COVID-19 susceptibility, hospitalization, and severity and the risk of brain cortical structure: a mendelian randomization study.

BACKGROUND: Observational studies have reported structural changes in the brains of patients with COVID-19; it remains unclear whether these associations are causal. AIM: We evaluated the causal effects of COVID-19 susceptibility, hospitalization, and severity on cortical structures. DESIGN: Mendelian randomization (MR) study. METHODS: Data on the different COVID-19 phenotypes were obtained from the latest large-scale genome-wide association study (GWAS) (R7) of the COVID-19 Host Genetics Initiative. Brain structure data, including cortical thickness (TH) and surface area (SA), were obtained from the ENIGMA Consortium. Additionally, we employed the round 5 dataset released in January 2021 as the validation cohort. The inverse-variance weighted (IVW) method was used as the primary analysis in MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. We performed enrichment analysis on the MR analyses that passed the sensitivity analysis filtering. RESULTS: After IVW and sensitivity analyses, we observed causal associations between COVID-19 susceptibility and rostral middle frontal SAw (P = 0.0308, ß=-39.1236), cuneus THw (P = 0.0170, ß=-0.0121), medial orbitofrontal THw (P = 0.0002, ß = 0.0225), postcentral THw (P = 0.0217, ß= -0.0106), temporal pole THw (P = 0.0077, ß = 0.0359), medial orbitofrontal SAnw (P = 0.0106, ß= -24.0397), medial orbitofrontal THnw (P = 0.0007, ß = 0.0232), paracentral SAnw (P = 0.0483, ß= -20.1442), rostral middle frontal SAnw (P = 0.0368, ß= -81.9719), and temporal pole THnw (P = 0.0429, ß = 0.0353). COVID-19 hospitalization had causal effects on medial orbitofrontal THw (P = 0.0053, ß = 0.0063), postcentral THw (P = 0.0143, ß= -0.0042), entorhinal THnw (P = 0.0142, ß = 0.0142), medial orbitofrontal THnw (P = 0.0147, ß = 0.0065), and paracentral SAnw (P = 0.0119, ß= -7.9970). COVID-19 severity had causal effects on rostral middle frontal SAw (P = 0.0122, ß=-11.8296), medial orbitofrontal THw (P = 0.0155, ß = 0.0038), superior parietal THw (P = 0.0291, ß= -0.0021), lingual SAnw (P = 0.0202, ß=-11.5270), medial orbitofrontal THnw (P = 0.0290, ß = 0.0039), paracentral SAnw (P = 0.0180, ß= -5.7744), and pars triangularis SAnw (P = 0.0151, ß=-5.4520). CONCLUSION: Our MR results demonstrate a causal relationship between different COVID-19 phenotypes and cortical structures.

Assessment of Outer Retina and Choroid Using Swept Source Optical Coherence Tomography and Angiography in Patients With Multiple Sclerosis.

BACKGROUND: For patients with multiple sclerosis (MS), both structure and microvasculature alterations in the inner retina have been investigated in several studies. However, little is known about the alterations in the outer retina and choroid. Hence, this study aimed to assess the outer retinal and choroidal changes in patients with MS with no history of optic neuritis (ON). METHODS: Patients with MS and healthy control participants were enrolled in this cross-sectional study. Quantitative analyses were performed using swept source optical coherence tomography and swept source optical coherence tomography angiography images to assess outer retina thickness (ORT) and choroid thickness (CT), vessel density (VD) of choriocapillaris, and choroidal vascularity index (CVI), which were then compared between the groups. RESULTS: A total of 37 participants with MS (72 eyes) and 74 healthy control participants (148 eyes) were included in this study. Compared with healthy controls, patients with MS with no history of ON showed reduced VD of the choriocapillaris and CVI. There was no significant difference in ORT and CT between 2 groups. Meanwhile, in patients with MS, no correlation between OCTA parameters and expanded disability status scale score were found in this study. CONCLUSIONS: Our study indicates that patients with MS with no history of optical neuritis have reduced choriocapillaris vessel density and decreased choroidal vascularity index without detectable alteration in outer retina thickness and choroid thickness. The findings complement the outer retinal and choroidal component of MS, providing deeper insight into the pathophysiology of MS.

