Neuromyelitis Optica Spectrum Disorder Research Articles

Effectiveness of double-filtration plasmapheresis in reducing immunoglobulin and culprit antibody levels in neuroimmune disorders: A single-center retrospective analysis from China

ObjectiveThis study aims to evaluate the effectiveness of double-filtration plasmapheresis (DFPP) in reducing immunoglobulins and culprit antibodies in neuroimmune disorders. MethodsA retrospective analysis was conducted on 51 patients with neuroimmune diseases treated with DFPP, immunotherapy, and symptomatic treatment. Immunoglobulin and antibody levels were measured pre- and post-treatment, along with neurological function assessments using scales like the modified Rankin Scale (mRS), Expanded Disability Status Scale (EDSS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), and Myasthenia Gravis-specific scales. ResultsThe cohort included patients with neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AIE), myasthenia gravis (MG), anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD), and paraneoplastic neurological syndromes (PNS). DFPP significantly reduced immunoglobulin levels (IgG, IgA, IgM) by ∼70 %. Most patients showed decreased antibody titers and significant neurological improvement. The median mRS score improved from 2 (IQR 2–3) to 1 (IQR 1–2) post-treatment, with further improvement at 90 days. Notable improvements were observed across various scales specific to NMOSD, MOGAD, AIE, and MG. Minor adverse events were reported, with no serious adverse events. ConclusionsDFPP is effective in reducing immunoglobulin and antibody levels, leading to improved neurological function in neuroimmune disorders. Further large-scale studies are warranted to confirm these findings.

Neuroimaging feature in identifying acute myelopathy etiologies: comparison between neuromyelitis optica spectrum disorder and cervical spondylotic myelopathy

ObjectiveThe clinical symptoms of neuromyelitis optica spectrum disorder (NMOSD) and acute cervical spondylotic myelopathy (CSM) may overlap in some cases. This study aimed to investigate the differences in imaging features between NMOSD and CSM in acute myelopathy.MethodsWe included 78 patients in this retrospective study, including 28 NMOSD patients and 50 CSM patients. The demographic characteristics and clinical symptoms of the two groups of patients were compared. The T1 signal intensity, length of the spinal cord involved by T2 hyperintensity, degree of intervertebral disc degeneration, proportion of thoracic and lumbar cord involvement, proportion of brain involvement and lesion enhancement rate in magnetic resonance imaging (MRI) were compared between the two groups of patients. The number, length, location on the sagittal image, pattern on the sagittal image, and distribution on the axial image of the lesions in the contrast-enhanced MRI of the two groups were evaluated.ResultsThere were differences between NMOSD and CSM patients in the proportion of women, the proportion of bowel and bladder symptoms, mRS levels, the length of the spinal cord involved by T2 hyperintensity, degree of intervertebral disc degeneration, the proportion of thoracic and lumbar cord involvement, the proportion of brain involvement, the enhancement rate and number of lesions (p < 0.05). Among NMOSD patients, linear, patchy and ring or semi-ring enhancement were present in 8(30.8%) ,14 (53.8%) and 4(15.4%)patients, respectively, and axial gray and white matter were involved in 17 (65.4%) patients. Among patients with CSM, 9(36.0%) patients showed longitudinal oriented flake, 16 (64.0%) patients showed pancake-like enhancement, and 21 (84.0%) patients showed axial white matter involvement only. The differences in enhancement pattern on sagittal images and axial involvement were statistically significant (p < 0.05).ConclusionsEarly differential diagnosis of NMOSD and CSM in acute myelopathy can be made by analyzing images and the number, length, sagittal enhancement pattern, and axial involvement of gadolinium-enhanced lesions.

