Relapsing Neuromyelitis Optica Research Articles

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare chronic neuroinflammatory autoimmune condition. Since the onset of the COVID-19 pandemic, there have been reports of NMOSD clinical manifestations following both SARS-CoV-2 infections and COVID-19 vaccinations. This study aims to systematically review the published literature of NMOSD clinical manifestations associated with SARS-CoV-2 infections and COVID-19 vaccinations. A Boolean search of the medical literature was conducted between December 1, 2019 to September 1, 2022, utilizing Medline, Cochrane Library, Embase, Trip Database, Clinicaltrials.gov, Scopus, and Web of Science databases. Articles were collated and managed on Covidence® software. The authors independently appraised the articles for meeting study criteria and followed PRISMA guidelines. The literature search included all case reports and case series that met study criteria and involved NMOSD following either the SARS-CoV-2 infection or the COVID-19 vaccination. A total of 702 articles were imported for screening. After removing 352 duplicates and 313 articles based on exclusion criteria, 34 articles were analyzed. A total of 41 cases were selected, including 15 patients that developed new onset NMOSD following a SARS-CoV-2 infection, 21 patients that developed de novo NMOSD following COVID-19 vaccination, 3 patients with known NMOSD that experienced a relapse following vaccination, and 2 patients with presumed Multiple Sclerosis (MS) that was unmasked as NMOSD post-vaccination. There was a female preponderance of 76% among all NMOSD cases. The median time interval between the initial SARS-CoV-2 infection symptoms and NMOSD symptom onset was 14 days (range 3-120 days) and the median interval between COVID-19 vaccination and onset of NMO symptoms was 10 days (range 1 to 97 days). Transverse myelitis was the most common neurological manifestation in all patient groups (27/41). Management encompassed acute treatments such as high dose intravenous methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG) and maintenance immunotherapies. The majority of patients experienced a favorable outcome with complete or partial recovery, but 3 patients died. This systematic review suggests that there is an association between NMOSD and SARS-CoV-2 infections and COVID-19 vaccinations. This association requires further study using quantitative epidemiological assessments in a large population to better quantify the risk.

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.

Compassionate open-label use of rituximab following a randomised clinical trial against neuromyelitis optica (RIN-2 study): B cell monitoring-based administration

ObjectiveThe aim of the RIN-2 study was a compassionate use of rituximab (RTX) for patients who completed the RIN-1 study, a multicentre, randomised, double-blind, placebo-controlled trial of RTX. We also investigated the long-term safety and efficacy of RTX. MethodsA study design was a prospective open-label extension study following the RIN-1 study. RTX was infused repeatedly under monthly monitoring of CD19-positive and CD 20-positive B cell lymphocyte subsets from 24 weeks after an infusion. ResultsThirty-three (87%) of 38 patients of the RIN-1 study were enrolled from February 2016 to March 2019 at six sites in Japan. In RIN-2, RTX was administered three times (median, range 1–5 times), and the interval of RTX administrations were 9.5 [2.5] months (mean [SD]). The observation period was 20.5 [10.1] months. During the trial, three patients dropped out due to two withdrawals and one adverse event. During the study, 28 (90%) of 31 patients were treated with RTX monotherapy. Neuromyelitis optica (NMO) relapses were observed in two patients. The annualized relapse rate (ARR) was 0.035 counts per person-years, ∼1/10th compared with 0.321 in the placebo arm of the RIN-1 study. We observed 14 severe adverse events in six (18%) and 156 adverse events, of which 135 were grade 1, 11 were grade 2 and 10 were grade 3. ConclusionsUnder B cell monitoring, the interval of RTX re-infusion was elongated to nine months, and NMO relapses were suppressed with 0.035 of ARR.

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.

A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder

A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder

The progress of research on the immune pathogenesis and biomarkers in optic neuritis related to neuromyelitis optica

The idiopathic optic neuritis (ION) which is related to neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) is called optic neuritis related to neuromyelitis optica (NMO-ON). Because of the high rates of blindness, disability and fatality of NMO, the heterogeneous clinical presentation, severity of neurologic disability following relapses, and variability of therapeutic responses, reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed. Currently, detecting aquaporin-4 (AQP4) antibodies (AQP4-IgG or NMO-IgG) in serum is employed as the major supporting approach for the diagnosis of seropositive NMO, however, AQP4-IgG seronegativity in 10% to 25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis. Collaborative international studies hold great promise for establishing and validating biomarkers of NMO. This article discusses known and potential biomarkers for NMO. The biomarkers of NMO maybe the potential biomarkers of NMO-ON, for ION is the initial presentation and the earliest stage. (Chin J Ophthalmol, 2019, 55:228-233).

