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This study assessed osteoporosis knowledge and awareness among multiple sclerosis patients. The findings reveal a concerning lack of knowledge and awareness regarding osteoporosis, emphasizing the necessity for educational interventions to enhance early detection and mitigate complications within this particular patient group., Aim: To assess the knowledge and awareness of osteoporosis in Turkish multiple sclerosis (MS) patients., Material-Methods: Three hundred twenty-five patients were asked to fill out the osteoporosis awareness scale (OAS), which has a scoring range of 31-124, and the revised osteoporosis knowledge test (R-OKT), which has a score range of 0-32. Fall risk assessment for patients was conducted using the timed up-and-go test (high risk: > 30, moderate risk: 29-20, low risk: 14-19, and no risk: < 13 s)., Results: An average score of 59.42 ± 19.63(31%) on the OAS and 14.99 ± 5.39 (47%) on the R-OKT was detected. No difference was found in R-OKT scores between genders, education levels, and patients with different fall risks and between genders and education levels in OAS scores. Patients with low, medium, and high fall risks exhibited higher OAS scores compared to those without any fall risk (p = 0.006, p < 0.001, and p < 0.001, respectively). No correlation was found between gender and education level with OAS and R-OKT scores and between the R-OKT scores and the risk of falls. There was a weak correlation between the OAS scores and an increased risk of falls (r = 0.269, p < 0.001). No differences between the age groups regarding OAS and R-OKT scores were observed., Conclusions: Turkish MS patients have inadequate knowledge and low awareness of OP compared to the healthy population. Urgent action is warranted to educate and support individuals with MS, implementing targeted interventions and awareness campaigns to improve early detection and prevent osteoporosis-related complications., Trial Registration: ClinicalTrials.gov Identifier: NCT05760651., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

So far, only a small number of medications are effective in progressive multiple sclerosis (MS). The sphingosine-1-phosphate-receptor (S1PR)-1,5 modulator siponimod, licensed for progressive MS, is acting both on peripheral immune cells and in the central nervous system (CNS). So far it remains elusive, whether those effects are related to the neurotrophin brain derived neurotrophic factor (BDNF). We hypothesized that BDNF in immune cells might be a prerequisite to reduce disease activity in experimental autoimmune encephalomyelitis (EAE) and prevent neurotoxicity. MOG 35-55 immunized wild type (WT) and BDNF knock-out (BDNF ko ) mice were treated with siponimod or vehicle and scored daily in a blinded manner. Immune cell phenotyping was performed via flow cytometry. Immune cell infiltration and demyelination of spinal cord were assessed using immunohistochemistry. In vitro, effects on neurotoxicity and mRNA regulation were investigated using dorsal root ganglion cells incubated with EAE splenocyte supernatant. Siponimod led to a dose-dependent reduction of EAE scores in chronic WT EAE. Using a suboptimal dosage of 0.45 µg/day, siponimod reduced clinical signs of EAE independent of BDNF-expression in immune cells in accordance with reduced infiltration and demyelination. Th and Tc cells in secondary lymphoid organs were dose-dependently reduced, paralleled with an increase of regulatory T cells. In vitro, neuronal viability trended towards a deterioration after incubation with EAE supernatant; siponimod showed a slight rescue effect following treatment of WT splenocytes. Neuronal gene expression for CCL2 and CX3CL1 was elevated after incubation with EAE supernatant, which was reversed after siponimod treatment for WT, but not for BNDF ko . Apoptosis markers and alternative death pathways were not affected. Siponimod exerts both anti-inflammatory and neuroprotective effects, partially related to BDNF-expression. This might in part explain effectiveness during progression in MS and could be a target for therapy., (© 2024. The Author(s).)

