Neuromyelitis Optica Spectrum Disorder Group Research Articles

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

OverviewDysphagia 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. MethodsSeventy-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. ResultsThe 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. ConclusionThe 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.

Association between FOXP3 polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.

Forkhead box P3 (FOXP3) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between FOXP3 polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population. We genotyped single nucleotide polymorphisms at loci of the FOXP3 gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of FOXP3 in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups. The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, p = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, p = 0.038). The proportions of the three genotypes of rs2232365 (p = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of FOXP3 was markedly greater in the NMOSD group than in the control group (p = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (p = 0.004 and 0.007, respectively). FOXP3 polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of FOXP3 rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. FOXP3 mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decreased in acute non-treatment patients compared with healthy controls.

A retrospective study of myelin oligodendrocyte glycoprotein antibody-associated disease from a clinical laboratory perspective.

To analyze the differences in laboratory data between patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The study included 26 MOGAD patients who visited Beijing Tiantan Hospital from 2018 to 2021. MS and NMOSD patients who visited the clinic during the same period were selected as controls. Relevant indicators were compared between the MOGAD group and the MS/NMOSD groups, and the diagnostic performance of meaningful markers was assessed. The MOGAD group showed a slight female preponderance of 57.7%, with an average onset age of 29.8 years. The absolute and relative counts of neutrophils were higher in the MOGAD group than in the MS group, while the proportion of lymphocytes was lower. The cerebrospinal fluid (CSF) IgG level, IgG index, 24-h IgG synthesis rate, and positive rate of oligoclonal bands (OCB) were lower in MOGAD patients than in the MS group. The area under ROC curve (AUC) was 0.939 when combining the relative lymphocyte count and IgG index. Compared to the NMOSD group, the MOGAD group had higher levels of serum complement C4 and lower levels of serum IgG. The AUC of serum C4 combined with FT4 was 0.783. Statistically significant markers were observed in the laboratory data of MOGAD patients compared to MS/NMOSD patients. The relative lymphocyte count combined with IgG index had excellent diagnostic efficacy for MOGAD and MS, while serum C4 combined with FT4 had better diagnostic efficacy for MOGAD and NMOSD.

Higher longitudinal brain white matter atrophy rate in aquaporin-4 IgG-positive NMOSD compared with healthy controls

We aimed to compare longitudinal brain atrophy in patients with neuromyelitis optica spectrum disorder (NMOSD) with healthy controls (HCs). The atrophy rate in patients with anti-aquaporin-4 antibody-positive NMOSD (AQP4 + NMOSD) was compared with age-sex-matched HCs recruited from the Japanese Alzheimer’s Disease Neuroimaging Initiative study and another study performed at Chiba University. Twenty-nine patients with AQP4 + NMOSD and 29 HCs were enrolled in the study. The time between magnetic resonance imaging (MRI) scans was longer in the AQP4 + NMOSD group compared with the HCs (median; 3.2 vs. 2.9 years, P = 0.009). The annualized normalized white matter volume (NWV) atrophy rate was higher in the AQP4 + NMOSD group compared with the HCs (median; 0.37 vs. − 0.14, P = 0.018). The maximum spinal cord lesion length negatively correlated with NWV at baseline MRI in patients with AQP4 + NMOSD (Spearman’s rho = − 0.41, P = 0.027). The annualized NWV atrophy rate negatively correlated with the time between initiation of persistent prednisolone usage and baseline MRI in patients with AQP4 + NMOSD (Spearman’s rho = − 0.43, P = 0.019). Patients with AQP4 + NMOSD had a greater annualized NWV atrophy rate than HCs. Suppressing disease activity may prevent brain atrophy in patients with AQP4 + NMOSD.