Neuromyelitis optica and neuromyelitis optica spectrum disorders

The review is devoted to up-to-date data on epidemiology, aspects of the pathogenesis of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD). The authors consider a role of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in the syndromes phenotypically similar to NMO and NMOSD. Special attention is drawn to the methods of MOG-IgG antibodies detection and indications for testing. The approaches and management for treatment and prevention of NMO relapses, risks of complications during pregnancy and immediately after delivery, as well as methods for their prevention and treatment, are described.

Efficacy and safety of long-term treatment with low-dose rituximab for neuromyelitis optica spectrum disorder

Objective To evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing neuromyelitis optica spectrum disorder (NMOSD). Methods A perspective study. 21 patients who were diagnosed with NMOSD one year ago were recruited for rituximab treatment. Of 21 patients, one was male, 20 were females. Onset age was 10 - 51 years, the mean onset age was (26.2±12.0) years. Duration of disease was 2.3 - 25.8 years, the mean duration was (9.2±5.9) years. Best corrected vision activity(BCVA), expanded disability status scale (EDSS), annualized relapsing rate (ARR) were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. The BCVA was examined using Snellen chart, and converted to logMAR. The mean BCVA was 1.13±1.09, the mean BCVA in better eyes was 0.4±0.68, the mean BCVA in latter eyes was 1.87±0.90. The mean EDSS was 3.09±0.70. The mean ARR was 1.04±0.65. All patients underwent two cycles of RTX treatment. The annually induction treatment was RTX 100 mg per week for 4 weeks. Of 21 patients, 12 patients had treatment within one month after attack. The mean follow-up period was (28.4±4.9) months. The side effects were recorded, BCVA, EDSS, ARR were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. Paired t test, independent sample t test and Chi-squared test were used. Results The mean BCVA at last follow-up was 0.62±0.91, the mean BCVA in better eye was 0.62±0.91, the BCVA in latter eye was 1.0±1.01. The mean EDSS was 2.26±1.07. The mean ARR was 0.21 ± 0.3. After the treatment, patient had significant improvement on BCVA in worst eye (t=4.256), ARR (t=2.900), EDSS (t=4.620) with the significant differences (P 0.05). There were 9 patients had relapse, 13 times in total. Of 13 relapses, B lymph cell count was performed in 12 relapses, and the counts were 0.01% - 0.14%. There were no significant difference between relapsed patients and non-relapsed patients on onset age (t=0.67, P=0.51), whether underwent plasma exchange treatment (χ2=1.61, P>0.05), with/without auto-immune antibody ratio (χ2=1.61, P>0.05). Of 21 patients, 8 patients had side effects, including 5 patients with infection, 4 patients with chest congestion, 3 patients with hair losing, 2 patients with skin rashes, headache and short of breath, 1 patient with tinnitus, palpitation and fatigue. Four patients had more than one symptom. Of all patients who had side effects, slowing down the infusion speed of RTX or infusing 5 mg of dexamethasone could relieve the discomfort. Conclusion Lose-dose rituximab reduces the frequency of NMOSD relapses and is well tolerated. Key words: Neuromyelitis optica/drug therapy; Antigens, CD20/administration & dosage; Protective agents; Recurrence

Neuromyelitis Optica in Children: A Rare Entity

Neuromyelitis optica (also known as Devic's disease or Devic's syndrome) is an uncommon disorder in pediatric age group, and is characterized by acute or subacute optic neuritis and transverse myelitis. Here we report an 11- year- old female child with relapsing Neuromyelitis optica (NMO) confirmed by positive NMO- IgG antibody and had clinical recovery with high dose methyl prednisolone therapy.

Safety and Efficacy of Bortezomib in Patients With Highly Relapsing Neuromyelitis Optica Spectrum Disorder

This study examines the safety and efficacy of bortezomib in patients with highly relapsing neuromyelitis optica spectrum disorder.

