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Background: Distance walking fatigability (DWF) in people with multiple sclerosis (pwMS) is defined as a decrease in the distance walking over time. However, declines in gait quality (i.e., gait quality fatigability- GQF) may occur independently or alongside DWF., Objective: i) to investigate how walking fatigability manifests and its prevalence in pwMS; ii) to describe the temporal pattern of the changes of specific gait characteristics during the 6-minute walking test (6MWT) METHODS: Eighty-eight pwMS (EDSS 4[0-6.5], 49[21-70] years) and 47 healthy controls (HC- 46[25-60] years) performed the 6MWT wearing inertial measurement units. Gait characteristics (stride length, sensor-based gait speed, cadence, double support, step duration, stance phase, step duration asymmetry, step duration variability, foot-strike, toe-off, and leg circumduction) and walking distance were recorded in 1-minute intervals. A fatigability index was calculated by comparing the last and first minute of the 6MWT to identify abnormal worsening based on cutoff scores. The manifestation of walking fatigability was counted. The temporal pattern of worsening of gait characteristics during the 6MWT was examined in pwMS exceeding the cutoff values, compared to pwMS without abnormal changes and HC, using a two-way ANOVA (group vs. minutes) RESULTS: Thirty-five pwMS presented both DWF and GQF, 2 presented isolated DWF, 27 presented isolated GQF, and 24 presented non-walking fatigability. PwMS having GQF presented worsening in gait characteristics (cadence, step duration, step duration variability, or toe-off angle) from minute 2 onwards of the 6MWT, while HCs and pwMS without abnormal changes stabilized gait from minute 2 towards the end of the 6MWT., Conclusion: Walking fatigability in pwMS manifests not only as a decrease in walking distance but also as changes in gait quality. Understanding changes in gait characteristics during walking can help tailor rehabilitation interventions., Competing Interests: Declaration of competing interest The Author (s) declare (s) that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Late-onset multiple sclerosis (LOMS or L; MS) and early-onset MS (EOMS or E) are less common, and their prognosis can be different. To characterize the demographic and clinical features, and clinical outcomes of LOMS and EOMS patients, comparing them to adult-onset MS (AOMS or A) patients., Methods: The study was conducted as a secondary analysis of a prospective study. The participants were divided into three groups according to age of MS onset: early onset (<18 years of age), adult-onset (20-40 years of age), and late-onset (>55 years of age). Demographic variables, oligoclonal bands, IgG index, and Expanded Disability Status Scale (EDSS) score in admission, first year, second year and current EDSS were evaluated. The Timed 25-Foot Walk Test (T25FW), Timed Up and Go (TUG), Multiple Sclerosis Walking Scale-12, Single Leg Standing Test, Activity-Specific Balance Confidence Scale, Nine-Hole Peg Test, Epworth Sleepiness Scale and Restless Legs Syndrome Severity Scale were performed. Appropriate statistical analysis was made., Results: A total of 658 pwMS was included in the study and divided into three groups: EOMS (n = 117), AOMS (n = 499), and LOMS (n = 42). Statistically significant differences were determined between groups in terms of age [L (mean:59.86±5.45 years-y-)> A (36.87±9.12 y)> E(26.56±8.85 y), p < 0.001], education level, current EDSS score (L > E, p < 0.001), EDSS score in first admission, EDSS score in the first year, EDSS score in the second year (L > A > E, p < 0.001), reached an EDSS score 6 (E > L p = 0.001, E > A p = 0.015), disease duration (E > A, E > L, mean E = 11.66±9.7 y, A = 7.99±7.4 y, L = 6.31±4.67 y) time switching second-line treatment to the third line (E > L p < 0.001, A > L p = 0.002, mean E = 171.73±83.29 months-m-, A = 136.13±65.75 m, L = 65.85±45.96 m), number of relapses (A > E > L, median E = 4.0, A = 3.0, L = 2.0), distribution of MS type and oligoclonal band types. Significant differences were found in T25FW and TUG. Post-hoc analysis showed that participants in the LOMS group have longer T25FW (mean L = 7.8 ± 6.11, A = 6.25±5.09, E = 5.72±3.13, p = 0.011) and TUG (mean L = 11.01±5.53, A = 9.57±8.04, E = 8.38±5.51, p = 0.007) times than the AOMS and EOMS groups., Conclusion: Our result revealed that individuals with LOMS face elevated disability levels and a heightened propensity to transition from first-line treatments to more advanced therapeutic interventions. LOMS have