Background: Many studies on multiple sclerosis (MS) reveal different prevalence and epidemiologic results., Objectives: In this study, we aimed to determine the epidemiologic profile of MS using official health records in Turkey., Methods: Patients diagnosed with MS from the official health data of the Ministry of Health, representing the entire population of Turkey, were included in the study. Prevalence and incidence calculations were performed using the data on gender, age, year of birth, city of residence, and year of diagnosis., Results: As a result of the study, the number of patients with the ICD code G35 was determined as 201,061 and the number of patients with this code entered at least three times was determined as 82,225. The prevalence of MS in Turkey was calculated as 96.4 per 100,000 and the female/male ratio as 2.1/1. The incidence of MS in 2022 was 6.2 per 100,000 and the mean patient age was 43.1 ± 13.3 years (female: 43.0 ± 13.1 vs male: 43.2 ± 13.7) while the mean age at first diagnosis was 34.0 ± 13.0 (female: 33.6 ± 12.6 vs male: 34.9 ± 13.7)., Conclusion: The research was conducted via Official Database of Turkey, which includes population of 85 million and provides valuable insights into the prevalence and incidence rates of this chronic disease., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Determining patients' perceptions of multiple sclerosis, a disease with varying symptoms and prognosis for each individual, can significantly contribute to directing care and treatment. Metaphors may be an opportunity to determine perceptions of this unique illness experience. The aim of this study was to reveal the perceptions of patients with multiple sclerosis about "multiple sclerosis" through metaphors., Methods: This study was conducted with metaphor analysis technique based on phenomenological method. The sample included 184 patients with multiple sclerosis. Data was collected face-to-face between July 2022 and January 2023. Each participant was interviewed individually and was asked to fill in the blanks in the sentence, "multiple sclerosis is like… because…". Content analysis was performed for metaphors., Results: The study revealed five main themes and twelve subthemes that provided insight into the participants' multiple sclerosis perceptions. The themes address (i) Manipulator multiple sclerosis; ambiguous multiple sclerosis, attritive multiple sclerosis, controller multiple sclerosis, demander multiple sclerosis, and conditional multiple sclerosis (ii) Temporal multiple sclerosis; cyclical multiple sclerosis and perpetual multiple sclerosis (iii) Follower multiple sclerosis; unaccepted multiple sclerosis, partner multiple sclerosis and ambusher multiple sclerosis (iv) Different multiple sclerosis; bittersweet multiple sclerosis and unique multiple sclerosis (v) Restorative multiple sclerosis., Conclusion: This study demonstrated that patients with multiple sclerosis mostly had negative perceptions regarding their relationship with multiple sclerosis. The results place a responsibility on healthcare professionals to improve how patients adapt to multiple sclerosis. This study's results can bridge theoretical knowledge and practice., (© 2024 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Objectives: Multiple sclerosis (MS), which is known as a young-adult age disease, is called late-onset MS (LOMS) when it occurs at the age of 50 and older. In our study, we aimed to analyse the clinical and demographic characteristics, comorbidities, diagnostic and treatment challenges and prognosis of LOMS., Methods: In a retrospective analysis of 136 patients diagnosed with multiple sclerosis (MS) after the age of 50, based on the 2017 McDonald criteria, and who were under observation in eight distinct MS centers across Turkey; demographic information, clinical characteristics of the disease, oligoclonal band (OCB) status, initial and current Expanded Disability Status Scale (EDSS) values, administered treatments, and the existence of spinal lesions on magnetic resonance imaging (MRI) were investigated., Results: The mean age of the 136 patients was 60.96±6.42 years (51-79), the mean age at diagnosis was 54.94±4.30 years, and 89 (65.4 %) of the patients were female. Most of the cases, 61.1 % (83) had at least one comorbidity. In 97 patients who underwent lumbar puncture (LP), OCB positivity was observed in 63.6 %. In 114 patients (83.8 %), spinal lesions were detected on MRI. Eighty-seven patients had relapsing-remitting MS (RRMS) (64 %), 27 patients had secondary progressive MS (SPMS) (19.9 %), and 22 patients had primary progressive MS (PPMS) (16.2 %). The mean EDSS at the time of diagnosis was 2.44±1.46, and the mean current EDSS was 3.15±2.14., Conclusions: In LOMS patients, the rates of delay in the diagnostic process, treatment disruption and progressive disease are higher than in the general MS population. The high rates of LP applying and OCB positivity of this study may indicate the habit of looking for clear evidences in advanged age in our country. This situation and comorbidities may cause a delay in diagnosis and eliminates the window of opportunity for early diagnosis. Although the high number of spinal lesions is a known marker for progressive disease, it is an issue that needs to be discussed whether the increased frequency of progressive course at older ages is due to the nature of the disease or immune aging itself., Competing Interests: Declaration 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Cognitive evaluation was considered to be very important in the relapse period, on the basis of the presence of isolated cognitive attacks and the necessity of monitoring the patient both physically and cognitively., Materials and Methods: People with MS (pwMS) who were hospitalized during relapse were included in the study. All MS patients were evaluated by the neurologist with Expanded Disability Status Scale (EDSS), The 9 Hole Peg Test (9HPT) and the Timed 25-Foot Walk Test (T25-FWT). Additionally, all participants were examined cognitively with the Turkish version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Also, schedules were indicated as during relapse before the treatment (pre-treatment) and the first month after relapse (1-month follow-up)., Results: A total of 140 MS patients (mean age; 34.98±10.09, mean disease duration; 6.05±5.29 years) and 86 healthy controls (mean age; 36.94±10.83) were