Case Presentation:
A 44 yo male, well except for diabetes and hypertension, presented to an outside hospital with 2‐3 weeks of headache and gait instability. Head CT was normal, and he was sent home. The HA persisted for the next week and he began to experience photophobia and confusion. He again went to an OSH where repeat brain imaging showed diffuse lesions, some contrast‐enhancing, as well as nodular leptomeningeal enhancement involving bilateral cerebellar hemispheres. A lumbar puncture was performed which revealed an opening pressure of 18 cm and an elevated white cell count of 625 cells/mcl with a lymphocytic predominance. Glucose was low at 12 mg/dL and protein was elevated at 217 mg/dL. Gram stain and bacterial culture were negative, and fungal studies were send‐out labs to another facility. Further history revealed that the patient lives in rural Missouri but travels around the country for work, often renovating old restaurants. He denied any tobacco, alcohol, illicit drug use or other unusual exposures.
The patient was started on broad‐spectrum antibiotics including amphotericin B and transferred to our facility. On arrival he complained of HA and was agitated. A repeat lumbar puncture was delayed due to the patient’s agitation, but a serum Cryptococcal antigen was positive at a titer of 1:32. Thus a presumptive diagnosis of Cryptococcal meningitis was made, and antifungals were continued. A lumbar puncture was performed on hospital day #3; encapsulated yeast were seen and Cryptococcal antigen titer was positive at 1:4. The opening pressure was elevated at 21 cm. During the next several days the patient’s mental status fluxuated and he continued to have HA and unsteady gait. Repeat lumbar punctures with removal of CSF were performed with the highest opening pressure being 33. Given his need for frequent spinal taps, Neurosurgery was consulted and placed a lumbar drain for continued treatment of elevated intracranial pressure.
Discussion:
Cryptococcus Neoformans is an encapsulated yeast which is ubiquitous in soil and reproduces in nature and in the human host by budding. Cryptococcus most frequently infects the lungs and CNS, with meningoencephalitis being the most common manifestation. Cryptococcal meningoencephalitis is rare, occuring in about 1 million people yearly worldwide. The vast majority of these have HIV infection. Other causes of immunosuppression can lead to cryptococcal infection, though 30 percent of HIV‐negative patients have no identifiable risk factors for immunosuppression. In HIV‐positive patients, the lumbar puncture usually reveals an elevated opening pressure and a relatively normal cell count; HIV‐negative patients tend to have lower opening pressure and a higher cell count. Though cultures are positive in most patients, cryptococcal antigen testing provides a very sensitive and specific marker for speedy diagnosis. Cryptococcal meningoencephalitis is most effectively treated initially with amphotericin B and flucytosine followed by a prolonged course of fluconazole. Aggressive treatment of elevated intracranial pressure is also critical, as this complication is associated with higher mortality.
Conclusions:
Cryptococcal meningoencephalitis is a rare infection, particularly in HIV‐negative patients., though it can occur in normal hosts. The clinician must include this on the differential diagnosis for patients who present with fever, headache, or a variety of other neurologic symptoms, especially in the setting of abnormal CSF studies with negative bacterial cultures.
