Neuromyelitis Optica

Disease / Phenomenon

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that attacks primarily the optic nerves and spinal cord. Attacks of optic neuritis cause eye pain and rapid vision loss, while longitudinally extensive transverse myelitis produces weakness, sensory loss, and bladder and bowel dysfunction below the affected level. Involvement of the area postrema in the brainstem produces a distinctive syndrome of intractable hiccups, nausea, and vomiting that often precedes other symptoms. NMOSD was historically misdiagnosed as multiple sclerosis, but it is a biologically separate disease with different treatment implications; attacks tend to be more severe and disability accumulates from the attacks themselves rather than gradual progression.

Most cases are driven by IgG autoantibodies against aquaporin-4, the principal water channel on astrocyte end-feet at the blood-brain barrier. Antibody binding triggers classical complement activation with C1q, formation of the membrane attack complex, and antibody-dependent cellular cytotoxicity, producing astrocyte destruction, secondary demyelination, and neuronal loss. Granulocyte recruitment, IL-6 signaling that supports plasmablast survival, and disruption of glutamate transport via EAAT2 amplify the injury. A seronegative subset instead carries antibodies to myelin oligodendrocyte glycoprotein. This page separates these processes into their pathways and biomarkers.