Assessing the Benefits of “Circle”: A Patient Support Program for Neuromyelitis Optica Spectrum Disorder for Patients Receiving Satralizumab Treatment

BackgroundVascular alterations are now recognized as important contributors to the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD). This study aimed to use optical coherence tomography (OCT) and OCT-angiography (OCTA) to assess alterations in the retinal structure and microvasculature in patients with NMOSD, so we can understand pathophysiology of NMOSD, implicating this on disease activity, visual outcome and management on the future.MethodsA case–control study was conducted on 40 NMOSD patients with (NMOSD + ON) and without (NMOSD – ON) history of optic neuritis and 36 healthy subjects. The following data were assessed in NMOSD patients: clinical history, EDSS, and visual function testing. Both groups underwent spectral domain (SD)-OCT and OCTA.ResultsIn this study, NMOSD + ON patients had a statistically significant reduction in all SD-OCT parameters compared to healthy control. Regarding OCTA, there was a significant reduction in radial peripapillary capillary density (RPCD) in NMOSD + ON (P-value < 0.001) and some sectors of NMOSD–ON compared to healthy control. NMOSD + ON patients had significant differences in RPCD compared to those without (P-value < 0.001).ConclusionsHere we show that the advance of this study is that retinal microvascular alterations have been noticed in NMOSD–ON eyes, indicating that subclinical primary retinal vasculopathy and disease activity may occur in NMOSD before onset of ON and retinal atrophy. This may have implications on early detection of disease activity, early interference in management and prognostic tool to visual outcome in following the patients.

This review summarizes the literature on sleep quality in neuromyelitis optica spectrum disorder (NMOSD) and discusses these findings in the context of current knowledge of sleep physiology. A literature search was performed using Ovid MEDLINE, Embase, and Scopus from inception to September 3, 2020. All included studies reported at least 1 measure of sleep quality in individuals with NMOSD. Pittsburgh Sleep Quality Index (PSQI) scores of individuals from 4 studies were compared with those from a data set of controls. Thirteen studies (1041 individuals with NMOSD) were included in the review. Disturbed sleep was demonstrated across subjective metrics based on patient surveys and objective metrics such as polysomnography. An estimated 70% of individuals with NMOSD can be classified as poor sleepers. Standardized mean difference between PSQI scores of 183 individuals with NMOSD and those of 9284 controls was 0.72 (95% CI, 0.57-0.86; P < .001). Decreased sleep quality was significantly associated with decreased quality of life and increased anxiety, depression, and disability status. Sleep disturbances in NMOSD were similar in severity to those in multiple sclerosis. Sleep disturbances are a major contributor to NMOSD disease burden and may arise from the disruption of sleep circuitry, in addition to physical and psychological complications. Multiple processes involved in sleep regulation may be affected, such as, but not limited to, neural circadian circuit disruption, direct effects of inflammation, aminergic projecting system abnormalities, glymphatic system impairment, and development of sleep disorders such as restless legs syndrome/sleep apnea. A better understanding of these mechanisms is necessary for developing effective therapies for NMOSD-associated sleep disturbances.