Granzyme B + CD8 + T cells with terminal differentiated effector signature determine multiple sclerosis progression.

BACKGROUND: Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing-remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS. METHODS: Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively. RESULTS: Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy. CONCLUSIONS: Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS.

Investigation on marital status of patients with neuromyelitis optica spectrum disorders in China.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) may have a great impact on patients' marriage, and marital status may also affect patients' compliance and prognosis. We investigated the marital status of 494 NMOSD patients in China to explore the mutual influence between them. METHODS: A cross-sectional survey was conducted by the online questionnaires or telephone follow-up. Basic information of all respondents was analyzed from NMOSD-database of West China hospital. All 444 married respondents finished self-assessment of NMOSD's effect on marriage and over 80% of them accepted Marital Cumulative Damage Score (MCDS). RESULTS: The proportion of unmarried male patients is higher than female (23.1% vs. 9.0%), especially in youth stage (44.0% vs. 20.2%). However, the females reported bigger impacts on their marriage among married NMOSD patients (97.5% vs. 70.7%). Compared to married patients, divorced patients costed more in hospital every time (29,857.1 CNY vs. 15,577.2 CNY), received longer education (12.75 years vs. 9.36 years), had longer duration of disease (117.16 vs. 93.62 months), more relapses (5.50 vs. 3.73) and higher EDSS score (3.58 vs. 2.59). EDSS scores are associated with MCDS (R2=0.267, P<0.0001), and divorced patients have higher MCDS (P<0.01). Decreased group activities (84.1%), declined working ability (73.7%) and alienation from friends (72.54%) are the first three factors in MCDS. CONCLUSION: NMOSD exerts cumulative damage for patients' marriage, and the progression of NMOSD is more likely to lead to marital breakdown. Healthy marriage may improve the prognosis of patients by providing the psychological support and improving treatment compliance.

Retinal structural and microvascular changes in myelin oligodendrocyte glycoprotein antibody disease and neuromyelitis optica spectrum disorder: An OCT/OCTA study.

Purpose: To compare the optical coherence tomography (OCT)/OCT angiography (OCTA) measures in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Methods: Twenty-one MOG, 21 NMOSD, and 22 controls were enrolled in our study. The retinal structure [retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL)] was imaged and assessed with the OCT; OCTA was used to image the macula microvasculature [superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP)]. Clinical information such as disease duration, visual acuity, and frequency of optic neuritis and disability was recorded for all patients. Results: Compared with NMOSD patients, MOGAD patients showed significantly reduced SVP density (P = 0.023). No significant difference (P > 0.05) was seen in the microvasculature and structure when NMOSD-ON was compared with MOG-ON. In NMOSD patients, EDSS, disease duration, reduced visual acuity, and frequency of ON significantly correlated (P < 0.05) with SVP and ICP densities; in MOGAD patients, SVP correlated with EDSS, duration, reduced visual acuity, and frequency of ON (P < 0.05), while DCP density correlated with disease duration, visual acuity, and frequency of ON. Conclusions: Distinct structural and microvascular changes were identified in MOGAD patients compared with NMOSD patients suggesting that the pathological mechanisms are different in NMOSD and MOGAD. Retinal imaging via the SS-OCT/OCTA might have the potential to be used as a clinical tool to evaluate the clinical features associated with NMOSD and MOGAD.

Efficacy and safety of drugs for people with type 2 diabetes mellitus and chronic kidney disease on kidney and cardiovascular outcomes: A systematic review and network meta-analysis of randomized controlled trials.