Downregulation of lncRNA XIST may promote Th17 differentiation through KDM6A-TSAd pathway in neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease with significant female preponderance. X inactive specific transcript (XIST) is a long non-coding RNA (lncRNA) and a key regulator of X-chromosome inactivation which is related to the sex-bias of autoimmunity. And Th17 cell proportion was significantly elevated in NMOSD according to our previous study. This study aimed to explore the expression levels of lncRNA XIST-KDM6A-TSAd pathway in lymphocytes of female NMOSD patients, and investigate its possible relationship with pathogenesis of NMOSD. The study enrolled 30 acute-phase untreated female NMOSD patients and 30 age-matched female healthy controls, their lymphocytes were collected for experiments. Microarray as well as validation experiments showed lncRNA XIST was significantly downregulated in the NMOSD group. And the levels of lysine demethylase 6A (KDM6A) decreased in NMOSD and showed significant positive correlation with XIST. The levels of T cell-specific adapter (TSAd) mRNA and protein levels were significantly lower in NMOSD. And Chromatin immunoprecipitation assay demonstrated that NMOSD had more H3K27me3 modification than control at TSAd promoter region. The present study introduced a potential pathway that following lncRNA XIST downregulation, which process may promote Th17 differentiation in NMOSD. These findings shed new light on the immune regulation mechanism about lncRNA XIST and related epigenetic features, which may contribute to develop female-specific treatment plans.

Establishment of a comprehensive diagnostic model for neuromyelitis optica spectrum disorders based on the analysis of laboratory indicators and clinical data.

To establish a comprehensive diagnostic model for neuromyelitis optica spectrum disorders (NMOSDs) based on laboratory indicators and clinical data. A retrospective method was used to query the medical records of patients with NMOSD from January 2019 to December 2021. At the same time, clinical data of other neurological diseases were also collected for comparison. Clinical data of the NMOSD group and non-NMOSD group were analyzed, and the diagnostic model was established based on these data. In addition, the model was evaluated and verified by the receiver operating curve. A total of 73 patients with NMOSD were included, and the ratio of males to females was 1:3.06. The indicators that showed differences between the NMOSD group and non NMOSD group included neutrophils (P = 0.0438), PT (P = 0.0028), APTT (P < 0.0001), CK (P = 0.002), IBIL (P = 0.0181), DBIL (P < 0.0001), TG (P = 0.0078), TC (P = 0.0117), LDL-C (P = 0.0054), ApoA1 (P = 0.0123), ApoB (P = 0.0217), TPO antibody (P = 0.012), T3 (P = 0.0446), B lymphocyte subsets (P = 0.0437), urine sg (P = 0.0123), urine pH (P = 0.0462), anti-SS-A antibody (P = 0.0036), RO-52 (P = 0.0138), CSF simplex virus antibody I-IGG (P = 0.0103), anti-AQP4 antibody (P < 0.0001), and anti-MOG antibody (P = 0.0036). Logistic regression analysis showed that changes in ocular symptoms, anti-SSA antibody, anti-TPO antibody, B lymphocyte subsets, anti-AQP4 antibody, anti-MOG antibody, TG, LDL, ApoB, and APTT had a significant impact on diagnosis. The AUC of the combined analysis was 0.959. The AUC of the new ROC for AQP4- and MOG- antibody negative NMOSD was 0.862. A diagnostic model was successfully established, which can play an important role in differential diagnosis of NMOSD.

Impact of dysautonomic symptom burden on the quality of life in Neuromyelitis optica spectrum disorder patients

BackgroundThis study aimed to investigate the clinical risk factors of dysautonomic symptom burden in neuromyelitis optica spectrum disorder (NMOSD) and its impact on patients’ quality of life.MethodsA total of 63 NMOSD patients and healthy controls were enrolled. All participants completed the Composite Autonomic Symptom Score 31 (COMPASS-31) to screen for symptoms of autonomic dysfunction. A comprehensive clinical evaluation was performed on NMOSD patients, such as disease characteristics and composite evaluations of life status, including quality of life, anxiety/depression, sleep, and fatigue. Correlated factors of dysautonomic symptoms and quality of life were analyzed.ResultsThe score of COMPASS-31 in the NMOSD group was 17.2 ± 10.3, significantly higher than that in healthy controls (P = 0.002). In NMOSD patients, the higher COMPASS-31 score was correlated with more attacks (r = 0.49, P < 0.001), longer disease duration (r = 0.52, P < 0.001), severer disability (r = 0.50, P < 0.001), more thoracic cord lesions (r = 0.29, P = 0.02), more total spinal cord lesions (r = 0.35, P = 0.005), severer anxiety (r = 0.55, P < 0.001), severer depression (r = 0.48, P < 0.001), severer sleep disturbances (r = 0.59, P < 0.001), and severer fatigue (r = 0.56, P < 0.001). The disability, total spinal cord lesions, and fatigue were revealed to be independently associated factors. Further analysis revealed that the COMPASS-31 score was independently correlated with scores of all the domains of patients’ quality of life scale (P < 0.05).ConclusionsDysautonomic symptom burden is correlated with decreased quality of life and certain clinical characteristics such as disability, the burden of spinal cord lesions, and fatigue in NMOSD patients. Investigation and proper management of autonomic dysfunction may help to improve the quality of life in patients with NMOSD.