worse lower extremity functional status than AOMS and EOMS patient. Clinical evaluations and treatment choices require more attention in LOMS. However, according to the low number of LOMS in our cohort, these results were considered cautious, and more wide and multi-center studies must be designed., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Competing Interest S. Sen and A. Tuncer has received honoraria or consultancy fees for participating to advisory boards, giving educational lectures and/or travel and registration coverage for attending scientific congresses or symposia from F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Biogen Idec/Gen Pharma. R. Karabudak has received honoraria for giving educational lectures, consultancy fees for participating advisory boards, and travel grants for attending scientific congresses or symposia from Roche, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Biogen Idec/Gen Pharma of Turkey, Abdi İbrahim İlac, Deva and ARIS. H. Efendi has received honoraria or consultancy fees for participating to advisory boards, giving educational lectures and/or travel and registration coverage for attending scientific congresses or symposia from F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Biogen Idec/Gen Pharma of Turkey and Abdi İbrahim İlac. A Siva has received honoraria or consultancy fees for participating to advisory boards, giving educational lectures and/or travel and registration coverage for attending scientific congresses or symposia from F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Biogen Idec/Gen Pharma of Turkey and Abdi İbrahim İlac. The rest of authors declares no conflict of interest with the study project., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Restless legs syndrome (RLS) is a sensory-motor disorder characterized by an uncomfortable sensation in the lower extremity, triggered by sitting and lying positions and release with motion. There is strong evidence that RLS prevalence is higher in persons with multiple sclerosis (MS, pwMS) than in the general population. Current literature has shown that exergaming as non-pharmacological therapy may be an effective method for symptoms such as balance, walking, fatigue, cognitive functions in pwMS, but the effects on RLS are not known. Therefore, the study's main aim is to investigate the effects of exergaming in pwMS with RLS., Methods: Thirty-one pwMS with RLS and 34 pwMS without RLS were randomly divided as exergaming group and control group. The outcome measures were International RLS Study Group Rating Scale, Modified Fatigue Impact Scale, MS Walking Scale, Timed 25-Foot Walk Test, Hospital Anxiety and Depression Scale, Godin-Shephard Leisure-Time Physical Activity Questionnaire, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, 6 min Walk Test, Timed and Up Go, MS International Quality of Life questionnaire, MS-Related Symptom Checklist., Results: 26 pwMS with RLS (11 exergaming group, 15 control group) and 27 pwMS without RLS (12 exergaming group, 15 control group) were included in 8-week post-treatment analyses. After an 8-week long-term follow-up, 16 pwMS with and without RLS completed the protocol. The RLS severity (p = 0.004), anxiety level (p = 0.024), sleep quality (0.005), walking (0.004), and balance functions (0.041) were improved in pwMS with RLS exergaming group, while RLS severity increased in control group (p = 0.004). At 8-week follow-up, the effect of exergaming on RLS severity, quality of life, sleep quality, and walking capacity was preserved. There was significant improvement in gait and balance functions in pwMS without RLS exergaming group, there was no significant differences control group. In 8-week follow-up, improvement obtained in pwMS without RLS exergaming group was not preserved., Conclusions: This study suggests that exergaming training could be an effective method for managing RLS severity, anxiety, sleep quality, gait, balance, and quality of life in pwMS with RLS., Competing Interests: Declarations of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Patients with relapsing-remitting multiple sclerosis (RRMS) who experience relapses on a first-line therapy (interferon, glatiramer acetate, dimethyl fumarate, or teriflunomide; collectively, "BRACETD") often switch to another therapy, including natalizumab or fingolimod. Here we compare the effectiveness of switching from a first-line therapy to natalizumab or fingolimod after ≥1 relapse., Methods: Data collected prospectively in the MSBase Registry, a global, longitudinal, observational registry, were extracted on February 6, 