included to the present study. The mean EDSS scores in pre-treatment in MS patients was 2.74±1.14 and decreased significantly in the 1-month follow-up (1.74±1.24; p<0.001). The mean SDMT score was lower by 8.76 points in MS patients than in HCs) in pre-treatment and 7.66 points in 1-month follow-up (p<0.001). The mean SDMT scores of all participants increased with measurement time gradually (p<0.001)., Conclusion: In this study, it was detected which cognitive domains were affected after relapse treatment and cognitive changes in pwMS during relapse and remission periods compared to the healthy controls. All three BICAMS test scores significantly increased in one-month follow-up than the pre-treatment period. The results showed that CVLT-II and BVMT-R scores improved more in pwMS than in HCs, and also SDMT scores of pwMS showed a trend of increase, but was not a significant improvement., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To effectively manage sexual dysfunction in women reporting overactive bladder, it is essential to know how patients perceive these problems, their lives, and their strategies., Aim: In this study we aimed to understand the sexual life experiences of women with multiple sclerosis (MS) who report overactive bladder from their point of view., Methods: This study included 12 women with MS and was conducted as a qualitative study with a hermeneutic phenomenological framework. The data were evaluated by using Van Manen's thematic analysis method. The Consolidated Criteria for Reporting Qualitative Research checklist was used., Outcomes: In this study, thematic codes of sexual symptoms in women with MS with overactive bladder were defined and evaluated., Results: As a result of the analysis of the data, four main themes and nine subthemes were identified. The main themes were "sexual self-concept," "sexual relationships," "sexual function," and "coping with problems". Subthemes such as body image, sexual esteem, the meaning of sexuality, communication, intimacy, coping with overactive bladder and sexual problems, and getting support showed that overactive bladder symptoms negatively affected women's sexual health., Clinical Implications: Given the variety of sexual problems experienced by women with MS who report overactive bladder, these problems should be a routine part of clinical evaluation., Strengths and Limitations: This study is to our knowledge the first to examine the sexual life experiences of MS women reporting overactive bladder in depth based on the holistic view of sexuality theory. However, the sample is small and includes only women with MS who have reported overactive bladder., Conclusions: The sexual experience of women with MS who reported overactive bladder was multi-dimensional. Women with MS cope with their sexual problems alone and cannot receive the necessary support from their husbands, nurses, or other health professionals., (© Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Declaration of Competing Interest M.Tutuncu, S. Demir, S. Sen, T. Gunduz, C Uzunköprü, H Gumus have received honoraria or consultancy fees for participating to advisory boards, giving educational lectures and/or travel and regis- tration coverage for attending scientific congresses or symposia from F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Biogen Idec/Gen Pharma. Asli 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. Serkan Ozakbas 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. 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 Ibrahim Rana 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 Ibrahim Ilac, Deva and ARIS. Aksel 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 Ibrahim Ilac. The rest of authors declare no conflict of interest with the study project., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: The study aimed to investigate inner retinal changes in multiple sclerosis (MS) patients by comparing them with healthy controls. The study also aimed to assess regional differences of inner retinal layer involvement in eyes with and without optic neuritis (ON)., Materials and Methods: This retrospective, cross-sectional study consisted of 141 eyes of 74 relapsing-remitting MS patients and 80 eyes of 40 healthy controls. The study group was separated into two subgroups according to the presence of ON history. Peripapillary retinal nerve fiber layer (pRNFL) thickness, total macular thickness, and thicknesses of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer were compared between the MS and healthy control groups and between eyes with and without ON history., Results: Mean pRNFL, total macular, mRNFL, GCL, and IPL thicknesses were significantly thinner in the MS group than in the control group (p<0.001) and in eyes with ON compared to those without ON (p<0.05). Comparison of inner retinal layer thicknesses in the inner 3-mm ring subfields of the ETDRS grid revealed significant thinning in all subfields of the GCL and IPL of eyes with ON (p<0.05). The inferior subfield demonstrated the highest difference., Conclusion: The study demonstrated that GCL and IPL thinning is a robust and reliable biomarker in all MS patients. The thinning was significantly greater in eyes with ON than in eyes without ON. The study also documented that the inferior region showed significantly greater GCL and IPL thinning in eyes with previous ON attacks., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Spasticity is one of the main symptoms that is most common in patients with Multiple Sclerosis and causes increased disability. The aim of this study is to understand the experiences of patients with Multiple Sclerosis about their spasticity from their perspective. This study was conducted as a qualitative study with a Hermeneutic phenomenological framework. The data were evaluated by using VanManen's thematic analysis method. As a result of the data analysis, four main themes were elicited, namely, "the meaning of spasticity for the patient," "the difficulties of living with spasticity," 'coping with spasticity," and "the new me created by spasticity." It was understood that spasticity is a symptom that brings about difficulties in psychological, social, and working life as well as physical difficulties. Nurses should be aware of the psychological symptoms as well as the physical symptoms that patients experience due to spasticity and should create a patient-specific management program.