AIM: To evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), aldosterone receptor agonists (MRAs), endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), on cardiovascular and kidney outcomes in type 2 diabetes (T2DM) and chronic kidney disease (CKD) population. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to August 12, 2022. We used the Bayesian model for network meta-analyses, registered in the PROSPERO (CRD42022343601). RESULTS: This network meta-analysis identified 2589 citations, and included 27 eligible trials, enrolling 50,237 patients. All results presented below were moderate to high quality. For kidney outcomes, SGLT-2Is were optimal in terms of reducing composite kidney events (RR 0.69, 95%CI 0.61-0.79), and slowing eGFR slope (MD1.34, 95%CI 1.06-1.62). Then MRAs (RR 0.77, 95%CI 0.68-0.88; MD 1.31, 95%CI 0.89-1.74), GLP-1RAs (RR 0.78, 95%CI 0.62-0.97; MD 0.75, 95%CI 0.46-1.05), and ERAs (RR 0.75, 95%CI 0.57-0.99; MD 0.7, 95%CI 0.3-1.1) were followed in parallel. For cardiovascular outcomes, SGLT-2 inhibitors were also among the best for lowing the risk of heart failure hospitalization (RR 0.67, 95%CI 0.57-0.78), followed by GLP-1RAs (RR 0.73, 95%CI 0.55-0.97) and MRAs (RR 0.79, 95%CI 0.67-0.92). SGLT-2Is (RR 0.8, 95%CI 0.71-0.89) and GLP-1RAs (RR 0.72, 95%CI 0.6-0.86) had comparable effects to reduce the risk of major adverse cardiovascular events. MRAs were possibly associated with increased drug discontinuation due to adverse events (RR 1.21, 95%CI 1.05-1.38). For the hyperkalemia outcome, MRAs (RR 2.08, 95%CI 1.86-2.33) were linked to the risk of hyperkalemia, whereas SGLT-2Is (RR 0.78, 95%CI 0.65-0.93) were in contrast. CONCLUSIONS: SGLT-2Is significantly reduced kidney and cardiovascular risk in T2DM and CKD, subsequently GLP-1RAs and MRAs. SGLT-2Is-MRAs combination might be a recommended treatment regimen for maximizing kidney and cardiovascular protection but with a low risk of hyperkalemia in T2DM and CKD.

Myocardial Injury in Hospitalized Patients with Myasthenia Gravis.

Objective: To investigate the clinical characteristics and outcome of myocardial injury in patients with myasthenia gravis (MG). Methods: We retrospectively searched medical records to screen hospitalized patients with MG at our hospital. The troponin T (TnT) levels were deemed necessary to be performed based on the patient's clinical symptoms and were used as biomarkers of myocardial injury. The patients' demographic and clinical information were collected. Death was the primary outcome. Results: A total of 336 patients with MG measured TnT levels and were included in the final analysis. The male MG patients with elevated TnT levels had a higher prevalence of infection (56.8% vs. 30.0%, p = 0.001) and myasthenic crisis (37.5% vs. 13.3%, p = 0.001) than those with normal TnT levels. Meanwhile, the female MG patients with elevated TnT levels were older (56.0 (16.6) vs. 49.2 (17.2)) years old, p = 0.007] and had a higher prevalence of infection (65.4% vs. 32.1%, p < 0.001), myasthenic crisis (33.6% vs. 17.9%, p = 0.015), and thymoma (38.5% vs. 16.7%, p = 0.001) than those with normal TnT levels. Older age (coef. = 0.004; p = 0.034), infection (coef. = 0.240; p = 0.001), myasthenic crisis (coef. = 0.312; p < 0.001), thymoma (coef. = 0.228; p = 0.001), and ICI therapy (coef. = 1.220; p < 0.001) were independent risk predictors for increasing log TnT levels. Thirty-seven patients died during hospitalization. High log TnT levels (OR = 8.818; p < 0.001), female sex (OR = 0.346; p = 0.023), thymoma (OR = 5.092; p = 0.002), and infection (OR = 14.597; p < 0.001) were independent risk predictors of death. Conclusions: Our study revealed that the surveillance of myocardial injury biomarkers in MG patients might be beneficial.

Effects of pregnancy on neuromyelitis optica spectrum disorder and predictors of related attacks.

