Multiple Sclerosis Research Research Articles

The MoXFo initiative – study design: Considerations related to study design and methodology in exercise research for people with multiple sclerosis

Background: Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleiotropic effects, but continued progression of the field requires better future designs and methodologies. Objectives: This paper outlines the work of the ‘Study design and methodology’ group of the MoXFo (moving exercise research forward) initiative, and addresses critical aspects and future directions when defining the research question of interest, and subsequently, designing the study and exercise intervention in MS patients. Methods: The work is based on the formation of an international expert panel formed within the MoXFo initiative. We provide a structured and concise synthesis of exercise-specific MS research challenges and considerations when designing randomized controlled trials (RCTs). Results: Challenges and considerations are presented using the Patient population, Intervention, Comparator, Outcomes, Timing, Setting (PICOTS) framework, thereby forming a new and specific MS exercise PICOTS framework. Conclusion: We propose that researchers should carefully consider and align all elements of this MS exercise PICOTS framework when developing future research questions and study designs, ultimately improving the quality of new exercise studies in people with MS.

The MoxFo initiative—Mechanisms of action: Biomarkers in multiple sclerosis exercise studies

Background: As exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. However, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established. Objective: Establish recommendations for future mechanistic exercise studies in MS. Methods: In regular meetings, members of the mechanisms of action group within the MoXFo (Moving eXercise research Forward in MS) initiative evaluated gaps of knowledge and discussed unmet needs in mechanistic MS research. Results: We concluded that biomarkers assessed in translational studies in humans and animals are essential to decipher the underlying mechanisms of exercise in MS. Consequently, we defined clear definitions of different types of biomarkers examined in MS exercise studies and operationalized their use to align with the research question and optimal testing time points. Furthermore, we provide key considerations to improve the rigor of translational studies and defined minimal reporting criteria for animal studies. Conclusion: The resulting recommendations are intended to improve the quality of future mechanistic exercise studies in MS and consequently lead to a better understanding of therapeutic approaches.

Self-reports by persons with multiple sclerosis are an adequate surrogate for healthcare provider data on disease-modifying therapy and multiple sclerosis type

IntroductionSelf-reports are a valuable and cost-effective method of data collection, though they can be influenced by bias. Limited evidence exists on the quality of self-reports by persons with multiple sclerosis (pwMS), particularly since more potent disease-modifying therapies (DMTs) have been introduced. This study aimed to assess the reliability and validity of self-reported DMT use and multiple sclerosis (MS) type in the Swiss Multiple Sclerosis Registry (SMSR) by comparing self-reports with reimbursement approval requests from the Swiss Association for Joint Tasks of Health Insurers. MethodsThe self-reported and reimbursement approval data were linked using privacy-preserving methods based on information available in both databases, i.e., date of birth, canton of residence, sex, and year of MS diagnosis. The SMSR baseline questionnaire data was utilized for the main analysis, while the SMSR follow-up survey data was utilized for the sensitivity analysis. For both analyses, we compared self-reported data with reimbursement approval data that corresponded to the respective periods of the SMSR data collection. Thus, the main analysis included the entirety of the data over the six-year period, while the sensitivity analysis captured a more recent snapshot of the data. To assess reliability, we estimated agreement using Cohen's kappa, and for validity, we estimated accuracy parameters using reimbursement approvals as the reference standard. Univariable and multivariable logistic regression models were employed to investigate factors associated with discordance between self-reports and reimbursement approvals in the main analysis. ResultsThe main analysis included 446 participants, and the sensitivity analysis included 193 participants. The agreement between self-reported and reimbursement approval data for medication use was near-perfect in both analyses (κ = 0.87, 95% confidence interval (CI) 0.85, 0.90 and κ = 0.82, 95% CI 0.76, 0.88). However, the agreement between self-reported and reimbursement approval-documented MS types ranged from fair to moderate (κ = 0.37, 95% CI 0.25, 0.48 to κ = 0.61, 95% CI 0.46, 0.77). The accuracy estimates for self-reported DMT use were generally high (≥ 0.80) with narrow CIs, except for less frequently reported drugs. While the sensitivity and specificity for RRMS were high, there was a notable possibility of false-negative self-reports for RRMS (NPV = 0.33, 95% CI 0.22, 0.45), and false-positive reports for SPMS (PPV = 0.36, 95% CI 0.21, 0.54). Multivariable logistic regression models showed that age (OR = 1.07, 95% CI 1.04, 1.10 per year) and education level (OR = 0.27, 95% CI 0.11, 0.65) were associated with discordance in reported and documented MS types, whereas possession of Swiss citizenship (OR = 0.32, 95% CI 0.14, 0.72) was associated with discordance in DMT use. ConclusionSelf-reported DMT use in pwMS is a reliable and valid information source, with near-perfect agreement and high accuracy. Self-reported MS types showed fair to moderate agreement and varying accuracy, likely reflecting the complexity of diagnosing progressive forms of MS and access to DMTs. In population-based MS research, self-reports of MS types, and particularly DMT use, can serve as a suitable surrogate for healthcare provider data.

