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Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin‐4 channelopathies
Author(s) -
Iorio Raffaele,
Pittock Sean J.
Publication year - 2014
Publication title -
clinical and experimental neuroimmunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 15
ISSN - 1759-1961
DOI - 10.1111/cen3.12103
Subject(s) - neuromyelitis optica , optic neuritis , transverse myelitis , medicine , multiple sclerosis , channelopathy , aquaporin 4 , spectrum disorder , myelitis , neuroscience , demyelinating disease , pathology , immunology , spinal cord , psychology , psychiatry
Water channels are a recognized “novel” target for central nervous system, inflammatory, autoimmune, demyelinating diseases, and represent an evolving spectrum of disorders termed neuromyelitis optica ( NMO ) spectrum disorders ( SD ). These disorders should now be considered under the umbrella term “autoimmune aquaporin‐4 channelopathy”. NMOSD represent the first multiple sclerosis ( MS )‐like disease for which a specific antigen has been identified – the astrocytic water channel aquaporin‐4 ( AQP 4). MS lacks a distinguishing biomarker. This discovery represents a seismic shift from historic emphasis on the oligodendrocyte and myelin to the astrocyte. The NMO of today represents a relapsing spectrum of disease, not necessarily restricted to the optic nerves and spinal cord, that is different from the monophasic disorder in which near simultaneous bilateral optic neuritis and transverse myelitis occur, as was originally described by Devic. Recent clinical, radiological and pathological findings have documented brain involvement in NMO spectrum disorders, particularly in children. Most patients with NMOSD have brain abnormalities on magnetic resonance imaging, and these are consistent with MS in up to 10% of patients. Others have lesions in areas that highly express AQP 4 including the circumventricular organs accounting for intractable nausea and vomiting, and the syndrome of inappropriate antidiuresis as presenting symptoms or heralds of relapse. Diencephalic involvement might explain recently recognized sleep disorders and endocrinopathies. Continued progress in our understanding of the immunobiology of AQP 4 autoimmunity necessitates continuing revision of the clinical diagnostic criteria for NMO spectrum disorders. As the clinical spectrum broadens, the importance of highly specific assays that detect pathogenic AQP 4‐immunoglobulin G targeting extracellular epitopes of AQP 4 cannot be overemphasized.