B-053 Four years summary of flow cytometry live cell based assay for detecting serum anti-aquaporin 4 IgG and anti-myelin oligodendrocyte glycoprotein IgG in a Korean reference laboratory

Abstract Background In the diagnosis of neuromyelitis optica spectrum disorder (NMOSD), it is important to sensitively detect anti-aquaporin 4 (AQP4) IgG and anti-myelin oligodenrocyte glycoprotein (MOG) IgG in patients' serum. NMOSD is a disease that shows 3-7 times more common prevalence in Far East Asia than in the West. According to the IPND diagnostic criteria, it is recommended to diagnose as a cell based assay using full length recombinant protein. In this study, we would like to review 4 years results of AQP4, MOG requested to Eone laboratories in Korea performed with flow cytometry live cell based assay (FC-CBA). Methods FC-CBA was performed using piRES2 cell transfected with AQP4, MOG and stained with DsRed2. Subcultured cells were counted with 10^6, and reacted with patients' serum for 1 hour in a refrigerated state. Thereafter, reaction with FITC anti-human IgG for 2nd antibody for 30 minutes, and 10,000 cells were read from Navius (Beckman Coulter). The mean fluorescence intensity (MFI) ratio , which is the ratio obtained by dividing the MFI value of both FITC and DsRed2 positive cells and DsRed2 positive cells to negative cells, was used to determine positive, borderline, and negative for the serum sample. AQP4 reviewed cases during the period from November 2018 to January 2024, and MOG reviewed cases during the period from December 2019 to January 2024. Indirect immunofluorescence assay using formalin fixed cells is commercially available and compared to the FC-CBA of this institution. Results During the study period, 4,733 cases of AQP4 were performed, and 23,540 cases of MOG were performed by FC-CBA. Among them, AQP4 was positive in 405 cases (8.5%) and borderline in 71 cases (1.5%), and all others were negative. MOG was 2,597 positive (11%), borderline in 1,144 cases (4.8%), and all others were negative. The positive and borderline cutoffs for MFI ratio were changed during the study period, and the positive rate was significantly changed. Conclusions Eone laboratories are the only institution in Korea that performs live cell based assay using flow cytometry for AQP4 and MOG IgG, and receives samples from patients suspected of NMOSD at university hospitals. When reading with MFI ratio, it is important to properly set the cutoff to determine the positivity rate.

Blood-Brain Barrier Disruption in Neuroimmunological Disease.

The blood-brain barrier (BBB) acts as a structural and functional barrier for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE), and paraneoplastic neurological syndrome (PNS). The transmigration of massive lymphocytes across the BBB caused by the activation of cell adhesion molecules is involved in the early phase of MS, and dysfunction of the cortical BBB is associated with the atrophy of gray matter in the late phase of MS. At the onset of NMOSD, increased permeability of the BBB causes the entry of circulating AQP4 autoantibodies into the central nervous system (CNS). Recent reports have shown the importance of glucose-regulated protein (GRP) autoantibodies as BBB-reactive autoantibodies in NMOSD, which induce antibody-mediated BBB dysfunction. BBB breakdown has also been observed in MOGAD, NPSLE, and AE with anti-NMDAR antibodies. Our recent report demonstrated the presence of GRP78 autoantibodies in patients with MOGAD and the molecular mechanism responsible for GRP78 autoantibody-mediated BBB impairment. Disruption of the BBB may explain the symptoms in the brain and cerebellum in the development of PNS, as it induces the entry of pathogenic autoantibodies or lymphocytes into the CNS through autoimmunity against tumors in the periphery. GRP78 autoantibodies were detected in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome, and they were associated with cerebellar ataxia with anti-P/Q type voltage-gated calcium channel antibodies. This review reports that therapies affecting the BBB that are currently available for disease-modifying therapies for neuroimmunological diseases have the potential to prevent BBB damage.

B-046 Development and Validation of an Automated Live Cell-Based Flow Cytometry Assay Platform for Measuring AQP4-IgG

