NMOSD

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic autoimmune inflammatory disorder of the central nervous system characterized by attacks of optic neuritis and/or transverse myelitis. It is distinct from multiple sclerosis and is most commonly associated with antibodies against aquaporin-4 (AQP4). A significant minority of patients test positive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG), which defines a related, but clinically separate, spectrum known as MOG antibody-associated disease.

The pathophysiology is autoantibody-mediated. AQP4-IgG binding to aquaporin-4 on astrocytes activates the complement system and inflammatory cascades, leading to astrocyte injury and secondary demyelination. MOG-IgG-associated disease is thought to involve a different target and may have distinct clinical features and prognosis. Relapses are common without preventive therapy.

Clinical features include acute optic neuritis and longitudinally extensive transverse myelitis, where spinal cord lesions extend over three or more vertebral segments. Area postrema syndrome (intractable nausea, hiccups, or vomiting) can occur, and brain involvement is less typical but may appear in certain regions. MRI findings support the diagnosis, with LETMs in the spinal cord and optic nerve abnormalities; brain lesions can occur in the diencephalon and periventricular regions, depending on serostatus.

Diagnosis relies on core clinical characteristics supported by serology. AQP4-IgG positivity strongly supports NMOSD, while MOG-IgG testing helps in seronegative cases. Cell-based assays are the standard diagnostic tests. Diagnostic criteria emphasize clinical features, serology, MRI findings, and exclusion of alternative diagnoses.

Treatment focuses on preventing and treating relapses. Acute attacks are typically treated with high-dose intravenous corticosteroids, with plasmapheresis for steroid-refractory cases. Long-term immunosuppression reduces relapse risk; options include rituximab, mycophenolate, azathioprine, and newer targeted therapies such as eculizumab, inebilizumab, and satralizumab. Overall prognosis depends on relapse frequency and disability accumulation, but early diagnosis and preventive therapy improve outcomes.