2018. Included patients were adults with RRMS with ≥1 relapse on BRACETD therapy in the year before switching to natalizumab or fingolimod. Included patients received natalizumab or fingolimod for ≥3 months after the switch., Results: Following 1:1 propensity score matching, 1000 natalizumab patients were matched to 1000 fingolimod patients. Mean (standard deviation) follow-up time was 3.02 (2.06) years after switching to natalizumab and 2.58 (1.64) years after switching to fingolimod. Natalizumab recipients had significantly lower annualized relapse rate (relative risk=0.66; 95% confidence interval [CI], 0.59-0.74), lower risk of first relapse (hazard ratio [HR]=0.69; 95% CI, 0.60-0.80), and higher confirmed disability improvement (HR=1.27; 95% CI, 1.03-1.57) than fingolimod recipients. No difference in confirmed disability worsening was observed., Conclusions: Patients with RRMS switching from BRACETD demonstrated better outcomes with natalizumab than with fingolimod., Competing Interests: Declaration of Competing Interest Dr Spelman has received honoraria for consultancy and funding for travel from Biogen and Novartis. Dr Horakova has received speaker honoraria and consulting fees from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva, as well as support for research activities from Biogen and the Czech Ministry of Education (project Progres Q27/LF1). Dr Alroughani has received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche, and Sanofi Genzyme. Dr Kalincik has served on scientific advisory boards for Biogen, Merck, Novartis, Roche, and Sanofi Genzyme and a steering committee for Genzyme's Brain Atrophy Initiative; has received conference travel support and/or speaker honoraria from BioCSL, Biogen, Merck, Novartis, Sanofi Genzyme, Teva, and WebMD Global; and has received research support from Biogen. Dr Terzi has received travel grants from Bayer Schering, Merck, Novartis, and Teva and has participated in clinical trials by Novartis, Roche, and Sanofi. Dr Grammond has served on advisory boards for Biogen, Genzyme, Merck, Novartis, and Teva Neuroscience and as a consultant for Merck; has received payments for lectures from Merck, Teva Neuroscience, and the Canadian Multiple Sclerosis Society; and has received grants for travel from Novartis and Teva Neuroscience. Dr Patti has received speaker honoraria or advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Mylan, Novartis, Roche, Sanofi Genzyme, and Teva and research funding from Biogen, Merck, the Italian Ministry of Education, University and Research, and the Italian Multiple Sclerosis Society Foundation. Dr Csepany has received speaker honoraria and/or conference travel support from Bayer Schering, Biogen, Merck, Novartis, Roche, Sanofi, and Teva. Dr Boz has received conference travel support from Bayer Schering, Biogen, Merck, Novartis, and Teva and has participated in clinical trials by Novartis, Roche, and Sanofi. Dr Lechner-Scott has received travel compensation from Biogen, Merck, and Novartis and has been involved in clinical trials with Biogen, Novartis, and Teva. Her institution has received honoraria for talks and advisory board service from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi Genzyme, and Teva. Dr Granella has received research funding from Biogen and Sanofi Genzyme; fees for advisory boards and speaker honoraria from Biogen, Merck Serono, Novartis, Roche, and Sanofi Genzyme; and travel funding from Biogen, Merck Serono, Roche, and Sanofi Genzyme. Dr Grand'Maison has received honoraria or research funding from Biogen, Genzyme, Mitsubishi, Novartis, Ono Pharmaceuticals, and Teva Neuroscience. Dr. van der Walt reports grants from Roche and Novartis; and has served on advisory boards for and received travel support from Merck, Roche, Biogen, Novartis, Alexion, and BMS. Dr Butzkueven has served on scientific advisory boards for Biogen, Novartis, and Sanofi and steering committees for trials conducted by Biogen and Novartis; has received conference travel support from Biogen, Novartis, and Sanofi; and has received research support from Biogen, Merck, and Novartis. Drs Ozakbas, Onofrj, Prat, and Zhu have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Epstein-Barr virus is considered a risk factor for the development of multiple sclerosis, and recent findings reveal infected plasma -cells in meningeal ectopic lymphoid deposits. Activation of the dormant virus could be responsible for the multiple sclerosis exacerbation AIMS: To compare Epstein-Barr nuclear IgG (EBNA IgG) titer in newly diagnosed treatment-naive multiple sclerosis patients regarding the diagnoses date, clinical and radiological activity., Methods: Treatment-naive multiple sclerosis patients were divided into two groups according to Poser (late group) and McDonald2017(early group) diagnostic criteria. EBNA IgG, EDSS, physical (Timed 25 Foot Walk test, Nine-hole Peg test), and cognitive tests (Brief International Cognitive Assessment for Multiple Sclerosis) were done before the methylprednisolone infusion. The lesion location was evaluated by an MRI. Myelitis was considered a severe attack, and optic neuritis a mild relapse., Results: In total, 69 patients were enrolled. 