Teaching NeuroImages: Methotrexate neurotoxicity Resolution and evolution of MRI changes within 48 hours

A 13-year-old girl presented with acute-onset right hemiparesis involving the face, arm, and leg equally. She was receiving weekly intrathecal methotrexate (last dose 6 days prior) for recently diagnosed acute lymphocytic leukemia. Brain MRI (figure 1) showed diffusion restriction in the left centrum semiovale with reduced apparent diffusion coefficient. Her hemiparesis resolved within 24 hours, but 2 hours later she developed 12-hour left hemiparesis involving face, upper limb, and dysarthria. Follow-up neurologic examination was normal. Repeat MRI (figure 2) 44 hours after the original MRI showed acute right centrum semiovale changes. The changes that were previously seen on the left side had resolved. As before, all changes noted were localized completely in white matter, nonvascular territory. This was consistent with methotrexate neurotoxicity,1,2 possibly secondary to homocysteine accumulation causing direct endothelial injury.3 The patient resumed intrathecal methotrexate 1 month later as part of her ongoing chemotherapeutic regimen without further incidents.