What Insights Can We Gain from the Scientometric Analysis of Scientific Publications Related to Multiple Sclerosis?

Background: Bibliometrics is one of the credible methods of evaluating scientific publications and research output. This is the first study in the multiple sclerosis (MS) field that can guide researchers and policy-makers in contributing more to MS. Objectives: The main purpose of this study is to conduct a bibliometric analysis and visualization of multiple sclerosis scientific products of the 17 Middle East countries during 1900 - 2020. Methods: Data from January 1, 1900, to December 31, 2020, were searched in the Web of Science database. Research productivity was evaluated by considering the country, year, number of publications, and time trend of these publications. Co-word and co-authorship analyses were done, and top authors, journals, active institutions, and country contributions to MS research were identified. Results: Middle Eastern countries produced 5.5% of the total number of MS research worldwide. Turkey (29.18%), Iran (23.54%), and Egypt (13.066%) had the top positions. King Saud University as a research center, Baser, Kemal Husnu Can as an author, and the Multiple Sclerosis Journal as a scientific journal, respectively, with a total of 1,582 (4.26%), 360 (0.97%) and 1,172 (3.15%) publications had the highest research productivities. Conclusions: Accurate policy-making in research centers, prioritizing research topics, promoting journals, and making more international collaboration can decrease the gap in research on MS and increase its quality and quantity. Despite rising trends in research results, more strategic planning and cooperation between researchers are needed for regional advancement in the field.

Toxoplasma gondii and multiple sclerosis: a population-based case-control seroprevalence study, Central Anatolia, Turkey.

Toxoplasma gondii, an obligate intracellular parasite, is prevalent in various mammalian species, as well as certain avian, reptilian, and cold-blooded organisms. While immunocompetent individuals generally remain asymptomatic, immunocompromised individuals may experience severe and life-threatening conditions. Multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system (CNS), is characterized by inflammation, demyelination, and axonal damage. Despite extensive research, the etiology and pathogenesis of MS remain incompletely understood. Given the strong affinity of T. gondii for the CNS, researchers have explored the potential association between T. gondii and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and MS. This study aimed to investigate the possible relationship between MS and T. gondii. A population-based incident cohort of MS patients in Sivas, Turkey, was used to randomly select MS patients. Age- and sex-matched controls were also randomly selected from the general population. A total of 182 MS patients and 182 controls were included in the study. Clinical and socio-demographic variables were recorded using a structured questionnaire. Blood samples were collected from MS patients, and Toxoplasma IgG and IgM antibodies were measured using the enzyme-linked immunosorbent assay technique. Anti-Toxoplasma IgG antibodies were detected in 78 cases (42.9%) and 73 controls (40.1%) (p>0.05). Age, female sex, and consumption of raw meat were identified as risk factors for toxoplasmosis in both MS patients and controls. In contrast to previous studies, this study did not find a significant difference in T. gondii seropositivity between the control group and MS patients. Further investigations are recommended to elucidate the precise relationship between MS patients and T. gondii.

