Neuromyelitis Optica Spectrum Disorder Research Articles

Long-term follow-up MR imaging in children with transverse myelitis

BackgroundWe recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity. ObjectiveTo study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM. Patients and methodsIn this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n=34), MS (n=20), NMOSD (n=5) and in double seronegative children (n=19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test. ResultsSignificant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P<0.001). ConclusionChildren with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD.

Aberrant hippocampal intrinsic morphological connectivity patterns in Neuromyelitis optica spectrum disorder with cognitive impairment: Insights from an individual-based morphological brain network

Aberrant hippocampal intrinsic morphological connectivity patterns in Neuromyelitis optica spectrum disorder with cognitive impairment: Insights from an individual-based morphological brain network

Prevalence of, and Disability Due to, Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder in Japan by the Fifth Nationwide Survey.

All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey. The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire. The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth. The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

Enhancing Lesion Detection in Inflammatory Myelopathies: A Deep Learning-Reconstructed Double Inversion Recovery MRI Approach.

The imaging of inflammatory myelopathies has advanced significantly over time, with MRI techniques playing a pivotal role in enhancing lesion detection. However, the impact of deep learning (DL)-based reconstruction on 3D double inversion recovery (DIR) imaging for inflammatory myelopathies remains unassessed. This study aims to compare acquisition time, image quality, diagnostic confidence, and lesion detection rates among sagittal T2WI, standard DIR, and DL -reconstructed DIR in patients with inflammatory myelopathies. In this observational study, patients diagnosed with inflammatory myelopathies were recruited between June 2023 and March 2024. Each patient underwent sagittal conventional turbo spin-echo sequences and standard 3D DIR (T2WI and standard 3D DIR used as references for comparison), followed by an undersampled accelerated DIRDL examination. Three neuroradiologists evaluated the images using a four-point Likert scale (from 1 to 4) for overall image quality, perceived signal-tonoise ratio, sharpness, artifacts, and diagnostic confidence. The acquisition times, and lesion detection rates were also compared between the acquisition protocols. A total of 149 participants were evaluated (mean age 40.6 ± 16.8 years; 71 females). The median acquisition time for DIRDL was significantly lower than for standard DIR (298 seconds [interquartile range (IQR), 288-301] vs 151 seconds [IQR, 148-155]; P < 0.001), showing a 49%time reduction. DIRDL images scored higher in overall quality, perceived signal-to-noise ratio, and artifact noise reduction (all P < 0.001). There were no significant differences in sharpness (P = 0.07), or diagnostic confidence (P = 0.06) between the standard DIR and DIRDL protocols. Additionally, DIRDL detected 37% more lesions compared to T2WI (300 vs. 219; P < 0.001). DIRDL significantly reduces acquisition time and improves image quality compared to standard DIR without compromising diagnostic confidence. Additionally, DIRDL enhances lesion detection in patients with inflammatory myelopathies, making it a valuable tool in clinical practice. These findings underscore the potential for incorporating DIRDL into future imaging guidelines. DL = deep learning; DIR = double inversion recovery; IQR = interquartile range; MS = multiple sclerosis; AQP4+NMOSD = AQP4-IgG positive neuromyelitis optica spectrum disorders; MOG = myelin oligodendrocyte glycoprotein; MOGAD = MOG antibody-associated diseases.

Eculizumab Use in Neuromyelitis Optica Spectrum Disorders: Routine Clinical Care Data From a European Cohort.

Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and safety of ECU in routine clinical care. We retrospectively evaluated patients with AQP4-IgG+ NMOSD treated with ECU between December 2014 and April 2022 at 20 German and 1 Austrian university center(s) of the Neuromyelitis Optica Study Group (NEMOS) by chart review. Primary outcomes were effectiveness (assessed using annualized attack rate [AAR], MRI activity, and disability changes [Expanded Disability Status Scale {EDSS}]) and safety (including adverse events, mortality, and attacks after meningococcal vaccinations), analyzed by descriptive statistics. Fifty-two patients (87% female, age 55.0 ± 16.3 years) received ECU for 16.2 (interquartile range [IQR] 9.6 - 21.7) months. Forty-five patients (87%) received meningococcal vaccination before starting ECU, 9 with concomitant oral prednisone and 36 without. Seven of the latter (19%) experienced attacks shortly after vaccination (median: 9 days, IQR 6-10 days). No postvaccinal attack occurred in the 9 patients vaccinated while on oral prednisone before starting ECU and in 25 (re-)vaccinated while on ECU. During ECU therapy, 88% of patients were attack-free. The median AAR decreased from 1.0 (range 0-4) in the 2 years preceding ECU to 0 (range 0-0.8; p < 0.001). The EDSS score from start to the last follow-up was stable (median 6.0), and the proportion of patients with new T2-enhancing or gadolinium-enhancing MRI lesions in the brain and spinal cord decreased. Seven patients (13%) experienced serious infections. Five patients (10%; median age 53.7 years) died on ECU treatment (1 from myocardial infarction, 1 from ileus with secondary sepsis, and 3 from systemic infection, including 1 meningococcal sepsis), 4 were older than 60 years and severely disabled at ECU treatment start (EDSS score ≥ 7). The overall discontinuation rate was 19%. Eculizumab proved to be effective in preventing NMOSD attacks. An increased risk of attacks after meningococcal vaccination before ECU start and potentially fatal systemic infections during ECU-particularly in patients with comorbidities-must be considered. Further research is necessary to explore optimal timing for meningococcal vaccinations. This study provides Class IV evidence that eculizumab reduces annualized attack rates and new MRI lesions in AQP4-IgG+ patients with NMOSD.

Current state and perspectives of CAR T cell therapy in central nervous system diseases.

B cell-directed CAR T cell therapy has fundamentally changed the treatment of hematological malignancies and its scope of application is rapidly expanding to include other diseases such as solid tumors or autoimmune disorders. Therapy-refractoriness remains an important challenge in various inflammatory and non-inflammatory disorders of the CNS. The reasons for therapy failure are diverse and include limited access of current therapies to the CNS, as well as enormous inter- and intraindividual disease heterogeneity. The tissue-penetrating properties of CAR T cells make them a promising option to overcome this problem and to tackle pathologies directly within the CNS. First application of B cell-directed CAR T cells in neuromyelitis optica spectrum disorder and multiple sclerosis patients has lately revealed promising outcomes, expanding the potential of CAR T cell therapy to encompass CNS diseases. Additionally, the optimization of CAR T cells for the therapy of gliomas is a growing field. As a further perspective, pre-clinical data reveal potential benefits of CAR T cell therapy also in the treatment of primary neurodegenerative diseases such as Alzheimer's disease. Considering the biotechnological optimizations in the field of T cell engineering, such as the extension to target different antigens or the variation of the modified T cell subtype, new and promising fields of application for CAR T cells are rapidly opening up. These innovations offer the potencial to address the complex pathophysiological properties of CNS diseases. To optimally utilize CAR T cell therapy for CNS diseases in the future while minimizing therapy risks, there is a need for further mechanistic research as well as prospective controlled trials to seriously assess the disease and patient-specific risk-benefit ratio.

Soluble TREM2 distinguishes neuromyelitis optica spectrum disorder from MOG antibody disease.

Soluble TREM2 distinguishes neuromyelitis optica spectrum disorder from MOG antibody disease.

Development of a Panel of Biomarkers for Differential Diagnosis of Multiple Sclerosis.

Demyelinating diseases are a group of heterogeneous pathologies that affect the nervous system and reduce the quality of life. One of such diseases is multiple sclerosis (MS), an inflammatory autoimmune neurodegenerative disease of the central nervous system (CNS). At the initial stages, MS can mimic some infectious, neoplastic, genetic, metabolic, vascular, and other pathologies. Accurate differential diagnosis of this disease is important to improve the quality of life of patients and reduce possible irreversible damage to the central nervous system. In this work, we confirmed the possibility of using our previously proposed candidate panel of MS biomarkers to distinguish MS from neuromyelitis optica spectrum disorder (NMOSD) and amyotrophic lateral sclerosis (ALS). We have shown that our proposed panel (SPTAN1601-644 + PRX451-494 + PTK6301-344 + LMP1285-330) allows us to distinguish MS from ALS (AUC = 0.796) and NMOSD (AUC = 0.779).

Secondary organising pneumonia associated to COVID-19 infection in patients with central nervous system inflammatory demyelinating diseases treated with anti-CD20 therapies.

Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited. To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20. Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023. Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID. In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered.

Effect of L-Carnitine Level on the Risk of Neuromyelitis Optica Spectrum Disorders: A Two-Sample Mendelian Randomization Study.

