To present a case of acute cerebral malaria with an unusual clinico-radiological discrepancy, in which prominent diffusion-restricted white-matter abnormalities contrasted with relatively mild neurological findings.

Cerebral malaria (CM) represents the most severe neurological complication of Plasmodium falciparum infection, with clinical presentations ranging from headache and encephalopathy to seizures and coma. Adults with CM are at risk for significant multi-system involvement, including renal, hepatic, and pulmonary dysfunction.

NA

A 37-year-old man with well-controlled HIV on HAART returned from Nigeria with one week of fever and headaches. Laboratory testing revealed leukocytosis, thrombocytopenia, and elevated lactate. A peripheral smear demonstrated P. falciparum parasitemia of 15.7% with ring forms on Giemsa stain. He was treated with atovaquone-proguanil, followed by a course of artemether-lumefantrine.

Neurologically, he exhibited fluctuating mentation characterized by irritability and slowed processing speed but no focal deficits. A non-contrast CT head demonstrated age-indeterminate lacunar infarcts. MRI brain confirmed chronic lacunar infarcts but also revealed striking bilateral, symmetric subcortical white-matter diffusion restriction without corresponding FLAIR or post-contrast abnormalities. CSF analysis was normal, with no pleocytosis, normal protein levels, and negative microbiologic PCR testing results. The autoimmune disease workup carried out was also unremarkable.

Cerebral malaria is an underrecognized cause of reversible neuroinflammation. Isolated subcortical white-matter diffusion restriction has been described in pediatric CM, and is often associated with milder disease and favorable outcomes. This case highlights a similar radiological pattern in an adult with only mild encephalopathy, suggesting that early antimalarial therapy and limited microvascular injury may underlie the clinico-radiological mismatch.

White-matter vulnerability in CM is thought to result from reversible microvascular sequestration, cytokine-mediated inflammation, and hematologic dysfunction leading to impaired perfusion. Long-term neurological sequelae of cerebral malaria include cognitive, motor, behavioral deficits, and epilepsy. This case highlights the importance of early recognition and treatment in reducing the risk of unfavorable neurological outcomes.