Clinical features and prognostic analysis of neuromyelitisoptica spectrum disease with sjogrensyndrome

Objective: To explore the clinical features and conduct prognostic analysis about visual recovery and relapse of neuromyelitisoptica (NMO) spectrum disease (NMOSD) with sjogren syndrome (SS). Methods: A retrospective and prospective observational study was conducted.Between July 2013 and June 2016, 172 patients with NMOSD (NMOSD-non SS: 116/172, 67.4%; NMOSD-SS: 56/172, 32.6%) were assessed at Beijing Tongren Hospital, Capital Medical University, Beijing, China.The prognostic factors of NMOSD-SS patients were also analyzed. Results: As compared with NMOSD-non SS patients, NMOSD-SS patients had worse visual impairment (percentage of patients with visual acuity less than 0.1, 83.9% vs 69.8%, P<0.05), higher positive rate of SSA (92.9% vs 0.0%, P<0.05), higher proportion of dryness of mouth and eye (66.1% vs 5.2%, P<0.05) as well as higher percentage of reduced visual evoked potential (VEP) amplitude (60.7% vs 43.1%, P<0.05). NMOSD-SS patients had a significantly higher average year recurrent frequency (0.58 vs 0.53) and significantly shorter mean recurrence time (6.7 months vs 12.4 months, P<0.05). The results showed that recurrent eyes, the worst visual acuities of onset less than 0.1 were independent risk factors of visual impairment (visual activity <0.1), according to at least six months' follow-up of all NMOSD-SS patients (OR=6.410 and 9.434, respectively, P<0.05). Meanwhile, immunosuppressive drugs were protective factors of relapse in NMOSD-SS patients (OR=0.107, P<0.05). Conclusions: NMOSD-SS patients have worse visual impairment, and they are more vulnerable to relapse than NMOSD-non SS patients, and the vision is lack of recovery for NMOSD-SS with recurrent eyes or the worst vision of onset less than 0.1.Immunosuppressive drugs can reduce the recurrence of NMOSD-SS relapse.

Quotient of cerebrospinal fluid/serum immunoglobulin G as a predictive factor for non‐responders to intravenous methylprednisolone therapy in patients with relapsing neuromyelitis optica spectrum disorder: Implication for early initiation of plasmapheresis

AbstractObjectivesWe aimed to determine the predictive factors for the ineffectiveness of intravenous methylprednisolone (IVMP) that lead to earlier use of plasmapheresis in patients with relapsing neuromyelitis optica spectrum disorder.MethodsA total of 40 patients were investigated retrospectively. The responders were defined as patients who showed IVMP effectiveness within 7 days from IVMP initiation, indicated by an improvement in the Kurtzke Expanded Disability Status Scale (EDSS) ≥0.5, whereas non‐responders were defined as those without such an improvement. We analyzed 10 clinical findings and four cerebrospinal fluid (CSF) parameters before IVMP, which included EDSS (baseline before relapse, before IVMP initiation, difference between them: ΔEDSS), CSF‐cells, CSF‐lactate dehydrogenase, CSF/serum quotient of albumin (Q‐ALB) and immunoglobulin G (Q‐IgG).ResultsThe 40 patients consisted of 22 responders and 18 non‐responders. The levels of ΔEDSS, EDSS before IVMP, CSF‐cells, CSF‐lactate dehydrogenase, Q‐ALB and Q‐IgG were significantly higher in non‐responders than in responders. Of these, univariate logistic regression analyses showed that the ΔEDSS, EDSS before IVMP, Q‐ALB and Q‐IgG were significantly related to IVMP ineffectiveness. Because of the significant correlation between ΔEDSS and EDSS before IVMP, and between Q‐ALB and Q‐IgG, the ΔEDSS and Q‐IgG were analyzed as dependent factors for IVMP ineffectiveness in multivariate analysis. The higher Q‐IgG level was found to be independently associated with ineffectiveness. The cut‐off level for Q‐IgG to discriminate non‐responders from responders was 4.7 (sensitivity 83, specificity 91%).ConclusionsQ‐IgG &gt;4.7 before IVMP is a predictive factor for IVMP ineffectiveness. Early use of plasmapheresis should be considered in relapsing neuromyelitis optica spectrum disorder with such high Q‐IgG values before IVMP.

Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus: A preliminary study

Background: Neuromyelitis optica (NMO)–systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. Objective: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute. Methods: In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission. Results: AQP4-IgG1 was present 1–2–5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC (p<0.05, respectively). CCL17/TARC correlated with levels of anti-nucleosome and anti-dsDNA (p<0.05, respectively). Compared to healthy subjects, concentration of IFN-γ and CCL17/TARC was higher in NMO/SLE (p<0.05). Conclusions: AQP4-IgG1 antibodies are present in the sera years before the first NMO attack in patients with SLE; elevation of anti-AQP4 is part of a polyclonal B cell response during NMO relapses; in spite of multiple autoantibodies in the serum, MOG antibodies were not present; Th1 responses accompany autoantibody responses in NMO/SLE.

In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology.

ObjectiveNeuromyelitis optica (NMO) is an autoimmune disease of the central nervous system, which resembles multiple sclerosis (MS). NMO differs from MS, however, in the distribution and histology of neuroinflammatory lesions and shows a more aggressive clinical course. Moreover, the majority of NMO patients carry immunoglobulin G autoantibodies against aquaporin‐4 (AQP4), an astrocytic water channel. Antibodies against AQP4 can damage astrocytes by complement, but NMO histopathology also shows demyelination, and — importantly—axon injury, which may determine permanent deficits following NMO relapses. The dynamics of astrocyte injury in NMO and the mechanisms by which toxicity spreads to axons are not understood.MethodsHere, we establish in vivo imaging of the spinal cord, one of the main sites of NMO pathology, as a powerful tool to study the formation of experimental NMO‐related lesions caused by human AQP4 antibodies in mice.ResultsWe found that human AQP4 antibodies caused acute astrocyte depletion with initial oligodendrocyte survival. Within 2 hours of antibody application, we observed secondary axon injury in the form of progressive swellings. Astrocyte toxicity and axon damage were dependent on AQP4 antibody titer and complement, specifically C1q.InterpretationIn vivo imaging of the spinal cord reveals the swift development of NMO‐related acute axon injury after AQP4 antibody‐mediated astrocyte depletion. This approach will be useful in studying the mechanisms underlying the spread of NMO pathology beyond astrocytes, as well as in evaluating potential neuroprotective interventions. Ann Neurol 2016;79:794–805

Neuromyelitis optica relapses: Race and rate, immunosuppression and impairment

ObjectiveNeuromyelitis optica (NMO) is a rare antibody-mediated CNS disease characterised by disabling relapses leading to high morbidity and mortality. Understanding relapse activity and severity is important for treatment decisions and clinical trial design. We assessed (1) whether clinical and demographic factors associate with different relapse rates and (2) the relative impact of immunosuppressive treatments on relapse rates and on attack-related residual disability. MethodsClinical, demographic and treatment data were prospectively collected from 79 consecutive aquaporin 4 antibody positive patients seen in the nationally commissioned Oxford NMO service. The influence of clinical features on annualised relapse rates (using multiple regression) and the effect of immunosuppression on relapse-associated residual disability for transverse myelitis and optic neuritis attacks (using a mixed effect model) were analysed. ResultsThe mean annualised relapse rate was 0.93. Relapse rates were significantly higher in Afro-Caribbeans, children and in those of shorter disease duration. Relapse rates reduced on treatment (from 0.87 to 0.42). Delay to first treatment did not influence eventual on-treatment relapse rate. Immunosuppressive treatment significantly reduced the residual disability from ON (p<0.01), and TM (p=0.029) attacks. ConclusionsRelapse rates in NMO are influenced by multiple factors, including age, ethnicity and disease duration. Current immunosuppressive treatments reduce but do not abolish relapses, however, they appear to additionally lessen the chronic disabling effect of a relapse.

Efficacy and Toxicity of Rituximab in Multiple Sclerosis

Context: Bothersome relapses or conditions that damage function in patients with multiple sclerosis (MS) need a well-focused strategy of appropriate management to return patients’ function and decrease the disability. A large number of clinical studies are being accompanied to evaluate the effectiveness and adverse effects of rituximab. Deteriorations assist as significant signs of disorder activity. In such conditions B cell-depleting regimens such as rituximab may be considered. To attain major motivation and gather talented satisfying evidence, strong review articles and research could try to focus on the best time to prescribe rituximab in MS. Evidence Acquisition: Clinical trials and review articles to achieve efficacy and safety of rituximab in MS were searched. The current study first offered an outline of the rituximab pharmacokinetics parameters in overall, suggested mechanisms of action that contribute to the beneficial effects of rituximab and the perfect timing of prescription-based therapies for MS. Results: A total of 647 articles (1997 - 2015) were found related to efficacy, safety and pharmacokinetics parameters of rituximab in MS. Six articles (3; 2009, 1; 2010 and 2; 2011) were related to the use of rituximab in: primary progressive MS, autoimmune disease, refractory and autoimmune pediatric disease, 52-week phase II clinical trials and relapsing neuromyelitis optica were studied further. In phase II clinical trials based on blinded radiological end-points pharmacotherapy using rituximab suggested to be effective. There is also report regarding to less increase in T2 lesion volume (P < 0.001) after two years of rituximab management. There was no change in brain volume (P = 0.62). There was a delay in patients less than 51 years related to the disease progression. Adverse effects were reported in < 5% of patients with rituximab. Also it has been reported that in 28 out of 30 patients with neuromyelitis optica, there was a significant reduction in the rate of relapse over two years. Conclusions: The current study aimed to evaluate the efficacy of rituximab in patients with MS. Due to inter and intra individual variability in disease presentation and its progression, rituximab should be prescribed cautiously.

