GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities.

AIMS: Growing evidence suggests that an imbalanced gut microbiota composition plays a crucial role in the development of neuromyelitis optica spectrum disorders (NMOSD), an inflammatory demyelinating disease primarily affecting the optic nerves and central nervous system (CNS). In light of this, we explored the potential therapeutic benefits of GV-971 in NMOSD. GV-971 is a drug used for treating mild-to-moderate Alzheimer's disease, which targets the gut-brain axis and reduces neuroinflammation. METHODS: To evaluate GV-971's effects, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model to establish NMOSD animal models. This was achieved by injecting NMO-IgG into aged mice (11 months old) or using NMO-IgG along with complement injection and microbubble-enhanced low-frequency ultrasound (MELFUS) techniques in young mice (7 weeks old). We assessed the impact of GV-971 on incidence rate, clinical scores, body weight, and survival, with methylprednisolone serving as a positive control. In NMOSD models of young mice, we analyzed spinal cord samples through H&E staining, immunohistochemistry, and Luxol Fast Blue staining. Fecal samples collected at different time points underwent 16S rRNA gene sequencing, while plasma samples were analyzed using cytokine array and untargeted metabolomics analysis. RESULTS: Our findings indicated that GV-971 significantly reduced the incidence of NMOSD, alleviated symptoms, and prolonged survival in NMOSD mouse models. The NMOSD model exhibited substantial neuroinflammation and injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that accelerates disease pathogenesis. Notably, GV-971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders. CONCLUSIONS: GV-971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders.

Paraneoplastic neuromyelitis optica spectrum disorder associated with ovarian dysgerminoma: a case report and literature review.

Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated using magnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. One month after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD.

Retinal Changes in Double-Antibody Seronegative Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND OBJECTIVES: To systematically describe the clinical picture of double-antibody seronegative neuromyelitis optica spectrum disorders (DN-NMOSD) with specific emphasis on retinal involvement. METHODS: Cross-sectional data of 25 people with DN-NMOSD (48 eyes) with and without a history of optic neuritis (ON) were included in this study along with data from 25 people with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD, 46 eyes) and from 25 healthy controls (HCs, 49 eyes) for comparison. All groups were matched for age and sex and included from the collaborative retrospective study of retinal optical coherence tomography (OCT) in neuromyelitis optica (CROCTINO). Participants underwent OCT with central postprocessing and local neurologic examination and antibody testing. Retinal neurodegeneration was quantified as peripapillary retinal nerve fiber layer thickness (pRNFL) and combined ganglion cell and inner plexiform layer thickness (GCIPL). RESULTS: This DN-NMOSD cohort had a history of [median (inter-quartile range)] 6 (5; 9) attacks within their 5 ± 4 years since onset. Myelitis and ON were the most common attack types. In DN-NMOSD eyes after ON, pRNFL (p < 0.001) and GCIPL (p = 0.023) were thinner compared with eyes of HCs. Even after only one ON episode, DN-NMOSD eyes already had considerable neuroaxonal loss compared with HCs. In DN-NMOSD eyes without a history of ON, pRNFL (p = 0.027) and GCIPL (p = 0.022) were also reduced compared with eyes of HCs. However, there was no difference in pRNFL and GCIPL between DN-NMOSD and AQP4-NMOSD for the whole group and for subsets with a history of ON and without a history of ON-as well as between variances of retinal layer thicknesses. DISCUSSION: DN-NMOSD is characterized by severe retinal damage after ON and attack-independent retinal neurodegeneration. Most of the damage occurs during the first ON episode, which highlights the need for better diagnostic markers in DN-NMOSD to facilitate an earlier diagnosis as well as for effective and early treatments. In this study, people with DN-NMOSD presented with homogeneous clinical and imaging findings potentially suggesting a common retinal pathology in these patients.

Digital symbol-digit modalities test with modified flexible protocols in patients with CNS demyelinating diseases.

Cognitive impairment (CI) is prevalent in central nervous system demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We developed a novel tablet-based modified digital Symbol Digit Modalities Test (MD-SDMT) with adjustable protocols that feature alternating symbol-digit combinations in each trial, lasting one or two minutes. We assessed 144 patients (99 with MS and 45 with NMOSD) using both MD-SDMT protocols and the traditional paper-based SDMT. We also gathered participants' feedback through a questionnaire regarding their preferences and perceived reliability. The results showed strong correlations between MD-SDMT and paper-based SDMT scores (Pearsons correlation: 0.88 for 2 min; 0.85 for 1 min, both p < 0.001). Among the 120 respondents, the majority preferred the digitalized SDMT (55% for the 2 min, 39% for the 1 min) over the paper-based version (6%), with the 2 min MD-SDMT reported as the most reliable test. Notably, patients with NMOSD and older individuals exhibited a preference for the paper-based test, as compared to those with MS and younger patients. In summary, even with short test durations, the digitalized SDMT effectively evaluates cognitive function in MS and NMOSD patients, and is generally preferred over the paper-based method, although preferences may vary with patient characteristics.

