Table 2:

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

Condition	Proposed Pathophysiology	Relevance to Cerebral Malaria
Acute toxic leukoencephalopathy	Intramyelinic edema, myelin vacuolization	Endothelial injury is a pathophysiologic mechanism in CM38
	Capillary endothelial injury
	Direct toxic demyelination16
Hypoglycemia	Energy failure leading to excitatory edema21	Hypoglycemia 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 state	Increased metabolic demand leading to energy failure and resultant cytotoxic and vasogenic edema40	Seizures, often recurrent, are a frequent manifestation of CM and associated with worse outcome29
Penumbra of ischemic infarct	Early white matter ischemic injury with axonal swelling and intramyelinic edema13	Sequestration in postcapillary venules of the brain and venous congestion are central to CM pathogenesis25
Demyelination	Immune-mediated perivenular inflammation and demyelination41	Vascular inflammatory markers are associated with CM, and perivenular inflammation is thought to contribute to CM pathogenesis38