Neuromyelitis Optica Spectrum Disorder Relapse Research Articles

Ravulizumab (Ultomiris)


 CADTH recommends that Ultomiris be reimbursed by public drug plans for the treatment of neuromyelitis optica spectrum disorder (NMOSD) if certain conditions are met.
 Ultomiris should only be covered to treat adult patients with anti–aquaporin 4 (AQP4) antibody–positive NMOSD. Patients must have had at least 1 relapse (also known as an “attack”) of NMOSD in the 12 months before initiation. Patients must have an Expanded Disability Status Scale score of 7 points or less.
 Ultomiris should only be reimbursed if prescribed by a neurologist with expertise in treating NMOSD and if the price is reduced by at least 73%. Ultomiris should not be initiated during an NMOSD relapse episode or when used in combination with rituximab, satralizumab, eculizumab, or inebilizumab.

Reduced serum IgG galactosylation is associated with increased inflammation during relapses of neuromyelitis optica spectrum disorders.

Post-translational modifications of antibodies, with a specific focus on galactosylation, have garnered increasing attention in the context of understanding the pathogenesis and therapeutic implications of autoimmune diseases. However, the comprehensive scope and the clinical significance of antibody galactosylation in the context of Neuromyelitis Optica Spectrum Disorder (NMOSD) remain enigmatic.The primary aim of this research was to discern disparities in serum IgG galactosylation levels between individuals in the acute stage of NMOSD relapse and their age- and sex-matched healthy counterparts. A total of fourteen untreated NMOSD patients experiencing an acute relapse phase, along with thirteen patients under medication, were enrolled, and an additional twelve healthy controls of the same age and gender were recruited for this investigation. Western blot and lectin enzyme techniques were used to determine the level of IgG galactosylation in the serum samples from these subjects. The expression of CD45+, CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD16+CD56+ in peripheral blood leukocytes was measured by flow cytometry. The enzyme-linked immunosorbent assay (ELISA) was also used to quantify the amounts of IgG. Magnetic particle luminescence assays are used to detect cytokines. Robust statistical analysis was executed to ascertain the potential associations between IgG galactosylation and the aforementioned immune indices. In the context of NMOSD relapses, serum IgG galactosylation exhibited a notable decrease in untreated patients (0.2482 ± 0.0261), while it remained comparatively stable in medicated patients when contrasted with healthy controls (0.3625 ± 0.0259) (p=0.0159). Furthermore, a noteworthy inverse correlation between serum IgG galactosylation levels and the Expanded Disability Status Scale (EDSS) score during NMOSD relapse was observed (r=-0.4142; p=0.0317). Notably, IgG galactosylation displayed an inverse correlation with NMOSD relapse among peripheral blood CD45+, CD3+, CD3+CD8+, CD19+ cells, as well as with IL-6 and IL-8. Nevertheless, it was not determined whether IgG galactosylation and CD3+CD4+ T cells or other cytokines are statistically significantly correlated. Our research identified reduced IgG galactosylation in the serum of NMOSD patients during relapses, significantly correlated with disease severity, thereby providing a novel target for the diagnosis and treatment of NMOSD in the realm of medical research.

Efficacy and safety of mycophenolate mofetil for steroid reduction in neuromyelitis optica spectrum disorder: a prospective cohort study

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease that can affect multiple generations and cause complications with long-term prednisolone treatment. This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) in preventing NMOSD relapse while reducing prednisolone dosage. The trial involved nine patients with NMOSD who received MMF along with prednisolone dose reduction. MMF was effective in achieving prednisolone dose reduction without relapse in 77.8% of patients, with a significant decrease in mean annualized relapse rate. All adverse events were mild. The findings suggest that MMF could be a viable treatment option for middle-aged and older patients who require steroid reduction. Clinical trial registration number: jRCT, jRCTs051180080. Registered February 27th, 2019-retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs051180080.

