Acute leukoencephalopathy due to pyrimethamine. An insight into methotrexate neurotoxicity?

A unique case of pyrimethamine-related stroke-like leukoencephalopathy is described. The imputability of the drug is discussed as well as the similarities with the well-known methotrexate neurotoxicity. Owing to the same mode of action of both drugs by inhibition of the enzyme dihydrofolate reductase, this case is highly suggestive of the pathogenetic role of methylation pathway blockade on myelin synthesis resulting in delayed demyelination. This complication could be avoided by a concurrent folinic acid supplementation.