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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Related Studies

Ontology: Meningitis, Cryptococcal (C0085436)

Definition (MSH) Meningeal inflammation produced by CRYPTOCOCCUS NEOFORMANS, an encapsulated yeast that tends to infect individuals with ACQUIRED IMMUNODEFICIENCY SYNDROME and other immunocompromised states. The organism enters the body through the respiratory tract, but symptomatic infections are usually limited to the lungs and nervous system. The organism may also produce parenchymal brain lesions (torulomas). Clinically, the course is subacute and may feature HEADACHE; NAUSEA; PHOTOPHOBIA; focal neurologic deficits; SEIZURES; cranial neuropathies; and HYDROCEPHALUS. (From Adams et al., Principles of Neurology, 6th ed, pp721-2)
Concepts Disease or Syndrome (T047)
MSH D016919
ICD9 321.0
ICD10 B45.1
SnomedCT 187092002, 14232007
English Cryptococcal Meningitides, Meningitides, Cryptococcal, Meningitis, Cryptococcal, Cryptococcal Meningitis, CRYPTOCOCCAL MENINGITIS, cryptococcal meningitis, cryptococcal meningitis (diagnosis), Meningitis cryptococcal, Cryptococcal neoformans meningitis, Meningitis torula, Meningitis, Cryptococcal [Disease/Finding], crypto meningitis, meningitis cryptococcal, Cryptococcal meningitis, Meningitis due to cryptococcus, Cryptococcal meningitis (disorder), Meningitis due to Cryptococcus
Italian Meningite criptococcica, Meningite da Criptococcus neoformans, Meningite torula, Meningite da criptococco, Meningite da Cryptococcus neoformans
Dutch Cryptococcus neoformans meningitis, cryptokokkenmeningitis, Torula-meningitis, cryptokokkenhersenvliesontsteking, Cryptokokkenmeningitis, Meningitis, cryptokokken-
French Méningite à Cryptococcus, Méningite à Cryptococcus neoformans, Méningite à torula, Méningite à cryptocoque, Méningite cryptococcique, Méningite à cryptocoques
German Cryptococcus neoformans Meninigitis, Torulameningitis, Meningitis durch Kryptokokken, Meningitis, Kryptokokken-, Kryptokokkenmeningitis
Portuguese Meningite por Cryptococcus neoformans, Meningite a torula, Meningite por criptococo, Meningite criptocócica, Meningite Criptocócica
Spanish Meningitis torula, Meningitis por Cryptococcus neoformans, meningitis criptocócica, meningitis por Cryptococcus, meningitis por criptococos (trastorno), meningitis por criptococos, Meningitis criptocócica, Meningitis Criptocócica
Japanese クリプトコッカス・ネオフォルマンス性髄膜炎, 酵母菌性髄膜炎, ｸﾘﾌﾟﾄｺｯｶｽｾｲｽﾞｲﾏｸｴﾝ, ｸﾘﾌﾟﾄｺｯｶｽﾈｵﾌｫﾙﾏﾝｽｾｲｽﾞｲﾏｸｴﾝ, ｺｳﾎﾞｷﾝｾｲｽﾞｲﾏｸｴﾝ, クリプトコッカス性髄膜炎, 髄膜炎-クリプトコッカス, クリプトコッカス髄膜炎
Swedish Hjärnhinneinflammation, kryptokock
Finnish Kryptokokin aiheuttama aivokalvotulehdus
Russian MENINGIT KRIPTOKOKKOVYI, МЕНИНГИТ КРИПТОКОККОВЫЙ
Czech Torulózní meningitida, Kryptokoková meningitida, Meningitida způsobená kvasinkou Cryptococcus neoformans, meningitida kryptokoková, kryptokoková meningitis, kryptokoková meningitida
Polish Zapalenie opon mózgowych kryptokokowe, Zapalenie opon kryptokokowe
Hungarian Cryptococcalis meningitis, Cryptococcus neoformans meningitis, cryptococcus meningitis, Torula meningitis
Norwegian Meningitt ved kryptokokkose, Kryptokokkmeningitt, Cryptococcus-meningitt
Derived from the NIH UMLS (Unified Medical Language System)

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