Neuromyelitis Optica Spectrum Disorder Research Articles

Overview of emerging therapies for demyelinating diseases.

This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types-oligodendrocyte precursor cells (OPCs), astrocytes, and microglia-and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients' quality of life.

C3a Mediates Endothelial Barrier Disruption in Brain-Derived, but Not Retinal, Human Endothelial Cells.

Neuromyelitis optica spectrum disorder (NMOSD) is associated with pathological aquaporin-4 immunoglobulin G (AQP4-IgG), which cause brain damage. However, the impact of AQP4-IgG on retinal tissue remains unclear. Additionally, dysregulated complement anaphylatoxins C3a and C5a, known to modulate the endothelial barrier, are implicated in NMOSD. This study evaluates the susceptibility of human brain microvascular endothelial cells (HBMEC) and human retinal endothelial cells (HREC) to C3a- and C5a-mediated stress using real-time cell barrier analysis, immunocytochemical staining, qPCR and IgG transmigration assays. The findings reveal that C3a induced a concentration-dependent paracellular barrier breakdown and increased transcellular permeability in HBMEC, while HREC maintained barrier integrity under the same conditions. C5a attenuated C3a-induced disruption in HBMEC, indicating a protective role. Anaphylatoxin treatment elevated transcript levels of complement component C3 and increased C5 gene and protein expression in HREC, with no changes observed in HBMEC. In HBMEC, C5a treatment led to a transient upregulation of C3a receptor (C3AR) mRNA and an early decrease in C5a receptor 1 (C5AR1) protein detection. Conversely, HREC exhibited a late increase in C5aR1 protein levels. These results indicate that the retinal endothelial barrier is more stable under anaphylatoxin-induced stress compared to the brain, potentially offering better protection against paracellular AQP4-IgG transport.

Dried blood spot improves global access to aquaporin-4-IgG testing for neuromyelitis optica.

This study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin-4-IgG (AQP4-IgG) testing. Prospective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live-cell-based assays (CBA) and enzyme-linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4-IgG detection between DBS and serum (gold standard) was compared. Among 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92-0.99). AQP4-IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74-0.95) and 100% specificity (95% CI: 0.96-1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43-0.84) and 95.2% specificity (95% CI: 0.76-0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47-0.87) and 98.4% specificity (95% CI: 0.91-0.99). The stability of DBS in detecting AQP4-IgG persisted over 24 months for most cases. The DBS represents a viable alternative for detecting AQP4-IgG in resource-limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point-of-care testing.

Racial, Ethnic, and Socioeconomic Disparities in Pediatric Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder

BackgroundOnly 5% of aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) cases emerge during childhood. Poorer outcomes have been suggested in black/African American (AA) adults with NMOSD; however, conflicting and limited data exist for pediatric-onset NMOSD. This study evaluates racial, ethnic, and socioeconomic disparities in pediatric AQP4+ NMOSD outcomes. MethodsThirty-eight pediatric patients with AQP4+ NMOSD cared for at three pediatric tertiary care centers between 2009 and 2021 were identified. Patient addresses connected to socioeconomic measures available from the US Census. Demographic characteristics, pertinent clinical outcomes, and health care utilization in the two years following diagnosis were captured. ResultsCompared with non-Hispanic White children, Black/AA children had a significantly higher Expanded Disability Status Scale (EDSS) (2.46 vs 0.33, P = 0.003), 2.37 more hospital admissions (P = 0.002), and 28.40 additional inpatient days (P = 0.002) in the two years following their NMOSD diagnosis. Additionally, children with public insurance had higher relapse rates than those with private insurance (P = 0.046). At two years and at the most recent follow-up, a significantly higher EDSS was correlated with children living in census tracts with a lower median income, higher deprivation index, and higher proportion of population on assisted income, in poverty, and with vacant housing (all P < 0.05). ConclusionsWe identified racial, ethnic, and socioeconomic disparities in clinical outcomes and health care utilization in pediatric AQP4+ NMOSD. Further prospective and household-level data are needed to dissect the interplay of genetics, structural racism, and social determinants of health so that interventions to optimize care and outcomes for this population may be developed.

The correlation between rituximab dose reduction and acute relapses of neuromyelitis optica spectrum disorder, lessons from COVID-19 epidemic