Clinical, Demographic, and Radiological Characteristics of Patients Demonstrating Antibodies Against Myelin Oligodendrocyte Glycoprotein

Background: Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. Aims: To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Study Design: Multicenter, retrospective, observational study. Methods: Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayis University's Faculty of Medicine were included in the study. Results: Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. Conclusion: For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.

Case report: Overlap syndrome of neuromyelitis optica spectrum disorder with anti-Argonaute antibodies.

Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute antibodies (AGO-Abs) present as potential biomarkers of the overlap syndrome between NMOSD and other autoimmune diseases. In this paper, we present the case of an adult woman with numbness, tingling, and burning sensations in her arms and subsequent bilateral internuclear ophthalmoplegia. Brain-cervical-thoracic magnetic resonance imaging (MRI) showed T2 hyperintensities in the dorsal brainstem and around the midbrain aqueduct and longitudinally transverse myelitis with homogeneous enhancement on gadolinium-enhanced MRI. The contemporaneous detection of AQP4- and AGO-Abs led to a definite diagnosis of overlap syndrome of NMOSD with AGO-Abs. The patient was treated with immunosuppressive agents, including corticosteroids and immunoglobulins, and achieved remission. This case highlights a novel phenotype of NMOSD with AGO-Abs overlap syndrome, which presents with relapsing brainstem syndrome and longitudinally extensive myelitis with acute severe neurological involvement. The promising prognosis of the disease could serve as a distinct clinical profile. Broad screening for antibodies against central nervous system autoimmune antigens is recommended in suspected patients with limited or atypical clinical manifestations.

Comparison of efficacy of plasma exchange versus intravenous immunoglobulin as an add-on therapy in acute attacks of neuromyelitis optica spectrum disorder.

INTRODUCTION: Plasma exchange (PE) is considered a Category II option for the treatment of acute attacks and relapse cases of neuromyelitis optica spectrum disorder (NMOSD). However, neurologists are also considering intravenous immunoglobulins (IVIg) as an add-on therapy for this disorder. AIMS: The aim of this study is to evaluate the efficacy of PE in acute attacks of NMOSD when compared with IVIg, in terms of improvement in the Expanded disability status scale (EDSS) and activities of daily living (ADL) scale score and levels of anti-Aquaporin P4 (AQP4) antibody in seropositive patients. METHODS: We enrolled 43 NMOSD patients in two groups: Group 1 (n = 29) received steroids and PE, and Group 2 (n = 14) received steroids with IVIg. The baseline EDSS and ADL scores were recorded and compared with scores at the end of therapy, 4 weeks, and 3 months after. Also, anti-AQP4 antibody was measured at baseline and post-therapy in seropositive patients of both groups. RESULTS: We observed a significant difference in EDSS (p = 0.00) and ADL score (p = 0.00) at day 10 and 3 months in both groups. However, no significant difference in EDSS, as well as ADL score from baseline (p = 0.83; p = 0.25) to 3 months (p = 0.85; p = 0.19), was observed when delta change of score at 3 months was compared across the two groups (p = 0.39; p = 0.52). We observed improved visual acuity in both groups with mild improvement in findings of magnetic resonance imaging at 3 months. We observed a significant decline in AQP4 antibody concentration (at day 10) in group 1 seropositive patients (p = 0.013) with improved EDSS (p = 0.027) and ADL scores (p = 0.026) of these patients. CONCLUSIONS: PE should be considered as a choice of an add-on therapy in anti-AQP4 antibody-positive NMOSD patients compared with IVIg as it is more effective in reducing antibody concentrations.

Interleukin-6 Signaling Blockade Induces Regulatory Plasmablasts in Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10. METHODS: Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19+ IgD-, CD27-) and plasmablasts (PBs; CD19+, CD27hi, CD38hi). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab. RESULTS: DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200+ PBs produced more IL-10 than CD200- PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200+ PBs than patients during the acute attacks. DISCUSSION: Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200+ PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.

Advanced Brain Imaging in Central Nervous System Demyelinating Diseases.

