Chapter 5-5: Cryptococcal Meningoencephalitis

TEXTBOOK PRESENTATION

Patients typically have a subacute headache, malaise, and fever that develop over days to weeks. Mental status changes may be seen. Importantly, meningismus is often absent due to the host’s inability to mount an inflammatory reaction.

DISEASE HIGHLIGHTS

1. Most common cause of meningoencephalitis in AIDS

2. Encapsulated fungus acquired via inhalation

3. CNS infection due to dissemination of primary infection

4. Usually in patients with CD4TL < 100 cells/mcL

5. Subacute onset over 2–4 weeks

6. Basilar meningitis or meningoencephalitis: classic meningeal symptoms and signs (neck stiffness, photophobia) present in a minority of patients (25–30%)

7. 70% of patients have increased intracranial pressure: > 20 cm H₂O in lateral decubitus position.

   1. Elevated intracranial pressure associated with increased risk of death

   2. Patients with elevated intracranial pressure have worse symptoms (headaches, clouded sensorium).

8. Meningovascular presentation (cerebrovascular accident from arteritis) and cryptococcoma (mass lesion) may be seen.

9. Mortality 6–12%

EVIDENCE-BASED DIAGNOSIS

1. History

   1. Fever: 65–95%

   2. Headache: 73–100%

   3. Median duration of symptoms: 31 days (1–120 days)

2. Physical exam

   1. Stiff neck: 22–27%

   2. Photophobia: 18–22%

   3. Mental status changes: 22%

   4. Focal neurologic signs or seizures: 10%

   5. No CNS signs or symptoms: 14%

Cryptococcal meningitis in AIDS patients is often indolent. Only a minority of patients exhibit meningismus or photophobia. Some patients have only low-grade fever and malaise. A supple neck does not rule out the diagnosis, and a high index of suspicion is required.

3. Laboratory findings

   1. Blood tests

      1. Blood cultures positive in 55% in AIDS, much higher than in other populations with cryptococcal meningitis

      2. Serum cryptococcal antigen (CRAG)

         1. 95–100% sensitive, 96% specific

         2. LR+, 24; LR–, 0.05

         3. Negative serum CRAG makes cryptococcal meningitis unlikely.

         4. A positive serum CRAG may precede clinical cryptococcal meningitis by weeks to months.

   2. LP

      1. Neuroimaging required before LP to rule out mass effect. Mass lesions are often due to concomitant toxoplasmosis or PCL, and only rarely due to cryptococcoma.

      2. A platelet count, prothrombin time, and partial thromboplastin time are performed before LP to rule out a bleeding diathesis, with its risk of spinal epidural hematoma.

      3. LP is required in patients with suspected cryptococcal meningoencephalitis regardless of serum CRAG results.

         1. In patients with positive serum CRAG, LP is necessary to confirm cryptococcal meningitis, measure opening pressure, manage high intracranial pressure, and exclude other diagnoses.

         2. In patients with negative serum CRAG, LP is necessary to evaluate other diagnoses.

      4. Routine CSF findings are often normal or minimally abnormal in patients with cryptococcal meningitis.

         1. Normal glucose, protein, and WBC: 19–30%

         2. Glucose < 50 mg/dL: 64%

         3. Protein > 40 mg/dL: 64%

         4. CSF WBCs > 5 cells/mcL: 35%

         5. Increased opening pressure: 50–75%

      Routine CSF findings in patients with cryptococcal meningitis may be normal. Specific studies (fungal culture, cryptococcal antigen) must be obtained.

      5. Special CSF studies

         1. CSF CRAG: 91–100% sensitive, 93–98% specific

         2. CSF fungal culture: 95–100% sensitive, 100% specific

         3. CSF Gram stain may be positive, and India ink detects encapsulated yeast in 60–80% of cases but is no longer performed routinely.

         4. Cryptococcus...