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 |