Seizures in HIV-associated Cryptococcal Meningitis: Predictors and Outcomes

Abstract

Background: Seizures commonly occur in patients with cryptococcal meningitis, yet risk factors and outcomes related to seizures are not well described. Methods: We performed post-hoc analyses on participants prospectively enrolled in three separate HIV-associated cryptococcal meningitis clinical trials during 2010–2017. Documentation of seizures at presentation or during hospitalization, and anti-seizure medication receipt identified participants with seizures. We summarized participant characteristics by seizure status via Kruskal-Wallis and Chi-square tests. Cox proportional hazards models analyzed the relationship between seizures and mortality. We compared mean quantitative neurocognitive performance Z (QNPZ-8) scores, and individual domain z-scores, at 3-months using independent t-tests. Results: Among 821 HIV-infected cryptococcal meningitis participants, 28% (231/821) experienced seizures: 15.5% (127/821) experienced seizures at presentation, and 12.7% (104/821) experienced incident seizures. Participants with seizures at presentation had a significantly lower Glasgow coma scale (GCS<15) (p<0.001), CD4 count (<50 cells/mcL) (p=0.02), and higher cerebrospinal fluid (CSF) opening pressure (>25 cm H2O) (p=0.004) when compared with participants who never experienced seizures. CSF fungal burden was higher among those with seizures at presentation (125,000 Cryptococcus colony forming units (CFU)/mL CSF) and with seizures during follow-up (92,000 CFU/mL) compared with those who never experienced seizures (36,000 CFU/mL, p<0.001). Seizures were associated with increased 10-week mortality (adjusted Hazard Ratio = 1.45, 95%CI: 1.11, 1.89). Participants with seizures had lower neurocognitive function at 3-months (QNPZ-8 = -1.87) compared with those without seizures (QNPZ-8 = -1.36; p<0.001). Conclusions: Seizures were common in this HIV-associated cryptococcal meningitis cohort and were associated with decreased survival and neurocognitive function.