Risk of fracture in neuromyelitis optica spectrum disorder and multiple sclerosis: a nationwide cohort study in South Korea.

Interest in fractures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has considerably increased in the last decade. However, few studies have compared the incidence of fractures between patients with MS and NMOSD using a nationwide database. This study aimed to evaluate the differences in the risk of fracture between patients with NMOSD and MS compared to that in healthy controls using cohort data from a Korean nationwide database. In this retrospective cohort study, data from the National Health Insurance Service (NHIS) database from January 2010 to December 2017 were analyzed. A total of 1,217/1,329 patients with MS/NMOSD free of fractures at the index date were included. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus, and dyslipidemia. The mean follow-up durations after the index date were 4.40/4.08years for patients with MS/NMOSD and 4.73/4.28 for their matched controls. The adjusted hazard ratios (aHRs) with 95% confidence intervals of any, hip, and vertebral fractures were 1.81 (1.43-2.28), 3.36 (1.81-6.24), and 2.01 (1.42-2.99) times higher for patients with MS than for controls, respectively, and they were 1.85 (1.47-2.34), 3.82 (2.05-7.11), and 2.84 (1.92-4.21) times higher for patients with NMOSD than for controls, respectively. No significant differences were observed in the incidence of fractures between the MS and NMOSD groups. Patients with MS/NMOSD had a 1.8-fold higher risk of fracture than matched controls, and the risk of hip fracture was especially high (3- to 4-fold higher). Clinicians need to regularly assess patients with MS/NMOSD for the risk of fractures and take preventative measures to reduce it.

Utility of the tibial nerve somatosensory evoked potentials in differentiating between neuromyelitis optica spectrum disorders and multiple sclerosis.

Somatosensory evoked potentials (SEPs) are widely used for the diagnosis and evaluation of neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). However, whether the parameters of tibial nerve SEPs can help to distinguish NMOSD from MS remains unclear. Thus, the aim of this study was to investigate the utility of tibial nerve SEP parameters in differentiating patients with NMOSD and MS. The clinical data of patients with NMOSD or MS treated in our institution between 2005 and 2021 were retrospectively extracted from our electronic database. Additional inclusion criteria were presentation with sensory symptoms in the lower extremities with corresponding lesions in the magnetic resonance images as well as available data on anti-aquaporin-4 antibodies and tibial nerve SEPs. The Z-scores of the N21-P38 interval (central sensory conduction time), P38 latency, and P38 amplitude were compared between the patients with NMOSD and MS. The relationship of disease severity with the parameters of the tibial nerve SEPs was also evaluated. Twenty patients with NMOSD and 13 patients with MS were enrolled. The Z-scores of the N21-P38 interval and P38 latency were significantly higher in the MS group than in the NMOSD group (p < 0.05 and p < 0.01, respectively), whereas there was no difference in the Z-scores of the P38 amplitude between the two groups. In the MS group, only the N21-P38 interval and P38 latency were significantly correlated with disease severity (p < 0.05 and p < 0.01, respectively). In contrast, none of the tibial nerve SEP parameters were significantly correlated with disease severity in the NMOSD group. Evaluation of the N21-P38 interval and P38 latency in tibial nerve SEPs potentially helps in differentiating between NMOSD and MS.

Enlarged choroid plexus related to cortical atrophy in multiple sclerosis.

