The appearance of intracranial hemorrhage at magnetic resonance (MR) imaging depends primarily on the age of the hematoma and the type of MR contrast (ie, T1 or T2 weighted). As a hematoma ages, the hemoglobin passes through several forms (oxyhemoglobin, deoxyhemoglobin, and methemoglobin) prior to red cell lysis and breakdown into ferritin and hemosiderin. Five distinct stages of hemorrhage can be defined: hyperacute (intracellular oxyhemoglobin, long T1 and T2), acute (intracellular deoxyhemoglobin, long T1, short T2), early subacute (intracellular methemoglobin, short T1, short T2), late subacute (extracellular methemoglobin, short T1, long T2), and chronic (ferritin and hemosiderin, short T2). The short T1 of methemoglobin is due to the paramagnetic dipole-dipole interaction. Another paramagnetic property, the magnetic susceptibility effect, is responsible for the short T2 observed when deoxyhemoglobin, methemoglobin, or hemosiderin is intracellular. T2 shortening can also be produced by hemoconcentration and clot retraction. The T2 shortening due to magnetic susceptibility effects is enhanced on higher-field-strength systems and on gradient-echo images and is reduced with "fast spin-echo" MR techniques.
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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