Table 2:

Conditions with reversible/transient white matter diffusion restriction and their pathophysiology

ConditionProposed PathophysiologyRelevance to Cerebral Malaria
Acute toxic leukoencephalopathyIntramyelinic edema, myelin vacuolizationEndothelial injury is a pathophysiologic mechanism in CM38
Capillary endothelial injury
Direct toxic demyelination16
HypoglycemiaEnergy failure leading to excitatory edema21Hypoglycemia is a frequent complication in children with severe falciform malaria39; local/focal hypoglycemia may occur due to sludging even in the absence of systemic hypoglycemia
Peri-/postictal stateIncreased metabolic demand leading to energy failure and resultant cytotoxic and vasogenic edema40Seizures, often recurrent, are a frequent manifestation of CM and associated with worse outcome29
Penumbra of ischemic infarctEarly white matter ischemic injury with axonal swelling and intramyelinic edema13Sequestration in postcapillary venules of the brain and venous congestion are central to CM pathogenesis25
DemyelinationImmune-mediated perivenular inflammation and demyelination41Vascular inflammatory markers are associated with CM, and perivenular inflammation is thought to contribute to CM pathogenesis38