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

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

4. 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

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

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

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

8. Cryptococcus in normal host
: 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

9. 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

10. 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

11. Cryptococcal Meningitis treatment in normal host
: 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

12. 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

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

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

15. 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

16. Questions?