Association between PROMIS10, SF-36 and NeuroQoL in persons with multiple sclerosis

BackgroundPatient reported outcome measures (PROs) are considered promising tools for use in clinical settings to measure the impact of disease on physical, mental and social well-being from the patient's perspective. The Patient Reported Outcome Measurement Information System Scale v1.1-Global Health (PROMIS-10) is a measure that is well-suited to clinical practice, but the relationships between this measure and longer PRO measures used in multiple sclerosis (MS) research are unknown. MethodsSubjects enrolled in SysteMS: A Systems Biology Study of Clinical, Radiological, and Molecular Markers in Subjects with MS at the Brigham and Women's Hospital were eligible to contribute to the study. 349 subjects completed three PRO measures at study entry: PROMIS-10, Medical Outcomes Study Short-Form 36 (SF-36), and Quality of Life in Neurological Disorders (Neuro-QoL™). All questions and global scores from PROMIS-10 were correlated with all domain and summary component scores for SF-36 and all domain scores for Neuro-QoL using Pearson's correlation coefficient. Further, the global scores from PROMIS-10 were correlated with the expanded disability status scale (EDSS) and compared between disease categories (relapsing vs progressive MS). ResultsStrong correlations were observed between PROMIS-10 questions and SF-36 domains aimed at measuring the same construct. Further, the PROMIS-10 Global Physical Health score was correlated with the Physical Component Score from the SF-36 (r = 0.798), and the PROMIS Global Mental Health score was correlated with the Mental Component Score from the SF-36 (r = 0.726). Strong correlations between PROMIS-10 questions and two Neuro-QoL domains (fatigue and lower extremity function) were observed, but other Neuro-QoL domains were not strongly correlated with PROMIS-10 questions. PROMIS-10 Global Physical Health had stronger relationship to EDSS and disease category compared to the Global Mental Health. ConclusionsPROMIS-10 questions and global scores are highly correlated with the corresponding domains of SF-36 in PwMS. Neuro-QoL provides different information regarding HRQOL since different domains are being measured.

Interim guidelines for the assessment and treatment of pain in children with multiple sclerosis.

Pain in multiple sclerosis (MS) is common, but literature on pain in children with MS remains scarce. Pain has physical, psychological, and social implications in MS, and both comprehensive assessment and interdisciplinary management approaches are needed. We sought to develop an interdisciplinary interim guideline for the assessment and management of pain in children with MS. We convened a modified Delphi panel composed of 13 experts in pediatric and adult MS neurology, physiotherapy, pain, patient lived-experience, advanced practice nursing, psychology, physiatry, and MS research. A survey was sent to panelists for anonymous completion. The panel discussed survey themes extracted by the panel chair. The process was repeated twice. Thirteen assessment and treatment recommendations were produced regarding pain in children with MS. Future studies will assess implementation of these pain assessment and treatment guidelines in the clinical setting.

A Comprehensive Review on Neuroimmunology: Insights from Multiple Sclerosis to Future Therapeutic Developments.

This review delves into neuroimmunology, focusing on its relevance to multiple sclerosis (MS) and potential treatment advancements. Neuroimmunology explores the intricate relationship between the immune system and the central nervous system (CNS). Understanding these mechanisms is vital for grasping the pathophysiology of diseases like MS and for devising innovative treatments. This review introduces foundational neuroimmunology concepts, emphasizing the role of immune cells, cytokines, and blood-brain barrier in CNS stability. It highlights how their dysregulation can contribute to MS and discusses genetic and environmental factors influencing MS susceptibility. Cutting-edge research methods, from omics techniques to advanced imaging, have revolutionized our understanding of MS, offering valuable diagnostic and prognostic tools. This review also touches on the intriguing gut-brain axis, examining how gut microbiota impacts neuroimmunological processes and its potential therapeutic implications. Current MS treatments, from immunomodulatory drugs to disease-modifying therapies, are discussed alongside promising experimental approaches. The potential of personalized medicine, cell-based treatments, and gene therapy in MS management is also explored. In conclusion, this review underscores neuroimmunology's significance in MS research, suggesting that a deeper understanding could pave the way for more tailored and effective treatments for MS and similar conditions. Continued research and collaboration in neuroimmunology are essential for enhancing patient outcomes.

