Recurrence of methotrexate-induced leukoencephalopathy after methotrexate rechallenge: A case report and literature review

Methotrexate (MTX) is potent chemotherapeutic agent, often administered intrathecally to treat or prevent central nervous system involvement in lymphomas and leukemias, particularly T-cell lymphoblastic leukemia (T-LBL). MTX has been linked to adverse neurologic effects that mimic acute stroke, including facial drooping, hemiplegia, impaired consciousness, and seizures, as well as changes on imaging—known as MTX-induced leukoencephalopathy (LE). We report a case of a 17-year-old male diagnosed with T-LBL, who had been receiving MTX chemotherapy for 4 months. After receiving his fourth dose of MTX, he presented to the emergency department with fever, facial drooping, and acute left-sided weakness. Brain magnetic resonance imaging (MRI) revealed bilateral deep white matter T2 hyperintense foci, increased on the right, with associated diffusion restriction in the right centrum semiovale—consistent with MTX-induced LE. After his symptoms resolved, he was discharged on leucovorin. Six months afterward, he was rechallenged with MTX and developed recurrence of symptoms. Repeat MRI showed well-defined T2/FLAIR hyperintensities in the right centrum semiovale without corresponding diffusion restriction. The left centrum semiovale hyperintensity became less conspicuous in comparison to the previous MRI study. We report a rare case of recurrence of LE after MTX rechallenge and discuss mechanisms, best imaging modalities, and possible treatment options for MTX-induced LE. Given the ominous presentation of MTX-induced LE, we urge clinicians to maintain a high index of suspicion for this condition. Further research is necessary to understand why only certain patients develop recurrence of LE after subsequent doses of MTX.