Case presentation: A 27 year-old Vietnamese man was diagnosed with HIV in April 2012 when he presented with cerebrospinal fluid (CSF)-culture positive Cryptococcus neoformans meningitis. CD4 count was 4 cells/µL and HIV viral load 228827 copies/mL. He was treated with two weeks of amphotericin B (0.7mg/kg/day) and 5-fluorocytosine (25mg/kg/QID), followed by consolidation and secondary prophylaxis with fluconazole. CSF cultures were negative at two weeks. A ventriculo-peritoneal shunt was inserted to manage persistently raised intracranial pressure and had to be replaced two weeks later due to bacterial shunt infection. Antiretroviral therapy (ART) was commenced after four weeks of treatment, and by September 2012, CD4 count was 107 cells/µL and viral load <150 copies/mL.
In October 2012 he presented with visual changes and auditory hallucinations. Electroencephalogram demonstrated epileptiform discharges, and symptoms resolved following commencement of levetiracetam. In December 2012 he presented with headache and confusion. Magnetic resonance imaging showed progressive leptomeningeal enhancement with extensive, deep white matter changes, especially along the shunt tract. CSF showed mild pleocytosis; cultures were negative. He was treated presumptively for bacterial shunt infection with no significant improvement. Dexamethasone was commenced empirically with partial improvement. CD4 count fell to 30 cells/µL, but viral load remained suppressed at <150 copies/mL. Brain biopsy in February 2013 showed cryptococcal organisms with relatively little surrounding inflammation; immunohistochemistry and PCR were negative for polyomavirus and mycobacterial and fungal cultures were negative. A presumptive diagnosis of cryptococcal IRIS was made and steroids were continued with progressive improvement in symptoms.
Discussion: The timing of symptoms, lack of evidence of mycological failure, exclusion of alternative diagnoses and response to corticosteroids in this case are best explained by a diagnosis of cryptococcal IRIS. However, the unusually protracted course, extensive white matter changes and development of seizures are not typical manifestations. The demonstration of numerous (non-viable) cryptococcal organisms in brain parenchyma suggests that these features resulted from an inflammatory reaction involving the brain and not just confined to the meninges. This case illustrates that the extent of central nervous system (CNS) involvement can affect the clinical and radiological expression of cryptococcal IRIS, resulting in a range of features that can mimic other HIV-related CNS processes, and it highlights the complexities in diagnosis and management of this condition.