In recent decades, advances in neuroimaging have profoundly transformed our comprehension of central nervous system demyelinating diseases. Remarkable technological progress has enabled the integration of cutting-edge acquisition and postprocessing techniques, proving instrumental in characterizing subtle focal changes, diffuse microstructural alterations, and macroscopic pathologic processes. This review delves into state-of-the-art modalities applied to multiple sclerosis, neuromyelitis optica spectrum disorders, and myelin oligodendrocyte glycoprotein antibody-associated disease. Furthermore, it explores how this dynamic landscape holds significant promise for the development of effective and personalized clinical management strategies, encompassing support for differential diagnosis, prognosis, monitoring treatment response, and patient stratification.

Diagnostic Criteria for Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorders, and Myelin Oligodendrocyte Glycoprotein-immunoglobulin G-associated Disease.

The diagnostic workup of multiple sclerosis (MS) has evolved considerably. The 2017 revision of the McDonald criteria shows high sensitivity and accuracy in predicting clinically definite MS in patients with a typical clinically isolated syndrome and allows an earlier MS diagnosis. Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease (MOGAD) are recognized as separate conditions from MS, with specific diagnostic criteria. New MR imaging markers may improve diagnostic specificity for these conditions, thus reducing the risk of misdiagnosis. This study summarizes the most recent updates regarding the application of MR imaging for the diagnosis of MS, NMOSD, and MOGAD.

Spinal Cord Imaging in Multiple Sclerosis and Related Disorders.

Spinal cord MRI plays an important role in the diagnosis and prognosis of multiple sclerosis (MS) and related disorders. The ANATOMICAL, pathologic, imaging and prognostic consideriations for the spinal cord for MS and the most important other demyelinating disorders, neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein-associated disease, are reviewed. Finally, differential diagnostic considerations of spinal cord MRI in MS and related disorders are discussed.

Optic Nerve Imaging in Multiple Sclerosis and Related Disorders.

Optic neuritis is a common feature in multiple sclerosis and in 2 other autoimmune demyelinating disorders such as aquaporin-4 IgG antibody-associated neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease. Although serologic testing is critical for differentiating these different autoimmune-mediated disorders, MR imaging, which is the preferred imaging modality for assessing the optic nerve, can provide valuable information, suggesting a specific diagnosis and guiding the appropriate serologic testing.

Human NMO-IgG Induced Different Pathological and Immunological Changes in the CNS and Peripheral Tissues of Mice.

OBJECTIVES: The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. METHODS: C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. RESULTS: We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. CONCLUSIONS: We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.

Blood-based inflammatory protein biomarker panel for the prediction of relapse and severity in patients with neuromyelitis optica spectrum disorder: A prospective cohort study.

BACKGROUND: To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity and prognostic predictive immune- and inflammation-related biomarkers are needed. We aimed to investigate the associations between plasma inflammatory biomarkers and relapse and attack severity in NMOSD. METHODS: This two-step, single-center prospective cohort study included discovery and validation cohorts. We quantified 92 plasma inflammatory proteins by using Olink's proximity extension assay and identified differentially expressed proteins in the relapse group (relapse within 1 year of follow-up) and severe attack group. To define a new molecular prognostic model, we calculated the risk score of each patient based on the key protein signatures and validated the results in the validation cohort. RESULTS: The relapse prediction model, including FGF-23, DNER, GDNF, and SLAMF1, predicted the 1-year relapse risk. The severe attack prediction model, including PD-L1 and MCP-2, predicted the severe clinical attack risk. Both the relapse and severe attack prediction models demonstrated good discriminative ability and high accuracy in the validation cohort. CONCLUSIONS: Our discovered biomarker signature and prediction models may complement current clinical risk stratification approaches. These inflammatory biomarkers could contribute to the discovery of therapeutic interventions and prevent NMOSD progression.

Serum Proteomics Distinguish Subtypes of NMO Spectrum Disorder and MOG Antibody-Associated Disease and Highlight Effects of B-Cell Depletion.