BackgroundCertain peripheral proteins are involved in the development of Neuromyelitis optica spectrum disorders (NMOSD), such as IL-6, complement proteins, and MHC class II molecules. However, the roles of other new protein biomarkers are unclear. Current NMOSD treatments (e.g., intravenous pulse methylprednisolone, or satralizumab for IL-6 receptor inhibition) can only manage symptoms, necessitating the identification of new drug targets to treat NMOSD. The objective of this study is to identify potential drug targets for NMOSD through Mendelian randomization (MR) analysis, thereby addressing the limitations of current treatments and providing better clinical options for patients.MethodsNMOSD potential drug targets were evaluated via MR. Data was obtained from a genome-wide association study (GWAS) with 132 individuals with AQP4-IgG-positive NMOSD and 1244 controls. Genetic instruments for plasma and cerebrospinal fluid (CSF) proteins were identified. Sensitivity analyses were conducted using Bayesian co-localization, reverse causality testing and phenotype scanning. Additionally, a comparison and analysis of protein-protein interactions (PPI) were conducted to identify potential causal proteins. The implications of these findings were further explored by evaluating existing NMOSD drugs and their respective targets.ResultsFour proteins were identified at the FDR correction via MR analysis (p < 0.05). Higher levels of PF4V1 (OR = 0.47; 95% CI, 0.29–0.78; p = 3.39 × 10−3) and FAM3B (OR = 0.12; 95% CI, 0.03–0.45; p = 1.65 × 10−3) were associated with a reduced risk of NMOSD, whereas elevated SERPINA1 (OR = 2.28; 95% CI, 1.29–4.04; p= 4.71 × 10−3) and CLEC11A (OR = 13.45; 95% CI, 1.29–4.04; p = 4.71 × 10−3) were related to an increased risk of NMOSD. Bayesian co-localization showed that the protein-related genes shared the same mutation as NMOSD (all PPH4>0.80). Reverse causality testing showed no evidence of NMOSD-driven protein changes (all p > 0.05). PPI analysis revealed SERPINA1 interacts with PF4V1 (combined score = 0.72). Drug evaluation identified Mercaptoethanol and Ferrous gluconate as repurposing candidates.ConclusionIncreased levels of plasma CLEC11A and SERPINA1 are correlated with an elevated risk of NMOSD, whereas elevated levels of plasma PF4V1 and CSF FAM3B are associated with a decreased risk of NMOSD. The opposing effects of risk or protective proteins suggest synergistic targeting could improve efficacy beyond current immunosuppressive regimens. Nonetheless, clinical trials are required to confirm the findings.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder affecting the central nervous system that is associated with significant morbidity and mortality. Early diagnosis and treatment are essential to minimize long-term disability. Recent advances in the understanding of the pathophysiology of NMOSD have led to multiple new therapies, but significant care and knowledge gaps persist. OBJECTIVES: To summarize current knowledge about the burden of disease and diagnosis and treatment of NMOSD in order to support managed care professionals and health care providers in making collaborative, evidence-based decisions to optimize outcomes among patients with NMOSD. In addition, this review also presents findings of a patient survey that provides insight into real-world experiences of those living with NMOSD. SUMMARY: Diagnosis of NMOSD is based on detection of immunoglobulin G antibodies to the water channel protein aquaporin-4 (AQP4-IgG) in the context of compatible clinical and magnetic resonance imaging features. Patients who are AQP4-IgG seronegative and/or who are positive for myelin oligodendrocyte glycoprotein antibodies may also satisfy criteria for NMOSD. The rarity of the condition combined with the significant overlap in clinical features with other autoimmune diseases affecting the central nervous system, most notably multiple sclerosis, can delay accurate diagnosis, which in turn can delay appropriate treatment, leading to the accumulation of long-term disability. Accumulating disability associated with NMOSD has a substantial negative impact on quality of life. The disease typically evolves as relapsing (ie, repeated) acute attacks. Treatment consists of management of acute attacks, prevention of subsequent attacks, and management of acute and chronic symptoms. The armamentarium of therapies to prevent attacks consists of several monoclonal antibodies (mAbs) approved to treat AQP4-IgG-seropositive disease and several off-label therapies used for patients with either seropositive or seronegative disease. There is limited evidence to guide treatment decision-making, including which therapies to use first line, when to switch, and when to use monotherapy vs combination therapy. In addition, therapies with the greatest demonstrated safety and efficacy in NMOSD are costly and may not be accessible to all patients. Moreover, the results of the patient survey revealed significant clinical and financial burdens to patients with NMOSD including frequent attacks, delays in therapy initiation, need for urgent care and repeat hospitalizations, new and worsening symptoms, accumulating disability, and difficulties affording care. As such, key stakeholders must weigh them against the substantial economic costs of untreated or suboptimal treatment of disease. DISCLOSURES: Dr Wingerchuk has served on the advisory board or panel for Alexion, Biogen, Genentech, Horizon, Mitsubishi Tanabe, Novartis, Roche, UCB, and Viela Bio and has received grants of research support from Alexion. Dr Weinshenker has served as a consultant or on the advisory board or panel for Alexion, Genentech, Horizon, Mitsubishi Tanabe, Roche, UCB, and Viela Bio, served on the speakers bureau or other promotional education for Genentech and Roche, and has received royalties from RSR Ltd.

COVID-19 in MS and NMOSD: A multicentric online national survey in Chile

Introduction Treatment options for patients suffering from neuromyelitis optica spectrum disorders (NMOSD) so far have relied on off-label and empiric drugs. The first drug for the therapy of anti-aquaporin-4 (AQP4) antibody-seropositive NMOSD patients has been approved in 2019: the C5 complement inhibitor eculizumab. The interleukin-6 receptor inhibitor satralizumab and anti-CD19 antibody inebilizumab have published positive phase III trial results and await approval in the near future. Areas covered We sum up current treatment options and portray in detail the new developments in NMOSD drugs focusing on phase III clinical trials, followed by an overview of emerging drugs in less advanced clinical trial stages. Expert opinion Eculizumab’s approval by the competent authorities marks a milestone in NMOSD treatment. Satralizumab and inebilizumab will most likely follow in approval given their presented results in efficacy and safety. All three drugs have shown efficacy in reducing relapse rates in NMOSD patients with anti-AQP4 antibodies. Although we will have even more evidence-based therapy options in the future, empirically used medications will keep their importance for now. The potential effect of new medications in AQP4 antibody-seronegative NMOSD and patients with an NMOSD phenotype and antibodies to myelin oligodendrocyte glycoprotein remains to be determined.

