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

doi:10.1093/OFID/OFZ478

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

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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 language	English (US)
Article number	OFZ478
Journal	Open Forum Infectious Diseases
Volume	6
Issue number	11
DOIs	https://doi.org/10.1093/OFID/OFZ478
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Pastick, K., Bangdiwala, A. S., Abassi, M., Flynn, A. G., Morawski, B. M., Musubire, A. K., Eneh, P. C., Schutz, C., Taseera, K., Rhein, J., Hullsiek, K. H., Nicol, M. R., Vidal, J. E., Nakasujja, N., Meintjes, G., Muzoora, C., Meya, D. B., & Boulware, D. R. (2019). Seizures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Predictors and Outcomes. Open Forum Infectious Diseases, 6(11), [OFZ478]. https://doi.org/10.1093/OFID/OFZ478

Pastick, K, Bangdiwala, AS , Abassi, M, Flynn, AG, Morawski, BM, Musubire, AK, Eneh, PC, Schutz, C, Taseera, K, Rhein, J, Hullsiek, KH, Nicol, MR, Vidal, JE, Nakasujja, N, Meintjes, G, Muzoora, C, Meya, DB & Boulware, DR 2019, 'Seizures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Predictors and Outcomes', Open Forum Infectious Diseases, vol. 6, no. 11, OFZ478. https://doi.org/10.1093/OFID/OFZ478

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title = "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 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.",

keywords = "cohort studies, cryptococcal, cryptococcus, HIV, meningitis, seizures",

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

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: {\textcopyright} 2022 The Author.",

year = "2019",

month = nov,

day = "1",

doi = "10.1093/OFID/OFZ478",

language = "English (US)",

volume = "6",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

number = "11",

}

TY - JOUR

T1 - Seizures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis

T2 - Predictors and Outcomes

AU - Pastick, Katelyn

AU - Bangdiwala, Ananta S.

AU - Abassi, Mahsa

AU - Flynn, Andrew G.

AU - Morawski, Bozena M.

AU - Musubire, Abdu K

AU - Eneh, Prosperity C

AU - Schutz, Charlotte

AU - Taseera, Kabanda

AU - Rhein, Joshua

AU - Hullsiek, Kathy Huppler

AU - Nicol, Melanie R

AU - Vidal, Jose E.

AU - Nakasujja, Noeline

AU - Meintjes, Graeme

AU - Muzoora, Conrad

AU - Meya, David B

AU - Boulware, David R.

N1 - 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.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - cohort studies

KW - cryptococcal

KW - cryptococcus

KW - HIV

KW - meningitis

KW - seizures

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DO - 10.1093/OFID/OFZ478

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JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

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ER -

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

Abstract

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