Background and Purpose: We know that treatment algorithms have changed in Multiple Sclerosis (MS) practice during the pandemic. In this study, we aimed to investigate whether there was a change in the patient population for ocrelizumab (OCR) treatment during the pandemic period, the treatment compliance of the patients, and the course of the Coronavirus Disease-19 (COVID-19) disease in the patients who received OCR., Methods: Our study was designed as a survey study. A questionnaire was sent to the patients assessing whether they had COVID-19 infection, whether they received treatments regularly before and after the pandemic, vaccination status and duration of OCR treatment. Demographic characteristics of the patients, treatments they used before, MS type, Expanded Disability Status Scale (EDSS) scores were determined from the database. Each group of OCR started before pandemic and OCR started after pandemic were compared., Results: We included into the study 86 patients who started OCR before pandemic period and 75 patients who started OCR after the pandemic. Demographic features were similar. EDSS scores were higher in the group that started OCR treatment before the pandemic (p<0.0001). The patients who started OCR treatment before the pandemic had more disruptions than which started during the pandemic (p<0.0001). No correlation was found between the duration of OCR treatment and COVID-19 infection (p=0.940). We observed that the patients who had severe COVID-19 infection had received OCR therapy for a longer period., Conclusion: This retrospective study concluded that the OCR treatment approach in our center had changed during the pandemic period. OCR therapy was started in patients with less disability. The possible reasons for this situation include the proven relationship between high EDSS and serious COVID-19 infection, and that the patients who have higher EDSS score had troubles in reaching health institutions during the pandemic. The result that patients with severe COVID-19 infection received OCR treatment for a longer period necessitates more evidence-based research to investigate the relationship between treatment duration and disease severity.

Objective: This study aims to evaluate and compare the effects of conventional and robot-assisted gait training (RAGT) programs on fatigue, mood, and quality of life in patients with multiple sclerosis who have fatigue., Methods: In this single-blinded, randomized controlled study, 37 patients with multiple sclerosis were randomized into two groups: RAGT ( n = 18) and conventional gait training ( n = 19). The RAGT group had gait training with RoboGait, whereas the conventional gait training group received conventional physiotherapist-assisted gait training. Outcome measures were the Fatigue Severity Scale, Hospital Anxiety Depression Scale, Multiple Sclerosis Quality of Life-54, Extended Disability Status Scale, Functional Ambulation Category, Berg Balance Test, and 6-min walk test., Results: Baseline demographic, clinic, and functional data were similar. Both groups showed improvements in the Fatigue Severity Scale, Hospital Anxiety Depression Scale-Depression, Multiple Sclerosis Quality of Life, Berg Balance Test, and 6-min walk test scores after treatment. Only the RAGT group showed an improvement in Hospital Anxiety Depression Scale-Anxiety score. The RAGT group had better Fatigue Severity Scale, and Hospital Anxiety Depression Scale scores., Conclusion: In combination with the standard rehabilitation program, both RAGT and conventional gait training are effective for multiple sclerosis. However, RAGT has superior effects in terms of fatigue, depression, and anxiety. Therefore, it may be preferred in multiple sclerosis patients who exhibit prominent symptoms of fatigue, depression, or anxiety., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pseudobulbar affect (PBA) has recently been added to the list of mental disorders commonly observed in patients with Multiple Sclerosis (MS). The emotional changes experienced by MS patients may be associated with other mental problems and adversely affect disease prognosis. However, there are limited studies in the international and national literature on this subject., Aim: This study aimed to evaluate the relationship between PBA and stress, anxiety, and depression levels in patients with MS., Design: This is a descriptive, relational, and cross-sectional study., Methods: A total of 442 MS patients followed in the neurology outpatient clinic of a hospital and registered with the MS Society in Turkey participated in this study. Data were collected using a personal information form, the Turkish version of the Center for Neurologic Study-Lability Scale (CNS-LS), and the Depression Anxiety Stress Scale (DASS)., Results: In this study, 63.3% of the patients had PBA, 21% had extremely severe depression, 41.6% had extremely severe anxiety, and 24.9% had severe stress. Correlation analysis revealed weak positive correlations between CNS-LS total score and DASS subscale and total scores. Depression, anxiety, and stress levels accounted for 22.5% of the variation in CNS-LS total score., Conclusion: The results of this study indicate that a majority of MS patients in Turkey experience PBA, depression, anxiety, and stress, and that PBA is positively associated with depression, anxiety, and stress., Impact Statement: This study, indicates that should be increased consultation-liaison psychiatry services in Turkey, and MS patients should benefit from comprehensive psychiatric services.