Abstract Background Live cell-based assays (CBA) are considered the gold-standard methodology for detecting pathogenic antibodies targeting neural cell surface antigens. However, the adoption of these methods in clinical laboratories has been limited by their manual nature and low throughput. Here, we describe the development and validation of an automated system utilizing a live flow cytometry-based CBA to detect AQP4-IgG. Establishing AQP4-IgG serostatus is a critical component of the diagnostic criteria for Neuromyelitis optica spectrum disorders (NMOSD) as it enables the differentiation of NMOSD from Multiple Sclerosis where there may be significant clinical overlap. The accurate diagnosis of the correct disease state is vital, as the prognosis and treatment approach differ significantly for these two conditions. Two redundant systems were built that automatically receive reagents (live cells in suspension, buffers, diluents, secondary antibodies, and patients’ samples) and generate flow cytometer ready 96-well plates (each containing up to 45 serum or CSF samples tested in duplicate). Methods We assessed the analytical performance of an AQP4-IgG live flow cytometry-based CBA on these new automated systems. We measured intra- and inter-assay imprecision at three levels in 5x5 format and for end-point titer assessment, accuracy (20 positive and 20 negative sera; 5 positive and 5 negative CSF; established on the current manual assay), reference range (20 negative sera and 20 negative CSF from disease controls), analytical sensitivity (LOB and LOD) and specificity (high IgG containing serum specimens), within-plate draft (1 positive sample near the diagnostic cut-off [IgG-binding index of 2.0] that was tested across the entire plate), instrument to instrument correlation (42 positive samples/dilutions tested simultaneously on both systems), and total throughput for both CSF and Serum. Results Imprecision testing yielded the following results: Serum Intra/Inter precision level 1 (IBI = 2) CV% (current method:4.6%/20.7%), (system 1: 3.1%/18.4%), (system 2: 2.6%/22.5%), serum Intra/Inter precision level 2 (IBI=4) CV% (current method:4.9%/23.3%), (system 1: 3.2%/21.9%), (system 2: 2.6%/24.1%), and serum Intra/Inter precision level 3 (IBI =10) pos CV% (current method:6.0%/31.1%), (system 1: 3.8%/27.4%), (system 2: 4.2%/29.4%), and CSF Intra/Inter precision (IBI =2) CV% (System 1: 11.7%/16.8%), (system 2: 6.1%/10.7%). The median end-point titers for all four samples assessed matched within one end-point titer. For accuracy, 100% qualitative agreement between current and both automated systems, and titration accuracy (5 positive serums, 1 positive CSF) all matched within one titer between current and both automated systems. All reference range samples were negative. LOB/LOD in serum (Current: 0.85/1.11), (System 1: 0.82/0.95), (system 2: 0.82/0.96) and CSF (Current: 1.06/1.52), (System 1: 1.02/1.38), (system 2: 1.02/1.64) were comparable. All high IgG samples were negative. Plate drift analysis showed improved whole plate %CV: (Current:6.52%), (system 1: 4.51%), (system 2: 3.46%). Instrument to instrument comparison utilizing linear regression indicated strong agreement across the two systems (slope = 0.93 and R2= 0.95). Assessment of throughput based on real-time timings indicated a maximum output of approximately &amp;gt;700 patient samples per 24hrs per system. Conclusions An automated system for performing live CBAs provides equivalent to superior analytical performance compared to pre-existing manual methods with improved testing capacity.

NMOSD and MOGAD: an evolving disease spectrum.

Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a relapsing inflammatory disease of the CNS, characterized by the presence of serum aquaporin 4 (AQP4) autoantibodies (AQP4-IgGs) and core clinical manifestations such as optic neuritis, myelitis, and brain or brainstem syndromes. Some people exhibit clinical characteristics of NMOSD but test negative for AQP4-IgG, and a subset of these individuals are now recognized to have serum autoantibodies against myelin oligodendrocyte glycoprotein (MOG)-a condition termed MOG antibody-associated disease (MOGAD). Therefore, the concept of NMOSD is changing, with a disease spectrum emerging that includes AQP4-IgG-seropositive NMOSD, MOGAD and double-seronegative NMOSD. MOGAD shares features with NMOSD, including optic neuritis and myelitis, but has distinct pathophysiology, clinical profiles, neuroimaging findings (including acute disseminated encephalomyelitis and/or cortical encephalitis) and biomarkers. AQP4-IgG-seronegative NMOSD seems to be a heterogeneous condition and requires further study. MOGAD can manifest as either a monophasic or a relapsing disease, whereas NMOSD is usually relapsing. This Review summarizes the history and current concepts of NMOSD and MOGAD, comparing epidemiology, clinical features, neuroimaging, pathology and immunology. In addition, we discuss new monoclonal antibody therapies for AQP4-IgG-seropositive NMOSD that target complement, B cells or IL-6 receptors, which might be applied to MOGAD in the near future.