Association between active and passive smoking and the clinical course of multiple sclerosis and neuromyelitis optica spectrum disorder

<i>Objective</i>: Active and passive smoking are common environmental risk factors, but there is no definite conclusion about their effects on relapse and disability progression in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). <i>Methods</i>: This was a retrospective cohort study. Patients were included from four centers. Demographic and clinical data were extracted from the clinical database, while data involving environmental exposures during daily life, relapse, and disability progression were obtained through telephone follow-up interviews. Determinants of relapse were assessed by Cox proportional models, and disability progression was assessed by linear regression. Kaplan‒Meier survival was used to estimate relapse within five years after the first attack. <i>Results</i>: A total of 130 MS patients and 318 NMOSD patients were included in this study, and females accounted for 60% and 79.6%, respectively. MS patients with an active smoking history had a higher risk of relapse, for which the association became borderline significant after accounting for covariates (aHR=1.52, 95% CI=1.00, 2.31; <i>p</i>=0.052). The relapse risk between ever-smokers who smoked more than 10 cigarettes per day and smokers who smoked less than 10 cigarettes per day was not significantly different (aHR=0.96, 95% CI=0.63, 1.47; <i>p</i>=0.859). However, exposure to passive smoking was associated with a reduced risk of MS relapse (aHR=0.75, 95% CI=0.56, 1.00; <i>p</i>=0.044) compared with never-exposed patients. No associations were observed between active smoking/passive smoking and the risk of NMOSD relapse, but patients with a history of smoking were associated with a lower annual progression rate by Expanded Disability Status Scale (EDSS) (aβ=−0.20, 95% CI=−0.38, −0.01; <i>p</i>=0.036) and Multiple Sclerosis Severity Score (MSSS) (aβ=−0.23, 95% CI=−0.44, −0.03; <i>p</i>=0.028). <i>Conclusion</i>: Our research shows that active smoking increases the relapse risk of MS and has a negative impact on disability progression; thus, smoking cessation should be encouraged.

The effect of lowering dose of rituximab on the neuromyelitis optica spectrum disorder relapse rate during COVID-19 epidemic period

The effect of lowering dose of rituximab on the neuromyelitis optica spectrum disorder relapse rate during COVID-19 epidemic period

A single relapse induces worsening of disability and health-related quality of life in patients with neuromyelitis optica spectrum disorder.

Cumulative damage from multiple relapses in neuromyelitis optica spectrum disorder (NMOSD) is associated with poor health-related quality of life (HRQoL) and long-term disability in patients positive for anti-aquaporin 4 antibodies (AQP4+). This study assessed the effect of an individual relapse on HRQoL and disability outcomes in AQP4+ NMOSD. Post hoc analyses of data pooled from the PREVENT study and its open-label extension, which evaluated the efficacy and safety of eculizumab in AQP4+ NMOSD, examined the effect of a single relapse on 3 disability and 4 HRQoL outcome measures. Assuming the effect of 1 relapse extends to multiple relapses, an extrapolation was done to assess the effect of 2 relapses on these outcomes. In 27 patients (placebo: n = 20; eculizumab: n = 7) experiencing an independently adjudicated relapse, 1 relapse led to significantly worse disability (modified Rankin Scale and Expanded Disability Status Scale [EDSS]) and HRQoL (36-item Short-Form Health Survey mental and physical component summaries; European Quality of Life 5-Dimension questionnaire 3-Level visual analogue scale and utility index) scores. In 4 of 7 outcomes, clinically meaningful worsening was more likely for relapsing versus non-relapsing patients (n = 116). Extrapolating the effect of 2 relapses predicted that clinically meaningful worsening was more likely in 6 out of 7 outcomes, including EDSS, for patients experiencing multiple relapses versus patients experiencing no relapses. Findings from these clinical trial data demonstrate that a single NMOSD relapse can worsen disability and HRQoL, underscoring the role of relapse prevention in improving long-term outcomes in patients with AQP4+ NMOSD.