44 (63.8%) of them were diagnosed by McDonald2017, and 25 (36.2%) were diagnosed with Poser criteria. There was a significant difference (p = 0.049) between the EBNA IgG titer of the late (median:238 U/ml, IQR: 154-362) and early (median: 154 U/ml, IQR:100.25-293.25). Severe relapse, having a spinal cord lesion, and not being treated with methylprednisolone was associated with higher EBNA IgG titer., Conclusion: Study results show that EBNA IgG was significantly associated with disease activity regarding relapse severity and lesion location and could be a potential biomarker for predicting disease exacerbation., Competing Interests: Declaration of Competing Interest Authors have nothing to disclose, neither financial interests nor non-financial interests. None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives and Aims: Disease modifying therapies used in multiple sclerosis can decrease humoral response after COVID-19 vaccines. This problem must be adequately addressed because new variants evolve, and COVID-19 still poses a risk to patients with comorbidities and immunosuppression. We aimed to evaluate the antibody response after the third dose of the COVID-19 vaccine in people with multiple sclerosis on disease-modifying therapies., Methods: People with multiple sclerosis who received the third dose of either mRNA or inactivated vaccine after two doses of inactivated vaccine were recruited for the study. Blood samples were collected at least two weeks after the third dose., Results: Blood samples of 339 (female 72.5%) people with multiple sclerosis and 52 (female 71.2%) healthy controls were evaluated. Healthy controls (mean: 4.07 ± 0.66) have higher antibody titers than people with multiple sclerosis (mean: 2.79 ± 2.95). Seronegative cases were observed only in the fingolimod and ocrelizumab treatment groups. Patients on fingolimod who received mRNA as a third dose had significantly higher antibody titer than those who had inactivated vaccines. Longer disease duration, having inactivated vaccine as a third dose, and DMT use was associated with lower antibody response., Conclusions: The study shows that even after inactivated vaccine schedule, mRNA still offers more protection in people with multiple sclerosis on disease-modifying therapies., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: There is no information about the effects and usability of rehabilitation during corticosteroid treatment. This randomized clinical trial was conducted to evaluate and compare the effects and safety of exergaming and conventional rehabilitation (CR) on persons with multiple sclerosis (MS, pwMS) during corticosteroid treatment., Methods: The participants were randomly divided into two groups: Exergaming (n=15) and CR (n=15). Rehabilitation was applied by a physiotherapist who has expertise in MS. Measurements were done at baseline (T1), immediately after discharge (T2), and 1 month after discharge (T3). The outcome measures included upper extremity functions, walking, balance, cognitive functions, quality of life, depression, and fatigue., Results: The Nine Hole Peg Test, California Verbal Learning Test, Symbol Digit Modalities Test, MS Walking Scale-12, Six Spot Step Test showed a significant difference between T1 to T2 and T1 to T3 in the exergaming and CR groups (p < 0.05). The Timed 25 Foot Walk and Multiple Sclerosis International Quality of Life Questionnaire were significantly different between T1 to T3 in the exergaming and CR groups (p < 0.05). Brief Visuospatial Memory Test-Revised was significantly different between T1 to T3 and T2 to T3 in the exergaming and CR groups (p < 0.05). The MFIS showed a significant difference between T1 to T2 and T1 to T3 in the exergaming group (p < 0.05)., Conclusions: This study suggests that exergaming and CR are effective and safe methods for improving upper extremity, cognitive functions, fatigue, quality of life, balance, and walking ability in pwMS during the hospitalization period., (Copyright © 2022. Published by Elsevier B.V.)

