The Mystery of a Negative Workup: A Diagnostic Dilemma in Seronegative Immune-Mediated Transverse Myelitis

Transverse myelitis (TM) is an acquired inflammatory disorder of the spinal cord with a heterogeneous aetiology that includes demyelinating, autoimmune, infectious, granulomatous, and paraneoplastic causes. Although advances in antibody testing, particularly aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), have refined the classification of many cases, a significant proportion remain seronegative, presenting diagnostic and therapeutic challenges. We report the case of a 44-year-old man who presented with progressive fatigue, significant weight loss, lower abdominal numbness, urinary urgency, and intermittent blurred vision. Magnetic resonance imaging of the thoracic spine demonstrated an intramedullary T2 hyperintense lesion at the T10-T11 level with patchy gadolinium enhancement, consistent with inflammatory myelitis. An extensive diagnostic evaluation excluded infectious, systemic autoimmune, granulomatous, endocrine, demyelinating, and paraneoplastic causes. The patient showed marked clinical improvement following high-dose intravenous methylprednisolone, with resolution of sensory and autonomic symptoms and stabilisation of weight, while mild fluctuating fatigue persisted. This case highlights the diagnostic grey zone of seronegative immune-mediated TM and underscores the importance of systematic exclusion, longitudinal assessment, and therapeutic responsiveness in establishing diagnosis and guiding management.