BackgroundCOVID-19 was a viral infection that led to a global pandemic in March 2020. At the beginning of the pandemic, clinicians encountered the challenge of how immunosuppressive treatments would affect the course of COVID-19 infection in people with autoimmune diseases. Neuromyelitis optica spectrum disorder is an autoimmune astrocytopathy that is caused by an inflammation in the CNS. Major treatments to prevent acute relapses include immunosuppressive drugs. Rituximab is a well-established immunosuppressive agent in NMOSD maintenance therapy. Some reports suggested that treatment with Rituximab might increase the risk of COVID-19 infection and its mortality in NMOSD. On the other hand, dose reduction or extended interval treatment might lead to acute relapses of NMOSD and permanent disability. MethodsIn this study, we evaluated the correlation between the dose of rituximab and the relapse rate of NMOSD during an epidemic. This was an observational study on 171 patients among whom 55 cases were seropositive. Some patients received full dose rituximab routinely (1000 mg/dose, every 6 months), but others were treated with half dose (500 mg/dose) during the epidemic. Also, some doses were prescribed with a delay, based on the level of CD19 and CD20. ResultsThe Pearson correlation coefficient (r) showed a negative and significant relation (r: - 0.19, p: 0.022) between the amount of drug and the number of relapses in the seropositive group, so low dosage of the drug was related to more acute relapses. In seronegative cases, there was not any valuable relationship. (p: 0.367). ConclusionLower dose of rituximab, especially in seropositive NMOSD patients, can potentially lead to acute relapses. So, the more frequent evaluation of the CD19, CD20, and, CD27 levels, and the general clinical condition of the patients should be considered.

Preceding hepatitis B virus infection is highly prevalent in patients with neuromyelitis optica spectrum disorder in Taiwan

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system, characterized by pathogenic anti-Aquaporin-4 antibodies (AQP4-Ab). Given that infections can trigger autoimmune responses, we investigated the association between Hepatitis B virus (HBV) infection and NMOSD. MethodsHBV and hepatitis C virus serologies were analyzed in 105 NMOSD patients, 85 multiple sclerosis (MS) patients, and 1,661 healthy Taiwanese controls. Participants were classified into four HBV infection statuses (acute, chronic, resolved, and never infected), and further grouped by vaccination status. Logistic regression was used to estimate odds ratios (OR) for NMOSD development in individuals with chronic or resolved HBV infection. ResultsAmong those born before the Taiwan's universal vaccination program, 63.4 % of NMOSD patients had resolved HBV infection, compared to 30.6 % of MS patients and 16.4 % of controls. Resolved HBV infection was associated with a 2.3-fold increased risk for NMOSD development (95 % CI, 1.4–3.8), but not with MS risk. In the post-vaccination cohort, resolved HBV infection remained more frequent in NMOSD patients (8.7 %) than in MS (0 %) and controls (1.8 %). NMOSD patients with resolved HBV infection had later disease onset by 14.6 years and higher Expanded Disability Status Scale (EDSS) scores compared to those without HBV infection, even after adjusting for age and sex (3.5 ± 1.9 vs. 2.2 ± 1.8, p < 0.001). ConclusionPreceding HBV infection is prevalent among Taiwanese NMOSD patients and is associated with increased disease risk, older age at onset, and greater disability. Screening for HBV is essential for NMOSD patients, particularly in endemic regions.

Socioeconomic Factors Associated with ≥2-year Delayed Diagnosis of Neuromyelitis Optica Spectrum Disorder (NMOSD) in the United States.

The objective of this study is to explore the impact of socioeconomic factors on risk of ≥2-year delayed diagnosis of NMOSD. Consequences of delayed diagnosis in NMOSD could be as severe as complete blindness or quadriplegia. Female sex and African ancestry are risk factors for delayed diagnosis across many disease states in the US. Patients with NMOSD are disproportionately represented by women of African descent suggesting that there may be socioeconomic barriers to timely diagnosis. This retrospective cohort study of patients with NMOSD used a closed claims database linked with socioeconomic market research and American Community Survey data at the zip-9 level. Patients were included if they had at least 2 NMOSD claims ≥30 days apart between January 2018 and December 2021. Symptom onset was defined as the first claim of associated NMOSD symptoms up to 15 years prior to diagnosis. ≥2-year delayed diagnosis was defined as diagnosis at or after 2 years of symptom onset. The conceptual causal framework was illustrated with a directed acyclic graph. Multivariable regression models were used to estimate associations of patient characteristics and several socioeconomic variables with risk of ≥2-year delayed NMOSD diagnosis. In multivariable regression analysis, factors associated with ≥2-year delayed diagnosis were female sex (OR 1.44; 95%CI 1.07-1.95) and Managed Medicaid coverage (OR 1.45; 95%CI 1.11-1.89). Factors associated with diagnosis in <2 years included age≤45 (OR 1.43; 95%CI 1.06-1.94), moderate and severe comorbidity [(Moderate OR 1.62, 95%CI 1.13-2.33), (Severe OR 1.56; 95%CI 1.04-2.35)], and western US regions (OR 1.56; 95%CI 1.12-2.16). There was no impact of other socioeconomic factors on ≥2-year delayed diagnosis. However, patient-level data on race/ethnicity was not available. This study demonstrated that otherwise healthy, female, Managed Medicaid beneficiaries, age >45 years may be at highest risk for ≥2-year delayed diagnosis of NMOSD.