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders.

Objective: This study aimed to assess the physical, emotional, medical, and socioeconomic conditions of patients with neuromyelitis optica spectrum disorder (NMOSD) in North China.Methods: A cross-sectional survey of patients with NMOSD was performed, based on an established questionnaire from the Multiple Sclerosis Patient Survival Report 2018. Logistic regression analysis was conducted to define the significant determinants of certain physical or emotional characteristics of patients. A total of 123 patients were included.Results: A total of 63.4% of participants were initially diagnosed with conditions other than NMOSD, with a median delay of 6 months for accurate diagnosis. An aggregate of 72.2% of patients had one or more relapses, corresponding to an annual relapse rate of 0.8. Paresthesia was the most frequent physical symptom among patients both at disease onset (53.7%) and throughout the duration of the disease (86.2%). Onset in elderly (>50 years) patients was associated with an annual Expanded Disability Status Scale increase ≥1, compared with onset in younger (<30 years) patients (P = 0.001, OR = 7.83). A total of 76.4% of patients had received attack-prevention treatments in the remission phase, and 31.7 and 10.6% of patients had ever been administered rituximab and traditional Chinese medicine, respectively. Additionally, 63.4 and 43.1% of patients reported participating in few or no social activities and being out of work because of the disease. To be noted, 76.4% of patients reported suffering from negative emotions, with the most frequent being worry (60.2%), with 20.3% of patients experiencing suicidal thoughts. The inability to work and participating in few or no social activities due to NMOSD were two determinants of experiencing negative emotions (Pwork = 0.03, ORwork = 3.34; Psocialactivities = 0.02, ORsocialactivities = 3.19).Conclusion: This study reported patient perspectives on NMOSD in North China, whereby demonstrating that the inability to work and participating in few or no social activities due to NMOSD rather than the physical impairment caused by the disease, was directly associated with patients experiencing negative emotions. This insight offers potential ways to manage patients' negative emotions by enhancing family and social support and facilitating active employment.

Is there a link between neuropathic pain and constipation in NMOSD and MOGAD? Results from an online patient survey and possible clinical implications

Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders

Early detection of neuromyelitis optica spectrum disorders (NMOSD), especially after optic neuritis, a presenting manifestation commonly observed also in multiple sclerosis (MS), is crucial for timely treatment and prognosis. Integrated visual pathway assessment with optical coherence tomography (OCT) and visual evoked potentials (VEP) may help in this task, showing in vivo different pathophysiological backgrounds. We evaluated combined VEP and OCT in a cross-sectional, single-centre study assessing 50 consecutive NMOSD patients, 57 MS patients and 52 healthy controls. After optic neuritis, VEP were more frequently absent in NMOSD compared to MS; most NMOSD eyes with recordable VEP showed prolonged latency, but extreme latency delays were less common than in MS. OCT showed predominantly axonal involvement in NMOSD, with 88% eyes (95% CI: 69–97%) displaying retinal nerve fibre layer thickness <60 µm even after first optic neuritis episode. Accuracy of OCT was further enhanced by combination with VEP into a new Z-score derived OCT-VEP index, measuring prevalence of axonal damage or demyelination. Our results suggest that integrated optic nerve assessment may elucidate differences in optic neuritis pathophysiology; conduction slowing with relatively preserved nerve fibre layer suggests MS, while severe neuroaxonal loss after optic neuritis, often hindering VEP response, characterizes NMOSD.

This article reviews the cardinal clinical features, distinct immunopathology, current diagnostic criteria, relapse-related risk factors, emerging biomarkers, and evolving treatment strategies pertaining to neuromyelitis optica spectrum disorders (NMOSD). The discovery of the pathogenic aquaporin-4 (AQP4)-IgG autoantibody and characterization of NMOSD as an autoimmune astrocytopathy have spearheaded the identification of key immunologic therapeutic targets in this disease, including but not limited to the complement system, the interleukin 6 (IL-6) receptor, and B cells. Accordingly, four recent randomized controlled trials have demonstrated the efficacy of three new NMOSD therapies, namely eculizumab, satralizumab, and inebilizumab. Currently, NMOSD poses both diagnostic and treatment challenges. It is debated whether individuals who are seropositive for myelin oligodendrocyte glycoprotein (MOG)-IgG belong within the neuromyelitis optica spectrum. This discussion is fueled by disparities in treatment responses between patients who are AQP4-IgG seropositive and seronegative, suggesting different immunopathologic mechanisms may govern these conditions. As our understanding regarding the immune pathophysiology of NMOSD expands, emerging biomarkers, including serum neurofilament light chain and glial fibrillary acidic protein (GFAP), may facilitate earlier relapse detection and inform long-term treatment decisions. Future research focal points should include strategies to optimize relapse management, restorative treatments that augment neurologic recovery, and practical solutions that promote equitable access to approved therapies for all patients with NMOSD.

