To emphasize that Brown-Séquard syndrome (BSS) can result from nontraumatic etiologies such as neuromyelitis optica (NMO) myelitis.

An 82-year-old man with hypertension, hyperlipidemia, and known cerebral meningiomas, but no trauma history, presented with four days of progressive left lower extremity weakness and contralateral sensory loss. Examination revealed severe left leg weakness, absent proprioception on the left, and diminished pinprick and temperature sensation on the right. MRI demonstrated a longitudinally extensive T6–T11 intramedullary T2 hyperintense lesion and T8–T9 disc herniation causing cord deformation, raising concern for disc herniation with vascular compromise versus autoimmune myelitis. CSF showed elevated protein without infection, and serum studies were normal except for low vitamin D. 

The combination of motor weakness and loss of proprioception on one side of the body, together with reduced pain and temperature sensation on the opposite side, is characteristic of Brown-Séquard syndrome (BSS). BSS classically results from hemisection, or unilateral injury to the spinal cord, disrupting three key pathways: the corticospinal, the dorsal column-medial lemniscus, and the spinothalamic tracts. While traumatic causes such as penetrating injuries remain most common, nontraumatic etiologies, including autoimmune disorders, can produce an identical clinical picture through focal or asymmetric cord involvement. In this patient, CSF and serum findings later revealed strongly positive aquaporin-4 (AQP4) IgG, confirming neuromyelitis optica spectrum disorder (NMOSD). 

This case underscores the importance of considering nontraumatic causes of BSS in patients presenting with asymmetric weakness and sensory changes. While traumatic etiologies remain classic, autoimmune processes such as neuromyelitis optica spectrum disorder (NMOSD) can mimic hemisection syndromes. This patient was treated with high-dose corticosteroids, followed by seven sessions of plasmapheresis. Outpatient therapy with ravulizumab, a complement C5 inhibitor, was initiated, leading to gradual neurological improvement. Recognizing atypical presentations of BSS within the context of autoimmune disease highlights opportunities for timely intervention to improve outcomes.