Pregnancy Management in NMO: A Case of MOG- Antibody Positive NMO and Literature Review

Neuromyelitis optica (NMO) is a rare but severely disabling disease, affecting predominantly the optic nerves and spinal cord. Aquaporin-4 (AQP4 IgG) antibodies have been described as characteristic and pathogenic for the disease. Some NMO cases are AQP4 IgG negative, of which a fraction has antibodies against myelin oligodendrocyte glycoprotein (MOG). We report the pregnancy of a 42 year old English woman who was diagnosed with neuromyelitis optica spectrum disorder (NMOSD), with anti-MOG antibodies. She fell pregnant prior to starting immunosuppressive therapy. At week 30 of gestation, she experienced a relapse and was treated with high dose steroids. She developed further right hand numbness in the week post-partum and had MRI confirmation of a new cervical lesion. This case suggests that unlike in multiple sclerosis (MS), pregnancy does not protect from relapses in NMO. Here we review the limited experience of pregnancy outcomes in anti-MOG antibodies positive NMO patients.

Rapid exacerbation of neuromyelitis optica after rituximab treatment

Studies have shown the efficacy of immunosuppressants against neuromyelitis optica (NMO). Rituximab is recommended as an off-label prescription to treat refractory NMO. However, we describe two such patients who were suboptimally responsive to rituximab and whose symptoms worsened after treatment. Our cautionary cases highlight that in a small proportion of patients with refractory NMO, rituximab may either fail or induce rapid relapse of NMO. This suggests we need to consider new treatment strategies for refractory NMO.

Bevacizumab is safe in acute relapses of neuromyelitis optica.

Neuromyelitis optica (NMO) is a relapsing autoimmune disease targeting the spinal cord and optic nerve leading to paralysis and blindness. Current treatment for acute NMO attacks is immunosuppression with high-dose corticosteroids and/or plasmapheresis. Preclinical animal studies suggest that bevacizumab might be beneficial in limiting the extent of inflammation during a NMO relapse by reducing the disruption of the blood-brain barrier. We carried out an open-label phase 1b safety and proof-of-concept trial in 10 participants with NMO immunoglobulin G seropositive NMO, NMO spectrum disease and those at high risk for developing NMO/NMO spectrum disease who presented with an acute attack of transverse myelitis, optic neuritis or brainstem inflammation. In addition to treating with 1 g of daily intravenous methylprednisolone, we infused 10 mg/kg of bevacizumab intravenously on day 1 of treatment. The primary outcome measure was safety and the secondary outcome measure was efficacy. Of the 10 participants enrolled, five presented with acute transverse myelitis, four with acute optic neuritis and one with a brainstem lesion. Bevacizumab was safe in all 10 participants, with only one serious adverse event within the 90-day follow up that was not attributed to the medication. Three patients recovered to pre-attack neurological function or better, and no patients required escalation to plasmapheresis. Bevacizumab is a safe add-on therapy to high-dose corticosteroids for NMO/NMO spectrum disease patients presenting with an acute relapse.

A placebo controlled trial for an NMO relapse prevention treatment: Ethical considerations

This paper addresses the ethical acceptability of a proposed placebo controlled trial of a new intervention as a possible relapse prevention treatment for Neuromyelitis Optica (NMO). In the analysis of this controversial ethical issue, the author points out significant factors that are often overlooked or ignored, such as the life-long implications for study participants and others living with the disease, and also addresses commonly noted issues, such as vulnerability, benefits, harms, and justice that always require attention in research review.