OBJECTIVE: Our study aimed to investigate the influence of pregnancy on the course of neuromyelitis optica spectrum disorders (NMOSD) and to explore the independent predictors of pregnancy-related attacks. METHODS: We performed a retrospective study of patients with NMOSD based on the Wingerchuk 2006 or the revised Wingerchuk 2015 criteria. Demographic, clinical, and pregnancy data were recorded. We compared the annualized relapse rate (ARR) before, during, and after pregnancy. The Expanded Disability Status Scale (EDSS) score was used to assess the degree of disability. Multivariate Cox proportional hazards models were used to identify the independent risk factors that predict pregnancy-related attacks. RESULTS: There were 202 informative pregnancies following symptom onset in 112 women with NMOSD. The ARR in the first-trimester postpartum period (1.44 ± 2.04) was higher than that before pregnancy (0.23 ± 0.48; p < 0.001) and during pregnancy. The EDSS score increased from 1.40 ± 1.38 before pregnancy to 1.99 ± 1.78 postpartum (p = 0.004). Multivariate Cox proportional hazards models indicated that increased disease activity 1 year before conception (HR = 1.79, 95% CI 1.09-2.92, p = 0.021) and lack of immunotherapy during pregnancy and the postpartum period (HR = 5.25, 95% CI 1.91-14.42, p = 0.001) were independent risk factors that predicted pregnancy-related attacks. INTERPRETATION: The postpartum period is a particularly high-risk time for the onset and relapse of NMOSD. Pregnancy exerted detrimental effects on the disease courses of NMOSD. Immunotherapy during pregnancy and the postpartum period might be recommended to decrease the risk of pregnancy-related attacks. Larger-scale prospective studies are warranted to confirm our findings.

The causal relationship between neuromyelitis optica spectrum disorder and other autoimmune diseases.

Objectives: The coexistence of neuromyelitis optica spectrum disorder (NMOSD) with other autoimmune diseases has been well recognized. However, the causal association between these two conditions has not been fully studied. The etiology and therapies of NMOSD coexisting with autoimmune diseases also need to be elucidated. Methods: We performed two-sample Mendelian randomization (MR) analysis to examine the causality. Genome-wide association (GWAS) summary data from NMOSD, autoimmune thyroid disease (AITD), systemic lupus erythematosus (SLE), and Sjogren's syndrome (SS) were used to identify genetic instruments. Causal single-nucleotide polymorphisms (SNPs) were annotated and searched for cis-expression quantitative trait loci (cis-eQTL) data. Pathway enrichment analysis was performed to identify the mechanism of NMOSD coexisting with AITD, SLE, and SS. Potential therapeutic chemicals were searched using the Comparative Toxicogenomics Database. Results: The MR analysis found that AITD, SLE, and SS were causally associated with NMOSD susceptibility, but not vice versa. Gene Ontology (GO) enrichment analysis revealed that MHC class I-related biological processes and the interferon-gamma-mediated signaling pathway may be involved in the pathogenesis of NMOSD coexisting with AITD, SLE, and SS. A total of 30 chemicals were found which could inhibit the biological function of cis-eQTL genes. Conclusions: Our findings could help better understand the etiology of NMOSD and provide potential therapeutic targets for patients with coexisting conditions.

Identifying different cognitive phenotypes and their relationship with disability in neuromyelitis optica spectrum disorder.

