Multiple Sclerosis Research Research Articles

Although the pivotal role of B cells in the pathogenesis of multiple sclerosis (MS) is well established, their precise functions in disease mechanisms remain incompletely understood. For decades, MS-related B cell research has focused on identifying B cell antigens that could induce pathogenic antibodies contributing to the initiation and maintenance of CNS lesion formation and inflammation. In this review, we conducted a systematic literature search to compile and critically assess proposed antigens with respect to their specificity for MS and the plausibility of findings across different publications. We identified 26 antigens in total. Among these, 15 antigens did not demonstrate high specificity for MS, 9 antigens yielded controversial or contradictory results, and 2 antigens may still be regarded as provisional at the time of our analysis. Based on these findings, a primarily antibody-mediated mechanism driving initial lesion formation is not supported by current evidence, although it cannot be excluded entirely. Instead, a secondary immune response to CNS tissue damage—characterized by local antibody production and alternative B cell functions such as antigen presentation, cytokine secretion and cell-to-cell communication—appears more plausible. Taken together, our review highlights the necessity of expanding B cell–oriented MS research beyond antibody production to include a broader spectrum of B cell functions.

In 2013, the "MS in the 21st Century" (MS21) initiative established a consensus statement for multiple sclerosis (MS) standards of care, with an overall vision including "Full access to personalised treatment, with reimbursement, to achieve freedom from disease." This update considers progress made since 2013 and priority areas for further improvement. A Delphi process with two rounds of anonymised voting was used to develop updated consensus statements based on three key themes: (1) optimising current MS care provision; (2) facilitating shared decision-making and patient education; and (3) continuing MS research and development. Voting panels (n=30), including people living with MS (PwMS), MS patient advocacy group (PAG) representatives and healthcare professionals (HCPs) indicated agreement using a sliding scale [1 (strongly disagree) to 5 (strongly agree)] and free-text feedback. Statements were revised after each voting round, with the consensus threshold set a priori as≥75% agreement. There was a 70% response rate at each round of voting, with respondents representing 13 countries. Seven original principles were expanded to 14, with emerging themes including unmet care needs in ageing PwMS, MS prevention, and treatments for progressive MS and remyelination. The top priority for both HCPs and PwMS/PAG representatives was "access to quick and decisive treatment after diagnosis." For PwMS to be unburdened by symptoms, professionals and stakeholders within the MS community should work together to meet the updated MS21 vision, including access to appropriate care, greater PwMS involvement in decisions, and further research and development to address unmet needs in MS.

Lost in translation: rethinking animal models of progressive MS (an industry perspective).

Recommendations for the critical reading of clinical trials on disease-modifying drugs for multiple sclerosis.

From pathogenesis to precision medicine: Targeting immune imbalance in multiple sclerosis.

BACKGROUNDMultiple sclerosis (MS) is known to affect many sensory systems, yet most auditory research in MS has focused on the afferent pathways, with relatively few studies examining efferent function. The brainstem is a common site for MS plaques, and the medial olivocochlear (MOC) system is located in the superior olivary complex (SOC) of the brainstem. The cochlear nuclei are also involved in the MOC reflex arc. Additionally, the temporal cortex can modulate the SOC and cochlear nucleus, so lesions in the brainstem or temporal cortex may affect the MOC reflex in MS.AIMTo investigate efferent auditory system activity in patients with multiple sclerosis via the MOC reflex.METHODSThe study included 50 patients with MS and 50 healthy controls. Patients with MS were divided into three subgroups according to cranial magnetic resonance imaging findings: Patients with brainstem lesions (Group 1, n = 20); patients with temporal cortex lesions without brainstem involvement (Group 2, n = 20); and patients without any lesions in the brainstem or temporal cortex (Group 3, n = 10). Tympanometry, acoustic stapedial reflex thresholds, pure-tone audiometry, and transient-evoked otoacoustic emission (TEOAE) tests (with and without contralateral noise) were performed for all participants.RESULTSThere was no significant difference in pure-tone hearing thresholds or baseline TEOAE amplitudes between the MS and control groups, indicating normal cochlear function in patients with MS; however, MOC reflex suppression was significantly reduced in patients with MS compared to controls (P = 0.021). In particular, Group 1 (MS with brainstem lesions) showed the lowest mean suppression values, which was significantly lower than that of Group 2 and the control group (P = 0.002). By contrast, Group 2 and Group 3 did not significantly differ from controls. Additionally, patients with MS exhibited a sex difference in MOC function: Male patients had significantly lower suppression compared to female patients both within Group 1 and in the MS group as a whole.CONCLUSIONThe findings indicate that the efferent auditory system (specifically the MOC reflex) is affected by MS. MOC reflex activity was most significantly decreased in patients with MS with brainstem lesions, while temporal cortex lesions alone did not appear to notably impair the MOC reflex. Diminished MOC activity may underlie various auditory difficulties in patients with MS (e.g., hearing in noise), and loss of efferent suppression could contribute to symptoms such as hyperacusis or tinnitus in this population. Further studies are needed to better understand the relationship between MOC dysfunction and auditory symptoms in MS, as well as the potential diagnostic value of MOC testing in MS.