Previous research has often focused on studying the CNS damage in neuromyelitis optica spectrum disorders (NMOSD), while the role of the peripheral blood in the development of NMOSD is also of significant importance. The relationship between metabolites in blood and cerebrospinal fluid (CSF) with neuroimmune is receiving increasing attention. L-carnitine, whose astrocytic accumulation is associated with neuroinflammation and demyelination, may participate in the pathogenesis of NMOSD. However, whether circulating L-carnitine level has a causal effect on NMOSD risk needs elucidation. With large data sets now available, we used two-sample Mendelian randomization (MR) to determine whether circulating L-carnitine level is causally associated with the risk of NMOSD. Genetic variants associated with circulating L-carnitine levels were derived from a genome-wide association study (GWAS) of 7797 individuals from TwinsUK and KORA F4 cohorts. NMOSD summary statistics, including 215 cases and 1244 controls, were obtained from a separate GWAS. Subgroup analyses included aquaporin-4 (AQP4)-IgG-seropositive NMOSD (132 cases) and AQP4-IgG-seronegative NMOSD (83 cases). We used two-sample MR to explore associations between circulating L-carnitine levels and NMOSD risk, as well as its seropositive and seronegative subtypes. 16 SNPs (single nucleotide polymorphisms) were significantly associated with circulating L-carnitine level (P < 5 × 10-8), all of which were independent and available in the NMOSD dataset, after 1 SNP removed for being palindromic with intermediate allele frequencies in harmonization. Finally, a high circulating L-carnitine level conferred a protective effect against combined NMOSD (OR = 2.216 × 10-4, 95% confidence interval [CI] = 2.335 × 10-7-2.104 × 10-1, P = 0.0161) as well as AQP4-IgG-seronegative NMOSD (OR = 7.678 × 10-7, 95% CI = 2.233 × 10-11-2.640 × 10-2, P = 0.0082). There is no causal effect on AQP4-IgG-seropositive NMOSD risk (OR = 5.471 × 10-3, CI = 1.090 × 10-6-27.465, P = 0.2798) by circulating L-carnitine. Results remained positive and robust after the horizontal pleiotropy test, heterogeneity test, and Bonferroni test. In the reverse MR analysis, there was no causal effect of NMOSD and its subtypes on circulating L-carnitine levels. Our findings suggest that higher circulating L-carnitine levels may reduce the risk of NMOSD, particularly in AQP4-IgG-seronegative patients. L-carnitine could serve as a valuable biomarker and potential therapeutic target for NMOSD, especially in cases without AQP4-IgG. The genetic evidence from this study supports further exploration of L-carnitine's role in managing NMOSD.

The Varying Faces of MOGAD: A Case Series.

Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated disease (MOGAD) is an immune mediated demyelinating disorder initially described as a subtype of neuromyelitis optica spectrum disorder with antibodies against MOG. Recently, it has been described as a separate disease entity with unique clinical and radiological features. We herein report the clinical details of eight MOG-IgG-positive patients to highlight the peculiar and varied clinical and radiological features of this condition. Encephalitis was the most common presenting feature in our study, especially in pediatric cases. Tremors and parkinsonism were noted in four cases, of which one was a child. Monophasic course was noted in seven patients. Relapsing course was noted only in a single patient who was initiated on immunosuppressants. The clinical pictures highlight the importance of screening for anti-MOG in individuals with encephalitic and multiaxial symptoms in spite of having normal imaging. Acute demyelinating encephalomyelitis such as imaging features in the pediatric age group may also be a consideration for MOG testing.

Imaging Transcriptomics of Brain Functional Alterations in MS and Neuromyelitis Optica Spectrum Disorder.