Decreased kynurenine in cerebrospinal fluid and potential role in neuromyelitis optica spectrum disorder.

Tryptophan (Trp) metabolism has been implicated in neuroinflammatory and neurodegenerative disorders, but its relationship with neuromyelitis optica spectrum disorder (NMOSD) is unclear. In this pilot study, cerebrospinal fluid (CSF) was prospectively collected from 26 NMOSD patients in relapse and 16 controls with noninflammatory diseases and 6 neurometabolites in the tryptophan metabolic pathway, including 5-hydroxytryptamine (5-HT), kynurenine (KYN), melatonin (MLT), 5-hydroxyindoleacetic acid (5HIAA), 3-hydroxy-o-aminobenzoic acid (3-HAA), and kynurenic acid (KYA), were measured by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The association of Trp metabolites with NMOSD and its clinical parameters was evaluated. The role of KYN, which is a Trp metabolite involved in the binding of NMOSD-IgG antibody to aquaporin 4 (AQP4), was also evaluated in vitro. CSF KYN was significantly decreased in patients with relapsing NMOSD compared to controls, and CSF KYN was associated with CSF white blood cells in NMOSD. In vitro experiments showed that NMOSD-IgG specifically recognized KYN, which reversed the NMOSD-IgG-induced downregulation of AQP4 expression. Our results show that abnormal Trp metabolism occurs in NMOSD and that KYN might be a potential target for the treatment of AQP4-IgG-positive NMOSD patients.

Relapsing neuromyelitis optica spectrum disorder due to noncompliance to oral corticosteroid therapy

Rationale: Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by severe optic neuritis and myelitis. NMO recurrence can be triggered by infection, pregnancy, and the tapering of oral corticosteroid medication. Patient concerns: A 14-year-old girl with no remarkable birth or developmental history was admitted to our hospital after experiencing visual loss in the right eye. The right eye was positive for relative afferent pupillary defects. Diagnosis: Orbital magnetic resonance imaging revealed a high-intensity area in the right optic nerve. Serum levels of anti–aquaporin 4 (AQP4) antibodies were high. She was diagnosed with anti-AQP4 antibody-positive right-sided optic neuritis. Interventions: Her symptoms improved after repeated intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy. Subsequently, she continued to take oral steroids as a long-term preventive measure. Outcomes: She relapsed twice, at the ages of 14 and 16 years, due to nonadherence to oral corticosteroid medication at her discretion (fears of steroid side effects and worsening infection without other causes), with anti-AQP4 antibody-positive NMO leading to multiple lesions in the cerebral cortex. Lessons: To our knowledge, this is the first report of NMO with increasing recurrence severity due to nonadherence to oral corticosteroid medication. This case demonstrates the importance of oral corticosteroid therapy in preventing relapses of anti-AQP4 antibody-positive NMO and suggests the need to educate patients regarding steroid therapy.

To be or not to be vaccinated: The risk of MS or NMOSD relapse after COVID-19 vaccination and infection

BackgroundCOVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelinating disorders of the central nervous system and to determine disease exacerbation risk factors. MethodsData in this retrospective, observational cohort study was collected via the Czech nationwide registry ReMuS from March 1, 2020, to October 30, 2021. We compared the proportion of patients with at least one clinical relapse in the 90 days following vaccination or infection to the 90-day intervals during the year before. For the evaluation of the risk factors of relapse, a comparison between groups with and without relapses after COVID-19 vaccination or infection was made. ResultsWe identified 1661 vaccinated (90.11% BNT162b2) patients with MS without a history of COVID-19 and 495 unvaccinated patients with MS who experienced COVID-19. A mild increase in the proportion of patients with at least one clinical relapse (-360 to -270 days: 4.46%; -270 to -180: 4.27%; -180 to -90: 3.85%; -90 to 0: 3.79% vs. 0 to +90 days: 5.30%) after vaccination in patients with MS was observed, as well as a rise in the proportion of patients with at least one clinical relapse after COVID-19. Lower age was associated with MS relapse after vaccination or infection. Although there were only 17 vaccinated and eight post-COVID-19 patients with NMOSD, the results were broadly consistent with those of patients with MS. ConclusionThere is a mild increase in the relapse incidence after the COVID-19 vaccination. The risks, however, need to be balanced against the risks of COVID-19 itself, also leading to the rise in relapse rate and particularly to morbidity and mortality.

