Cryptococcal Meningoencephalitis

India Ink preparation of CSF showing encapsulated yeast form of cryptococcus.

India Ink preparation of CSF showing encapsulated yeast form of cryptococcus.

Today Dr. Chesteen presented a case of an elderly immunosuppressed woman with history of transplant presenting with a subacute progressive headache and falls found to have cryptococcus meningoencephalitis.

Remember to look for Red Flag Symptoms with headache to guide your next steps.

  • the "worst headache" or abrupts onset "thunderclap"
  • progressive or fundamental change
  • abnormal physical exam or focal neurologic deficts
  • a new headache in:
    • patient less than 5 or greater than 50 years old
    • patient with cancer
    • patient who is immunosuppressed
    • patient who is pregnant
  • headache triggered by exertion, sex or valsalva

One way to thing about headaches or whether they are primary or secondary. Primary headache syndromes include: migraine, tension, and trigeminal cephalgias. Secondary headaches can be post-traumatic, vascular (SAH, ICH, SDH, aneurysm, dissection, arteritis, venous sinus thrombosis, CVA/TIA), mass effect (neoplasm- primary or metastatic, abscess), infectious (meningitis, encephalitis, etc) or other which includes PRES, pseudotumor cerebri, intracranial hypotenion, an medical effects. Remember that immunosuppressive individuals may have more subtle presentations and you often need to have a high degree of suspicion for infections and malignancy.

Cryptococcus meningoencephalitis can occur in immunocompromised individuals with HIV, prolonged steroid use and post-transplanation, It is the third most common fungal infection in solid-organ transplant patients. In HIV seronegative patients, the presentation can be more variable and symptoms present for several months prior to diagnosis. Lumbar puncture is the key to diagnosis. A few key points:

  • the opening pressure MAY be >200mmH20 however, increased intracranial pressure is observed less often in non-HIV patients
  • India Ink stain may demonstrate the encapsulated yeast (75% in HIV + and 50% in HIV negative)
  • cell counts are typically 0-50 in HIV + and 20-200 in HIV negative, mononuculear cells predominate
  • glucose is low and protein often elevated
  • Crytococcal antigen should be checked as it will return much sooner than the CSF culture. In a studyof 4 agglutination assays and 1 ELISA, the sensitivities were 93-100% and specificities 93-98%

For additional informaiton on CSF studies, please see the following by Dr. Alan Hunter.

With regard to treatment of Cryptococcus, remember the importance of the subtype. Cryptococcus neoformans is much more likely to respond to fluconazole than cryptococcus gattii. With Crypto meningoencephalitis, induction antifungal therapy is necessary with a combination of amphotericin B, flucytosine and fluconazole.