The underlying transcriptomic signatures driving brain functional alterations in MS and neuromyelitis optica spectrum disorder (NMOSD) are still unclear. Regional fractional amplitude of low-frequency fluctuation (fALFF) values were obtained and compared among 209 patients with MS, 90 patients with antiaquaporin-4 antibody (AQP4)+ NMOSD, 49 with AQP4- NMOSD, and 228 healthy controls from a discovery cohort. We used partial least squares (PLS) regression to identify the gene transcriptomic signatures associated with disease-related fALFF alterations. The biologic process and cell type-specific signature of the identified PLS genes were explored by enrichment analysis. The correlation between PLS genes and clinical variables was explored. A prospective independent cohort was used to validate the brain fALFF alterations and the repeatability of identified genes. MS, AQP4+ NMOSD, and AQP4- NMOSD showed decreased fALFF in cognition-related regions and deep gray matter, while NMOSD (both AQP4+ and AQP4-) additionally demonstrated lower fALFF in the visual region. The overlapping PLS1- genes (indicating that the genes were overexpressed as regional fALFF decreased) were enriched in response to regulation of the immune response in all diseases, and the PLS1- genes were specifically enriched in the epigenetics profile in MS, membrane disruption and cell adhesion in AQP4+ NMOSD, and leukocyte activation in AQP4- NMOSD. For the cell type transcriptional signature, microglia and astrocytes accounted for the decreased fALFF. The fALFF-associated PLS1- genes directly correlated with Expanded Disability Status Scale of MS and disease duration across disorders. We revealed the functional activity alterations and their underlying shared and specific gene transcriptional signatures in MS, AQP4+ NMOSD, and AQP4- NMOSD.

Exploring subcortical pathology and processing speed in neuromyelitis optica spectrum disorder with myelin water imaging.

Neuromyelitis optica spectrum disorder (NMOSD) affects the optic nerves and spinal cord but can also cause focal brain inflammation. Subcortical pathology may contribute to the etiology of cognitive deficits in NMOSD. Using myelin water imaging, we investigated cerebral normal-appearing white matter (NAWM) and thalamic metrics and their association with cognition in NMOSD participants compared to healthy controls (HC). Seventeen NMOSD participants and 21 HC were scanned on a 3.0-Tesla MRI scanner using a multicomponent driven-equilibrium single-pulse observation of T1 and T2 protocol. Tissue compartment and thalamic volumes (normalized to intracranial volume), T1 relaxation time, and myelin water fraction (MWF) were reported. Eleven NMOSD participants underwent the Symbol Digit Modalities Test (SDMT) for cognitive evaluation. Group comparisons were performed using Student's t-test. The association between thalamic metrics and SDMT score was assessed using multiple regression analysis with age as a covariate. Compared to HC, NMOSD participants had reduced white matter volume (-14.2%, p<.0001), increased T1 relaxation time (+2.29%, p=.022), and lower MWF (-3.64%, p=.024) in NAWM. NMOSD group had a trend for smaller thalamic volumes than HC (-5.52%, p=.082) and no differences in thalamic MWF (p=.258) or T1 (p=.714). Thalamic T1 predicted SDMT score (adjusted R2=.51, p=.04) when controlling for age. NAWM in NMOSD demonstrates diffuse abnormalities with increased water content and demyelination, suggesting a diffuse disease process overlooked by focal inflammation measures. Increased water content, as a biomarker for diffuse thalamic pathology, may partially explain cognitive impairment in NMOSD.

How to avoid missing a diagnosis of neuromyelitis optica spectrum disorder.

Recognizing neuromyelitis optica spectrum disorder (NMOSD) and differentiating NMOSD from multiple sclerosis (MS) and other disorders can be challenging yet it is extremely important to prevent misdiagnosis, defined in this review as the incorrect diagnosis of patients who truly have NMOSD, particularly in aquaporin-4-IgG (AQP4-IgG)-seronegative cases. The heterogeneity of clinical presentations and wide range of differential diagnoses often lead to missed diagnoses of NMOSD. Misapplication of the 2015 NMOSD criteria and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis in clinical practice. Despite the presence of a specific biomarker for NMOSD (AQP4-IgG), misdiagnosis rates have been reported as high as 35%. Studies indicate that misdiagnosed patients often undergo unnecessary prolonged immunotherapy, leading to health risks and increased morbidity. Accurate definitive diagnosis is crucial as long-term outcomes and treatment approaches differ based on the correct diagnosis, and inappropriate immunotherapy can lead to disability in NMOSD patients. This review outlines factors linked to NMOSD misdiagnosis and briefly discusses strategies to reduce misdiagnosis.

Barriers in Healthcare to the Use of Optical Coherence Tomography Angiography in Multiple Sclerosis.

Optical coherence tomography angiography (OCT-A) is a state-of-the-art imaging technique for the retinal vasculature to accurately segment the capillary network and assign it to retinal layers. OCT-A is a promising technique to better understand neurological diseases with visual system manifestations, such as multiple sclerosis (MS), and to identify and characterize vascular biomarkers. Initial studies suggested vascular changes in MS and its differential diagnoses such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Here we review clinical and technical aspects of OCT-A imaging and discuss the potential for the MS field as well as barriers that need to be overcome before OCT-A can be established in clinical application.