Background: Disease-modifying therapy could weaken the immune system and decrease the immune response to vaccines. It is essential to know which vaccine is more protective against SARS-CoV-2 in the multiple sclerosis population., Objective: To assess immune response after messenger RNA BNT162b2 (Pfizer/BioNTech) and inactivated Sinovac vaccines in people with multiple sclerosis (pwMS) treated with a disease-modifying therapy (DMT) compared to healthy controls., Methods: This single-center cross-sectional study included 526 MS patients treated with DMT, 44 healthy controls, and 21 untreated patients with MS between May 2021 and September 2021. Serum samples were collected at least two weeks after the second dose of the vaccine., Results: Participants vaccinated with BNT162b2 had a higher antibody titer than the Sinovac group (95%CI=1.023 - 1.473; p< .001). No significant difference between antibody titer of pwMS without treatment and HC was found [95%CI= -0.882; - 0.935 p > .99]. In 65 adults without DMT use (HC+pwMSwithout treatment), no seronegative cases were observed in any vaccine group. In patients treated with DMT, BNT162b2 was associated with a 16.3% greater absolute risk of seropositivity than Sinovac., Conclusion: The mRNA vaccine could be a preferred choice of protection against SARS-CoV-2 in pMS treated with DMT., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Examining leisure-time physical activity in people with multiple sclerosis (PwMS) from different environmental backgrounds might increase understanding and awareness of inactivity in PwMS. Therefore, the study objective was twofold; to compare the level of physical activity in PwMS in Israel and Turkey and to examine the relationship between the level of physical activity with common disease-related symptoms and demographical characteristics of PwMS., Methods: Cross-sectional data collected by two centers were combined. The physical activity level was determined by the Godin Leisure-Time Exercise Questionnaire, and subsequently, classified into one of three subgroups: "active", "moderately active" and "insufficiently active". Logistic regressions determined the risks of insufficiently active PwMS, according to age, gender, body mass index, disability, impact of walking impairment, disease duration, type of MS and perceived fatigue. The analysis of variance test determined the differences between countries in terms of outcome variables., Results: The study comprised 458 patients from Israel and 575 from Turkey; 68.2% Turkish PwMS were classified as insufficiently active compared with 52.0% of Israeli PwMS. The percentage of insufficiently active PwMS was significantly higher in those categorized as fatigued compared to non-fatigued in the total cohort (72.4% vs. 51.9%, p<0.001) and in each country separately. Based on the regression analysis, fatigue was the main factor associated with the insufficiently physically active group; odds ratio=1.968., Conclusion: PwMS with increased fatigue tend to participate in less leisure-time physical activities compared with the non-fatigued. This observation is supported by the merged data collected from two countries, Turkey and Israel, representing PwMS from different environmental backgrounds., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening., Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting., Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod., Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS., Objective: To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS., Methods: The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics., Results: 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity., Conclusion: The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cognitive reserve (CR) is the ability to counteract brain damage through differential recruitment of brain networks. Besides, it has also been observed that lifetime intellectual enriching skills reduce the effect of disease burden on cognitive status. The Cognitive Reserve Index questionnaire (CRIq), which is a method for the quantitative measurement and comprehensive evaluation of the CR, that individuals have accumulated throughout their lifetimes. The present study aimed to adapt CRIq to the Turkish population., Methods: CRIq is a 20-item questionnaire consisting of 3 sub-scales (CRI-Education, CRI- Working Activity, CRI-Leisure Time). 