To investigate the correlation between choroid plexus volume and whole brain morphology in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Fifty-one patients with MS, 42 patients with NMOSD, and 56 healthy controls (HC) were recruited. The morphological changes in choroid plexus and whole brain tissue were compared between three groups and the correlations between choroid plexus volume and brain atrophy were further investigated. The longitudinal alterations of brain morphology in 25 MS and 20 NMOSD patients were compared. Compared to the HC group, the choroid plexus volumes were increased in the MS group (p < 0.001) but not in the NMOSD group (p > 0.05). Compared to the HC group, the MS group showed reduced cortex thickness, deep gray matter volume, and increased ventricle system volume, and the NMOSD group showed increased third ventricle volume (all p < 0.05, false discovery rate corrected). In the MS group, there were widespread correlations between enlarged choroid plexus volume and reduced cerebral cortex thickness (p < 0.05, r = -0.292~-0.538, false discovery rate corrected). The interval time was not significantly different between the MS (median: 1.37 years) and NMOSD group (median: 1.25 years) (p > 0.05). In MS, compared with the baseline, the right hippocampus and nucleus accumbens volumes were decreased in long follow-up, and bilateral lateral ventricle volumes were increased both in short and long follow-up (all p < 0.05, false discovery rate corrected). The enlarged choroid plexus related to reduced cortical thickness and progressive local brain atrophy are shown in MS patients, but not obvious in NMOSD patients. • MS and NMOSD have different altered patterns in choroid plexus volume and brain atrophy. • The enlarged choroid plexus related to brain atrophy is shown in MS patients, but not obvious in NMOSD patients. • Progressive local brain atrophy is shown in MS patients, but not obvious in NMOSD patients.

The utility of diffusion-weighted imaging in patients with spinal cord infarction: difference from the findings of neuromyelitis optica spectrum disorder

BackgroundMagnetic resonance imaging (MRI) plays a crucial role in diagnosing spinal cord infarction (SCI). However, the findings are often indistinguishable from those of other intramedullary diseases, such as neuromyelitis optica spectrum disorder (NMOSD). Although diffusion-weighted imaging (DWI) is a promising technique, the utility for discriminating SCI from NMOSD remains unclear because the DWI findings of acute NMOSD lesions have not been investigated in detail.MethodsClinical and MRI findings were retrospectively evaluated in 15 and 12 patients with acute SCI and NMOSD, respectively. First, clinical characteristics were compared between the SCI and NMOSD groups. Second, MRI abnormalities were examined to find differences between these groups. Third, in the SCI group, factors influencing T2 and DWI abnormalities were analyzed using the mixed-effects logistic regression analysis.ResultsThe proportion of female patients was higher in the NMOSD group (92%) than in the SCI (40%). The time from symptom onset to nadir was smaller in the SCI group (median [interquartile range]; 4 [0.1–8.3] hours) than in the NMOSD (252 [162–576]). On T2-weighted images, SCI lesions had smaller length than NMOSD (2 [1–2] and 5 [2–7] vertebral segments, respectively). Focal lesions within the T9–L2 level were found only in patients with SCI. DWI hyperintensity was observed both in the SCI (frequency, 100%) and NMOSD (60%) groups. On apparent diffusion coefficient (ADC) maps, the hyperintensities of SCI had corresponding hypointensities, whereas those of NMOSD were isointense and a large portion of NMOSD lesions had hyperintense signals. Owl’s eyes sign and pencil-like hyperintensity, typically reported as T2 findings suggestive of SCI, were also found on DWI. Posterior linear hyperintensity was frequently detected on DWI in patients with posterior spinal artery infarction. The presence of MRI abnormality revealing SCI was modeled with the time from symptom onset, imaging sequence and plane, and affected vascular territory.ConclusionsDWI and ADC maps help distinguish SCI from NMOSD. The time from symptom onset, imaging sequence, and imaging plane should be considered when MRI findings are interpreted in patients with suspected SCI.

Brain age gap in neuromyelitis optica spectrum disorders and multiple sclerosis

ObjectiveTo evaluate the clinical significance of deep learning-derived brain age prediction in neuromyelitis optica spectrum disorder (NMOSD) relative to relapsing-remitting multiple sclerosis (RRMS).MethodsThis cohort study used data retrospectively collected from...

Dorsal medulla surface texture: Differentiating neuromyelitis optica spectrum disorder from multiple sclerosis.