Aquaporin-4 Immunoglobulin G-seropositive Neuromyelitis Optica Spectrum Disorder MRI Characteristics: Data Analysis from the International Real-World PAMRINO Study Cohort.

Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD (n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data (n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI (n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

Serum Low-Density Lipoprotein Cholesterol Levels are Associated with Relapse in Neuromyelitis Optica Spectrum Disorder.

The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients. We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan-Meier Plot. Over a mean disease course of 100±87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (p<0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (p< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76-4.04, p<0.001), and 2.38 (1.48-3.83, p<0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795mmol/L with potential benefits to prevent relapse in NMOSD. In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD.

Evaluation of Brain and Spinal Cord Lesions and Cerebrospinal Fluid Analysis in Detecting Demyelinating Diseases in Patients with Optic Neuritis

ABSTRACT Optic neuritis can be an early sign of demyelinating diseases like multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). We investigated the presence or absence of head and spinal cord lesions on magnetic resonance imaging (MRI) and assessed whether cerebrospinal fluid (CSF) tests are useful in detecting demyelinating disease in patients with first diagnosed optic neuritis. We conducted a retrospective study of 111 patients (47 idiopathic, 19 NMOSD, 16 MOGAD, 16 MS, 6 optic neuritis with cerebral lesions but that does not meet the McDonald’s criteria for MS (ON+)), and 7 chronic relapsing inflammatory optic neuropathy) diagnosed with optic neuritis without cerebral or spinal symptoms. Patients underwent evaluations including orbital, head, and spine MRI, along with CSF analysis. Among the 111 patients, 20 (35.1%: 4 NMOSD, 4 MOGAD, 7 MS, and 6 ON+) exhibited intracerebral or spinal cord lesions. Twelve patients showed findings on both orbital and head MRI, while six had no orbital MRI findings except for optic neuritis but exhibited lesions on head MRI. Five patients had spinal lesions without intracerebral lesions. CSF analysis revealed positive oligoclonal bands and elevated myelin basic protein levels indicate the high likelihood with systemic inflammatory demyelinating diseases. Even in the absence of concomitant encephalitis or myelitis symptoms or a history of these conditions, MRI images of patients with optic neuritis sometimes reveal lesions in the brain or spinal cord. CSF abnormalities were indicative of systemic demyelinating disease presence, extending beyond MS to NMOSD and MOGAD.

Interleukin-6 Inhibitors for Neuromyelitis Optica Spectrum Disorder (NMOSD): a Systematic Review and Meta-analysis

BackgroundInterleukin-6 (IL-6) inhibitors recently emerged as a promising therapy for neuromyelitis optica spectrum disorder (NMOSD). ObjectiveWe performed a systematic review and meta-analysis comparing IL-6 inhibitors to placebo or traditional immunosuppressants in NMOSD. MethodsWe searched PubMed, Embase, and Cochrane Central for eligible studies. Efficacy endpoints included hazard ratio (HR) for relapse, annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) change over time. Safety outcomes comprised any adverse event, serious adverse events and infections. Statistical analysis was performed using RevMan Web and R studio package meta. Heterogeneity was assessed with I² statistics. ResultsFour studies involving 361 patients (228 treated with IL-6 inhibitors) were included. IL-6 inhibitors significantly reduced HR for relapse (HR 0.35; 95% CI 0.23, 0.55); p<0.00001; I²=0%) and ARR (mean difference -0.79 relapses/year; 95% CI -1.54, -0.03; p=0.04; I²=96%) compared to placebo or traditional immunosuppressants. No significant differences were observed in EDSS change over 24 weeks of follow-up (mean difference -0.18; 95% CI 0.41, 0.05; p=0.93; I²=0%), adverse events (odds ratio (OR) 1.59; 95% CI 0.45, 5.63; p=0.48; I²=48%), serious adverse events (OR 0.76; 95% CI 0.40, 1.44; p=0.50; I²=0%) and infection rates (OR 1.10; 95% CI 0.67, 1.79; p=0.71; I²=0%). ConclusionIL-6 inhibitors demonstrate superior efficacy in preventing relapses in NMOSD compared to placebo or traditional immunosuppressants, without a notable increase in safety risks.

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.MethodsTo investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP).ResultsOur analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression.ConclusionsOur comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.