Perturbed Microbial Ecology in Neuromyelitis Optica Spectrum Disorder: Evidence from the Gut Microbiome and Fecal Metabolome

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD. MethodsMetagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC-MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (n=25), the remission phase (n=11), and a group of healthy controls (HCs) (n = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing. Results(1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium CAG 238, and Lactobacillus fermentum. (3) The relative abundances of Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia sp.CAG 471, Veillonella tobetsuensis, Proteobacteria bacterium CAG 139, Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii, and Streptococcus cristatus were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of Flavonifractor (P = 0.049) and Clostridium aldenense (P = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-free mice and revealed a significant increase in the levels of IL-6, IL-17A, and IL-23 in the blood of mice belonging to the NMOSD fecal transplantation (NFMT) group. Additionally, the IL-10 level exhibited a significant reduction. Moreover, the proportion of Th17 cells displayed a significant increase, while the proportion of Treg cells exhibited a significant decrease in the spleens of NFMT mice. ConclusionPatients in the acute phase of neuromyelitis optica spectrum disorder (NMOSD) exhibited imbalances in their gut microbiota and a deficiency in short-chain fatty acids (SCFAs). Following drug treatment, the composition of intestinal microbes in NMOSD patients during the remission phase closely resembled that of the healthy control population. The FMT experiment provided evidence of the significant association between intestinal flora and the pathogenesis of NMOSD. Consequently, investigating gut microbiota and identifying novel microbial markers hold promise for the diagnosis and treatment of NMOSD patients.

Efficacy and Safety of Inebilizumab, an Anti-CD19 Monoclonal Antibody, for the Treatment of Neuromyelitis Optica Spectrum Disorder: Based on the N-MOmentum Trial

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathic disease of the central nervous system characterized by severe optic neuritis and transverse myelitis. The antibody against aquaporin 4 (AQP4), a water channel mainly expressed in astrocytes, is specific to NMOSD and may be detected in >70% of all cases. Inebilizumab is a humanized IgG1 monoclonal antibody against CD19. Anti-AQP4 antibodies are produced by CD19-positive plasmablasts, and inebilizumab administration significantly reduces the number of CD19-positive B cells and has therapeutic effects on NMOSD. The efficacy and safety of inebilizumab have been verified in the N-MOmentum trial, an international double-blind, placebo-controlled phase II/III study, in which Japanese patients also participated. Inebilizumab was approved for the treatment of NMOSD with AQP4-IgG in Japan in March 2021. In this review, we summarize the efficacy and safety of inebilizumab in the treatment of NMOSD and, focus on findings from the primary and additional analyses of the N-MOmentum trial. These results suggest that inebilizumab is effective and safe in preventing the recurrence of NMOSD in populations with different backgrounds and that long-term treatment with inebilizumab is beneficial.

A Case of the Anti-aquaporine-4 Antibody-negative Neuromyelitis Optica Spectrum Disorders Associated with Atopic Disease with High Concentration of Anti-IgE Autoantibody and HyperIgEemia

We report a 70-year-old male patient with the sero-negative neuromyelitis optica spectrum disorders (NMOSD) associated with atopic disease (AD). He was diagnosed with allergic rhinitis at the age of 20. When he was 61 years old, he subacutely developed orthostatic hypotension, bilateral optic neuritis, quadriparesis, urinary retention, and constipation. The laboratory results revealed allergen-specific IgE positivity for cryptomeria japonica and hinoki, hyperIgEemia, and Th (helper T cell) 1 dominance. The serological tests for autoantibodies revealed negative anti-aquaporine 4 antibody, and high concentration of anti-IgE autoantibody (anti-IgE AAb). Cerebrospinal fluid was negative for anti-myelin-oligodendrocyte glycoprotein antibody and glial fibrillary acidic protein antibody. Fluid-attenuated inversion recovery on brain magnetic resonance imaging (MRI) showed high signal intensities in bilateral cerebral deep white matter. T2 weighted image on spine MRI showed longitudinally extensive high signal intensities in the spinal cord, specifically involving C1 vertebral level to conus medullaris. Intravenous methylprednisolone (IVMP) and plasma exchange resulted in partial improvement. Following the onset of NMOSD, he had relapse of NMOSD four times. In each episode, IVMP was to be partially effective with anti-IgE AAb reduction. Anti-IgE AAb may be a reasonable clinical indicator of increased disease activity in the sero-negative NMOSD associated with AD.