О ВОЗМОЖНОСТИ ПРАКТИЧЕСКОГО ПРИМЕНЕНИЯ ИССЛЕДОВАНИЙ МИКРОФЛОРЫ КИШЕЧНИКА ПРИ ПРОФИЛАКТИКЕ, ДИАГНОСТИКЕ, ОЦЕНКЕ И МОДИФИЦИРОВАННОМ ЛЕЧЕНИИ РАССЕЯННОГО СКЛЕРОЗА У ЛИЦ ИЗ ГРУПП РИСКА

Research into the gut microbiota (GM) in multiple sclerosis (MS) has the potential to lead to a number of practical applications in the prevention, diagnosis, assessment of, and treatment modification for, MS. Four most promising areas include biomarkers, treatment personalization, drug development as well as disease prevention and mitigation. Changes in the GM have been observed in individuals with MS; analysis of the GM composition may help to identify individuals at risk of developing the disease or to monitor disease progression. Dietary interventions aimed at improving gut health could be used as a complementary approach to traditional MS treatments in order to reduce inflammation thereby potentially improving MS symptoms and lessening disease progression. Differences in the GM between individuals with MS suggest that personalized treatment approaches based on an individual's microbiome composition could be effective. Manip-ulating the GM could therefore be a potential avenue for drug development in MS. In addition, the exploration of bacteria or bacterial metabolites as therapeutic agents to modulate the immune system and reduce inflammation is also promising. Such explorations may even help identify strategies for preventing the development of MS in at-risk individuals. Overall, practical applications of gut microbiome research in MS are still in the early stages and further research is needed to fully understand the mechanisms underlying the relationship between the gut microbiome and MS and to determine the most effective interventions for improving gut health in individuals with the disease.

On possible practical applications of the gut microbiome research in the prevention, diagnosis, assessment of, and treatment modification for multiple sclerosis in patients from risk groups

Research into the gut microbiota (GM) in multiple sclerosis (MS) has the potential to lead to a number of practical applications in the prevention, diagnosis, assessment of, and treatment modification for, MS. Four most promising areas include biomarkers, treatment personalization, drug development as well as disease prevention and mitigation. Changes in the GM have been observed in individuals with MS; analysis of the GM composition may help to identify individuals at risk of developing the disease or to monitor disease progression. Dietary interventions aimed at improving gut health could be used as a complementary approach to traditional MS treatments in order to reduce inflammation thereby potentially improving MS symptoms and lessening disease progression. Differences in the GM between individuals with MS suggest that personalized treatment approaches based on an individual's microbiome composition could be effective. Manipulating the GM could therefore be a potential avenue for drug development in MS. In addition, the exploration of bacteria or bacterial metabolites as therapeutic agents to modulate the immune system and reduce inflammation is also promising. Such explorations may even help identify strategies for preventing the development of MS in at-risk individuals. Overall, practical applications of gut microbiome research in MS are still in the early stages and further research is needed to fully understand the mechanisms underlying the relationship between the gut microbiome and MS and to determine the most effective interventions for improving gut health in individuals with the disease.

Investigation of the safety of live attenuated varicella-zoster virus vaccination in patients with relapse-remitting multiple sclerosis treated with natalizumab: A case series and review of the literature.

It is generally recommended to avoid live attenuated vaccines in patients treated with high efficacy disease-modifying treatment (DMT). However, a delay in starting DMT in highly active or aggressive multiple sclerosis (MS) might lead to a significant disability. We aimed to report a case series of 16 highly active RRMS patients who received the live-attenuated varicella-zoster virus (VZV) vaccine during treatment with natalizumab. This retrospective case series was conducted between September 2015 and February 2022 at the MS Research Center of Sina and Qaem hospital, Tehran, Mashhad, Iran, to identify the outcome of highly active MS patients who received the live-attenuated VZV vaccine on natalizumab. Two males and 14 females were included in this study, with a mean age of 25.5±8.4-year-old. 10 patients were naïve cases of highly active MS, and six were escalated to natalizumab. The patients received two doses of live attenuated VZV vaccine after a mean of 6.72 cycles of natalizumab treatment. Except for the one who experienced mild chickenpox infection, no serious adverse event or disease activity was evident after vaccination. While our data do not confirm the safety of the live attenuated VZV vaccine in natalizumab recipients, it highlights the importance of case-by-case decision-making in MS management based on the risk-benefit assessment.

