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N Engl J Med. 2015 Mar 19;372(12):1126-37. doi: 10.1056/NEJMoa1400116.

Brain swelling and death in children with cerebral malaria.

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From the Department of Osteopathic Medical Specialties, College of Osteopathic Medicine (K.B.S., L.L.F., T.E.T.), Department of Radiology (M.J.P., C.A.H.), and Department of Neurology and Ophthalmology, International Neurologic and Psychiatric Epidemiology Program (G.L.B.), Michigan State University, East Lansing; the Blantyre Malaria Project (K.B.S., S.D.K., D.A.M., F.W.M., L.L.F., T.E.T.) and Malawi-Liverpool-Wellcome Trust Clinical Research Programme (R.S.H., M.E.M.), Queen Elizabeth Central Hospital (S.D.K., C.A.C.) and the Department of Anatomy (S.J.G.), University of Malawi College of Medicine - both in Blantyre, Malawi; the Department of Immunology and Infectious Diseases, Harvard School of Public Health (C.V., D.A.M.), and the Department of Pathology, Brigham and Women's Hospital (D.A.M.) - both in Boston; the Department of Radiology, University of California San Diego, San Diego (W.G.B.); and the Liverpool School of Tropical Medicine, Liverpool, United Kingdom (M.E.M.).



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.


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.


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.


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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