To present a case report of a patient with Cryptococcal meningoencephalitis (CM) on anti-fungal therapy who developed postinfectious inflammatory response syndrome (PIIRS) and was successfully treated with corticosteroids.

CM is the leading cause of non-viral meningitis in the United States. Approximately one-third of cases occur in immunocompetent patients, and mortality is higher than in immunosuppressed patients. One complicating factor in the management of CM in immunocompetent patients is the development of PIIRS which results in deterioration in neurological status after appropriate anti-fungal treatment and conversion to negative cultures. This syndrome is thought to result from a heightened activation of the immune system, and the optimal treatment course of PIIRS is not well-defined.

An immunocompetent 40-year-old man presented to the emergency department with two weeks of worsening headache, nausea, vomiting, gait difficulties, and diplopia. Brain MRI demonstrated obstructive hydrocephalus, and he subsequently underwent EVD placement. Initial CSF analysis demonstrated evidence of CM, with a Cryptococcal antigen titer of 1:320. Patient received induction anti-fungal therapy with amphotericin B and flucytosine. He did well for approximately three weeks, until he suddenly developed fevers and worsened encephalopathy. A repeat brain MRI demonstrated worsening ventriculitis, with abnormal signal in the periventricular white matter and area surrounding the fourth ventricle, extending into the cervical spinal cord diffusely. Fungal cultures were negative. He was started on a seven-day course of methylprednisolone 1000 mg IV daily, which resulted in improved mental status. Patient ultimately required VP shunt, and steroids were tapered over the following three months. He remains on daily fluconazole.

This case outlines the clinical course of an immunocompetent patient who developed PIIRS after starting anti-fungal therapy for CM. This condition, while rare, highlights how heightened host immune responses can result in significant damage to the CNS that causes deterioration of the patient’s neurological status.