BACKGROUND AND OBJECTIVES: AQP4 antibody-positive NMOSD (AQP4-NMOSD), MOG antibody-associated disease (MOGAD), and seronegative NMOSD (SN-NMOSD) are neuroautoimmune conditions that have overlapping clinical manifestations. Yet, important differences exist in these diseases, particularly in B-cell depletion (BCD) efficacy. Yet, the biology driving these differences remains unclear. Our study aims to clarify biological pathways distinguishing these diseases beyond autoantibodies and investigate variable BCD effects through proteomic comparisons. METHODS: In a retrospective study, 1,463 serum proteins were measured in 53 AQP4-NMOSD, 25 MOGAD, 18 SN-NMOSD, and 49 healthy individuals. To identify disease subtype-associated signatures, we examined serum proteins in patients without anti-CD20 B-cell depletion (NoBCD). We then assessed the effect of BCD treatment within each subtype by comparing proteins between BCD-treated and NoBCD-treated patients. RESULTS: In NoBCD-treated patients, serum profiles distinguished the 3 diseases. AQP4-NMOSD showed elevated type I interferon-induced chemokines (CXCL9 and CXCL10) and TFH chemokine (CXCL13). MOGAD exhibited increased cytotoxic T-cell proteases (granzyme B and granzyme H), while SN-NMOSD displayed elevated Wnt inhibitory factor 1, a marker for nerve injury. Across all subtypes, BCD-treated patients showed reduction of B-cell-associated proteins. In AQP4-NMOSD, BCD led to a decrease in several inflammatory pathways, including IL-17 signaling, cytokine storm, and macrophage activation. By contrast, BCD elevated these pathways in patients with MOGAD. BCD had no effect on these pathways in SN-NMOSD. DISCUSSION: Proteomic profiles show unique biological pathways that distinguish AQP4-NMOSD, MOGAD, or SN-NMOSD. Furthermore, BCD uniquely affects inflammatory pathways in each disease type, providing an explanation for the disparate therapeutic response in AQP4-NMOSD and MOGAD.

Effects of Plasmapheresis on Serum Lithium Levels in an ICU Patient with Bipolar Disorder: A Case Study.

ABSTRACT: This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.

A protective effect of lower MHC-II expression in MOGAD.

Myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) is a demyelinating central nervous system disorder. We aimed to uncover immune pathways altered in MOGAD to predict disease progression. Using nanostring nCounter technology, we analyzed immune gene expression in PBMCs from MOGAD patients and compare it with healthy controls (HCs). We found 35 genes that distinguished MOGAD patients and HCs. We then validated those results in a larger cohort including MS and NMOSD patients. Expressions of HLA-DRA was significantly lower in MOGAD patients. This reduction in HLA-DRA, correlated with a monophasic disease course and greater brain volume, enhancing our ability to predict MOGAD progression.

Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). METHODS: This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. RESULTS: Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). DISCUSSION: Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.

Dysphagia in neuromyelitis optica spectrum disorder and multiple sclerosis: A comparison of frequency, severity, and effects on quality of life.

OVERVIEW: Dysphagia has been previously discussed as a potential life-threatening condition secondary to chronic neurological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, its impact on the quality of life (QoL) of patients with NMOSD has never been studied before. This study aims to determine the frequency of dysphagia and its impact on QoL in NMOSD patients in comparison with MS people and healthy individuals. METHODS: Seventy-five MS and sixty-five NMOSD patients with an expanded disability status scale (EDSS) score ≥ 3.5 in addition to 106 healthy controls were enrolled in this cross-sectional study. All the participants completed the self-report dysphagia in MS (DYMUS) and 36-item short-form health survey (SF-36) questionnaires. In case of positive answers to at least one of the questions in DYMUS, they were asked to fill out the dysphagia handicap index (DHI) questionnaire. RESULTS: The frequency of dysphagia in NMOSD, MS, and control groups was 61.54 %, 72.97 %, and 27 %, respectively. Patients with swallowing problems had reduced scores across different swallowing-related QoL domains compared to non-dysphagic patients (p < 0.05). NMOSD (1, IQR [0-3.5]) and MS patients (2, IQR [0-4]) had a significantly higher median total DYMUS score than control (0, IQR [0-1]) (p < 0.01). However, there was no discernible difference between the two patient groups. NMOSD had the highest mean total DHI score (21.22 ± 21), followed by MS (15.25 ± 18.94) and control (7.08 ± 5.12). A significant correlation was seen in the NMOSD group between the DHI total score and the SF-36 total score (r = 0.62, p < 0.05). The DHI and SF-36 subscales showed a strong association as well. The overall SF-36 scores in both the control and MS groups was not significantly correlated with DHI. The generalized linear model analysis showed that the NMOSD group's age (p-value = 0.005), EDSS (p-value < 0.001), and total DYMUS score (p-value = 0.018) significantly affected overall health status. CONCLUSION: The presence of dysphagia significantly impacts the QoL in NMOSD patients, particularly in aspects related to swallowing. These findings underscore the critical need for diligent dysphagia screening and emphasize the importance of educating both caregivers and NMOSD patients about managing this challenging symptom.