Using Electroencephalography to Assess Coma Etiology in Children with Retinopathy-Negative Cerebral Malaria

Mrinmayee Takle, Division of Neurology, The George Washington University/Children's National Hospital, Washington, District of Columbia.
Alexander Andrews, Division of Neurology, The George Washington University/Children's National Hospital, Washington, District of Columbia.
Brittany A. Riggle, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Rockville, Maryland.
Tesfaye Zelleke, Division of Neurology, The George Washington University/Children's National Hospital, Washington, District of Columbia.
Dana Harrar, Division of Neurology, The George Washington University/Children's National Hospital, Washington, District of Columbia.
Jiahui Zhang, Department of Statistics, University of Washington, Seattle, Washington.
Bo Zhang, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Kyle J. Wilson, Department of Eye & Vision Sciences, University of Liverpool, Liverpool, United Kingdom.
Nicholas A. Beare, Department of Eye & Vision Sciences, University of Liverpool, Liverpool, United Kingdom.
Terrie E. Taylor, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Karl B. Seydel, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Stephen Ray, Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Douglas G. Postels, Division of Neurology, The George Washington University/Children's National Hospital, Washington, District of Columbia.

Document Type

Journal Article

Publication Date

7-22-2025

Journal

The American journal of tropical medicine and hygiene

DOI

10.4269/ajtmh.25-0377

Abstract

Autopsy studies of children dying of cerebral malaria (CM) have revealed that those with malarial retinopathy exhibited high levels of sequestration in the cerebral vasculature, whereas children with retinopathy-negative CM exhibited lower sequestration levels and possible nonmalarial causes of death. This suggests that children dying of retinopathy-negative CM have nonmalarial coma etiologies with concomitant incidental parasitemia, which is common in high malaria transmission areas. Subsequent studies have challenged this assertion, positing that retinopathy-negative CM and retinopathy-positive CM are variants of the same disease pathophysiology or host biology, both caused by acute malaria infection. We recently determined that electroencephalography (EEG) can be used to discriminate between a malarial coma (CM) and a nonmalarial coma. To better understand the contribution of acute malaria infection in the pathophysiology of retinopathy-negative CM, we compared qualitative and quantitative EEG findings from 30-minute EEG recordings of Malawian children aged 3 months to 14 years hospitalized at Queen Elizabeth Central Hospital with retinopathy-negative CM, retinopathy-positive CM, and nonmalarial coma. Neither qualitative nor quantitative EEG interpretation methods allow for the discrimination between children with retinopathy-positive CM and those with retinopathy-negative CM. Conversely, quantitative EEG readily differentiated children with retinopathy-negative CM from those with nonmalarial coma (area under the receiving operating characteristic [AUROC] curve of 0.83). When combining qualitative and quantitative EEG interpretation methods, the ability of EEG to distinguish retinopathy-negative CM from nonmalarial EEG increases (AUROC of 0.87). The EEGs of children with retinopathy-negative CM are similar to those of children with retinopathy-positive CM and significantly different from those of children with nonmalarial coma, supporting the hypothesis that acute malarial infection is pathophysiologically important in retinopathy-negative CM.

Department

Neurology

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