Impact of COVID-19 on pregnancy and fetal outcomes in women with multiple sclerosis.

BACKGROUND: In the general population, maternal COVID-19 is associated with worse maternal and fetal outcomes. Two previous studies have assessed COVID-19 clinical outcomes in pregnant women with multiple sclerosis (MS), but there are no data about maternal and fetal outcomes. OBJECTIVES: In this multicenter study, we aimed to assess maternal and fetal outcomes in pregnant women with MS and COVID-19 infection. METHODS: We recruited pregnant patients with MS who contracted COVID-19 and were followed up in Italian and Turkish Centers, during 2020-2022. A control group was extracted from a previous Italian cohort. Associations between group (COVID-19 or healthy patients) and clinical outcomes (maternal complications, fetal malformations, and spontaneous abortion) were investigated with a weighted logistic regression where propensity score-based inverse probability of treatment weighting (IPTW) approach was applied for adjusting for difference in baseline confounders. RESULTS: In the multivariable analysis, COVID-19 during pregnancy was associated with a higher risk of maternal complications (odd ratio (OR) = 2.12; 95% confidence interval (CI) = 1.32-3.48; p = 0.002), while it was not associated with higher risk of spontaneous abortion and fetal malformations. CONCLUSION: Our data indicate that COVID-19 during pregnancy increases the risk of maternal complications, while it seems to have no significant impact on fetal outcomes.

Sars-CoV2 infection in pregnant women with multiple sclerosis.

BACKGROUND: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. OBJECTIVE: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. METHODS: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). RESULTS: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. CONCLUSION: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.

Volumetric changes in hypothalamic subunits in patients with relapsing remitting multiple sclerosis.

PURPOSE: Studies on hypothalamic changes in patients with relapsing remitting multiple sclerosis (RRMS) are very scarce, despite the fact that the relationship with the hypothalamus is frequently reported. The aim of the study was to determine the volume of the hypothalamic subunits and the total hypothalamus and its relationship with the total demyelinating lesion volume (TLV) and expanded disability status scale (EDSS) in RRMS patients. METHODS: In this cross-sectional study, anterior-superior, superior tubular, posterior hypothalamus, anterior-inferior, inferior tubular subunits of hypothalamus, and total hypothalamus volume were calculated, with fully automatic analysis methods using volumetric T1 images of 65 relapsed RRMS patients and 68 healthy controls (HC). Volume changes in the hypothalamus and its subunits in RRMS patients were examined using multivariate analysis of covariance (MANCOVA). The relationship of these volumes with EDSS and TLV was investigated by partial correlation analysis. RESULTS: There is volume reduction in total hypothalamus (F = 13.87, p < 0.001), anterior-superior (F = 19.2, p < 0.001), superior tubular (F = 10.1, p = 0.002) subunits, and posterior hypothalamus (F = 19.2, p < 0.001) volume in RRMS patients. EDSS correlates negatively with anterior-superior (p = 0.017, r = - 0.333), superior tubular subunits (p = 0.023, r = - 0.439), posterior hypothalamus (p < 0.001, r = - 0.511), and whole hypothalamus volume (p = 0.001, r = - 0.439). TLV correlates negatively with anterior superior (p < 0.001, r = - 0.565), anterior inferior (p = 0.002, r = - 0.431), superior tubular subunits (p = 0.002, r = - 0.432), posterior hypothalamus (p < 0.001, r = - 0.703), and whole hypothalamus (p < 0.001, r = - 0.627) volumes. CONCLUSION: This study demonstrates a reduction in total hypothalamus volume, anterior-superior, superior tubular, and posterior hypothalamus in patients with RRMS. Anterior-superior and superior tubular subunit, posterior hypothalamus, and total hypothalamus volume were negatively correlated with TLV and EDSS scores.

Cortical morphological changes in multiple sclerosis patients: a study of cortical thickness, sulcal depth, and local gyrification index.