Blending citizen science with natural language processing and machine learning: Understanding the experience of living with multiple sclerosis.

The emergence of new digital technologies has enabled a new way of doing research, including active collaboration with the public ('citizen science'). Innovation in machine learning (ML) and natural language processing (NLP) has made automatic analysis of large-scale text data accessible to study individual perspectives in a convenient and efficient fashion. Here we blend citizen science with innovation in NLP and ML to examine (1) which categories of life events persons with multiple sclerosis (MS) perceived as central for their MS; and (2) associated emotions. We subsequently relate our results to standardized individual-level measures. Participants (n = 1039) took part in the 'My Life with MS' study of the Swiss MS Registry which involved telling their story through self-selected life events using text descriptions and a semi-structured questionnaire. We performed topic modeling ('latent Dirichlet allocation') to identify high-level topics underlying the text descriptions. Using a pre-trained language model, we performed a fine-grained emotion analysis of the text descriptions. A topic modeling analysis of totally 4293 descriptions revealed eight underlying topics. Five topics are common in clinical research: 'diagnosis', 'medication/treatment', 'relapse/child', 'rehabilitation/wheelchair', and 'injection/symptoms'. However, three topics, 'work', 'birth/health', and 'partnership/MS' represent domains that are of great relevance for participants but are generally understudied in MS research. While emotions were predominantly negative (sadness, anxiety), emotions linked to the topics 'birth/health' and 'partnership/MS' was also positive (joy). Designed in close collaboration with persons with MS, the 'My Life with MS' project explores the experience of living with the chronic disease of MS using NLP and ML. Our study thus contributes to the body of research demonstrating the potential of integrating citizen science with ML-driven NLP methods to explore the experience of living with a chronic condition.

Current and future trends in multiple sclerosis management: Near East perspective.

Multiple sclerosis (MS) prevalence is rising in the Middle East. Most MS medications are available in the region, but not all, possibly affecting neurologists' prescribing habits. To provide an overview of the current practices of Near East (NE) healthcare practitioners by probing their prescribing decisions, to report the COVID-19 impacts on neurologists' prescribing habits, and to explore the future relevance of current medication used in MS management among other newcomers. A cross-sectional study was carried out using an online survey from April 27, 2022, to July 5, 2022. The questionnaire was designed with the input of five neurologists representing five NE countries (Iran, Iraq, Lebanon, Jordan & Palestine). They identified several factors that play a crucial role in the optimal care of MS patients. The link was shared among neurologists using snowball sampling. The survey included 98 neurologists. Effectiveness and safety balance was the most important factor considered when selecting the MS treatment. Among patients with MS, the most challenging factor for the patients was thought to be related to family planning, followed by affordability and tolerability of side effects. In the treatment of mild to moderate relapsing remitting multiple sclerosis (RRMS) in men, Interferon beta 1a SC, Fingolimod, and Glatiramer acetate were the most commonly recommended treatments. Dimethyl fumarate substituted fingolimod in female patients. Interferon beta 1a SC was the safest treatment for mild to moderate RRMS. Interferon beta 1a SC was preferred over other treatments for patients with mild to moderate MS and planning for pregnancy (56.6%) or breastfeeding (60.2%). Fingolimod was not a choice for these patients. Neurologists seemed to discuss the top three treatments of Natalizumab, Ocrelizumab, and Cladribine with patients with highly active MS. When asked to position future disease-modifying therapies five years from today, more than 45% of physicians expressed a lack of information on Bruton's tyrosine kinase (BTK) inhibitors. Most neurologists in the NE region followed Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) recommendations for prescribing treatment. The treatment choice also depended on the availability of disease-modifying therapies (DMTs) in the region. Regarding the use of upcoming DMTs, there is a clear need for real-world data, long-term extension studies, and comparative studies to support their efficacy and safety profiles in treating patients with MS.

