Neuromyelitis optica: Diagnosis, pathogenesis, and treatment

Although the co-occurrence of myelitis and optic neuritis that characterizes neuromyelitis optica (NMO) was recognized over a century ago, distinguishing NMO from multiple sclerosis relied solely on clinical criteria until recently. The identification of a biomarker that has high specificity for NMO is clinically useful for distinguishing NMO from multiple sclerosis and identifying patients at high risk for recurrent myelitis and optic neuritis. That fact that the biomarker is an autoantibody that recognizes aquaporin 4 (AQP4), a water channel expressed on astrocyte podocytes, has substantially contributed to the hypothesis that NMO is a humorally mediated autoimmune disease. This review discusses the discovery of the NMO-IgG biomarker, the identification of AQP4 as its target, the clinical applications of these advances, the pathologic implications for the anti-AQP4 antibody, and advances in NMO treatment.