Clinical outcomes of optic neuritis: A retrospective study at a tertiary medical center in Saudi Arabia.

To investigate the clinical results of optic neuritis (ON) patients in a tertiary medical facility in Makkah, Kingdom of Saudi Arabia. The data of patients assessed for ON at Makkah, Saudi Arabia's King Abdullah Medical Center (KAMC), was examined retrospectively. We identified 15 patients with ON. The ON was caused by multiple sclerosis (MS) in 73.3% of patients and neuromyelitis optica spectrum disorder (NMOSD) in 26.7% of patients. The disease was bilateral in 60% of patients and unilateral in 40% of patients. Additionally, 60% of patients had 2 or more episodes of ON, whereas 40% had a single episode. Patients with ON who presented with painful eye movements had a significantly longer disease duration (p=0.032). Moreover, patients whose disease duration was 11-15 days did not achieve a complete resolution of their symptoms and experienced some residual vision loss compared to 30.8% who had continued visual changes (p=0.049). In the studied population, multiple sclerosis was the most prevalent cause of ON. Women were more likely to have ON. The prognosis for eyesight was substantially connected with the length of ON.

Characterizing the clinical, radiological and serological features of children diagnosed with neuromyelitis optica spectrum disorder at pediatric neurology unit

Background. Neuromyelitis optica spectrum disorder is a rare autoimmune disease with a chronic inflammatory demyelinating characteristics that affects the central nervous. The aim of the study is to characterize the clinical, serological and radiological features of neuromyelitis optica disease in a sample of children from Iraq. Methods. A cross-sectional descriptive study has been carried out in the period from August 2019 to September 2020, in pediatric neurology ward in Children Welfare Teaching Hospital, Baghdad. In 12 retrospectively gathered cases, the medical registration of the ward was assessed. A total of 13 patients, aged 3-16 years were included. Results. Among the patients, girls represented 61.5% (8), and the females: males ration was (1.6:1). The patients' ages ranged from 3 to 16 years (mean 9.3 ± 4.02 years). All patients younger than 6 years were AQP-ve, in contrast to 15.3% in those older than 6 years. Negative AQP patients equally distributed between males and females. While females predominated in those with AQP positive status (5,71.4%). Weakness of the limbs and sphincteric disturbance were the first two common clinical features in both AQP positive and negative patients. The three most common brain sites insulted were deep white matter (10, 76.9%), periaqueductal area (5, 38.4%), and brainstem (4, 30.7%). All patients showed long spinal lesions, affecting predominantly the cervico-thoracic (61.53%). Conclusion. The demographic characteristics of the present cohort were comparative to that reported in the literature. Transverse myelitis phenotype was the most common and consistent one. Vomiting was more common in AQP +ve patients.

Quality of life in patients with myelin oligodendrocyte glycoprotein antibody associated disease compared to patients with AQP4-IgG positive neuromyelitis optica spectrum disorders: A Korean multicenter study

BackgroundLittle is known about the quality of life (QOL) of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We compared QOL and associated factors in patients with MOGAD and aquaporin4 IgG (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD). MethodsThis multicenter questionnaire study compared the QOL of 41 patients with MOGAD and 78 with AQP4-IgG positive NMOSD. Patients who were positive for AQP4-IgG or MOG antibodies were included. WHO Quality of Life Scale Brief Version was used to assess QOL in physical, psychological, social, and environmental domains. QOL, sleep quality, pain, fatigue, and depression were compared between the two groups. The factors associated with QOL in each group and the entire cohort were analyzed. ResultsThe proportion of patients with poor QOL was not significantly different between MOGAD (51.22 %) and AQP4-IgG positive NMOSD (58.97 %, p = 0.054). In the MOGAD group, the pain score (β=-1.032, p = 0.001) and depression score (β=-0.694, p = 0.007) were negatively associated with physical and psychological QOL, respectively. Sleep quality was negatively associated with physical (β=-1.506, p = 0.034) and psychological (β =-2.064, p = 0.033) QOL. When the entire cohort was analyzed, a positive MOG antibody was independently associated with worse psychological QOL (β=-8.998, p = 0.013) compared to positive AQP4-Ab after adjustment for sleep quality, depression, fatigue, and pain. ConclusionsThe overall QOL of the patients of MOGAD was comparable to that of AQP4-IgG positive NMOSD. Patients with MOGAD were experiencing sleep disorder, fatigue, and depression at similar degrees to those of patients with AQP4-IgG positive NMOSD. Further consideration of sleep quality and psychological QOL is required to improve QOL in patients with MOGAD.