The impact of disease modifying therapies on cognitive functions typically impaired in multiple sclerosis patients: a clinician's review.

Over the last few decades clinicians have become aware that cognitive impairment might be a major cause of disability, loss of employment and poor quality of life in patients suffering from multiple sclerosis [MS].The impact of disease modifying therapies [DMTs] on cognition is still a matter of debate. Theoretically, DMTs could exert a substantial beneficial effect by means of reducing neuroinflammation and brain atrophy, which are established correlates of cognitive dysfunction. The aim of the study was to review the evidence concerning the effect of DMTs on cognitive functions. PubMed, Scopus, and the European Committee for Treatment and Research in Multiple Sclerosis [ECTRIMS] Library were searched for articles concerning the pediatric and adult populations of patients with multiple sclerosis, including clinical trials and RWD, where psychometric results were analyzed as secondary or exploratory endpoints. We reviewed a total of 44 studies that were found by our search strategy, analyzed the psychological tests that were applied, the length of the follow-up, and possible limitations. We pointed out the difficulties associated with assessing of DMTs' effects on cognitive functions, and pitfalls in cognitive tools used for evaluating of MS patients. There is a need to highlight this aspect of MS therapies, and to collect adequate data to make informed therapeutic decisions, to improve our understanding of MS-related cognitive dysfunction and provide new therapeutic targets.

The Role of Vitamin D in Neuroprotection in Multiple Sclerosis: An Update.

Multiple sclerosis (MS) is a complex neurological condition that involves both inflammatory demyelinating and neurodegenerative components. MS research and treatments have traditionally focused on immunomodulation, with less investigation of neuroprotection, and this holds true for the role of vitamin D in MS. Researchers have already established that vitamin D plays an anti-inflammatory role in modulating the immune system in MS. More recently, researchers have begun investigating the potential neuroprotective role of vitamin D in MS. The active form of vitamin D, 1,25(OH)2D3, has a range of neuroprotective properties, which may be important in remyelination and/or the prevention of demyelination. The most notable finding relevant to MS is that 1,25(OH)2D3 promotes stem cell proliferation and drives the differentiation of neural stem cells into oligodendrocytes, which carry out remyelination. In addition, 1,25(OH)2D3 counteracts neurodegeneration and oxidative stress by suppressing the activation of reactive astrocytes and M1 microglia. 1,25(OH)2D3 also promotes the expression of various neuroprotective factors, including neurotrophins and antioxidant enzymes. 1,25(OH)2D3 decreases blood-brain barrier permeability, reducing leukocyte recruitment into the central nervous system. These neuroprotective effects, stimulated by 1,25(OH)2D3, all enhance neuronal survival. This review summarizes and connects the current evidence supporting the vitamin D-mediated mechanisms of action for neuroprotection in MS.

Cellular and Molecular Evidence of Multiple Sclerosis Diagnosis and Treatment Challenges.

Multiple sclerosis (MS) is a chronic autoimmune disease that impacts the central nervous system and can result in disability. Although the prevalence of MS has increased in India, diagnosis and treatment continue to be difficult due to several factors. The present study examines the difficulties in detecting and treating multiple sclerosis in India. A lack of MS knowledge among healthcare professionals and the general public, which delays diagnosis and treatment, is one of the significant issues. Inadequate numbers of neurologists and professionals with knowledge of MS management also exacerbate the situation. In addition, MS medications are expensive and not covered by insurance, making them inaccessible to most patients. Due to the absence of established treatment protocols and standards for MS care, India's treatment techniques vary. In addition, India's population diversity poses unique challenges regarding genetic variations, cellular and molecular abnormalities, and the potential for differing treatment responses. MS is more difficult to accurately diagnose and monitor due to a lack of specialized medical supplies and diagnostic instruments. Improved awareness and education among healthcare professionals and the general public, as well as the development of standardized treatment regimens and increased investment in MS research and infrastructure, are required to address these issues. By addressing these issues, it is anticipated that MS diagnosis and treatment in India will improve, leading to better outcomes for those affected by this chronic condition.