Background: The existence, frequency, and features of cognitive impairment (CI) in patients with neuromyelitis optica spectrum disorder (NMOSD) are still debated. A precise classification and characterization of cognitive phenotypes in patients with NMOSD are lacking. Methods: A total of 66 patients with NMOSD and 22 healthy controls (HCs) underwent a neuropsychological assessment. Latent profile analysis (LPA) on cognitive test z scores was used to identify cognitive phenotypes, and ANOVA was used to define the clinical features of each phenotype. Univariate and multivariate analyses were used to explore the predictors of severe CI, and a corresponding nomogram was created to visualize the predictive model. Results: LPA results suggested four distinct meaningful cognitive phenotypes in NMOSD: preserved cognition (n = 20, 30.3%), mild-attention (n = 21, 31.8%), mild-multidomain (n = 18, 27.3%), and severe-multidomain (n = 7, 10.6%). Patients with the last three phenotypes were perceived to have CI, which accounts for 67.6% of patients with NMOSD. Patients with NMOSD and worse cognitive function were older (p < 0.001) and had lower educational levels (p < 0.001), later clinical onset (p = 0.01), worse Expanded Disability Status Scale scores (p = 0.001), and poorer lower-limb motor function (Timed 25-Foot Walk, p = 0.029; 12-item Multiple Sclerosis Walking Scale [MSWS-12], p < 0.001). Deterioration of Nine-Hole Peg Test (odds ratio, OR: 1.115 [1, 1.243], p = 0.05) and MSWS-12 (OR: 1.069 [1.003, 1.139], p = 0.04) were the independent risk factors for severe cognitive dysfunction. Finally, a nomogram was built based on the entire cohort and the above factors to serve as a useful tool for clinicians to evaluate the risk of severe cognitive dysfunction. Conclusions: We introduced a classification scheme for CI and highlighted that the deterioration of upper- and lower-limb motor disability potentially predicts cognitive phenotypes in NMOSD.

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

BACKGROUND: The 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. METHODS: In 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. RESULTS: In 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%). CONCLUSION: Our results indicate that inactivated SARS-CoV-2 vaccines appear safe for patients with CNS demyelinating diseases.

Neuromyelitis optica spectrum disorder in Western China impacts employment and increases financial burden in women.

Background: Neuromyelitis optica spectrum disorder (NMOSD) often leads to disability and exerts a heavy toll on the work and life of affected female patients. This study aimed to analyze the current employment situation and economic burden as well as the risk factors for unemployment in female patients with NMSOD. Methods: We compared the following unemployment- and employment-related aspects in with NSMOD, which were investigated using questionnaires: the specific impact of NMOSD on work, medical expenses, and factors affecting unemployment. Results: We enrolled 351 female patients with NMOSD. More than half (54.1%, 190/351) of participants reported that the disease led to unemployment. The unemployment group was significantly older (46.9 ± 12.1 years vs. 39.3 ± 9.4 years, P = 0.000), had a higher annual recurrence rate (ARR) (0.6 [inter quartile range [IQR]:0.4-0.9] vs. 0.5 [IQR: 0.3-0.8], P = 0.141), and a higher severe disability rate (44.2% vs. 11.2%, P = 0.000) than the employment group. Moreover, unemployed patients had lower education levels. The factors influencing unemployment included low education (junior middle-school or below), age, higher ARR, and severe disability (odds ratio [OR] = 6.943, P = 0.000; OR = 1.034, P = 0.010; OR = 1.778, P = 0.038; and OR = 4.972, P = 0.000, respectively). Medication and hospitalization costs constituted the principal economic burdens. Conclusion: The heavy financial burden, employment difficulties, and high unemployment rate are the most prominent concerns of female patients with NMOSD who require more social support and concern.

Effectiveness and tolerability of different therapies in preventive treatment of MOG-IgG-associated disorder: A network meta-analysis.

Background: Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear. Aim: To identify the efficacy and tolerability of different treatments for MOG-AD. Methods: Systematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI). Results: Twelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=-0.85, 95% CrI: -1.7 to -0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies. Conclusions: Whilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives.

Development and Validation of a Nomogram for Predicting Generalization in Patients With Ocular Myasthenia Gravis.