Neuromyelitis optica spectrum disorder. Clinical case

Background. Neuromyelitis optica spectrum disorder (NMOSD) has been masked under other diagnoses for many years. Modern diagnostic criteria expand diagnosis possibilities, but they need approbation in real clinical practice. The purpose was through the analysis of a clinical case and literature search to analyze the algorithm for making a diagnosis of neuromyelitis optica based on the new clinical guideline “Diagnosis and treatment of the neuromyelitis optica spectrum disorders” developed in 2023 in Ukraine, to identify marker signs that exclude alternative diagnoses, to analyze the effectiveness of patient treatment in dynamics. Materials and methods. We used the bibliosemantic method, as well as methods of systematic and comparative analysis. We presented the results of our own clinical experience and conducted a dynamic analysis of a clinical case of neuromyelitis optica. Results. Over the past six years, 23 patients diagnosed with neuromyelitis optica were treated at the neurological department of the Lviv Regional Clinical Hospital: 1 patient in 2018, 5 in 2019, 3 in 2020, 6 in 2021, 8 in 2022. We examined the clinical case of a 52-year-old patient who sought medical help at the Department of Neurology of Danylo Halytskyi Lviv National Medical University in 2023. We analyzed the patient’s path to the diagnosis of neuromyelitis optica with the dynamics of changes on magnetic resonance imaging from 2019, considering current diagnostic criteria in which neuromyelitis optica was included in the single term NMOSD. The presence of even one of the six main clinical manifestations, in combination with the presence of AQP4-IgG, gives grounds for making a diagnosis of NMOSD. We carried out a differential diagnosis with other pathologies. Based on this, we identified marker signs to exclude multiple sclerosis, acute disseminated encephalomyelitis, infectious myelitis, and other diseases. Diagnostic aspects of NMOSD and treatment options were considered. An analysis of the effectiveness of the patient’s treatment in dynamics was carried out. Conclusions. The new Ukrainian clinical guideline for neuromyelitis optica spectrum disorder, which is based on international consensus diagnostic criteria, improves the standardization of the approach to patients with NMOSD and can be effectively used in real clinical practice. In our clinical case of a patient with myelitis without optic neuritis, the presence of AQP4-IgG and careful differential diagnosis with other pathologies play a key role in the diagnosing.

Early relapse after rituximab treatment in a patient with seronegative neuromyelitis optica spectrum disorder: a case report

Early relapse after rituximab treatment in a patient with seronegative neuromyelitis optica spectrum disorder: a case report

A Case of Optic Neuritis in a Patient with Anti-Aquaporin 4 and Anti-Myelin Oligodendrocyte Glycoprotein Antibody Double-Seropositive Neuromyelitis Optica Spectrum Disorder

A Case of Optic Neuritis in a Patient with Anti-Aquaporin 4 and Anti-Myelin Oligodendrocyte Glycoprotein Antibody Double-Seropositive Neuromyelitis Optica Spectrum Disorder

Decreased NETosis-related regulators in neuromyelitis optica spectrum disorders after plasma exchange

