DOI: https://doi.org/10.36347/sjmcr.2026.v14i02.008

Pages: 208-211

Background: Methotrexate (MTX) is widely used in the treatment of malignancies and autoimmune diseases. Although generally well tolerated, neurotoxicity represents a rare but potentially serious adverse effect, with presentations ranging from mild encephalopathy to focal neurological deficits mimicking acute ischemic stroke. Case Presentation: We report the case of a 67-year-old man with rheumatoid arthritis treated with methotrexate who presented with acute onset left-sided hemiplegia and dysarthria. Initial clinical suspicion was ischemic stroke. Brain magnetic resonance imaging (MRI) demonstrated findings consistent with toxic leukoencephalopathy. Methotrexate was discontinued, and folinic acid rescue with supportive intensive care management was initiated, resulting in progressive neurological recovery. Discussion: Methotrexate-induced neurotoxicity remains poorly understood and is likely multifactorial, involving folate pathway disruption, homocysteine-mediated excitotoxicity, adenosine accumulation, and direct white matter injury. Advanced age, renal dysfunction, and impaired drug clearance are recognized risk factors. Diffusion-weighted MRI plays a central role in diagnosis by revealing characteristic reversible white matter lesions. Management is primarily supportive, with early drug withdrawal and folinic acid supplementation. Adjunctive therapies such as aminophylline and dextromethorphan have been described in selected cases. Conclusion: Methotrexate-induced neurotoxicity should be considered in patients presenting with acute neurological deficits during methotrexate therapy. Early recognition, appropriate neuroimaging, and prompt supportive management are essential to prevent permanent neurological sequelae.