Background: This study aims to develop and validate a nomogram for predicting 1- and 2-year generalization probabilities in patients with ocular myasthenia gravis (OMG). Methods: In total, 501 eligible patients with OMG treated at seven tertiary hospitals in China between January 2015 and May 2019 were included. The primary outcome measure was disease generalization. A nomogram for predicting 1- and 2-year generalization probabilities was constructed using a stepwise Cox regression model. Nomogram performance was quantified using C-indexes and calibration curves. Two-year cumulative generalization rates were analyzed using the Kaplan-Meier method for distinct nomogram-stratified risk groups. The clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA). Result: The eligible patients were randomly divided into a development cohort (n=351, 70%) and a validation cohort (n=150, 30%). The final model included five variables: sex, onset age, repetitive nerve stimulation findings, acetylcholine receptor antibody test results, and thymic status. The model demonstrated good discrimination (C-indexes of 0.733 and 0.788 in the development and validation cohorts, respectively) and calibration, with good agreement between actual and nomogram-estimated generalization probabilities. Kaplan-Meier curves revealed higher 2-year cumulative generalization rates in the high-risk group than that in the low-risk group. DCA demonstrated a higher net benefit of nomogram-assisted decisions compared to treatment of all patients or none. Conclusion: The nomogram model can predict 1- and 2-year generalization probabilities in patients with OMG and stratified these patients into distinct generalization risk groups. The nomogram has potential to aid neurologists in selecting suitable patients for initiating immunotherapy and for enrolment in clinical trials of risk-modifying treatments.

Brain structural and functional connectivity alterations are associated with fatigue in neuromyelitis optica spectrum disorder.

BACKGROUND: Many patients with neurological disorders experience chronic fatigue, but the neural mechanisms involved are unclear. OBJECTIVE: Here we investigated whether the brain structural and functional connectivity alterations were involved in fatigue related to neuromyelitis optica spectrum disorder (NMOSD). METHODS: This prospective pilot study used structural and resting-state functional brain magnetic resonance imaging to compare total cortical thickness, cortical surface area, deep gray matter volume and functional connectivity (FC) between 33 patients with NMOSD and 20 healthy controls (HCs). Patients were subgrouped as low fatigue (LF) and high fatigue (HF). RESULTS: HF patients scored higher on the Hamilton Anxiety Rating Scale and Hamilton Rating Scale for Depression than LF patients and HCs. The two patient subgroups and HC group did not differ significantly in cortical thickness, cortical surface area and volumes of the bilateral caudate nucleus, bilateral putamen, bilateral amygdala, bilateral hippocampus, bilateral thalamus proper or right nucleus accumbens (p > 0.05). However, after correcting for age, sex, years of education, anxiety and depression, HF patients showed larger left pallidum than HCs (0.1573 ± 0.0214 vs 0.1372 ± 0.0145, p = 0.009). Meanwhile, both LF patients (0.0377 ± 0.0052 vs 0.0417 ± 0.0052, p = 0.009) and HF patients (0.0361 ± 0.0071 vs 0.0417 ± 0.0052, p = 0.013) showed smaller left nucleus accumbens than HCs.. Compared with LF patients, HF patients showed significantly decreased FC between the left pallidum and bilateral cerebellar posterior lobes. CONCLUSIONS: This was the first evidence linking structural and functional alterations in the brain to fatigue in NMOSD, and in the future, long term follow-up was necessary.

Sparser macula microvasculature in neuromyelitis optica spectrum disorder occurs independently of optic neuritis.

PURPOSE: To evaluate the macula microvascular perfusion in neuromyelitis optica spectrum disorder (NMOSD) patients and assess the correlation with their clinical features. METHODS: 35 aquaporin-4 seropositive NMOSD patients (38 NMOSD eyes without optic neuritis, NMOSD-NON, and 32 NMOSD eyes with optic neuritis) and 35 healthy controls (HC) were included in our study. Swept-source optical coherence tomography angiography (SS-OCTA) was used to image and segment the macula microvasculature into the inner macula vascular complex (IVC), superficial vascular plexus (SVC), and deep vascular plexus (DVC). An inbuilt software within the OCTA tool was used to measure the microvascular perfusion in these two plexuses. RESULTS: NMOSD eyes without optic neuritis showed sparser (P < 0.05) IVC and SVC compared with healthy controls; NMOSD eyes with optic neuritis showed significantly sparser (P < 0.001) IVC, SVC, and DVC when compared with healthy controls respectively. NMOSD eyes with optic neuritis showed significantly sparser IVC (P = 0.002), SVC (P = 0.001) and DVC (P = = 0.040) when compared with eyes without optic neuritis. CONCLUSIONS: Microvascular impairment in NMOSD patients occurs independently of ON. Microvascular impairment is associated with reduced visual acuity and frequency of ON.