PURPOSE: Multiple sclerosis (MS) is a disease that progresses not only with demyelination but also with neurodegeneration. One of the goals of drug treatment in MS is to prevent neurodegeneration. Cortical thickness (CT), sulcal depth (SD), and local gyrification index (LGI) are indicators related to neurodegeneration. The aim of this study is to investigate changes in CT, SD, and LGI in patients with relapsing-remitting MS (RRMS). METHODS: T1 images of 74 RRMS patients and 65 healthy controls were used. T1 hypointense areas in RRMS patients were corrected using fully automated methods. CT, SD, and LGI were calculated for each patient. RESULTS: RRMS patients showed widespread cortical thinning, especially in bilateral temporoparietal areas, decreased SD in bilateral supramarginal gyrus, superior temporal gyrus, postcentral gyrus, and transverse temporal gyrus, and decreased LGI, especially in the left posterior cingulate gyrus and insula. The decrease in cortical thickness was associated with the number of attacks and lesion volume. EDSS was related to CT in the right lingual, inferior temporal, and fusiform gyrus. The LGI was correlated with T2 lesion volume in bilateral insula, with EDSS in the right insula and transverse and superior temporal gyri, and with the number of attacks in the right paracentral gyrus and pre-cuneus. However, SD did not show any correlation with EDSS, T2 lesion volume, or the number of attacks. CONCLUSION: Our results demonstrate widespread cortical thinning, decreased sulcal depth in local areas, and decreased gyrification in folds in RRMS patients, which are related to clinical parameters.

SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study.

BACKGROUND: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. OBJECTIVE: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. METHODS: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. RESULTS: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). CONCLUSION: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: A real-world study from Turkey.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. OBJECTIVE: To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. METHOD: This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12 months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. RESULTS: A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21 months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45 ± 1.53 to 0.15 ± 0.34 (P < .001). In subgroup analyses, the mean ARR decreased from 1.61 ± 1.65 to 0.20 ± 0.39 in the seropositive group and 1.10 ± 1.19 to 0.05 ± 0.13 in the seronegative group. The mean EDSS improved from 3.98 ± 2.04 (prior to treatment onset) to 2.71 ± 1.59 (at follow-up) (P < .001). In the seropositive group, mean EDSS decreased from 3.94 ± 1.98 to 2.67 ± 1.54, and in the seronegative group, mean EDSS decreased from 4.07 ± 2.21 to 2.79 ± 1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. CONCLUSION: Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.

Safety of IV pulse methylprednisolone therapy during breastfeeding in patients with multiple sclerosis.

BACKGROUND: Women with multiple sclerosis (MS) experience an increased risk of relapse in the postpartum period. High-dose methylprednisolone is the first-line treatment for acute relapses. OBJECTIVES: To determine the transfer of methylprednisolone into human milk in breastfeeding MS patients. METHODS: Methylprednisolone therapy was given for postpartum relapse to nine patients for three consecutive days, and seven patients received a daily infusion once a month. Breast milk samples were obtained before infusion and 1, 2, 4, 8, and 12 hours after completion of infusion. RESULTS: Methylprednisolone concentrations in milk were below detection limits immediately before infusion. Cmax was measured at 1, 2, 4, 8, and 12 hours after infusion and levels of 2.100, 1.659, 0.680, 0.174, and 0.102 µg/mL were determined, respectively. The absolute infant dose was 98.98 µg/kg/day, and the relative infant dose (RID) was 0.71% of the weight-adjusted maternal dose. CONCLUSION: The level of methylprednisolone transfer into breast milk is very low. The RID for methylprednisolone was lower than the generally accepted value. As methylprednisolone therapy is of short duration, infant exposure would be very low should a mother choose to breastfeed 1 hour after infusion. Waiting 2-4 hours after infusion will limit infant exposure still further.

Phenobarbital-induced pellagra resulted in death.

Pellagra is caused by deficiency of niacin or its precursor tryptophan. While cutaneous lesions are the most prominent feature of the disease, gastrointestinal, neurological and psychiatric signs and symptoms are the other characteristics of the disease. In this case report, we present a 29-year-old female patient with discoloration of hands and feet diagnosed with pellagra.

An Evaluation of Fit Indices Used in Model Selection of Dichotomous Mixture IRT Models.

