Methotrexate-associated Demyelinating Leukoencephalopathy after Low-dose Oral Therapy in a Patient with Post-viral Polyarthralgia

Abstract

Background: Methotrexate is a widely used disease-modifying antirheumatic drug. Neurological toxicity is uncommon, particularly after short-term, low-dose oral treatment, and may resemble acute cerebrovascular disease. Case Presentation: A 44-year-old woman receiving oral methotrexate 7.5 mg once weekly and iguratimod 25 mg twice daily for post-viral inflammatory polyarthralgia developed persistent vomiting, followed by diplopia, visual blurring, horizontal nystagmus, and gait ataxia within several days of treatment initiation. Neurological examination demonstrated bilateral sixth cranial nerve palsy and cerebellar dysfunction. Brain magnetic resonance imaging showed restricted diffusion in the left thalamic region. Cerebrospinal fluid analysis did not demonstrate findings suggestive of infectious or inflammatory central nervous system disease. Laboratory investigations identified microcytic hypochromic anaemia and elevated inflammatory markers, while renal, hepatic, electrolyte, and routine metabolic parameters remained within normal limits. The temporal association with methotrexate exposure, exclusion of major alternative causes, objective neurological findings, imaging abnormalities, and improvement after withdrawal supported a diagnosis of probable methotrexate-associated demyelinating leukoencephalopathy. Methotrexate was discontinued, and dexamethasone, folic acid, thiamine, and supportive care were administered. Diplopia, visual symptoms, and gait instability improved progressively. Conclusion: Clinicians should consider methotrexate-associated neurotoxicity when acute neurological symptoms arise after low-dose oral therapy. Prompt recognition and withdrawal of the suspected drug may support neurological recovery.