Cerebral Venous Thrombosis in Previously Healthy Patients with Cryptococcal Meningitis

Cerebral venous sinus thrombosis (CVST), though a recognized complication of cryptococcal meningitis (CM), has been rarely reported. This study investigates the clinical features of CVST in a retrospective cohort of previously healthy, non-HIV CM patients.

We reviewed medical records of 89 immunocompetent CM patients admitted between January 2005 and April 2024. CVST incidence, clinical course, neuroimaging, and laboratory data were analyzed. Genetic analysis was performed to detect thrombophilia-associated variants. To explore thrombosis-related gene expression during neuroinflammation, cerebrospinal fluid (CSF) cells collected at the time of cryptococcal post-infectious inflammatory response syndrome (cPIIRS) diagnosis were subjected to single-cell RNA sequencing.

CVST occurred in 5.6% (CI 1.9%-12.6%) of CM patients, a rate comparable to bacterial CNS infections. No known pathogenic variants in known thrombophilia-associated genes were identified. However, 44 genes previously linked to thrombosis showed elevated expression-defined as ≥150 single-cell sequencing reads-in a cPIIRS patient.

CVST is a potentially treatable complication of CM. MRI and MRV of the brain are valuable diagnostic tools. The absence of thrombophilia mutations suggests that neurologic infection itself contributes to thrombotic risk. Notably, CSF gene expression patterns may serve as biomarkers for CVST susceptibility. Future case-control studies may validate these findings and uncover genetic risk factors contributing to CVST.