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.

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.

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.

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.

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.

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.].

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-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.

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.

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.

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.

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.

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.

A multiparametric score for assessing the individual risk of severe Covid-19 among patients with Multiple Sclerosis.

BACKGROUND: Many risk factors for the development of severe forms of Covid-19 have been identified, some applying to the general population and others specific to Multiple Sclerosis (MS) patients. However, a score for quantifying the individual risk of severe Covid-19 in patients with MS is not available. The aim of this study was to construct such score and to evaluate its performance. METHODS: Data on patients with MS infected with Covid-19 in Italy, Turkey and South America were extracted from the Musc-19 platform. After imputation of missing values, data were separated into training data set (70%) and validation data set (30%). Univariable logistic regression models were performed in the training dataset to identify the main risk factors to be included in the multivariable logistic regression analyses. To select the most relevant variables we applied three different approaches: (1) multivariable stepwise, (2) Lasso regression, (3) Bayesian model averaging. Three scores were defined as the linear combination of the coefficients estimated in the models multiplied by the corresponding value of the variables and higher scores were associated to higher risk of severe Covid-19 course. The performances of the three scores were compared in the validation dataset based on the area under the ROC curve (AUC) and an optimal cut-off was calculated in the training dataset for the score with the best performance. The probability of showing a severe Covid-19 course was calculated based on the score with the best performance. RESULTS: 3852 patients were included in the study (2696 in the training dataset and 1156 in the validation data set). 17% of the patients required hospitalization and risk factors for severe Covid-19 course were older age, male sex, living in Turkey or South America instead of living in Italy, presence of comorbidities, progressive MS, longer disease duration, higher Expanded Disability Status Scale, Methylprednisolone use and anti-CD20 treatment. The score with the best performance was the one derived using the Lasso selection approach (AUC= 0.72) and it was built with the following variables: age, sex, country, BMI, presence of comorbidities, EDSS, methylprednisolone use, treatment. An excel spreadsheet to calculate the score and the probability of severe Covid-19 is available at the following link: https://osf.io/ac47u/?view_only=691814d57b564a34b3596e4fcdcf8580. CONCLUSIONS: The originality of this study consists in building a useful tool to quantify the individual risk for Covid-19 severity based on patient's characteristics. Due to the modest predictive ability and to the need of external validation, this tool is not ready for being fully used in clinical practice to make important decisions or interventions. However, it can be used as an additional instrument to identify high-risk patients and persuade them to take important measures to prevent Covid-19 infection (i.e. getting vaccinated against Covid-19, adhering to social distancing, and using of personal protection equipment).

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.

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.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BACKGROUND: COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. OBJECTIVE/METHODS: The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. RESULTS: The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. CONCLUSION: In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

Coexistence of restless legs syndrome and multiple sclerosis aggravates anxiety and depression / A coexistência da síndrome das pernas inquietas e esclerose múltipla agrava ansiedade e depressão

ABSTRACT 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.

RESUMO Antecedentes: Considerando-se as comorbidades que acompanham a esclerose múltipla (EM), a síndrome das pernas inquietas (SPI) é uma das mais comuns, e ansiedade e depressão são comorbidades psicológicas comuns que afetam a qualidade de vida de pacientes com EM, bem como de pacientes com SPI. Objetivo: Investigar a carga psiquiátrica da coexistência de EM e SPI por meio de uma pesquisa nacional, multicêntrica e transversal. Métodos: Os participantes foram avaliados por parâmetros demográficos e clínicos, além da versão turca das escalas de ansiedade e depressão de Hamilton (HAM-A e HAM-D). Resultados: Dos 1.068 participantes, 173 (16,2%) apresentaram SPI [SPI (+)] e 895 (83,8%) não [SPI (-)]. As pontuações médias no HAM-A e no HAM-D foram significativamente maiores em indivíduos com SPI (+) do que naqueles com SPI (-) (p <0,001 para todas as variáveis). Conclusões: De acordo com nossos dados, a presença de SPI na EM pode aumentar a ocorrência de sintomas de ansiedade e depressão. A conscientização e o tratamento da SPI na EM podem reduzir os sintomas de comorbidades psiquiátricas originadas da SPI.

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.

A comprehensive assessment of patient experience and disease-related awareness in multiple sclerosis: A questionnaire-based nation-wide survey in Turkey.

BACKGROUND: Comprehensive assessment of multiple sclerosis (MS) patients in terms of patient profile, clinical and disease-related factors has great epidemiological value. This study aimed to evaluate patient experience and disease-related awareness in MS patients through a nation-wide survey in Turkey Methods: A total of 1379 MS patients participated in this cross-sectional questionnaire survey conducted between November 2018 and December 2018. The online questionnaire form included items on sociodemographic, disease-related, first-admission, treatment and follow up characteristics as well as the disability status. RESULTS: Patients were diagnosed at median 28.0 years of age, while the average time from admission to diagnosis and time from diagnosis to treatment were 1.2 years and 2.5 months, respectively. Neurology (45.4%) and ophthalmology (23.3%) were the most common clinics for the first admission, while numbness-weakness in lower and upper extremities (37.6%) and double vision-visual problems (30.6%) were the most common symptoms on initial admission. Treatment was initiated after the diagnosis in 1213(88.0%) patients, while 166 (12.0%) patients were treatment-naïve. Treatment discontinuation, treatment switch and use of alternative treatment methods were reported by 31.3%, 49.3% and 22.8% of patients, respectively. The ophthalmology admissions (with double vision or visual problems) were associated with the shortest time from presentation to diagnosis as compared with neurosurgery and internal medicine admissions (median 1.0 vs. 3.0 and 4.0 months, p<0.001). The neurology admissions (with numbness-weakness in extremities) were associated with more prompt (median 0.3 vs. 0.5 months, p=0.032) and more frequent onset of treatment after diagnosis (64.5% vs. 2.2% to 15.2%, p<0.001). Time from presentation to diagnosis was longer in patients aged >50 years (median 6.0 months vs. 2.0 months, p<0.001), in patients using alternative medicine (median 3.0 months vs. 1 month, p=0.001) and in patients admitted to a non-MS-center (median 3.0 months vs. 2.0 months, p=0.002). Median (min-max) age at diagnosis was significantly lower in patients with vs. without treatment discontinuation for any reason (26.0(10-56) vs. 29.0(3-60) years, p<0.001) and treatment switching (27.0(5-93) vs. 30.0(3-60) years, p<0.001). CONCLUSIONS: In conclusion, our findings revealed higher likelihood of earlier diagnosis and earlier treatment in patients admitted to an MS-center and in those presenting with ocular problems and sensory-motor deficits, respectively. Our findings also emphasize the association of older patient age with higher likelihood of diagnostic delay, and increased likelihood of treatment discontinuation for any reason and/or treatment switching in case of older patient age, younger age at diagnosis and diagnostic delay. In this regard, our findings highlight the need for improved awareness among patients as well as clinicians on initial manifestations of MS to enable admission or referral to an MS-center and to prevent delay in diagnosis, particularly for onset symptoms other than ocular or sensory-motor characteristics.