CD4 < 50 to 100 cells per mm3 or
    2. AIDS-Defining Illness

V. Symptoms

  1. Insidious onset
    1. Typically starts as occult, asymptomatic infection in 50% of cases
    2. Symptoms are often nonspecific at onset
  2. Headache (91%)
  3. Weight Loss (90%)
  4. Fever (52%)
  5. Altered Level of Consciousness or confusion

VI. Signs

  1. Fever (91%)
  2. Muscle wasting (90%)
  3. Motor weakness (40%)
  4. Cranial Nerve palsy (29%)
    1. Hearing Loss
    2. Vision Loss (Optic Neuritis related)
      1. May progress within 12 hours following onset of Optic Neuritis
  5. Organ Involvement
    1. Neurologic involvement (Meningitis) (85-90%)
    2. Lung or skin involvement (25%)

VII. Precautions

  1. Do not rely on lack of meningismus (meningeal signs) to exclude Cryptococcal Meningitis
    1. Meningeal signs are only present in one quarter of Cryptococcal Meninigitis

VIII. Evaluation

  1. Headache in HIV

IX. Labs

  1. Blood Cultures positive (>75%)
  2. Serum cryptococcal Antigen positive (98%)
    1. High titer (>1024:1)
  3. CSF Exam
    1. Glucose usually normal
    2. Protein mildly elevated
    3. White Blood Cell Count usually less than 20
    4. India Ink stain usually shows organism
    5. Cryptococcal Ag test (>95% sensitive, specific)
    6. Increased CSF Opening Pressure
      1. Typically CSF Opening Pressure >350 mm H2O
      2. Results from high fungal burden in CNS interfering with CSF reabsorption
      3. Risk of obstructrive Hydrocephalus presenting as cognitive deficit and ataxic gait
      4. High pressure responsible for adverse sequelae
      5. Treat with serial LPs, lumbar drain or VP Shunt
      6. Differential diagnosis (other causes of increased CSF Opening Pressure in HIV)
        1. Toxoplasma Encephalitis
        2. CNS Lymphoma
        3. Tuberculous Meningitis

X. Management: Acute (CNS and extraneural involvement)

  1. Amphotericin B (High dose): 0.7 mg/kg/day
    1. Flucytosine (100 mg/kg/day) may be added
  2. Fluconazole (200 to 400 mg/day) Indications
    1. Normal Mental Status at baseline
    2. Time to sterilization of CSF is slower
    3. Prefer amphotericin B (short course first)
  3. Avoid harmful measures
    1. Avoid Dexamethasone
      1. Associated with increased mortality
      2. Beardsley (2016) N Engl J Med 374(6): 542-4 +PMID: 26863355 [PubMed]

XI. Management: Prophylaxis

  1. General
    1. Relapse occurs in >80% if no suppression given
  2. Fluconazole 200 mg/day

XII. Prognosis

  1. Uniformly fatal if left untreated
  2. Overall Mortality: 12%

XIII. References

  1. Perkins (2013) Crit Dec Emerg Med 27(3): 2-9
  2. Friedmann (1995) Arch Intern Med 155(20): 2231-7 [PubMed]
  3. Mwaba (2001) Postgrad Med J 77(814): 769-73 [PubMed]

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