A Monte Carlo simulation study was conducted to compare fit indices used for detecting the correct latent class in three dichotomous mixture item response theory (IRT) models. Ten indices were considered: Akaike's information criterion (AIC), the corrected AIC (AICc), Bayesian information criterion (BIC), consistent AIC (CAIC), Draper's information criterion (DIC), sample size adjusted BIC (SABIC), relative entropy, the integrated classification likelihood criterion (ICL-BIC), the adjusted Lo-Mendell-Rubin (LMR), and Vuong-Lo-Mendell-Rubin (VLMR). The accuracy of the fit indices was assessed for correct detection of the number of latent classes for different simulation conditions including sample size (2,500 and 5,000), test length (15, 30, and 45), mixture proportions (equal and unequal), number of latent classes (2, 3, and 4), and latent class separation (no-separation and small separation). Simulation study results indicated that as the number of examinees or number of items increased, correct identification rates also increased for most of the indices. Correct identification rates by the different fit indices, however, decreased as the number of estimated latent classes or parameters (i.e., model complexity) increased. Results were good for BIC, CAIC, DIC, SABIC, ICL-BIC, LMR, and VLMR, and the relative entropy index tended to select correct models most of the time. Consistent with previous studies, AIC and AICc showed poor performance. Most of these indices had limited utility for three-class and four-class mixture 3PL model conditions.

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

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

The Impact of Sample Size and Various Other Factors on Estimation of Dichotomous Mixture IRT Models.

The purpose of this study was to examine the effects of different data conditions on item parameter recovery and classification accuracy of three dichotomous mixture item response theory (IRT) models: the Mix1PL, Mix2PL, and Mix3PL. Manipulated factors in the simulation included the sample size (11 different sample sizes from 100 to 5000), test length (10, 30, and 50), number of classes (2 and 3), the degree of latent class separation (normal/no separation, small, medium, and large), and class sizes (equal vs. nonequal). Effects were assessed using root mean square error (RMSE) and classification accuracy percentage computed between true parameters and estimated parameters. The results of this simulation study showed that more precise estimates of item parameters were obtained with larger sample sizes and longer test lengths. Recovery of item parameters decreased as the number of classes increased with the decrease in sample size. Recovery of classification accuracy for the conditions with two-class solutions was also better than that of three-class solutions. Results of both item parameter estimates and classification accuracy differed by model type. More complex models and models with larger class separations produced less accurate results. The effect of the mixture proportions also differentially affected RMSE and classification accuracy results. Groups of equal size produced more precise item parameter estimates, but the reverse was the case for classification accuracy results. Results suggested that dichotomous mixture IRT models required more than 2,000 examinees to be able to obtain stable results as even shorter tests required such large sample sizes for more precise estimates. This number increased as the number of latent classes, the degree of separation, and model complexity increased.

Newly Diagnosed Tumefactive Demyelinating Lesion and Multiple Sclerosis After COVID-19 Infection.

Introduction: To describe the parainfectious or postinfectious effects of COVID-19 infection on the first demyelinating presentation of Multiple Sclerosis and tumefactive demyelinating lesion (TDL) developing with Longitudinally Extensive Transverse Myelitis (LETM). Methods: We present six patients who presented with a first CNS demyelination event or whose demyelinating lesions had aggravated after COVID-19 infection between May and December 2020. Nasopharyngeal swab SARS-CoV-2 PCR positivity was detected in five cases and cerebrospinal fluid (CSF) PCR was positive in one. The symptoms, neurological signs, radiological and CSF findings of the cases were examined. Results: A 24-year-old woman presented with LETM aggravated by COVID-19, accompanied by a newly developed open-ring enhanced TDL. Four patients were diagnosed with the first presentation of MS, and one presented with clinically isolated syndrome according to the McDonald 2017 criteria. The interval between SARS-CoV-2 infection and the onset of clinical symptoms ranged from 4-93 days. All of the cases present with pyramidal or brain stem findings and have high brain and/or spinal MRI load. This suggests the moderate activity of CNS demyelinating disease after COVID-19 infection. Conclusions: Based on this case series, all these first demyelinating events suggested that COVID-19 infection might trigger or exacerbate CNS demyelinating disease. SARS-CoV-2 plays a role in the clinical onset of Multiple Sclerosis. Active delayed demyelination developed within the first three months. This can be explained by COVID-triggered neuroimmune response that had been latent, and the initiation of the active disease process began with triggering or aggravation of the lesions in MRI. Multiple Sclerosis should be maintained during the COVID-19 pandemic.

