Neuromyelitis optica: Diagnosis, pathogenesis, and treatment

Abstract

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.

Biomarkers of disease activity in multiple sclerosis

“…Identification of the neuromyelitis optica (NMO) antibody to aquaporin-4 predicts a different clinical course of aggressive disease with predominant spinal cord and optic nerve disease and likely accumulation of early fixed disability as well as death compared to traditional multiple sclerosis [46]. The clinical differences are so striking that some experts consider NMO a completely separate disease from MS, though cases with overlapping features do occur and a wider spectrum of clinical NMO is now being described besides the traditional concept of bilateral optic neuritis with simultaneous longitudinal transverse myelitis [46]. As many as 20-40% of patients meeting clinical criteria for diagnosis of NMO will not have detectable serum antibody, depending on the method used [46,47].…”

The Prevalence of Long Spinal Cord Lesions and Anti-Aquaporin 4 Antibodies in Neuromyelitis Optica Patients in Taiwan

“…Many patients with NMO were initially diagnosed with multiple sclerosis (MS) [2,3,4]. The clinical course of NMO is usually more severe than that of MS [5].…”

Relevance of Autoantibodies for the Classification and Pathogenesis of Neurological Diseases

“…In contrast to MS, it has several unique features (Table 1). NMO is characterized by the occurrence of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM) extending over three or more vertebral segments (Wingerchuk et al, 1999;Cree, 2008), which can lead to blindness and paraplegia within several years of disease onset (Wingerchuk et al, 1999;Wingerchuk & Weinshenker, 2003). Furthermore, NMO commonly follows a more aggressive disease course compared to MS and has a high rate of morbidity and mortality in patients who receive no special treatment (Wingerchuk & Weinshenker, 2003).…”