ObjectivesTo investigate the impact of plasma exchange (PLEX) on NETosis-related regulators and their correlation with neurological improvement in NMOSD patients. MethodsTwelve aquaporin-4 antibodies seropositive NMOSD patients were enrolled. NETosis-related regulators (myeloperoxidase [MPO], citrullinated histone H3 [CIT-H3], peptidyl arginine deiminase 4 [PAD4], neutrophil elastase [NE], CD64), pro-inflammatory cytokines (IL-1, IL-6, IL-12, TNF-α) and anti-inflammatory cytokines (IL-10, TGF-β1) were quantitatively assessed before and after PLEX treatment. Clinical assessments included expanded disability status scale (EDSS) and visual outcome scale (VOS) scores. ResultsFollowing PLEX, all patients showed symptom improvement, with 66.7 % achieving marked-to-moderate improvement (MMI) at 3 months. Key regulators, such as MPO, CIT-H3, PAD4, NE, and pro-inflammatory cytokines such as IL-1, IL-6, IL-12, and TNF-α, exhibited a statistically significant decrease immediately after the initial PLEX session (P < 0.05). Furthermore, CD64 levels demonstrated a substantial decline after the second PLEX session (P < 0.05). Conversely, the levels of anti-inflammatory cytokines, including IL-10 and TGF-β1, displayed an ascending trend post-PLEX. In clinical relevance analysis, among patients who reached MMI, the reductions in MPO, IL-1, and IL-6 exhibited statistically significant differences when compared to patients in the mild-to-no improvement group (P < 0.05). Pearson correlation analysis revealed that the percentage reduction in IL-6 levels after PLEX was positively correlated with the percentage reduction in patient EDSS/VOS scores (r = 0.638, P < 0.05). ConclusionsThis study highlights that reduced levels of NETosis-related regulators after PLEX contribute to clinical improvement, suggesting the potential involvement of NETosis in the acute neurological impairment observed in NMOSD.

Clinical characteristics and predictive factors of recurrent idiopathic transverse myelitis.

Idiopathic transverse myelitis (iTM) is defined as an inflammatory myelopathy of undetermined etiology, even after a comprehensive workup to identify other possible causes. Generally, the characteristics of recurrent iTM are not clearly defined. This study aimed to identify the clinical characteristics and predictive factors of recurrence in patients with iTM. We retrospectively recruited patients with transverse myelitis (TM) who visited Chungnam National University Hospital between January 2011 and December 2021. We included patients who were followed up for at least 2 years and excluded those diagnosed with multiple sclerosis or neuromyelitis optica spectrum disorder (NMOSD) during the initial episode or follow-up period. Patients with iTM were categorized into two groups: monophasic idiopathic TM (mTM) and recurrent idiopathic TM (rTM). We compared the clinical characteristics and spinal magnetic resonance imaging findings between the two groups. In total, 167 patients were reviewed, of whom 112 were excluded. Finally, we included 55 patients with iTM. In 55 patients, 11 (20.0%) and 44 (80%) were classified into the rTM and mTM groups, respectively. Male predominance was observed in the iTM, rTM, and mTM groups. The percentage of patients with low vitamin D levels was significantly higher in the rTM group (100.0%) compared with the mTM group (70%) (p = 0.049). In addition, longitudinally extensive transverse myelitis (LETM) was observed more frequently in the rTM group, in 8 of 11 (72.7%) patients, compared with 15 of 44 (34.1%) patients in the mTM group, with the difference being statistically significant (p = 0.020). In multivariate regression analysis, female sex, younger age at onset, low serum vitamin D level (<30 ng/mL), and LETM were risk factors for recurrence. LETM was a significant predictor of relapse in iTM (p = 0.043, odds ratio = 13.408). In this study, the clinical features of mTM and rTM are nearly indistinguishable. In conclusion, >20% of the patients with iTM experience recurrence, and LETM is the most significant risk factor for recurrence. In cases of recurrence, there is a favorable response to immunotherapy, and the prognosis is generally good. Although LETM may be the initial symptom of NMOSD, it may be manifestation of iTM, and in cases of idiopathic LETM, it is important to be mindful of the elevated risk of recurrence. Based on these results, idiopathic rTM has good clinical prognosis and response to immunosuppressive treatment.

Macular vascular density alteration patterns in paediatric optic neuritis patients with serum MOG antibody positivity detected by optic coherence tomography angiography