Immunosuppressant and neuromyelitis optica spectrum disorder: optimal treatment duration and risk of discontinuation.

Preventing relapse by immunosuppressants (ISs) is critical for the prognosis of neuromyelitis optica spectrum disorder (NMOSD); however, the optimal duration of IS treatment is still under discussion. The objective was to explore the optimal duration of IS treatment and the risk of IS discontinuation for NMOSD. This cohort study was conducted at a major neurological center that housed the largest NMOSD database in South China. Eligible participants were patients with NMOSD undergoing IS treatment. The main outcome measures were changes in relapse risk based on IS treatment duration, clinical outcomes and predictors of relapse following IS discontinuation. In total, 343 patients were included in this study. The duration of IS treatment was strongly associated with a decrease in relapse risk (hazard ratio [HR] 0.53, p < 0.001). Continuous IS treatment resulted in decreased relapse HRs within 5 years of receiving IS medication, with a mild rebound starting at 5 years. Rituximab reduced the risk of NMOSD relapse to approximately zero within 3 years. The rate of relapse after IS withdrawal was high (77.5%). As opposed to other ISs, a delayed relapse following rituximab withdrawal was observed in this study. Longitudinal extensive transverse myelitis (HR=2.023, p=0.006) was associated with a higher risk of relapse after IS discontinuation. Long-term IS medication for NMOSD is generally suitable. Patients with longitudinal extensive transverse myelitis had a higher risk of relapse after IS discontinuation. Future studies should explore individualized strategies of rituximab maintenance treatment.

Clinical significance of anti-SSA/Ro antibody in Neuromyelitis optica spectrum disorders

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), also described as CNS autoimmune astrocytopathy, due to the production of pathogenic antibodies against aquaporin-4 (AQP4) expressed on the foot of astrocytes. NMOSD coexists with autoimmune diseases and related autoantibodies [anti-Sjogren's syndrome A (anti-SSA)/Ro antibody, anti-Sjogren's syndrome B (anti-SSB)/La antibody, anti-nuclear (anti-ANA) antibodies, anti-double-stranded DNA (anti-dsDNA) antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody].Objectives: No precise conclusion has been drawn on the role of the anti-SSA/Ro antibody in NMOSD. Therefore, the aim of this work was to evaluate whether the anti-SSA/Ro antibody has an impact on the clinical manifestation or prognosis of NMOSD.Methods: Data were retrospectively collected from 102 patients with NMOSD diagnosed by experienced neurologists. The study population was divided into two groups based on the serum anti-SSA/Ro antibody status: NMOSD with or without anti-SSA/Ro antibody. The clinical, neuroimaging and laboratory parameters were compared between the two groups, including the neurological symptoms, MRI results, frequency of systemic autoantibodies, Expanded Disability Status Scale (EDSS), and NMOSD relapse rate. The EDSS and relapse were applied as measures of the NMOSD patient prognostic value. Cox regression analysis was used to evaluate the prognostic impact of anti-SSA/Ro antibody on NMOSD.Results: Among the 102 NMOSD patients, striking differences were observed in the positive rate of AQP4-IgG (89.2% vs. 72.3%, p = 0.046) between those patients with and without the anti-SSA/Ro antibody. In addition, NMOSD patients with anti-SSA/Ro antibody showed the presence of more frequent anti-ANA antibodies (p = 0.002), anti-SSB/La antibody (p < 0.001), anti-dsDNA antibody (p < 0.002), Sjogren's syndrome (SS, p < 0.001) and systemic lupus erythematosus (SLE, p = 0.045). Univariate and multivariate Cox regression analysis were performed to confirm that the anti-SSA/Ro antibody affected the EDSS score and the relapse of NMOSD patients. The analysis of the survival curve revealed that the EDSS score in the NMOSD patients positive for the anti-SSA/Ro antibody reached 4.0 (p = 0.035) and relapsed (p = 0.039) earlier than in the negative group.Conclusion: The anti-SSA/Ro antibody could be associated with disease activity and severe disability in NMOSD.