The timely and accurate diagnosis of neuromyelitis optica spectrum disorder (NMOSD) is essential and exposure to multiple sclerosis (MS) disease-modifying therapies may result in permanent neurological disability. Standardized 3-Tesla 3-dimensional brain MRI studies were retrospectively studied from people with NMOSD, MS, other CNS neurological diseases, and healthy control subjects. Comparisons of surface texture characteristics at the area postrema involving absolute introverted planar triangle counts, representing more complex and concave tissue topography, along with the spatial dissemination pattern of these triangles were performed cross-sectionally and longitudinally. An ideal introverted planar triangle threshold separating groups with NMOSD and MS was accomplished using the highest Youden's J statistic. For the classification of NMOSD, out-of-sample and in-sample measurements of the following were acquired: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The study cohort included 60 people with NMOSD, 100 people with MS, 12 with other neurological diseases, and five healthy controls. Significantly higher cross-sectional median introverted triangle counts were observed when the NMOSD (median [interquartile range]: 100 [23.5]) group was compared to MS (65 [20.25]; p&lt;.0001) and other neurological diseases (66 [13.75]; p&lt;.0001). Distinct spatial dissemination patterns of triangles extending craniocaudally at the region of interest within the dorsal medulla was also seen between groups with NMOSD and MS (p&lt;.0001). For the identification of NMOSD, out-of-sample sensitivity (83%), specificity (100%), PPV (100%), and NPV (60%) were achieved. Cross-sectional and longitudinal dorsal medulla surface texture differences within selective regions of vulnerability differentiate NMOSD from MS.

Concentrations of B cell-activating factor, aquaporin-4 antibody and brain-derived neurotrophic factor in neuromyelitis optica spectrum disorder

Abstract Objectives To explore the correlations of B cell-activating factor (BAFF), aquaporin-4 antibody (AQP4-Ab) and brain-derived neurotrophic factor (BDNF) with the severity of neuromyelitis optica spectrum disorder (NMOSD). Methods Sixty-eight NMOSD patients were selected as an NMOSD group, and 65 patients with non-inflammatory neurological diseases hospitalized in the same period were selected as a control group. The severity of the disease was assessed using the expanded disability status scale (EDSS). Logistic regression analysis was conducted on the influencing factors for the severity of NMOSD. The correlations of BAFF, AQP4-Ab and BDNF with clinical characteristics were studied by Spearman’s analysis. Results The patients with EDSS score ≥7 points, number of involved spinal segments ≥5 and recurrence ≥3 times had a lower level of BAFF in the cerebrospinal fluid than the level of those with 4 points ≤ EDSS score &lt;7 points, EDSS score &lt;4 points, number of spinal segments &lt;5 and recurrence &lt;3 times (p&lt;0.05). BAFF concentration was negatively correlated with disease duration, EDSS score, number of involved spinal segments and recurrence status (p&lt;0.05). AQP4-Ab concentration was positively correlated with disease duration, EDSS score, number of involved spinal segments and recurrence status (p&lt;0.05). Conclusions The concentrations of BAFF and AQP4-Ab in the cerebrospinal fluid can well predict the progression of NMOSD, correlated with the severity.

Relapses after SARS-CoV-2 vaccination in patients with neuromyelitis optica spectrum disorder and multiple sclerosis

BackgroundThe COVID-19 pandemic outbreak raises the question of whether immunization is recommended for patients with CNS demyelinating diseases. On the one hand, existing studies suggested that SARS-CoV-2 vaccinations are not associated with increased risk of relapse activity. On the other hand, case reports with acute CNS demyelinating disease post vaccination were emerging and raising clinicians’ attention. MethodsIn this longitudinal observational study, we included 556 patients with neuromyelitis optica spectrum disorder (NMOSD) and 280 patients with relapsing-remitting multiple sclerosis (RRMS). Each vaccinated patient was matched to two unvaccinated patients according to age, gender, ARR and immunotherapy status, based on propensity score matching model (PSM). The primary outcome is the short- and medium-term risk of relapse, which were evaluated by Kaplan–Meier analysis between groups. ResultsIn our cohort, 649 patients (77.6%) have not yet been vaccinated, mainly due to their concerns about relapse. After PSM, 109 vaccinated patients with NMOSD, 218 PS-matched unvaccinated patients with NMOSD, 78 vaccinated patients with RRMS, and 156 PS-matched unvaccinated patients with RRMS were included in the survival analysis to explore the safety of vaccines, with a median of 9-month follow-up. Following the first vaccination dose, 10 patients with NMOSD (9.2%) and four with RRMS (5.1%) experienced an acute relapse. Meanwhile, in the PS-matched unvaccinated group, 15 patients with NMOSD (6.9%) and 12 patients with RRMS (7.7%) presented with an acute relapse. There was no significant difference between the two curves in both NMOSD and RRMS groups over the course of the observation period. There were no significant differences in demographic characteristics, clinical characteristics, and symptoms of relapses between the vaccinated and PS-matched unvaccinated groups. Post vaccination adverse events (ADE) were reported in 39 individuals (20.9%). ConclusionOur results indicate that inactivated SARS-CoV-2 vaccines appear safe for patients with CNS demyelinating diseases.