PurposeThe retinal microvascular network plays a crucial role in inflammatory injury in paediatric optic neuritis (PON) with serum MOG antibody positivity (MOG + PON). This study compared retinal microvascular densities and structural alterations in MOG + PON eyes with paediatric isolated optic neuritis (PION) eyes and followed up with the final best-corrected visual acuity (BCVA) after 6 months. MethodsA total of 29 children (52 eyes) with PON, including 15 MOG + PON cases (28 eyes), 6 PION cases (10 eyes), 2 neuromyelitis optica spectrum disorders associated PON(NMOSD-PON) cases (4 eyes), 6 MOG-associated disease (MOGAD) patients without ON-affected eyes (MOG + NPON) cases (10 eyes) and age- and gender-matched healthy controls (HCs) underwent superficial/deep retinal angiography density (SAD/DAD) by optical coherence tomography angiography (OCTA). Their BCVAs were followed up until 6 months after PON onsets. ResultsMOG + PON cases had better final BCVAs than PION and NMOSD-ON. MOG + PON (35.7 ± 10.3 %) and PION (40.1 ± 10.3 %) eyes experienced severe SAD reductions in contrast to MOGAD+NPON (48.7 ± 5.2 %) and HCs eyes (55.6 ± 8.2 %). However, DAD in MOG + PON eyes (48.5 ± 9.2 %) and MOG + NPON eyes (53.1 ± 3.3 %) increased compared to HC eyes (45.7 ± 9.6 %; p = 0.028 and 0.009, respectively). SAD reduction occurred in acute PON and was detected as early as 2 weeks after PON onset. ConclusionsMOG + PON eyes had better final BCVAs than PION eyes, which displayed superficial retinal microvascular perfusion reductions and deep microvascular perfusion increases. SAD could be a sensitive surrogate for PON attacks in children with MOGAD.

Neuromyelitis Optica Spectrum Disorders – from pathophysiology to treatment

Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune diseases characterized by severe, inflammatory attacks predominantly affecting the optic nerves and spinal cord and central nervous system. NMOSD presents with clinical features such as optic neuritis, acute myelitis, and area postrema syndrome, making it a challenging condition to diagnose due to its varied clinical manifestations. Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their first attack. Historically considered a variant of multiple sclerosis, NMOSD is now recognized as a distinct entity, largely due to the discovery of the pathogenic role of aquaporin-4 (AQP4) antibodies. Approximately 75% of patients have antibodies against aquaporin-4, a water channel expressed on astrocytes. These antibodies target astrocytes, leading to complement activation, inflammation, and subsequent damage to the central nervous system. Relapses are treated with high-dose steroids and plasma exchanges to prevent residual disability. Advances in understanding the pathophysiology of NMOSD have paved the way for targeted therapies, including monoclonal antibodies that inhibit complement activation, B-cell depletion strategies, and interventions targeting interleukin-6 signaling. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab inebilizumab, and satralizumab. These treatments have significantly improved disease outcomes, offering hope for better management of NMOSD, although challenges remain in early diagnosis, treatment accessibility, and preventing relapses. Further research is essential to refine therapeutic approaches and explore novel targets to enhance patient care.

Vitamin D in Primary Sjogren's Syndrome (pSS) and the Identification of Novel Single-Nucleotide Polymorphisms Involved in the Development of pSS-Associated Diseases.

Sjögren's syndrome (SS) is a chronic autoimmune disorder characterised by lymphocytic infiltration of the exocrine glands, which leads to dryness of the eyes and mouth; systemic manifestations such as arthritis, vasculitis, and interstitial lung disease; and increased risks of lymphoma and cardiovascular diseases. SS predominantly affects women, with a strong genetic component linked to sex chromosomes. Genome-wide association studies (GWASs) have identified numerous single-nucleotide polymorphisms (SNPs) associated with primary SS (pSS), revealing insights into its pathogenesis. The adaptive and innate immune systems are crucial to SS's development, with viral infections implicated as environmental triggers that exacerbate autoimmune responses in genetically susceptible individuals. Moreover, recent research has highlighted the role of vitamin D in modulating immune responses in pSS patients, suggesting its potential therapeutic implications. In this review, we focus on the recently identified SNPs in genes like OAS1, NUDT15, LINC00243, TNXB, and THBS1, which have been associated with increased risks of developing more severe symptoms and other diseases such as fatigue, lymphoma, neuromyelitis optica spectrum disorder (NMOSD), dry eye syndrome (DES), and adverse drug reactions. Future studies should focus on larger, multi-ethnic cohorts with standardised protocols to validate findings and identify new associations. Integrating genetic testing into clinical practise holds promise for improving SS management and treatment strategies, enabling personalised interventions based on comprehensive genetic profiles. By focusing on specific SNPs, vitamin D, and their implications, future research can lead to more effective and personalised approaches for managing pSS and its complications.