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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that affects the central nervous system. It is characterized by attacks or relapses of symptoms such as optic neuritis, transverse myelitis, and area postrema syndrome. Magnetic resonance imaging (MRI) is used to confirm a diagnosis of NMOSD and to detect specific lesion patterns. Relapse prevention is the primary goal of treatment, and the use of MRI in relapse assessment is recommended. However, there is a lack of universally accepted criteria for defining relapses, and further research is needed to validate the use of MRI in relapse assessment. [Extracted from the article]

Background: The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD). Objective: Evaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum. Methods: Adults (n = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed. Results: A total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (>2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks. Conclusion: AC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks. [ABSTRACT FROM AUTHOR]

During PREVENT (a phase 3, randomized, double-blind, placebo-controlled, time-to-event study) and its open-label extension (interim analysis), 33 adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) received eculizumab monotherapy for a median of 2.8 years (range, 14 weeks–5.2 years). At 192 weeks (~4 years), 96% of these patients were free from adjudicated relapses (Kaplan–Meier analysis; 95% confidence interval, 75.7–99.4). During PREVENT, 95% (20/21) of patients receiving eculizumab monotherapy had no disability worsening. Eculizumab monotherapy provides effective long-term relapse prevention, relieving the chronic immunosuppression burden in patients with AQP4-IgG + NMOSD. ClinicalTrials.gov; PREVENT: NCT01892345; open-label extension: NCT02003144. [ABSTRACT FROM AUTHOR]

Objective: Determine the utility of aquaporin 4 IgG (AQP4-IgG) testing (live cell-based assay) for Neuromyelitis Optica Spectrum Disorders (NMOSD). Methods: We included Mayo Clinic patients (1/1/2018-12/31/2019) tested for serum AQP4-IgG by live cell-based flow-cytometric assay. Medical records were reviewed to assess if patients fulfilled 2015 NMOSD criteria. Results: Of 1371 patients tested, 41 were positive (3%) and all fulfilled NMOSD criteria with AQP4-IgG (specificity = 100%). Only 10/1330 testing negative met NMOSD criteria without AQP4-IgG (sensitivity = 80%) and seven of these 10 were MOG-IgG positive. Conclusions: AQP4-IgG by live cell-based assay was highly specific and without false positives in a high throughput setting. [ABSTRACT FROM AUTHOR]

Diverse acute neurological injuries may cause acute cardiopulmonary events including neurogenic pulmonary edema (NPE) and neurogenic stunned myocardium (NSM). The mechanism is probably mediated by sympathetic nervous system activation. Focal central nervous system (CNS) lesions, such as demyelinating lesions in multiple sclerosis (MS), may also cause cardiopulmonary disturbances. We aim to review the acute cardiopulmonary events associated with MS relapses. We performed a literature search using PubMed, and selected case reports of acute cardiac and/or pulmonary events related to MS exacerbations. We grouped these events into three categories: 1) NPE with normal cardiac function; 2) NSM and Takotsubo cardiomyopathy (TTC); 3) coexisting myocardial dysfunction and pulmonary edema. In some cases, cardiac and pulmonary symptoms preceded the onset of neurological symptoms. The majority of cases were associated with acute demyelinating lesions located in the medulla. Acute brainstem MS relapses, with demyelinating lesions affecting the medulla, may cause acute cardiac and pulmonary events presumably secondary to sympathetic hyperstimulation. Specific regions in the medulla that regulate cardiac function, systemic blood pressure and pulmonary hydrostatic pressure seem to be responsible for these events. [ABSTRACT FROM AUTHOR]

Background: Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. Objective: We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. Methods: We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. Results: In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p < 0.0001) and 0.12 (seronegative; p = 0.0001). In those started on mycophenolate mofetil, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.79 and 1.45, respectively. On-treatment annualized relapse rates declined to 0.29 (seropositive; p < 0.0001) and 0.30 (seronegative; p < 0.005). Conclusion: In this international collaboration involving a large number of neuromyelitis optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments. [ABSTRACT FROM AUTHOR]

Disease-modifying therapies should be stopped in NMOSD patients in remission - Commentary The emergence of the first generation of disease-modifying therapies (DMTs) for multiple sclerosis (MS) and clinically isolated syndrome sparked debate about when to start treatment. We monitor brain magnetic resonance imaging (MRI) in MS, but although most NMOSD patients gradually accumulate nonspecific and asymptomatic subcortical brain lesions,[9] it is not clear whether the lesions represent disease activity that should be extinguished or prevented. [Extracted from the article]

The authors present insights on the importance of sensitivity and specificity for the diagnostic criteria of neuromyelitis optica spectrum disorder (NMOSD). Topics discussed include the consensus diagnostic criteria proposed by the International Panel for NMOSD in 2015, the effects of diagnostic categorization on diagnosing NMOSD, and the relevance of distinction between criteria types to multiple sclerosis (MS) and NMOSD.

Neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) are associated with autoantibodies that target aquaporin-4 and, in many cases, multiple other autoantibodies, including antinuclear antibody and antibodies to extractable nuclear antigens. The clinical syndromes that define NMO and NMOSD, especially longitudinally extensive transverse myelitis and optic neuritis, can also occur in the context of established rheumatologic diseases such as systemic lupus erythematosus and Sjögren syndrome and other organ-specific autoimmune diseases. These observations raise questions fundamental to both clinical practice and etiologic research. For example, they could suggest that NMO is one manifestation of a genetic tendency toward humoral autoimmunity. Alternatively, they might indicate that NMO is a central nervous system complication of a multisystem rheumatologic disease. We describe the historical background of this controversy, summarize the current evidence that addresses NMO–systemic autoimmunity relationships, and discuss the practical implications for clinical management. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is associated with both genetic and environmental factors that influence disease susceptibility. Exposure to cigarette smoke is emerging as a viable environmental risk factor for MS that contributes to both increased disease susceptibility and more rapid disease advancement. The relative risk for MS development is approximately 1.5 for smokers compared with nonsmokers. Furthermore, there may be important interactions between smoking, an individual’s genetic background, and other environmental risk exposures. This review summarizes the current evidence supporting the association of smoking with MS risk and disease course, with additional comments on causation. [ABSTRACT FROM PUBLISHER]