Diagnosis, pathogenesis, and treatment of neuromyelitis optica (NMO) spectrum disorders

NMO and the evolving spectrum of water channel autoimmunity Water channels are a newly recognized target for central nervous system (CNS), inflammatory autoimmune demyelinating diseases. Neuromyelitis optica (NMO; aka optic spinal multiple sclerosis) is a devastating disease that disproportionally affects non-Caucasians. It is characterized by recurrent episodes of optic neuritis and transverse myelitis, which may result in blindness and paraplegia. It is frequently misdiagnosed as multiple sclerosis (MS). NMO is the first MS-like disease for which a specific antigen has been identified – the astrocytic water channel aquaporin-4 (AQP4). This discovery represents a seismic shift from historic emphasis on the oligodendrocyte and myelin to the astrocyte. An autoantibody specific for AQP4 (NMO/AQP4-IgG) is a clinically validated serum biomarker that distinguishes relapsing NMO from MS. MS has no distinguishing biomarker and calls for different therapies. The traditional view-Devic's disease In 1894, Devic reported a case of combined optic neuritis and myelitis that was fatal and provided a review of 16 similar cases from the literature. The syndrome that Devic described was a monophasic illness characterized by both bilateral optic neuritis and transverse myelitis occurring at the same time. The lack of involvement of the brain was emphasized. Over the following 100 years, many investigators reported single cases or case series of patients with variations on this theme. It became increasingly recognized that patients may have (1) unilateral rather then bilateral optic neuritis, and (2) interval of weeks to years between attacks of optic neuritis and myelitis rather then simultaneous onset. Subsequently it was recognized that NMO was a relapsing disease in at least 80% of cases. Investigators put forward diagnostic criteria for NMO, all of which emphasized restriction of clinical symptoms and signs to the optic nerves and spinal cord and a normal brain MRI.– Longitudinally extensive T2 signal abnormalities spanning three or more vertebral segments were reported to be characteristic of NMO, a situation rarely found in MS where lesions (at least in adults) are generally asymmetric and short. Over this period of time, NMO or Devic's syndrome was considered by most to be a variant of MS.