Randomized Controlled Trials for Neuromyelitis Optica Spectrum Disorder: A Review of Trial Architecture.

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory disease that primarily affects the optic nerves and the spinal cord. Randomized controlled trials (RCTs) assessing treatments for NMOSD have only been performed in the past decade, and to date, there are 3 drugs approved by the US Food and Drug Administration (FDA) for antiaquaporin-4 immunoglobulin G seropositive NMOSD. This review assesses the characteristics and challenges of RCTs when evaluating treatments for NMOSD. We conducted a review using the terms ("neuromyelitis optica" OR "NMO" OR "NMOSD") AND "clinical trial" in any language on March 28, 2021. Seven RCTs were included, and the trials' architecture was analyzed and synthesized. Overall, 794 subjects were randomized [monoclonal antibody intervention group, n= 493 (62.1%), placebo, n=196 (24.7%), and active control, n=105 (13.2%)]; 709 (89.3%) were females; and 658 (82.9%) were aquaporin-4 (AQP4) antibody seropositive. The primary outcome was time to relapse in 6/7 of the trials, and annualized relapse rate in the remaining one. Four RCTs used placebo in their design. Among the seven published RCTs, the trial design differed by the criteria used to define NMOSD relapse, selection of subjects, proportion of AQP4 immunoglobulin G seronegative patients, and baseline characteristics indicating NMO disease severity. Ethical considerations for the use of placebo should change in light of the approval of 3 therapies for seropositive NMOSD. Remaining challenges for clinical trials in NMOSD include the assessment of long-term safety and efficacy, standardization of trial design and endpoints, and head-to-head study designs.

Efficacy of azathioprine, mycophenolate mofetil, and rituximab in the treatment of neuromyelitis optica spectrum disorder and analysis of prognostic factors.

The study aims to compare the efficacies of the immunosuppressants most commonly prescribed for patients with neuromyelitis optica spectrum disorder (NMOSD). The predictors, which might be associated with relapse and disability in NMOSD, were also analyzed. This retrospective study included NMOSD patients treated with azathioprine (AZA), mycophenolate mofetil (MMF), and rituximab (RTX). The annual relapse rate (ARR) and the incidence rates of adverse events were compared. Cox proportional-hazards model calculated the potential predictors of NMOSD relapse and disability. A total of 83 patients were included. The median treatment time of AZA group (n = 34), MMF group (n = 20), and RTX group (n = 29) were 19.5, 15.5, and 12months, respectively. ARR of the three groups reduced significantly after treatment. In the three groups, 55.9%, 50%, and 79.3% of patients, respectively, were free from relapse. However, the difference among the three groups was of no statistical significance, possibly due to the small sample size. During the treatment, 32.4%, 15%, and 24.1% of patients experienced adverse events in the AZA group, MMF group, and RTX group, respectively. Additionally, the multivariate Cox analyses indicated that history of a severe attack and disease duration were associated with the risk of relapse after immunotherapy. Late-onset (≥ 50years old) NMOSD patients were probably more susceptible to motor disability, and those with optic neuritis at onset were more likely to develop visual disability. AZA, MMF, and low-dose RTX were all effective in reducing the relapse rate in NMOSD. The age at onset, disease duration, history of severe attacks, and primary syndromes might be significant prognostic predictors in NMOSD.