BackgroundAs knowledge is limited about the real-world impact of relapse among patients with neuromyelitis optica spectrum disorder (NMOSD), we aimed to assess the impact of relapse(s) on patient disability, clinical outcomes, and patient and caregiver burden in a real-world setting.ObjectiveTo assess how NMOSD relapses impacts patient and caregiver burden.MethodsData were drawn retrospectively from the Adelphi Real World NMOSD Disease Specific Programme, a cross-sectional survey of neurologists and patients with NMOSD patients in five European countries from January–June 2023. Neurologists reported patients’ demographics, caregiver involvement and clinical outcomes. Analyses were bivariate.ResultsOverall, 99 neurologists provided data for 433 patients. In total, 128 patients had a relapse since their initial attack (1 relapse, 64.1%; 2 relapses, 18.8%; ≥ 3 relapses, 17.2%). Patients who had relapsed once had higher rates of control deficit for bladder (40.2% vs. 25.6%, p < .001) and bowel (8.5% vs. 5.6%, p = .042), which increased with additional relapses. Relapsed patients also required more caregiver support (41.4% vs. 31.1%, p = .048), often their partner (41.4% vs. 31.1%, p = .046).ConclusionsNMOSD relapse occurrence was associated with debilitating symptoms and more caregiver support, highlighting the need for more highly effective interventions to prevent patient and caregiver burden.

Objective: To explore the clinical characteristics of the neuromyelitis optica spectrum disorders (NMOSD) with the area postrema syndrome as the initial symptom. Methods: A total of 14 cases were enrolled in the study with the diagnose of NMOSD and the area postrema syndrome as the initial symptom. All the clinical data and imaging profiles by the contrasted magnetic resonance imaging (MRI) of the head and spinal cord were collected and analyzed. Results: The median age of onset was (38.1±17.0) years old and the gender ratio of female to male was 10∶4. The serum aquaporin-4(AQP4)-IgG was positive in 11 subjects and several autoimmune antibodies was positive in 7 subjects. The lesions revealed by MRI of the head mainly located in the area postrema and ependymal periphery which often presented as the linear medullary lesion, while linear lesions over three pieces of vertebra were shown by MRI of the spinal cord which mainly in the grey matter and with a"H" shape around the spinal central canal. Misdiagnose happened in 11 subjects with seven of gastroesophageal reflux disease, two of neurogenic vomiting, one of spinal cord tuberculosis and one of stroke. Conclusions: NMOSD should be considered in patients with unexplained intractable nausea, vomiting and/or hiccups lasted for 48 hours or above, especially in those with positive nervous signs. Contrasted MRI and serum AQP4-IgG need to be performed in the suspected patients. Early detection is crucial for patients with NMOSD.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory central nervous system disorder that preferentially affects the optic nerve and the spinal cord. Although NMOSD is more commonly an idiopathic autoimmune condition associated with antibodies against aquaporin-4 (AQP4)-IgG, the disease may also occur as a paraneoplastic syndrome in rare instances. In these cases, the expression of AQP4 by the tumor is likely the trigger of the autoimmune response. Case Presentation: We describe the case of a 32-year-old woman who presented with progressive tetraparesis, cranial involvement, respiratory failure, and spinal cord MRI compatible with longitudinally extensive transverse myelitis, few days after being diagnosed with a T3N1M0 triple-negative right breast cancer. Due to the history of concurrent breast cancer and after ruling out metastatic spinal cord involvement, the possibility of a paraneoplastic origin was raised. AQP4-IgG were found in the serum and CSF by cell-based assay, confirming the diagnosis of NMOSD. The patient was treated with corticosteroids, plasma exchange, and rituximab. Concomitantly, breast cancer therapy was started with an adapted neoadjuvant chemotherapy scheme based on carboplatin and paclitaxel. An initial slight improvement slowed down; so, a right mastectomy with lymphadenectomy was performed. Expression of AQP4 was demonstrated in the tumor. The patient presented a significant neurological improvement after combined treatment regaining muscular balance and strength in upper and lower extremities. Conclusion: NMOSD may have a paraneoplastic origin associated with breast cancer and the importance of its early detection since the combination of tumoral and immunosuppressive therapy may improve the patient’s prognosis.