Altered functional connectivity associated with cognitive impairment in neuromyelitis optica spectrum disorder

BackgroundCognitive impairment is one of the common symptoms in patients with neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism remains unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to reveal the patterns of brain activity in patients with different cognitive states. Accordingly, this study investigated functional connectivity (FC) abnormalities within and between the main cognitive networks in cognitively impaired (CI) patients with NMOSD and their correlations with cognitive performance. MethodsThirty-four patients with NMOSD and 39 healthy controls (HC) were included. Neuropsychological evaluations and rs-fMRI scanning were performed. Patients were classified as CI (n = 16) or cognitively preserved (CP; n = 18) according to neuropsychological evaluations. Seven components representing six main cognitive networks were selected by group independent component analysis. The differences in inter- and intranetwork FC among CI, CP, and HC groups were assessed. The correlation between FC values and neuropsychological data in NMOSD was calculated. ResultsThe CI group showed decreased intranetwork connectivity in the posterior default mode network (pDMN) compared with the HC group (P < 0.05, GRF corrected), and decreased internetwork connectivity between the salience network (SN) and pDMN, and between the SN and right frontoparietal network (rFPN) compared with CP and HC groups. The altered FC values were significantly correlated with cognitive performance in the whole NMOSD group. ConclusionThe disconnection within the pDMN and between the SN and pDMN or rFPN might suggest the neural substrates underlying cognitive impairment in NMOSD.

Altered non-coding RNA profiles and potential disease marker identification in peripheral blood mononuclear cells of patients with NMOSD

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelination disorder, and dysregulation of RNAs contributes to its pathogenesis. We aimed to reveal the expression profiles of RNAs, including messenger RNA (mRNA), circular RNA (circRNA) and long non-coding RNA (lncRNA), in the peripheral blood mononuclear cells (PBMCs) of patients with NMOSD. Seven NMOSD patients and seven healthy controls (HCs) were enrolled in the competitive endogenous RNA (ceRNA) microarray analysis. Bioinformatics analysis was then performed on the microarray data. Selected RNAs were validated by RT-qPCR. Differentially expressed (DE) RNA profiles of patients and HCs were related to NK cell mediated cytotoxicity, the IL-17 signaling pathway, and the B cell receptor signaling pathway. Moreover, DE non-coding RNAs (DE ncRNAs) including DE circRNAs and DE lncRNAs, may participate in the transforming growth factor beta (TGF-β) signaling pathway, leukocyte migration and neutrophil chemotaxis. Immune cell infiltration analysis showed that the abundance of M1 macrophages and plasma cells significantly increased, while that of M2 macrophages significantly decreased in the NMOSD group. Finally, through RT-qPCR validation, lnc-HELZ-7:1 (95% confidential interval of area under curve [95%CI of AUC] = 0.6633–1.0000), ring finger protein-LIM domain interacting (RLIM; 95%CI of AUC = 0.6980–1.0000), and hsa_circ_0026993 (95%CI of AUC = 0.7550–1.0000) could discriminate NMOSD from HCs by receiver operating characteristic curve analysis. To our knowledge, this is the first study to preliminarily investigate the RNA profiles, especially circRNA profiles in PBMCs of NMOSD patients from North China. We identified lnc-HELZ-7:1, RLIM, and hsa_circ_0026993 as the potential disease markers for NMOSD.

Clinical Characteristics and Outcomes of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder With Brainstem Lesions as Heralding Prodrome.