Efficacy and safety of modified reduced-dose rituximab in Chinese patients with neuromyelitis optica spectrum disorder: A retrospective cohort study

ObjectiveTo evaluate the long-term efficacy and safety of a modified reduced-dose rituximab (mRTX) regimen compared with azathioprine (AZA) and mycophenolate mofetil (MMF) in Chinese patients with neuromyelitis optica spectrum disorder (NMOSD). MethodsIn this retrospective cohort study, 71 patients with NMOSD were treated with AZA (n = 24), MMF (n = 18), or mRTX (n = 29). The primary outcome was initial relapse after first-line immunosuppressant therapy. The annualized relapse rate (ARR), expanded disability status scale (EDSS) score, activities of daily living (ADL) scale score, and treatment-related adverse events were compared between groups. ResultsSignificant ARR reductions were observed in the three groups, with relapse-free rates of 37.5%, 72.2%, and 79.3% in the AZA, MMF, and RTX groups, respectively. Compared with AZA, mRTX and MMF significantly reduced the NMOSD relapse risk. Relapse within 1 year before immunosuppressant therapy or ARR before immunosuppressant therapy increased the NMOSD relapse risk. mRTX and MMF were superior to AZA in reducing the EDSS score and increasing the ADL score, but there was no significant difference between the mRTX and MMF groups. Additionally, mRTX-treated patients were less likely to use steroids concurrently than those treated with AZA and MMF. The adverse event rate in the AZA group was relatively higher than that in the MMF and mRTX groups, though no significant difference was noted among the three groups. ConclusionsCompared with AZA, mRTX and MMF significantly reduced the NMOSD relapse risk. mRTX-treated patients presented less concomitant steroid use than those treated with AZA and MMF, fewer adverse events, and better tolerance.

Randomized controlled trials for neuromyelitis optica spectrum disorder: a systematic review of trial architecture

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory disease that primarily affects the optic nerves and the spinal cord. Randomized controlled trials (RCTs) assessing treatments for NMOSD have been performed only in the past decade, and to date, there are three drugs approved by the U.S. Food and Drug Administration for anti-aquaporin-4 IgG seropositive NMOSD. This review assesses the characteristics and challenges of RCTs when evaluating treatments for NMOSD.MethodsWe conducted a systematic review using the search term [“neuromyelitis optica” OR “NMO” OR “NMOSD”] AND “clinical trial” in any language on December 28, 2020.ResultsSeven RCTs were included (see reference list below), and the trials’ architectures were analyzed and synthesized. Overall, 794 patients were randomized (monoclonal antibody intervention group, n=493 [62.1%]; placebo, n=196 [24.7%]; active control, n=105 [13.2%]); 709 (89.3%) were women; and 658 (82.9%) were anti-aquaporin IgG seropositive. The primary outcome was time to relapse in 6/7 of the trials, and annualized relapse rate in the remaining one. Four RCTs used placebo in their design. Among the seven published RCTs, the trial designs differed by the criteria used to define NMOSD relapse, selection of patients, proportion of anti-aquaporin-4 IgG seronegative patients, and baseline characteristics indicating NMOSD disease severity.ConclusionEthical considerations for the use of placebo should change in light of the approval of three therapies for seropositive NMOSD. Remaining challenges for clinical trials in NMOSD include the assessment of long-term safety and efficacy, standardization of trial design and endpoints, and head-to-head study designs. Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory disease that primarily affects the optic nerves and the spinal cord. Randomized controlled trials (RCTs) assessing treatments for NMOSD have been performed only in the past decade, and to date, there are three drugs approved by the U.S. Food and Drug Administration for anti-aquaporin-4 IgG seropositive NMOSD. This review assesses the characteristics and challenges of RCTs when evaluating treatments for NMOSD. We conducted a systematic review using the search term [“neuromyelitis optica” OR “NMO” OR “NMOSD”] AND “clinical trial” in any language on December 28, 2020. Seven RCTs were included (see reference list below), and the trials’ architectures were analyzed and synthesized. Overall, 794 patients were randomized (monoclonal antibody intervention group, n=493 [62.1%]; placebo, n=196 [24.7%]; active control, n=105 [13.2%]); 709 (89.3%) were women; and 658 (82.9%) were anti-aquaporin IgG seropositive. The primary outcome was time to relapse in 6/7 of the trials, and annualized relapse rate in the remaining one. Four RCTs used placebo in their design. Among the seven published RCTs, the trial designs differed by the criteria used to define NMOSD relapse, selection of patients, proportion of anti-aquaporin-4 IgG seronegative patients, and baseline characteristics indicating NMOSD disease severity. Ethical considerations for the use of placebo should change in light of the approval of three therapies for seropositive NMOSD. Remaining challenges for clinical trials in NMOSD include the assessment of long-term safety and efficacy, standardization of trial design and endpoints, and head-to-head study designs.