Safety, adherence, and compliance in a RCT of supervised exercise training among persons with multiple sclerosis who have slowed cognitive processing speed.

The accurate segmentation of multiple sclerosis (MS) lesions in magnetic resonance imaging (MRI) is essential for diagnosis, disease monitoring, and therapeutic assessment. Despite the significant advances in deep learning-based segmentation, the current boundary-aware approaches are limited by their reliance on spatial distance transforms, which fail to fully exploit the rich texture and intensity information inherent in MRI data. This limitation is particularly problematic in regions where MS lesions and normal-appearing white matter exhibit overlapping intensity distributions, resulting in ambiguous boundaries and reduced segmentation accuracy. To address these challenges, we propose a novel Mahalanobis distance map (MDM) and a corresponding Mahalanobis distance loss, which generalize traditional distance transforms by incorporating spatial coordinates, the FLAIR intensity, and radiomic texture features into a unified feature space. Our method leverages the covariance structure of these features to better distinguish ambiguous regions near lesion boundaries, mimicking the texture-aware reasoning of expert radiologists. Experimental evaluation on the ISBI-MS and MSSEG datasets demonstrates that our approach achieves superior performance in both boundary quality metrics (HD95, ASSD) and overall segmentation accuracy (Dice score, precision) compared to state-of-the-art methods. These results highlight the potential of texture-integrated distance metrics to overcome MS lesion segmentation difficulties, providing more reliable and reproducible assessments for MS management and research.

Due to recent progress in multiple sclerosis (MS) research, a range of disease-modifying therapies (DMT) is increasingly available. According to the personalized therapeutic approach, the choice of DMT for a particular patient is based on complex analysis of disease-related and drug-related aspects, with emphasis on patient's preferences and shared decision-making. The aim of this study was to evaluate the perspective of the disease and various aspects of treatment in Polish patients with MS (pwMS), with reference to sociodemographic and clinical data. The nationwide survey was conducted, addressed to adult pwMS treated with DMT and undergoing regular follow-up in regional MS Centers. The questionnaire contained sociodemographic data, and questions about major troublesome and feared aspects of disease, and about the importance of various aspects of treatment. In addition, MS-related data were provided by neurologists. The responses have been summarized and analyzed for their relationships with sociodemographic and clinical data. A total of 2032 pwMS (70% women; mean age 42.1±10.8years) were included from 14 MS Centers. Over 90% had relapsing-remitting MS, mean disease duration was 12years and the median Expanded Disability Status Scale (EDSS) was 2.4±1.5. Fatigue (50%), limb weakness (47%), and balance and gait disturbances (30%) were the most common and troublesome symptoms reported by the respondents. Their main concerns about disease consequences included disability (46%) and dependence on others (17%). All aspects of DMT efficacy were very important for more than 70% of patients, with preventing disability progression, maintaining social participation, and reduction of relapses as top priorities (86-95%). Treatment safety concerns were focused on risk of cancer (74%), effect on comorbidities (63%), and severe infections (60%). Drug efficacy (93%), modernity (60%), and mechanism of action (59%) were most commonly indicated factors influencing patients' preference for DMT. Significant relationships were found between pwMS opinion about aspects of treatment and their age, sex, family status and vocational activity, as well as type and duration of MS, EDSS score, and type of DMT used. The Polish pwMS perspective of disease is focused on emerging disability and its social context. Regarding aspects of treatment, sufferers are highly concerned about its efficacy (especially in preventing the mentioned disease consequences), followed by safety and convenience. Individual differences in patients' responses should be highlighted, associated with combined impact of demographic and clinical data. The study findings should inform complex and personalized therapeutic approaches to MS management in clinical practice.

