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Title: Seizures in childhood cerebral malaria
Author: Crawley, Jane Margaret Stewart
ISNI:       0000 0001 3396 1818
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2001
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Every year, more than one million children in sub-Saharan Africa die or are disabled as a result of cerebral malaria. Seizures complicate a high proportion of cases, and are associated with an increased risk of death and neurological sequelae. This thesis examines the role of seizures in the pathogenesis of childhood cerebral malaria. The clinical and electrophysiological data presented suggest that seizures may contribute to the pathogenesis of coma in children with cerebral malaria. Approximately one quarter of the patients studied had recovered consciousness within 6 hours of prolonged or multiple seizures, or had seizures with extremely subtle clinical manifestations. EEG recording also demonstrated that electrical seizure activity arose consistently from the posterior temporo-parietal region, a watershed area of the brain that is particularly vulnerable to hypoxia. Cerebral computerised tomography (CT) scans from children who had multiple seizures during their clinical course, and who subsequently developed a hemiplegia, revealed infarction in this area. The thesis discusses the aetiology of seizures in cerebral malaria, and explores the hypotheses that chloroquine may precipitate seizures, and that some of the neurological manifestations of cerebral malaria may be explained by an excitotoxic mechanism. If anticonvulsant prophylaxis can reduce the incidence of seizures complicating cerebral malaria, this may in turn reduce the risk of neurological sequelae and death. The thesis describes a randomised, controlled intervention study, in which a single intramuscular dose of phenobarbitone 20mg/kg reduced the incidence of seizures by 50% but was associated with an unacceptable doubling of mortality. Post hoc analysis revealed that mortality was highest among those who had been treated with phenobarbitone and multiple doses of diazepam, raising the possibility that respiratory depression was responsible for the increased mortality in the phenobarbitone-treated group. The thesis concludes with a discussion of alternative strategies for anticonvulsant prophylaxis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Death