To describe a case of cryptococcal meningoencephalitis complicated by immune reconstitution inflammatory syndrome (IRIS), vasculitis, ischemic strokes, and hydrocephalus.

Cryptococcus neoformans is the most common cause of fungal meningitis worldwide and typically affects individuals with defects in cell-mediated immunity. A 71-year-old female with giant cell arteritis on daily prednisone and monthly Tocilizumab infusions presented with worsening headaches for 2 weeks and new-onset confusion for 3 days. Initial workup revealed hyponatremia (sodium 125 mmol/L) and community acquired pneumonia. She was treated with antibiotics, but her mental status rapidly declined necessitating endotracheal intubation. MRI Brain demonstrated multifocal areas of diffusion restriction in the bilateral cerebral and cerebellar hemispheres, basal ganglia, and brainstem with diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) studies revealed an elevated opening pressure of 28 cm H₂O, positive CSF cryptococcal antigen, and CSF fungal cultures grew cryptococcus neoformans. She was started on empiric liposomal amphotericin B and flucytosine before the cryptococcal antigen and cultures resulted. Despite treatment, her neurological status continued to decline with repeat MRI showing new ischemic infarctions, subarachnoid hemorrhages, and leptomeningeal and parenchymal enhancement. Digital subtraction angiography revealed cerebral vasospasm and possible vasculitis. Repeat lumbar puncture demonstrated persistently elevated opening pressure, continued pleocytosis, and increased protein. She was continued on antifungal therapy and received IV methylprednisolone for IRIS. She additionally underwent ventriculoperitoneal (VP) shunt placement. Despite these interventions, her clinical status continued to deteriorate and she was palliatively extubated. 

This patient presented with cryptococcal meningoencephalitis in the setting of immune suppression from prednisone and tocilizumab, a monoclonal antibody that targets the IL-6 receptor. Despite early and appropriate treatment, she continued to worsen with multiple complications including IRIS, a dysfunctional inflammatory response to infection precipitated by immune recovery. In patients treated appropriately for cryptococcal meningoencephalitis, a failure to respond should raise concern for complicating conditions.