Relapsing neuromyelitis optica spectrum disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disorder of the central nervous system. Relapsing NMOSD (RNMOSD) is being reported frequently, leading to severe and permanent relapse related disability.Aims and Objectives: To study the clinical profile and imaging features of the NMOSD cases at the index time and addressing the long-term clinical spectrum of relapsing type of NMOSD who presented to the tertiary care hospital. Materials and Methods: All patients who attended the King George Hospital, Visakhapatnam and fulfilled the diagnostic criteria of NMOSD were studied for the epidemiological details, type of clinical spectrum on relapses, imaging features and treatment prescribed, and were studied between April, 2011 and March, 2018.Results: Total diagnosed cases were 28, out of which relapsing type were seen in 11 patients and all tested positive for antibodies. Female to male ratio is 3:1, and in RNMOSD group all were females. Most common clinical presentation was myelitis followed by optic neuritis. Noted clinical spectrum in the RNMOSD was unusual presentations like one each patient of Area-Postrema syndrome, diencephalic syndrome, cerebral syndrome, acute brainstem syndrome, and frequent relapses within a month in two. Five cases had also associated systemic autoimmune disorders.Conclusion: RNMOSD is very rapidly evolving disease, affecting primarily young women with wide spectrum of neurological presentations and also other non-neurological systemic features. Early diagnosis and aggressive immune therapy in the early phase might be warranted in NMOSD for relapse prevention and improving the quality of life.

Клинико-эпидемиологическая характеристика заболеваний спектра оптиконевромиелита в Республике Татарстан

The purpose — to study the clinical and epidemiological characteristics of neuromyelitis optica spectrum disorders (NMOSD) in the Republic of Tatarstan (RT). Material and methods. A retrospective analysis of the patients with NMOSD (according to 2015 diagnostic criteria), observed in our Centre in 2017–2021 (n = 35), was carried out. The parameters analyzed were demographic features, age of the disease onset, first clinical manifestations and course of disease, anti-AQP4 serum status, disease modifying therapy, and EDSS on baseline and follow up visits. Results and conclusions. We found that the prevalence of NMOSD in RT in 2021 was 0.9/100,000, the averaged (for 2017–2020) incidence was 0.83/1,000,000 per year. Among 35 patients (average age 43,4 (12,7) years old), 24 (69%) were female and 11 (31%) were male. The most common clinical manifestations at onset included optical neuritis and/or myelitis (94%). Most cases (83%) had relapsing course. Positive anti-AQP4 serum status was revealed in 49% of patients. The probably monophasic disease (n = 6) was observed predominantly in anti-AQP4 negative patients (5 vs. 1). DMT was prescribed to all patients with relapsing NMOSD, the most commonly used agents included corticosteroids, azathioprine and mitoxantron (49, 20, and 11% accordingly). The rate of remission rate for all DMT varied from 35 to 57%. Ultimately all patients with relapsing NMOSD showed EDSS increase over the follow-up period, which was more prominent among anti-AQP4 positive patients (from 3,8 to 5,4 over 4,4 (3,3) years, compared to 2,9 to 3,8 over 4,0 (3,0) years accordingly).

