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

Katelyn A 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

doi:10.1093/ofid/ofz478

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

Open Forum Infect Dis. 2019 Nov 5;6(11):ofz478. doi: 10.1093/ofid/ofz478. eCollection 2019 Nov.

Authors

Katelyn A Pastick^{1

2}, Ananta S Bangdiwala¹, Mahsa Abassi^{1

2}, Andrew G Flynn¹, Bozena M Morawski¹, Abdu K Musubire², Prosperity C Eneh¹, Charlotte Schutz³, Kabanda Taseera⁴, Joshua Rhein^{1

2}, Kathy Huppler Hullsiek¹, Melanie R Nicol¹, Jose E Vidal^{5

6}, Noeline Nakasujja², Graeme Meintjes^{3

7}, Conrad Muzoora⁴, David B Meya^{1

2}, David R Boulware¹

Affiliations

¹ University of Minnesota, Minneapolis, Minnesota, USA.
² Infectious Diseases Institute, Makerere University, Kampala, Uganda.
³ Wellcome Center for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁴ Mbarara University of Science and Technology, Mbarara, Uganda.
⁵ Instituto de Infectologia Emilio Ribas, São Paulo, São Paulo, Brazil.
⁶ Divisão de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
⁷ Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa.

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 χ ² 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.

Keywords: HIV; cohort studies; cryptococcal; cryptococcus; meningitis; seizures.

Abstract

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