# Corticosteroid Therapy and Long-Term Outcomes of Post-Infectious Inflammatory Syndrome in Non-HIV Immunosuppressed Cryptococcal Meningitis: A Multicenter Case Series

## TL;DR

Corticosteroids improved neurological outcomes in non-HIV immunosuppressed patients with post-infectious inflammation from cryptococcal meningitis.

## Contribution

Demonstrates corticosteroid efficacy in non-HIV immunosuppressed patients with post-infectious inflammatory syndrome following cryptococcal meningitis.

## Key findings

- Corticosteroid therapy significantly improved Karnofsky scores and neurological symptoms in non-HIV immunosuppressed patients.
- CSF inflammatory parameters and MRI findings showed improvement following corticosteroid treatment.
- Three patients died due to complications unrelated to cryptococcal meningitis itself.

## Abstract

Post-infectious inflammatory response syndrome (PIIRS) is recognized as a cause of neurologic deterioration in previously healthy patients with cryptococcal meningoencephalitis (CM). However, data on non-human immunodeficiency virus (HIV), immunosuppressed patients remain limited.

Between July 2018 and April 2025, 13 non-HIV immunosuppressed patients with CM who subsequently developed PIIRS were included. Clinical features, Karnofsky performance scores, cerebrospinal fluid (CSF) parameters, and magnetic resonance imaging (MRI) findings were compared at PIIRS diagnosis and during follow-up after corticosteroid therapy.

All patients showed evidence of CNS inflammation, including abnormal CSF, MRI findings, and neurological symptoms such as altered mental status or visual/hearing loss. Corticosteroid therapy was associated with significant improvements in Karnofsky scores at 1 month (P = .001), with sustained benefit at 6 and twelve months (P = .002); all 10 surviving patients demonstrated resolution of neurological symptoms. CSF inflammatory parameters including white blood cell (WBC) count, protein, and CSF/serum glucose ratio also significantly improved at 1 month. Brain MRI findings also showed a trend toward improvement. All patients remained culture-negative post-PIIRS diagnosis. Three patients died: 1 from complications of alcoholic cirrhosis, the second from liver failure in the setting of systemic lupus erythematosus and immunosuppression, and the third from sepsis after initiation of corticosteroids.

Corticosteroids were associated with improvement in neurological status and neuroinflammation in non-HIV, immunosuppressed patients with PIIRS following CM. These findings support its potential role as salvage therapy in this population and highlight the need for systematic data collection or randomized trials to better guide corticosteroid use.

Corticosteroid therapy improved neurologic function and reduced neuroinflammation in non-HIV immunosuppressed patients with cryptococcal PIIRS. These findings support its potential as salvage therapy and highlight the need for systematic data collection to inform a future clinical trial.