271 females and 228 males, a total of 499 healthy volunteers participated in the study (mean age: 39.54±14.05, mean education years 13.14±4.84). Participants were evaluated with the "Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)" and CRIq was applied. BICAMS was used to determine the validity of the CRIq. To determine the reliability, the questionnaire was applied again two weeks after the first application. Internal consistency and test-retest reliability were measured for reliability analysis. Independent sample t-test was conducted to observe the difference between genders., Results: The Cronbach alpha coefficient of the questionnaire was 0.78, and the reliability of the questionnaire was acceptable. The findings showed that inter-rater reliability was quite high (ICC:0.95, 95% CI=1.000, n=36). The correlation between the first and second application of the questionnaire was found to be acceptable for both the sub-scales and the whole questionnaire. The highest CRIq scores were shown for young adults in CRI-Education and CRI-LeisureTime, for the middle-aged in CRIq-WorkingActivity, no significant differences in total CRIq scores. The males scored significantly higher in CRIq total scores than females, but there was not a significant difference in CRI-LeisureTime between genders., Conclusion: The Turkish version of CRIq was found to be a valid and reliable method for evaluating cognitive reserve in healthy individuals., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Developments in rehabilitation technology such as video-based exergaming contributes to the treatment process as well as to increase the active participation of persons with multiple sclerosis (pwMS). The aim was to investigate the effect of video-based exergaming training on upper extremity and cognitive function as well as core stability, walking, depression, fatigue, and quality of life in pwMS., Methods: This randomized controlled trial included 60 pwMS who were randomly divided into three groups; video-based exergaming (n = 21), conventional rehabilitation (n = 19), and control groups (n = 20). The experimental groups received therapy sessions once a week for 8 weeks. All the participants were assessed at baseline and after 8 weeks. The outcome measures included upper extremity and cognitive functions as well as core stability, walking, depression, fatigue, and quality of life measures., Results: Significant improvements were observed in the primary outcome, measured by Nine-Hole Peg Test in the video-based exergaming [before= 25.8 (11.1) s; after= 22.3 (11.0) s] and conventional rehabilitation [before= 23.3 (8.1) s; after= 19.9 (3.8) s] groups (p < 0.05). Cognitive functions (with the exception of processing speed in the conventional rehabilitation group), most of the lower extremity functions, balance-related measures, fatigue and quality of life levels were significantly improved in the video-based exergaming and conventional rehabilitation groups, however, only the depression level was significantly decreased in the video-based exergaming (p < 0.05). Several significant differences were observed in the changes of the control group compared to the video-based exergaming and conventional rehabilitation groups (p < 0.05)., Conclusion: This study suggests that video-based exergaming is almost as effective as conventional rehabilitation regarding improving walking, upper and lower extremity functions, cognitive functions, fatigue, depression, and health-related quality of life in pwMS., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD., Method: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model., Results: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024)., Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort., Competing Interests: Declaration of Competing Interest The authors declare no competing interests directly related to the presented work., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Fingolimod and teriflunomide are commonly used in the treatment of relapsing-remitting multiple sclerosis (RRMS). These have not been compared in controlled trials, but only in observational studies, with inconclusive results. Comparison of their effect on relapse and disability in a real-world setting is therefore needed., Objectives: The objective of this study was to compare the efficacy of fingolimod and teriflunomide in reducing disease activity in RRMS., Methods: This multicenter, retrospective observational study was carried out with prospectively collected data from 15 centers. All consecutive RRMS patients treated with teriflunomide or fingolimod were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), disability accumulation, percentage of patients with active MRI and treatment discontinuation over a median 2.5-year follow-up period were compared., Results: Propensity score matching retained 349 out of 1388 patients in the fingolimod group and 349 out 678 in the teriflunomide group for final analyses. Mean ARR decreased markedly from baseline after 1 and 2 years of treatment in both the fingolimod (0.58-0.17 after 1 year and 0.11 after 2 years, p < 0.001) and teriflunomide (0.56-0.29 after 1 year and 0.31 after 2 years, p < 0.001) groups. Mean ARR was lower in fingolimod-treated patients than in those treated with