Cryptococcal Meningoencephalitis Nicole Wilde MD, MPH 7/10/09

Cryptococcal Meningoencephalitis Most typical manifestation Underlying brain parenchyma involved Important OI in immunosuppressed pts

Pathogenesis C. neoformans inhalation Disseminates hematogenously Localizes in CNS CSF may be good growth medium Production of mannitol may cause edema and inhibit phagocyte function Dopamine may promote virulence by serving as a substrate for melanin production

Epidemiology Majority are immunocompromised 157 cases, 30% had no apparent underlying condition HIV, steroid tx, organ transplant, cancer, sarcoid, liver failure

Presentation Symptoms for several months Fever in only 50% HA, lethargy, coma, MS changes, fever Develop over 2-4 weeks

Cryptococcus in normal host From 1956-1962: 40 patients age 12 to 66 50% with comorbidities + CSF: 97% + UCx: 37% + BCx: 25% 20/35 had + india ink NEJM 1964; 270: 59

Cryptococcus in normal host 1957-1969: 31 patients: age 22 to 71 Sx: HA, fever, wt loss, mental aberration Signs: fever, AMS, meningeal signs + CSF cx: 30/31 19/27 with + india ink Annals 1969; 71: 1079

Diagnosis Difficult due to subacute onset LP necessary Opening pressure >200mmH2O India ink 50-75% Cryptococcal ag testing Low WBC’s, low glucose, elevated protein Culture from CSF 3-5 days

Treatment Uniformly fatal if untreated Induction, consolidation and maintenance Amphotericin B 0.7mg/kd/d, Flucytosine 100mg/kg per day, 2 weeks Fluconazole 400mg day for 8 weeks Fluconazole 200mg day 1-12 months Increased intracranial pressure Lp’s and lumbar shunt

Cryptococcal Meningitis treatment in normal host 1956-62: 40 patients 36/40 Rx with AmphoB (? dose) 31 improved, 5 died 17/31 relapse free 11 relapsed, 3 died Disseminated crypto died ↑ relapse rate with protein < 100 or cells < 70 NEJM 1964; 270: 59

Cryptococcal treatment in normal host 66 patients randomized to either 10 weeks AmphoB (0.4mg/kg/d) or 6 weeks AmphoB (0.3) + flucytosine (37.5m/k) 51 adhered to protocol, 27 with ampho alone and 24 with combination Combo tx w/improvement/cure: 16/24 v. 11/27 => fewer relapses, quicker CSF sterilization and less nephrotoxicity with combo therapy Trial stopped early due to clear superiority of combo therapy NEJM 1979; 301: 126

Cryptococcal Meningitis treatment in normal host 1957-69: 31 patients All Rx with IV +/- IT AmphoB 12/31 died Annals 1969; 71: 1079

Prognosis Underlying illness Malignancy had shorter median survival when compared to HIV Relapse vs IRIS Most are cured

Prognostic factors 1956-73: 111 patients (most receiving monotherapy) Death or relapse associated with: positive india ink high OP low glucose < 20 cells extraneural + cx ongoing steroid therapy Annals 1974; 80: 176

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