European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. We aimed to develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in subpopulations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

Feasibility Meets Implementation Science: Narrowing the Research-To-Practice Gap for Exercise Activity in Multiple Sclerosis

Background There is a need to identify why multiple sclerosis exercise research is not translating into real-world participation. To lay the foundations of strong clinical research, considering the translational element of implementation science at the feasibility phase of a trial is vital. Methods Document analysis was used to examine document sources on exercise activity interventions designed for people living with multiple sclerosis. Document sources focused on multiple sclerosis research that incorporated exercise prescription elements and behaviour change and were feasibility studies incorporating aspects of implementation science. Results Implementation science should come much earlier than the efficacy or effectiveness research pipeline. An alternate view is outlined where feasibility and implementation science should meet based on case examples that have not yet shown strong efficacy or effectiveness. Findings from our key themes indicate a need for a cyclical iterative approach to the translational process. Multiple aspects of feasibility and how it can be assessed using an implementation science lens to support more successful interventions are provided. The determination of feasibility in behaviour change should involve implementation science as feasibility is drawn on for theory development, optimising the intervention design and quality of implementation strategies, and identifying those delivering the intervention before conducting efficacy and effectiveness research. Conclusions Document analysis methodology is underused in qualitative research and was appropriate to use as it was a very resource, time-efficient and an unobtrusive process that could track change and development to explore the integration of implementation science at the feasibility phase, with the findings indicating the earlier implementation science is introduced into multiple sclerosis exercise interventions the better.

Triggering multiple sclerosis at conception and early gestation: The variation in ultraviolet radiation is as important as its intensity

Background and objectivesMedical science needs to further elucidate the role of ultraviolet radiation (UVR), geographic latitude, and the role of vitamin D in the autoimmune disease multiple sclerosis (MS). We separated several papers into categories out of the thousands published and used their conclusions to explore the relationship between UVR and MS. RelevanceMS is increasing in incidence, particularly in women where MS is two to three times that in men and particularly severe in African Americans. MethodsWe collected UVR data at our observatory in Central Maine and calculated the average coefficient of variation (CVUVR) for each month for 15 years (2007–2021, inclusive). ResultsThe month of conception (MOC) is more important than the month of birth (MOB) in explaining how UVR triggers the variable genetic predisposition to MS. We hypothesize that the rapidly increasing CVUVR is important in preventing an increase in the activity of the vitamin D receptor (VDR) from August to December, which then requires a higher intensity of UVR later in life to suppress the immune system, therefore predisposing to more MS. LimitationsOne observatory at about 44° latitude. ConclusionsWhile variation in UVR is important at the MOC if UVR exceeds a threshold (e.g., if the sunspot number equals or is greater than 90, usually at a solar cycle MAX, or at elevations above approximately 3,000 feet above sea level), the MS mitigating vitamin D-VDR mechanism is overwhelmed and the genotoxic effects of higher-intensity UVR promote MS in those with a genetic predisposition. What is new in this researchThis paper offers a new concept in MS research.

MS becomes a treatable disease: 30 years later

30 years ago the first disease-modifying therapy for relapsing multiple sclerosis was approved for use in the United States and soon thereafter across the globe. Since then the field of MS therapeutics, and studies of immunopathogenesis and genetics, have advanced our understanding of the disease and raised the hope of better addressing the next challenges of treating progressive disease, enhancing repair of the damaged nervous system and, hopefully, of a cure. Thirty years into the MS treatment era, the field continues to debate fundamental aspects of MS, and there exists a widening chasm between the triumphs in relapsing disease and the desolation of MS progression, which remains the principal unmet need. In this Personal Viewpoint, we outline lessons learned from the first era of great therapeutic development, as we look to the future of MS research and therapeutics.