1 of 1

Seizures in HIV-Associated Cryptococcal Meningitis Associated with Possible Decreased Immune Activation in CSF Immune Response

Annika Duryea 1, Samuel Okurut 2, David B Meya 2, Abduljewad Wele 1, David R Boulware 1

1: University of Minnesota, 2: Infectious Diseases Institute, Makerere University

Cryptococcal meningitis (CM) is a prevalent opportunistic infection and a leading cause of death in people with HIV [1]. Typical symptoms include headache, fever, altered mental status and vomiting, with seizures also common, correlating with increased mortality and worse cognitive outcomes [2]. This study examines cerebrospinal fluid (CSF) profiles in HIV-associated CM patients, comparing those with baseline seizures to those without. The goal is to identify immunological factors and patterns that could improve diagnosis and treatment, enhancing outcomes for these patients.

Introduction

Appreciation to the Medical Student Summer Research Program in Infection and Immunity (T35AI118620), R01NS086312, and R01AI162786

Acknowledgements

  • Among 80 participants with HIV-associated cryptococcal meningitis, 27% (22/80) had seizures at presentation.
  • Those with seizures had:
    • Lower Glasgow coma scale (GCS) score <15; (P=0.01)
    • Higher CSF opening pressure (P=0.09),
    • Higher 10-week mortality (P = 0.30)
    • Fewer CSF white cells (P = 0.20).
  • A variety of cellular activation markers were significantly lower in those with baseline seizures, including B cell activation with CD69 (P=0.05) & HLA-DR (P = 0.05), NK cell activation CD69 (P=0.03) and exhaustion CD4 PD-1 (P = 0.12).

Results

  1. Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017; 17:873-81.
  2. Pastick KA, Bangdiwala AS, Abassi M, et al. Seizures in human immunodeficiency virus-associated cryptococcal meningitis: Predictors and outcomes. Open Forum Infectious Diseases. 2019; 6(11); ofz478

References

  • Participants were prospectively enrolled in a clinical trial for HIV-associated cryptococcal meningitis.
  • Baseline seizures were identified by pre-admission history as well as antiseizure medication use after admission.
  • Patient characteristics and baseline CSF parameters were compared by seizure status using Kruskal-Wallis tests and Chi-square tests for continuous and categorical variables, respectively.
  • Cox proportional hazard models were utilized to assess the relationship between seizures and mortality.
  • Flow cytometry results were compared using the Wilcoxon test for seizure group.

Methodology

Results

  • Seizures are common and associated with worse outcomes for those with HIV-related cryptococcal meningitis.
  • Distinct immunological CSF profiles in patients with baseline seizures compared to those without highlight differences that warrant further investigation.
  • Understanding the role of immune response and cellular activation markers in the pathophysiology of seizures could lead to improved diagnosis and treatment strategies, potentially reducing the morbidity and mortality.

Conclusions

Figure 1.

10-Week Mortality by Baseline Seizure Status

P=0.12

​

​

P=0.03

​

​

P=0.03

​

​

P=0.05

​

​

P=0.05

​

​

P=0.20

Figure 3.

CSF Profiles: Immune Activation Markers

Figure 2.

GCS Scores by Baseline Seizure Status

Template ID: persuadingsapphire Size: 48x36