Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Long segments of spinal cord infl ammation (myelitis), severe optic neuritis, and/or bouts of intractable vomiting and hiccoughs (area postrema syndrome) are classic presentations of the disease and may alert the clinician to the diagnosis. Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their fi rst attack. Unlike multiple sclerosis, a progressive clinical course is very unusual and the accrual of disability is related to relapses. Approximately 75% of patients have antibodies against aquaporin-4, a water channel expressed on astrocytes. Relapses are treated aggressively to prevent residual disability with highdose steroids and often plasma exchange. Relapse prevention is crucial and achieved with long-term immuno suppression. In this article we review the pathogenesis, clinical features, diagnosis and management of NMOSD.

IMPORTANCE Antibodies to myelin oligodendrocyte glycoprotein IgG (MOG-IgG) are increasingly detected in patients with non-multiple sclerosis-related demyelination, some of whom manifest a neuromyelitis optica (NMO) phenotype. Cortical involvement, encephalopathy, and seizures are rare in aquaporin 4 antibody (AQP4-IgG)-related NMO in the white European population. However, the authors encountered several patients with seizures associated with MOG-IgG disease. OBJECTIVE To compare incidence of seizures and encephalitis-like presentation, or both between AQP4-IgG-positive and MOG-IgG-positive patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series of all patients who were seropositive for MOG-IgG (n = 34) and the last 100 patients with AQP4-IgG disease (NMO spectrum disorder) seen in the NMO service between January 2013 and December 2016, and analysis was completed January 4, 2017. All patients were seen in a tertiary neurological center, The Walton Centre NHS Foundation Trust in Liverpool, England. MAIN OUTCOMES AND MEASURES The difference in seizure frequency between the AQP4-IgG-positive and MOG-IgG-positive patient groups was determined. RESULTS Thirty-four patients with MOG-IgG disease (20 female) with a median age at analysis of 30.5 years (interquartile range [IQR], 15-69 years), and 100 AQP4-IgG-positive patients (86 female) with a median age at analysis of 54 years (IQR, 12-91 years) were studied. Most patients were of white race. Five of the 34 patients with MOG-IgG (14.7%) had seizures compared with 1 patient with AQP4-IgG (2-sided P < .008, Fisher test). On magnetic resonance imaging, all 5 MOG-IgG-positive patients had inflammatory cortical brain lesions associated with the seizures. In 3 of the 5 MOG-IgG-positive patients, seizures occurred as part of the index event. Four of the 5 presented with encephalopathy and seizures, and disease relapsed in all 5 patients. Four of these patients were receiving immunosuppressant medication at last follow-up, and 3 continued to take antiepileptic medication. In contrast, the only AQP4-IgG-positive patient with seizures had a diagnosis of complex partial epilepsy preceding the onset of NMO by several years and experienced no encephalitic illness; her magnetic resonance imaging results demonstrated no cortical, subcortical, or basal ganglia involvement. CONCLUSIONS AND RELEVANCE Patients with MOG-IgG-associated disease were more likely to have seizures and encephalitis-like presentation than patients with AQP4-IgG-associated disease.

B-cell depleting anti-CD20 monoclonal antibody therapies are being increasingly used as long-term maintenance therapy for neuroinflammatory disease compared to many non-neurological diseases where they are used as remission-inducing agents. While hypogammaglobulinaemia is known to occur in over half of patients treated with medium to long-term B-cell-depleting therapy (in our cohort IgG 38, IgM 56 and IgA 18%), the risk of infections it poses seems to be under-recognised. Here, we report five cases of serious infections associated with hypogammaglobulinaemia occurring in patients receiving rituximab for neuromyelitis optica spectrum disorders. Sixty-four per cent of the whole cohort of patients studied had hypogammaglobulinemia. We discuss the implications of these cases to the wider use of anti-CD20 therapy in neuroinflammatory disease.

Myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG)–associated disease (MOGAD) is increasingly recognized as a distinct nosological entity from aquaporin‐4 antibody IgG–positive neuromyelitis optica spectrum disorder (AQP4‐IgG NMOSD). The advent of highly specific MOG‐IgG cell‐based diagnostic assays have helped to refine our understanding of the clinical spectrum of MOGAD. To date, treatment approaches have been largely extrapolated from AQP4‐IgG NMOSD experience, but there is growing evidence of distinct differences in treatment response between these conditions. This review summarizes the current status and understanding of acute and chronic treatments for MOGAD. Timing and duration of treatment, pregnancy, and emerging therapies are also discussed.