Seizures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Predictors and Outcomes

Katelyn Pastick, Ananta S. Bangdiwala, Mahsa Abassi, Andrew G. Flynn, Bozena M. Morawski, Abdu K Musubire, Prosperity C Eneh, Charlotte Schutz, Kabanda Taseera, Joshua Rhein, Kathy Huppler Hullsiek, Melanie R Nicol, Jose E. Vidal, Noeline Nakasujja, Graeme Meintjes, Conrad Muzoora, David B Meya, David R. Boulware

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 3 separate human immunodeficiency virus (HIV)-associated cryptococcal meningitis clinical trials during 2010-2017. Documentation of seizures at presentation or during hospitalization and antiseizure medication receipt identified participants with seizures. We summarized participant characteristics by seizure status via Kruskal-Wallis and χ2 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 of 821) experienced seizures: 15.5% (127 of 821) experienced seizures at presentation, and 12.7% (104 of 821) experienced incident seizures. Participants with seizures at presentation had a significantly lower Glasgow coma scale ([GCS] <15; P < .001), CD4 count (<50 cells/mcL; P = .02), and higher cerebrospinal fluid (CSF) opening pressure (>25 cm H2O; P = .004) when compared with participants who never experienced seizures. Cerebrospinal fluid 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 < .001). Seizures were associated with increased 10-week mortality (adjusted hazard ratio = 1.45; 95% confidence interval, 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 < .001). Conclusions. Seizures were common in this HIV-associated cryptococcal meningitis cohort and were associated with decreased survival and neurocognitive function.

Original languageEnglish (US)
Article numberOFZ478
JournalOpen Forum Infectious Diseases
Volume6
Issue number11
DOIs
StatePublished - Nov 1 2019

Bibliographical note

Funding Information:
This research was funded by the National Institute of Neurologic Diseases and Stroke and the Fogarty International Center (R01NS086312, R25TW009345), Grand Challenges Canada (S4- 0296-01), and National Institute of Allergy and Infectious Diseases (U01AI089244, T32AI055433). This work was supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. A. G. F. was a Doris Duke International Clinical Research Fellow. K. A. P. is a 2018 HIVMA Medical Students Program Awardee

Funding Information:
Financial support. This research was funded by the National Institute of Neurologic Diseases and Stroke and the Fogarty International Center (R01NS086312, R25TW009345), Grand Challenges Canada (S4-0296-01), and National Institute of Allergy and Infectious Diseases (U01AI089244, T32AI055433). This work was supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. A. G. F. was a Doris Duke International Clinical Research Fellow. K. A. P. is a 2018 HIVMA Medical Students Program Awardee.

Publisher Copyright:
© 2022 The Author.

Keywords

  • cohort studies
  • cryptococcal
  • cryptococcus
  • HIV
  • meningitis
  • seizures

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