Brain Swelling and Death in Children with Cerebral Malaria
Open accessAbstract
BACKGROUND: Case fatality rates among African children with cerebral malaria remain in the range of 15 to 25%. The key pathogenetic processes and causes of death are unknown, but a combination of clinical observations and pathological findings suggests that increased brain volume leading to raised intracranial pressure may play a role. Magnetic resonance imaging (MRI) became available in Malawi in 2009, and we used it to investigate the role of brain swelling in the pathogenesis of fatal cerebral malaria in African children. METHODS: We enrolled children who met a stringent definition of cerebral malaria (one that included the presence of retinopathy), characterized them in detail clinically, and obtained MRI scans on admission and daily thereafter while coma persisted. RESULTS: Of 348 children admitted with cerebral malaria (as defined by the World Health Organization), 168 met the inclusion criteria, underwent all investigations, and were included in the analysis. A total of 25 children (15%) died, 21 of whom (84%) had evidence of severe brain swelling on MRI at admission. In contrast, evidence of severe brain swelling was seen on MRI in 39 of 143 survivors (27%). Serial MRI scans showed evidence of decreasing brain volume in the survivors who had had brain swelling initially. CONCLUSIONS: Increased brain volume was seen in children who died from cerebral malaria but was uncommon in those who did not die from the disease, a finding that suggests that raised intracranial pressure may contribute to a fatal outcome. The natural history indicates that increased intracranial pressure is transient in survivors. (Funded by the National Institutes of Health and Wellcome Trust U.K.).
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Death from cerebral malaria results from the accumulation of water in the cranium and brainstem herniation.
“Similar to LCMV meningitis, death from cerebral malaria results from the accumulation of water in the cranium and brainstem herniation (156, 157).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [156]
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- Authors
- Seydel, K. B., Kampondeni, S. D., Valim, C., Potchen, M. J., Milner, D. A., Muwalo, F. W., Birbeck, G. L., Bradley, W. G., Fox, L. L., Glover, S. J., Hammond, C. A., Heyderman, R. S., Chilingulo, C. A., Molyneux, M. E., & Taylor, T. E.
- Affiliations
- University of Malawi (MW)
- Harvard University (US)
- Michigan State University (US)
- Brigham and Women's Hospital (US)
- University of California San Diego (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-03-19
- Volume
- 372
- Issue
- 12
- Pages
- 1126-1137
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4450675
- OpenAlex
- W2118846793
- Cited by
- 404
- References
- 43
- Citations by year
- 2026: 21 · 2025: 44 · 2024: 24 · 2023: 42 · 2022: 42 · 2021: 36 · 2020: 42 · 2019: 35 · 2018: 41 · 2017: 33 · 2016: 31 · 2015: 13
- FWCI
- 42.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- St Andrews Research Repository (St Andrews Research Repository) (submittedVersion)
- Funders
- Michigan State University
- Wellcome Trust (101113)
- National Institutes of Health
- College of Engineering, Michigan State University
- National Institute of Allergy and Infectious Diseases (R01AI034969)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- cerebral malaria, cerebral edema, intracranial pressure, case fatality, pediatric malaria, retinopathy, brain volume, coma, natural history (disease)
- MeSH terms
- Brain, Brain Edema, Child, Child, Preschool, Female, Humans, Infant, Magnetic Resonance Imaging, Malawi, Male, Organ Size, Papilledema, Malaria, Cerebral
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