Neuromyelitis Optica Spectrum Disorder: A Clinical Review

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy in which antibodies against the aquaporin-4 (AQP4) water channel produce a stereotyped group of syndromes determined by the anatomical distribution of AQP4 expression. Six core clinical presentations are recognized: optic neuritis, longitudinally extensive transverse myelitis, area postrema syndrome, acute brainstem syndrome, diencephalic syndrome, and cerebral syndrome. Because disability in NMOSD almost always accrues at discrete, treatable relapses rather than through insidious progression, early recognition, supported by prompt AQP4-IgG testing and pattern recognition on MRI, is essential to preserving vision, mobility, and independence. This review summarizes the pathophysiology, clinical and radiologic features, diagnostic evaluation, and differential diagnosis of each core syndrome and synthesizes contemporary evidence for relapse prevention. Over the past decade, the therapeutic landscape has been transformed: agents targeting complement (eculizumab, ravulizumab), the interleukin-6 receptor (satralizumab, tocilizumab), and B cells (rituximab, inebilizumab) now have randomized evidence of efficacy in seropositive disease, with complement inhibitors ranking highest across indirect treatment comparisons. Evidence in seronegative disease remains limited, no approved agents have been compared head-to-head, and the optimal role of early plasma exchange is unsettled. Emerging neuroprotective strategies and chimeric antigen receptor T-cell therapy, both of which remain experimental, may further expand options for refractory disease. Once uniformly disabling, AQP4-IgG NMOSD is now a highly treatable condition in which timely diagnosis and sustained immunotherapy can meaningfully alter long-term outcomes.