Objectives: Vitamin D is an important regulator of the immune system, and it has been shown that deficiency of vitamin D is significant environmental factor in some immune-mediated diseases such as Multiple Sclerosis (MS). In this study, we have compared serum 25 hydroxyvitamin (OH) D levels in Relapsing-Remitting Multiple Sclerosis (RRMS), clinically isolated syndrome (CIS), and control groups., Methods: Forty patients with CIS and 60 patients who have been diagnosed RRMS between age 18-45, respectively, and followed up at Pamukkale University Faculty of Medicine, Department of Neurology, and 60 healthy individuals have been included in this study. Serum 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, parathormone, insulin, and fasting blood glucose levels were studied for all three groups., Results: A statistically significant difference was determined in the comparison of three groups for mean 25(OH) vitamin D levels. In the intergroup comparison of mean 25(OH) vitamin D; mean 25(OH) vitamin D level was determined to be statistically significantly lower in both RRMS and CIS groups compared to control group (p<0.05)., Conclusions: Since vitamin D deficiency poses a problem from the early stage of disease spectrum in both CIS patients and MS patients, 25(OH) vitamin D level should be routinely controlled, and replacement should be administered upon any deficiency state., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

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: 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., (Copyright © 2021. Published by Elsevier B.V.)

Background: The multi-drug resistance transporter ABCG2, a member of the ATP-binding cassette (ABC) transporter family, mediates the efflux of different immunotherapeutics used in multiple sclerosis (MS), e.g., teriflunomide (teri), cladribine, and mitoxantrone, across cell membranes and organelles. Hence, the modulation of ABCG2 activity could have potential therapeutic implications in MS. In this study, we aimed at investigating the functional impact of abcg2 modulation on teri-induced effects in vitro and in vivo., Methods: T cells from C57BL/6 J wild-type (wt) and abcg2-knockout (KO) mice were treated with teri at different concentrations with/without specific abcg2-inhibitors (Ko143; Fumitremorgin C) and analyzed for intracellular teri concentration (HPLC; LS-MS/MS), T cell apoptosis (annexin V/PI), and proliferation (CSFE). Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6J by active immunization with MOG 35-55 /CFA. Teri (10 mg/kg body weight) was given orally once daily after individual disease onset. abcg2-mRNA expression (spinal cord, splenic T cells) was analyzed using qRT-PCR., Results: In vitro, intracellular teri concentration in T cells was 2.5-fold higher in abcg2-KO mice than in wt mice. Teri-induced inhibition of T cell proliferation was two fold increased in abcg2-KO cells compared to wt cells. T cell apoptosis demonstrated analogous results with 3.1-fold increased apoptosis after pharmacological abcg2-inhibition in wt cells. abcg2-mRNA was differentially regulated during different phases of EAE within the central nervous system and peripheral organs. In vivo, at a dosage not efficacious in wt animals, teri treatment ameliorated clinical EAE in abcg2-KO mice which was accompanied by higher spinal cord tissue concentrations of teri., Conclusion: Functional relevance of abcg2 modulation on teri effects in vitro and in vivo warrants further investigation as a potential determinant of interindividual treatment response in MS, with potential implications for other immunotherapies.

Background: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS., Methods: MOG(35-55) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses., Results: EAE disease course was slightly attenuated in male apoE-deficient (apoE (-/-) ) mice compared to wildtype mice (cumulative median score: apoE (-/-)  = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE (-/-) mice compared to wildtype mice (cumulative median score: apoE (-/-)  = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex., Conclusions: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.