Severe disease reactivation in seropositive neuromyelitis optica spectrum disorders patients after stopping eculizumab treatment.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune, inflammatory disease of the central nervous system affecting the optic nerves and spinal cord. Most NMOSD patients have autoantibodies against the astrocyte water channel protein aquaporin-4 (AQP4). Eculizumab treatment is used effectively and safely in AQP4-IgG+ NMOSD. Our study evaluated the prognosis and outcomes of all clinical trial (PREVENT) patients from Turkey who received eculizumab treatment for AQP4-IgG+ NMOSD. METHOD: Clinical and demographic data of all patients enrolled in the PREVENT and OLE clinical trial in Turkey were analyzed during the study period and after the study ended. Clinical follow-up results were recorded in detail in patients who had to discontinue eculizumab treatment. RESULTS: The study included 10 patients who participated in PREVENT and OLE. Seven patients completed the studies, three patients did not continue the study and were switched to other treatments. Only one of the seven patients was able to continue treatment after eculizumab was approved in AQP4-IgG+NMOSD. The other six patients could not continue treatment due to reimbursement conditions. Four of the six patients who could not continue eculizumab treatment experienced early relapse (within the first three months after stopping the drug). All of these patients had high disease activity before eculizumab and had never relapsed under eculizumab treatment over the long term. CONCLUSION: Eculizumab was used effectively and safely in Turkish AQP4-IgG+NMOSD patients with high disease activity. Disease reactivation and relapse may occur after discontinuation of eculizumab treatment in patients with a long-term stable course. In these cases, close monitoring for disease reactivation is recommended.

The Effect of Smoking on Inactivated and mRNA Vaccine Responses Applied to Prevent COVID-19 in Multiple Sclerosis.

Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982±326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903±545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383±51 AU/mL) and non-smokers (n=270; 388±49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group.

Clinical and Demographic Characteristics and Two-Year Efficacy and Safety Data of 508 Multiple Sclerosis Patients with Fingolimod Treatment.

Introduction: Fingolimod is the first oral immunomodulatory treatment used as secondary care therapy in the treatment of multiple sclerosis for the last 10 years. The objective of our study is to reveal the experiences of the first generic fingolimod active ingredient treatment in different centers across Turkey. Method: The first generic fingolimod efficacy and safety data of patients followed-up in 29 different clinical multiple sclerosis units in Turkey were analyzed retrospectively. Data regarding efficacy and safety of the patients were transferred to the data system both before the treatment and on the 6th, 12th and 24th month following the treatment. The data were analyzed using the IBM SPSS 20.00. P value of <0.05 was considered to be statistically significant. Results: A total of 508 multiple sclerosis patients, 331 of whom were women, were included in the study. Upon comparing the Expanded Disability Status values before and after the treatment, a significant decrease was observed, especially at month 6 and thereafter. Since bradycardia occurred in 11 of the patients (2.3%), the first dose had to be longer than 6 hours. During the observation of the first dose, no issues that could prevent the use of the drug occured. Side effects were seen in 49 (10.3%) patients during the course of fingolimod treatment. Respectively, the most frequent side effects were bradycardia, hypotension, headache, dizziness and tachycardia. Conclusion: The observed results regarding efficacy and safety were similar to clinical trial data in the literature and real life data in terms of the first equivalent with fingolimod active ingredient.

Erratum: Clinical and Demographic Characteristics and Two-Year Efficacy and Safety Data of 508 Multiple Sclerosis Patients with Fingolimod Treatment.

[This corrects the article on p. 23 in vol. 60, PMID: 36911568.].

mRNA versus inactivated virus COVID-19 vaccines in multiple sclerosis: Humoral responses and protectivity-Does it matter?

