Background <p>Tumor necrosis factor-alpha (TNF-α) inhibitors are widely used for immune-mediated inflammatory diseases, including Crohn’s disease. Although generally effective, TNF-α blockade has been linked to uncommon but clinically significant paradoxical immune-mediated neurologic adverse events, including inflammatory demyelinating disorders of the central nervous system (CNS).</p> Case presentation <p>A 32-year-old woman with Crohn’s disease (perianal fistula) treated with infliximab for one year presented with progressive dizziness, headache, and bilateral lower-limb weakness. Neurologic examination demonstrated ataxic gait, intention tremor, dysarthria, brisk reflexes (right-predominant), and a positive right Babinski sign, with preserved sensation. Initial laboratory testing and head CT were unremarkable. Brain MRI revealed multiple multifocal T2/FLAIR hyperintense lesions involving bilateral periventricular and deep white matter, with plaques affecting the thalami, internal capsule, corpus callosum, cerebellum, and cerebellar peduncles; spinal MRI showed no active lesions. Cerebrospinal fluid studies were normal; infectious testing and autoimmune screening were negative, and oligoclonal bands and serum aquaporin-4 antibodies were negative. Infliximab was discontinued, and high-dose pulse corticosteroids were administered, resulting in mild symptomatic improvement; however, ataxia and dysarthria persisted. At three months, follow-up MRI showed stable lesions without radiologic activity alongside slow clinical improvement with rehabilitation.</p> Conclusion <p>This case highlights a clinically significant, infliximab-associated CNS demyelinating syndrome with an MS-like radiologic pattern in a patient without prior neurologic history. Prompt recognition, discontinuation of the suspected agent, and early immunotherapy are essential; nonetheless, incomplete recovery may occur, underscoring the need for careful neurologic vigilance in patients receiving anti-TNF therapy.</p>