Neuromyelitis Optica Spectrum Disorder (NMOSD) in a Patient with Noonan Syndrome and Prior Juvenile Myelomonocytic Leukemia

Neuromyelitis Optica Spectrum Disorder (NMOSD) in a Patient with Noonan Syndrome and Prior Juvenile Myelomonocytic Leukemia

Efficacy and Safety of Ravulizumab in Adults With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Interim Analysis From the Ongoing Phase 3 CHAMPION-NMOSD Trial

Efficacy and Safety of Ravulizumab in Adults With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Interim Analysis From the Ongoing Phase 3 CHAMPION-NMOSD Trial

A Global, Long-Term, Prospective, Observational Registry of Patients With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) Treated With Complement Component 5 Inhibitor Therapies (C5ITs) Eculizumab or Ravulizumab

A Global, Long-Term, Prospective, Observational Registry of Patients With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) Treated With Complement Component 5 Inhibitor Therapies (C5ITs) Eculizumab or Ravulizumab

Safety Findings in Patients With Anti-Aquaporin-4-Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) Who Received Eculizumab or Ravulizumab in the PREVENT and CHAMPION-NMOSD Studies and Had Received Rituximab Within 1 Year Prior to Enrollment

Safety Findings in Patients With Anti-Aquaporin-4-Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) Who Received Eculizumab or Ravulizumab in the PREVENT and CHAMPION-NMOSD Studies and Had Received Rituximab Within 1 Year Prior to Enrollment

The Path to Diagnosis and Treatment Among Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD): Health Disparities Among Persons of Color From Project ASPIRE

The Path to Diagnosis and Treatment Among Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD): Health Disparities Among Persons of Color From Project ASPIRE

Neuromyelitis Optica Spectrum Disorder with Overlapping Lupus Cerebritis: A Case Report

Neuromyelitis Optica Spectrum Disorder with Overlapping Lupus Cerebritis: A Case Report

Evaluation of Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels During Eculizumab and Ravulizumab Treatments in Anti-Aquaporin-4-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Evaluation of Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels During Eculizumab and Ravulizumab Treatments in Anti-Aquaporin-4-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Incidence of Relapses After Meningococcal Vaccination in Clinical Trials of Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Incidence of Relapses After Meningococcal Vaccination in Clinical Trials of Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Immunogenicity dynamics and covariate effects after satralizumab administration predicted with a hidden Markov model.

Immunogenicity is the propensity of a therapeutic protein to generate an immune response to itself. While reporting of antidrug antibodies (ADAs) is increasing, model-based analysis of such data is seldom performed. Model-based characterization of factors affecting the emergence and dissipation of ADAs may inform drug development and/or improve understanding in clinical practice. This analysis aimed to predict ADA dynamics, including the potential influence of individual covariates, following subcutaneous satralizumab administration. Satralizumab is a humanized IgG2 monoclonal recycling IL-6 receptor antagonist antibody approved for treating neuromyelitis optica spectrum disorder (NMOSD). Longitudinal pharmacokinetic (PK) and ADA data from 154 NMOSD patients in two pivotal Phase 3 studies (NCT02028884, NCT02073279) and PK data from one Phase 1 study (SA-001JP) in 72 healthy volunteers were available for this analysis. An existing population PK model was adapted to derive steady-state concentration without ADA for each patient. A mixed hidden Markov model (mHMM) was developed whereby three different states were identified: one absorbing Markov state for non-ADA developer, and two dynamic and inter-connected Markov states-transient ADA negative and positive. Satralizumab exposure and body mass index impacted transition probabilities and, therefore, the likelihood of developing ADAs. In conclusion, the mHMM model was able to describe the time course of ADA development and identify patterns of ADA development in NMOSD patients following treatment with satralizumab, which may allow for the formulation of strategies to reduce the emergence or limit the impact of ADA in the clinical setting.

Comparative Effectiveness and Safety of Disease-modifying Treatments (DMTs) in a Real-World Neuromyelitis Optica Spectrum Disorder Cohort (NMOSD)

Comparative Effectiveness and Safety of Disease-modifying Treatments (DMTs) in a Real-World Neuromyelitis Optica Spectrum Disorder Cohort (NMOSD)

Further Investigation of the Unclear Role of Aquaporin-4 Antibodies in HIV Infection Associated Neuromyelitis Optica Spectrum Disorder

Further Investigation of the Unclear Role of Aquaporin-4 Antibodies in HIV Infection Associated Neuromyelitis Optica Spectrum Disorder

May Steroids Wake You Up! A Rare Case of Diencephalic Syndrome of Neuromyelitis Optica Spectrum Disorder

May Steroids Wake You Up! A Rare Case of Diencephalic Syndrome of Neuromyelitis Optica Spectrum Disorder

Neurologic Outcomes in People with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder Exposed To Immune Checkpoint Inhibitors

Neurologic Outcomes in People with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder Exposed To Immune Checkpoint Inhibitors