Abstract
BACKGROUND Methotrexate-induced encephalopathy is an uncommon but potentially serious neurotoxic complication of high-dose methotrexate therapy. Its clinical and radiological features can closely resemble acute ischemic stroke, leading to diagnostic confusion and unnecessary interventions. Early recognition is crucial to prevent mismanagement and ensure appropriate care. CASE REPORT We report a 16-year-old girl with high-grade osteosarcoma of the distal femur who developed sudden neurological symptoms, beginning with dysphasia and cognitive slowing, progressing within 1 hour to global aphasia and altered consciousness following high-dose methotrexate infusion. Laboratory findings were normal. Magnetic resonance imaging performed 2 hours after symptom onset revealed bilateral diffusion restriction in the centrum semiovale, without corresponding fluid-attenuated ınversion recovery (FLAIR) abnormalities, suggestive of acute ischemia. Intravenous thrombolysis with alteplase (0.9 mg/kg) was administered, but subsequent imaging showed shifting diffusion abnormalities without vascular occlusion, inconsistent with stroke. Methotrexate was withheld, and supportive care alone led to complete neurological recovery within 3 days. The patient resumed chemotherapy 1 week later and remained asymptomatic at 1-year follow-up. CONCLUSIONS Methotrexate-induced encephalopathy is an important stroke mimic in oncology patients. Diffusion restriction without FLAIR changes and a reversible clinical course help distinguish it from true ischemic stroke. Awareness of this condition is essential, as full recovery can occur with supportive care alone, without the need for specific therapeutic interventions.