E.U. paediatric MOG consortium consensus: Part 1 - Classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

Over the past few years, increasing interest in the role of autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs) as a new candidate biomarker in demyelinating central nervous system diseases has arisen. MOG-abs have now consistently been identified in a variety of demyelinating syndromes, with a predominance in paediatric patients. The clinical spectrum of these MOG-ab-associated disorders (MOGAD) is still expanding and differs between paediatric and adult patients. This first part of the Paediatric European Collaborative Consensus emphasises the diversity in clinical phenotypes associated with MOG-abs in paediatric patients and discusses these associated clinical phenotypes in detail. Typical MOGAD presentations consist of demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM) in younger, and optic neuritis (ON) and/or transverse myelitis (TM) in older children. A proportion of patients experience a relapsing disease course, presenting as ADEM followed by one or multiple episode(s) of ON (ADEM-ON), multiphasic disseminated encephalomyelitis (MDEM), relapsing ON (RON) or relapsing neuromyelitis optica spectrum disorders (NMOSD)-like syndromes. More recently, the disease spectrum has been expanded with clinical and radiological phenotypes including encephalitis-like, leukodystrophy-like, and other non-classifiable presentations. This review concludes with recommendations following expert consensus on serologic testing for MOG-abs in paediatric patients, the presence of which has consequences for long-term monitoring, relapse risk, treatments, and for counselling of patient and families. Furthermore, we propose a clinical classification of paediatric MOGAD with clinical definitions and key features. These are operational and need to be tested, however essential for future paediatric MOGAD studies.

Eculizumab in the treatment of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) isa rare autoimmune diseaseof the CNS which is distinct from multiple sclerosis and typically presents with a relapsing course of optic neuritis, myelitis and midline brain inflammatory lesions. In at least two-thirds of cases, antibodies against the water channel AQP4can be found, which lead to an antibody-mediated activation of the complement system with consecutive damage to neuronal structures. Eculizumab, a humanized monoclonal antibody against the terminal complement component 5, was shown to significantly reduce the risk of NMOSD relapse in a Phase III placebo-controlled trial. Based on this, eculizumab (Soliris®) was the first drug to be formally approved for the treatment of anti-AQP4-antibody positive NMOSD in 2019.

Risk of COVID-19 infection in MS and neuromyelitis optica spectrum disorders.

ObjectiveDisease-modifying drugs (DMDs) may alter the immune status and thus increase the susceptibility to coronavirus disease 2019 (COVID-19) in patients with MS or neuromyelitis optica spectrum disorders (NMOSD). However, evidence supporting this notion is currently lacking. In this study, we conducted a survey on the risk of COVID-19 in patients with MS and NMOSD.MethodsThe survey was conducted through the Chinese Medical Network for Neuroinflammation. Patients in 10 MS centers from 8 cities including Wuhan were included. Information about MS and NMOSD disease duration and the usage of DMDs were collected. Data of suspected cases of COVID-19 were obtained from hospital visits, questionnaires, and patient self-reporting. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed through clinical evaluation by a panel of experts in conjunction with chest CT and viral RNA detection.ResultsEight hundred eighty-two of 1,804 (48.89%) patients with MS and 2,129 of 3,060 (69.58%) patients with NMOSD were receiving DMDs. There were no alterations in the patients' DMD regimen during January 15, 2020, to March 15, 2020, the 3-month period. None of the patients with MS treated with DMDs had COVID-19. However, 2 patients with relapsing NMOSD were diagnosed with COVID-19-related pneumonia. After treatment, both patients recovered from pneumonia and neither patient experienced new attacks due to predisposing SARS-CoV-2 infection in the following 2 months.ConclusionsNo increased risk of COVID-19 infection was observed in patients with MS or NMOSD, irrespective of whether these patients received DMDs. A battery of stringent preventive measures adopted by neurologists to reduce COVID-19 infection in these patients may have contributed to low risk of COVID-19 infection.