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Seizures in Human Immunodeficiency Virus-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 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 ??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.

SUBMITTER: Pastick KA

PROVIDER: S-EPMC7001112 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Pastick Katelyn A KA Bangdiwala Ananta S AS Abassi Mahsa M Flynn Andrew G AG Morawski Bozena M BM Musubire Abdu K AK Eneh Prosperity C PC Schutz Charlotte C Taseera Kabanda K Rhein Joshua J Hullsiek Kathy Huppler KH Nicol Melanie R MR Vidal Jose E JE Nakasujja Noeline N Meintjes Graeme G Muzoora Conrad C Meya David B DB Boulware David R DR

Open forum infectious diseases 20191105 11

<h4>Background</h4>Seizures commonly occur in patients with cryptococcal meningitis, yet risk factors and outcomes related to seizures are not well described.<h4>Methods</h4>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 seizur ...[more]

PMID: 32042847

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Project description:Background:High mortality rates among asymptomatic cryptococcal antigen (CrAg)-positive patients identified through CrAg screening, despite preemptive fluconazole treatment, may be due to undiagnosed cryptococcal meningitis. Methods:Symptoms were reviewed in CrAg-positive patients identified by screening 19233 individuals with human immunodeficiency virus infection and CD4 cell counts <100/µL at 17 clinics and 3 hospitals in Johannesburg from September 2012 until September 2015, and at 2 hospitals until June 2016. Cerebrospinal fluid samples from 90 of 254 asymptomatic patients (35%) and 78 of 173 (45%) with headache only were analyzed for cryptococcal meningitis, considered present if Cryptococcus was identified by means of India ink microscopy, culture, or CrAg test. CrAg titers were determined with stored blood samples from 62 of these patients. The associations between blood CrAg titer, concurrent cryptococcal meningitis, and mortality rate were assessed. Results:Cryptococcal meningitis was confirmed in 34% (95% confidence interval, 25%-43%; 31 of 90) of asymptomatic CrAg-positive patients and 90% (81%-96%; 70 of 78) with headache only. Blood CrAg titer was significantly associated with concurrent cryptococcal meningitis in asymptomatic patients (P < .001) and patients with headache only (P = .003). The optimal titer for predicting cryptococcal meningitis was >160 (sensitivity, 88.2%; specificity, 82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95% confidence interval, 8.3-143.1; P < .001). Conclusions:About a third of asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More effective clinical assessment strategies and antifungal regimens are required for CrAg-positive patients, including investigation for cryptococcal meningitis irrespective of symptoms. Where it is not possible to perform lumbar punctures in all CrAg-positive patients, blood CrAg titers should be used to target those most at risk of cryptococcal meningitis.

Dataset Information

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

Publications

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

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