ObjectiveThe present study sought to differentiate multiple sclerosis and neuromyelitis optica spectrum disorder patients at their first attack by describing and distinguishing their clinical features, radiographic characteristics, and immunologic characteristics of serum and cerebrospinal fluid.MethodsWe retrospectively studied 58 patients with multiple sclerosis (MS) and 52 patients with neuromyelitis optica spectrum disorder (NMOSD) by referencing brainstem lesions as the prodromal events. Their demographics and presentation at the time of the first attack was evaluated including their gender, age, clinical features of the first attack, the expanded disability status scale (EDSS), brainstem lesion(s) by head MRI, and immunological indices of serum and cerebrospinal fluid.ResultsThe NMOSD group had more female patients (4.8 vs. 1.9, p < 0.05), and was older than the MS group (37.81 ± 16.60 vs. 27.57 ± 11.17, p <0.001). NMOSD patients also had a significantly higher association with autoimmune diseases or positive autoimmune antibodies (p < 0.01). There was no significant difference in the EDSS scores between the two groups (p = 0.420). Central hiccups, vomiting, and pyramidal tract signs were more common in the NMOSD group than the MS group (p < 0.001, p < 0.001, p < 0.01), while eye movement abnormalities were more common with MS (p < 0.01). There were no significant differences in other clinical manifestations such as vertigo, diplopia, limb weakness, numbness, and eating difficulty. MS patients were more likely to have midbrain and pons imaging lesions (p < 0.001, p < 0.001), while NMOSD patients had more lesions in the medulla oblongata (p < 0.001). The lesions in the MS group were mostly located in the periphery, while those in the NMOSD group were centrally located (p < 0.001, p < 0.001). Patchy lesions were more common in MS patients (p < 0.001), while large lesions were more common in the NMOSD group (p < 0.001). Finally, serum AQP4 Ab was found only in the NMOSD group (p < 0.001).ConclusionPatients with MS and NMOSD have differentiating clinical manifestations at the time of their first brainstem lesions which include central hiccups, vomiting, pyramidal tract signs, and abnormal eye movements. Additionally, distinct imaging manifestations such as lesion location(s) and morphology may also aid in the development of pathognomonic criteria leading to timely initial diagnosis of MS and NMOSD.

Disrupted structural network of inferomedial temporal regions in relapsing\u2013remitting multiple sclerosis compared with neuromyelitis optica spectrum disorder

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two representative chronic inflammatory demyelinating disorders of the central nervous system. We aimed to determine and compare the alterations of white matter (WM) connectivity between MS, NMOSD, and healthy controls (HC). This study included 68 patients with relapsing–remitting MS, 50 with NMOSD, and 26 HC. A network-based statistics method was used to assess disrupted patterns in WM networks. Topological characteristics of the three groups were compared and their associations with clinical parameters were examined. WM network analysis indicated that the MS and NMOSD groups had lower total strength, clustering coefficient, global efficiency, and local efficiency and had longer characteristic path length than HC, but there were no differences between the MS and NMOSD groups. At the nodal level, the MS group had more brain regions with altered network topologies than did the NMOSD group when compared with the HC group. Network alterations were correlated with Expanded Disability Status Scale score and disease duration in both MS and NMOSD groups. Two distinct subnetworks that characterized the disease groups were also identified. When compared with NMOSD, the most discriminative connectivity changes in MS were located between the thalamus, hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and inferior and superior temporal gyri. In conclusion, MS patients had greater network dysfunction compared to NMOSD and altered short connections within the thalamus and inferomedial temporal regions were relatively spared in NMOSD compared with MS.

Microstructural white matter abnormalities in multiple sclerosis and neuromyelitis optica spectrum disorders: Evaluation by advanced diffusion imaging

IntroductionDespite differences in the pathogenesis and treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), it remains difficult to distinguish them. In this study, we aimed to discriminate between MS and NMOSD using diffusion tensor imaging (DTI), free water (FW) imaging, and neurite orientation dispersion and density imaging (NODDI). MethodsThirty patients with relapsing-remitting (RR) MS, 18 NMOSD patients with positive anti-aquaporin-4 immunoglobulin G seroreactivity, and 20 age- and sex- matched currently healthy subjects underwent MRI. The differences in the DTI (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]), FW and FW-corrected DTI, and NODDI indices between the three groups were evaluated using tract-based spatial statistics (TBSS) and region-of-interest (ROI) analyses. ResultsThe ROI analysis of lesions indicated that the RRMS group had significantly higher AD, MD, RD, ISO and FW-corrected AD, and MD; and lower intracellular volume fraction (ICVF) than the NMOSD group. TBSS analysis showed increased water content in RRMS patients compared to NMOSD patients. Compared with healthy controls (HCs) using TBSS and ROI analysis, the changes in FW imaging indices were more limited than those of in DTI in RRMS patients. ConclusionFW imaging and NODDI were useful for identifying the etiology of neurodegeneration- and neuroinflammation-related microstructural changes in RRMS and NMOSD patients.