teriflunomide at years 1 (p = 0.02) and 2 (p = 0.004). Compared to teriflunomide, the fingolimod group exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients after 2.5-year follow-up. Disability worsening was similar between the two groups. Patients were less likely to discontinue fingolimod than teriflunomide (p < 0.001)., Conclusion: Fingolimod was associated with a better relapse control and lower discontinuation rate than teriflunomide. The two oral therapies exhibited similar effects on disability outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Patients attending multiple sclerosis (MS) clinics experience less disability compared to previous years., Objective: This study was conducted retrospectively examining the patient records of our MS Clinic. The patient records in 1996 were compared to those in 2016., Methods: Demographic data, duration of disease, time to diagnosis, course of the disease, Expanded Disability Status Scale (EDSS) scores, and whether or not patients used disease modifying therapies were recorded in both 1996 and 2016., Results: The mean frequency of visits were significantly higher in 1996 compared to 2016 (p = 0.003). There were significantly more number of patients with clinically isolated syndrome (p = 0.004) and secondary progressive MS (p = 0.001) in 1996; however, significantly less number of patients with relapsing-remitting MS (p < 0.001). EDSS scores of ≤3 were significantly higher in 2016 (p < 0.001). On the other hand, the number of patients with the EDSS scores of 6-6.5 and ≥7 were significantly less in 2016 (p < 0.001). Significantly more patients with secondary progressive MS, EDSS scores of 6-6.5 and ≥7 (wheel-chair dependent patients) came to the clinic in 1996 compared to 2016., Conclusion: The emergence of treatment options in MS and the increasing availability of new treatment options for patients with no/inadequate treatment response have changed the MS patient profile over the 20 years. The number of wheelchair-dependent patients dramatically reduced., (Copyright © 2019. Published by Elsevier B.V.)

Objective: The aim of the study was to investigate the effects of smoking on respiratory symptoms and functional levels by questioning use of cigarette in Multiple Sclerosis (MS) patients., Methods: A questionnaire was sent via e-mail to the 135 MS patients, who clinically diagnosed with MS and EDSS score was determined.Perceived dyspnea was assessed by the mMRC scale.The severity of dyspnea and fatigue perceived during rest and effort was assessed by the mBORG scale.Functional levels of the patients were assessed by asking the average daily walking distance and the average sitting time daily., Results: The mean EDSS score of the smoker and the non-smoker group were 2.85 ± 0.75, 2.96 ± 1.03 respectively(p = 0.48).There was no statistically difference found between groups in terms of age,height,weight,BMI,gender,EDSS scores(p > 0.05).The rate of cough, sputum and severity of perceived dyspnea was statistically higher in the smoker group(p < 0.05).The mean walking distance daily of the smokers was statistically lower (p < 0.001).The smoker group had a high level of sedanter lifestyle(p < 0.05)., Conclusion: It has been proven that smoking increases respiratory problems even in MS patients with a good EDSS score.Moreover, these problems lead to a further reduction in the functional levels of the patients, in addition to the disease progression., (Copyright © 2018. Published by Elsevier B.V.)

Background: Cognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in early or late phase of the disease, and impairs quality of life., Objectives: This study aimed to determine the prevalence of CI and related risk factors in relapsing-remitting MS (RRMS) patients in Turkey., Methods: The present cross-sectional, multi-center, and nationally representative study included RRMS patients. Sociodemographic characteristics, cognitive functions and additional outcomes were compared between patients with and without CI., Results: The analyses included 487 RRMS patients. According to the BRB-N battery results, CI prevalence was 53.7%. There was a negative significant correlation of BRB-N subtests with age, disease duration, and EDSS and MSNQ-patient rated scores. On the logistic regression analysis, increased age, living in village/rural area, high income level, and high EDSS score were significant increasing risk factors in the development of CI., Conclusions: This is the first national cognitive data obtained from MS in Turkey, which is a country between Europe and Asia and thus has characteristics of both continents. The similarity of the results of the present study obtained from Turkey to the Western-based data indicates that CI is universal in MS and the main factors affecting CI have not changed., (Copyright © 2018 Elsevier B.V. All rights reserved.)