BACKGROUND: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs. METHODS: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups. RESULTS: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI). CONCLUSION: mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.

Gender and COVID-19 related fear and anxiety: A meta-analysis.

Studies conducted during the pandemic revealed strong associations between gender and COVID-19 related fear and anxiety. Females perceive coronavirus as a greater threat to personal health and population than males. The aim of the current meta-analysis is to estimate gender difference in COVID-19 related fear and anxiety. The second purpose of this study is to clarify the role of potential moderators in COVID-19 fear and anxiety. For these reasons, studies published between March 2020 and October 2021 were searched in various databases (Web of Science, SCOPUS, PubMed, and Google Scholar). In total, 315 studies met the inclusion criteria, and 60 studies for COVID-19 related fear and 23 studies for COVID-19 related anxiety were included in the current study. Cohen's d effect size values were calculated based on these individual studies showing the difference between males and females in terms of COVID-19 related fear and anxiety. Results revealed that gender has a moderate and statistically significant effect on COVID-19 related fear (ES = 0.307) and anxiety (ES = 0.316) in favor of females. Moderator analyses showed that continent variable was a statistically significant moderator of gender difference in COVID-19 related fear and anxiety. The highest effect size of gender differences in COVID-related fear and anxiety were obtained from the studies conducted in Europe. However, other moderators (the average age of sample, culture, timing, and population) were not statistically significant. Although this meta-analysis has a few limitations, the findings showed that COVID-19 outbreak negatively affected females more.

The Socioeconomic and Psychological Impact of the COVID-19 Pandemic on People with Multiple Sclerosis in Turkey.

Introduction: Various restrictions due to the coronavirus infection have affected working life globally. People with multiple sclerosis (pwMS) have several difficulties in social life, patient follow-up, and receiving treatments. In this study, we aimed to evaluate the experiences of pwMS during the COVID-19 pandemic. Method: We developed a 50-question survey aiming to determine fears, anxieties, and the problems experienced by patients regarding their diseases and social lives during the COVID-19 pandemic. The questionnaire was released online via the Turkish MS Society website, local MS societies websites, and social media accounts. Only the answers of the patients who filled out the questionnaire completely were evaluated. Results: In total, 6008 patients took the survey, and 3255 of them completed the questionnaire. Among all, 378 patients (11.6%) were positive for COVID-19. The most common COVID-19-related symptom was fatigue (48.4%). The routine medical follow-up was interrupted in 61.4% and the medication was discontinued in 14% of the patients. Approximately 25% of the patients reported different symptoms related to relapse activity. The main concern of the patients related to the COVID-19 pandemic was the disruption of the health of the ones they loved. Among all the patients, 4.4% lost their jobs. Conclusion: Our data showed that the COVID-19 pandemic strongly affected the working lives of pwMS. Also, the pandemic changed the attitudes of patients and neurologists. Therefore, the long-term effects of the COVID-19 pandemic on disease approach, patient follow-up, social conditions, and working life should be monitored.

Coexistence of restless legs syndrome and multiple sclerosis aggravates anxiety and depression.

BACKGROUND: Among the comorbidities that accompany multiple sclerosis (MS), restless legs syndrome (RLS) is one of the most common. Anxiety and depression are common psychological comorbidities that impact the quality of life of patients with MS (PwMS), as well as patients with RLS. OBJECTIVE: To investigate the psychiatric burden of MS and RLS coexistence, we conducted a nationwide, multicenter and cross-sectional survey. METHODS: Participants were assessed by using demographic and clinical parameters along with the Hamilton Anxiety and Hamilton Depression Scales (HAM-A and HAM-D). RESULTS: Out of the 1,068 participants, 173 (16.2%) were found to have RLS [RLS(+)] and 895 (83.8%) did not [RLS(-)]. The mean scores for HAM-A and HAM-D were significantly higher among RLS(+) subjects than among RLS(-) subjects (p<0.001 for all variables). CONCLUSIONS: According to our data, the presence of RLS in PwMS may increase the occurrence of both anxiety and depression symptoms. Awareness and treatment of RLS in PwMS could possibly reduce the symptoms of psychiatric comorbidities originating from RLS.