Methotrexate-Induced Stroke-Like Syndrome in Pediatric Acute Lymphoblastic Leukemia: A Case Series from a Resource-Limited Center in Mexico

Methotrexate (MTX)-induced stroke-like syndrome (SLS) is a very rare complication that presents up to three weeks after chemotherapy treatment with a constellation of nonspecific neurological signs and symptoms that may suggest alternative pathologies. During the consolidation phase, methotrexate is a key antimetabolite drug that reduces the synthesis of DNA and RNA. It occasionally causes transient neurotoxicity by damaging white matter. Three patients with ALL without prior central nervous system (CNS) involvement were studied; they developed focal neurological deficits within the first 8 days following intrathecal (MTX-IT) and high-dose MTX (HDMTX) administration. Imaging studies showed focal frontotemporal hyperintensity with self-limitation within 48 to 72 hours without sequelae; two of the three patients received specific pharmacological treatment. A relevant methodological limitation is that homocysteine levels (the central biomarker in pathophysiology) were not measured in any of the three patients, as the necessary reagent was not available at the institutional laboratory. The purpose of this case series is to document the signs and symptoms, their clinical course and resolution, and to report the chemotherapy protocol followed by each patient for comparison with the existing literature. Early recognition of signs and symptoms, neuroimaging findings, and laboratory characteristics is essential for adequate management and to ensure continuity of oncological treatment.

Keywords: Acute lymphoblastic leukemia, methotrexate, stroke, pediatrics