Neuromyelitis Optica Spectrum Disorder

Abstract

Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system, also known as Devic’s syndrome, that typically manifests with optic neuritis and transverse myelitis and, like other antibody-mediated autoimmune diseases, primarily affects women. Most NMO cases are caused by a circulating autoantibody termed NMO-IgG or AQP4-IgG that targets the astrocytic water channel protein aquaporin-4 (AQP4). Some NMO cases are caused by a circulating autoantibody against the myelin oligodendrocyte glycoprotein termed MOG-IgG. A small proportion of NMO cases, termed seronegative NMO, are not associated with an autoantibody. AQP4-IgG binds extracellular conformational epitopes on AQP4, activates complement, which in turn causes inflammatory cell infiltration, demyelination and pan-necrosis. Acute NMO exacerbations are treated with methylprednisolone or plasmapheresis. Some drugs used to treat multiple sclerosis, such as interferon beta and natalizumab, exacerbate NMO. Maintenance treatment options include prednisolone, mycophenylate, mitoxantrone, cyclophosphamide, azathioprine, rituximab, tocilizumab and eculizumab. The discoveries of AQP4-IgG and MOG-IgG have shown that NMO is a distinct entity from multiple sclerosis with fundamentally different pathophysiology and treatment.