Neuromyelitis optica: a new perspective

Abstract

The traditional view of neuromyelitis optica (NMO) as a monophasic inflammatory disorder that affects both the optic nerves and the spinal cord is expanding. Over the last decade, a combination of clinical, radiological, pathological, and serological findings have resulted in evolving definitions of NMO and the appreciation that it likely constitutes a broader, more diverse spectrum of disease that is pathogenically distinct from multiple sclerosis. Neuromyelitis optica-immunoglobulin (Ig)G is the first antibody marker for any inflammatory central nervous system disorder, and is both sensitive and specific for NMO. Its target antigen, aquaporin-4, the most abundant water channel in the central nervous system, has opened up new research directions into demyelinating disorders of the central nervous system. The identification of NMO-IgG in patients with recurrent optic neuritis or longitudinally extensive myelitis and its ability to predict subsequent relapse support the concept of a spectrum of NMO disorders. Preliminary in vitro studies and recent immunopathological evidence support a role for NMO-IgG as the initiator of the NMO lesion. Definitive proof of pathogenesis is needed and will require the development of active immunization and passive transfer animal models, which will hopefully lead to more effective targeted therapies.