Multiple sclerosis (MS) is a neuroinflammatory disorder that is characterized by demyelination, neurodegeneration, and immune dysregulation. The experimental autoimmune encephalomyelitis (EAE) model has helped to elucidate MS pathophysiology and test therapies. This review synthesizes current literature on the development, applications, and translational significance of EAE models in MS research. It discusses various EAE induction protocols, including active and passive immunization, and highlights advancements such as humanized mice and induced pluripotent stem cell (iPSC)-derived neuronal models. The review evaluates the role of EAE in identifying immune pathways, validating therapeutic agents like glatiramer acetate and natalizumab, and exploring precision medicine approaches through biomarker discovery. The EAE model replicated the key features of MS, including inflammation, demyelination, and axonal loss, facilitating therapy development. However, its predictive validity faces limitations, such as heterogeneity in disease induction, underrepresentation of chronic progression, and species differences. Innovations, such as humanized mouse models and iPSC-derived neurons, show promise in addressing these challenges. EAE research has advanced biomarker-based personalized treatments, although further validation is required. Despite its widespread use, EAE has limitations in terms of variability in disease induction, incomplete MS feature replication, species-specific responses, and clinical translation. Addressing these limitations remains crucial for therapeutic development, focusing on analyzing model limitations and strategies to overcome translational barriers. This review offers immunologists a comprehensive overview of EAE's contributions of EAE to MS research and its potential to inform the development of novel therapeutic approaches for this debilitating disease.

Multiple Sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, with evidence suggesting that age-related brain changes may influence its progression. Clinically Isolated Syndrome (CIS) often marks an early phase of MS, with optic neuritis frequently presenting as a symptom. Despite recognition as an early indicator, the mechanisms driving optic neuritis and its contribution to MS progression remain unclear. Traditionally, immune-mediated inflammation has dominated MS research; however, emerging evidence highlights neurotransmitter dysregulation—especially involving dopamine—as a crucial factor in disease pathophysiology. The impact of dopamine imbalance on neural circuits and its role in advancing MS requires further investigation. This paper proposes a system-level, dopamine-based hypothesis to explain MS origins, focusing on early stages in CIS. Building on a review of recent literature linking dopaminergic dysfunction, neuroinflammation, and demyelination, the model suggests that optic nerve demyelination, as seen in optic neuritis, disrupts dopamine signaling, triggering a cascade of neural alterations that drive MS pathogenesis. By emphasizing dopamine role in CIS and early MS, this framework offers a novel perspective on the neurobiological mechanisms underlying the disease. This approach complements current research on neurotransmitter involvement in age-related conditions, expanding understanding of how neurotransmitter imbalances may influence MS and related disorders.

Diagnostic evolution in multiple sclerosis: A narrative review of the McDonald criteria from 2001 to 2024.

B-cell antigen presentation in central nervous system autoimmunity.

Objective: We aimed to quantify multiple sclerosis (MS)-related work productivity and to illustrate the longitudinal trends for relapses, disease progression, and utilization of health care resources in a nationally representative cohort of working North Americans living with MS. Background: The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) is a multicentered physician-reported registry which prospectively collects clinical information including imaging data over a long period of time from people with MS from sites across the U.S. and Canada. The Health Economics Outcomes Research (HEOR) Advisory Group has also incorporated Health-Related Productivity and Health Resource Utilization questionnaires, which collect information about health care economics of people with MS and its effects on daily life. Design/Methods: This is a prospective observational study utilizing data from NARCRMS. Socio-demographic, clinical, and health economic outcome data were collected through previously validated and structured questionnaires. Logistic regression was used to calculate the relative odds of symptom impact, with a generalized logit link for number of relapses. Cox proportional hazards regression was used to calculate hazard ratios for time to first relapse. Results: Six hundred and eighty-two (682) people with MS were enrolled in NARCRMS and had completed the HEOR questionnaires at the time of the analysis. Among the participants, 61% were employed full-time and 11% were employed part time. Fatigue was the leading symptom reported to impact both work and household chores. Among the employed participants, 13% reported having missed work with a median of 6.8 (IQR: 3.0–9.0) missed hours due to MS symptoms (absenteeism), while 35% reported MS having impacted their work output (presenteeism). The odds of higher disease severity (EDSS 2.0–6.5 vs. 0.0–1.5) were 2.29 (95% CI = 1.08, 4.88; p = 0.011) times higher for participants who identified reduction of work output. Fatigue was the most identified symptom attributed to work output reduction. Among all participants, 33% reported having missed planned household work with a median of 3.0 (IQR: 2.0–5.0) hours. The odds of higher disease severity were 2.49 (95% CI = 1.37, 4.53; p = 0.006) times higher for participants who identified reduction in household work output, and 1.70 (CI = 1.27, 2.49; p = 0.006) times higher for those whose fatigue affected housework output as compared to other symptoms. Conclusions: A preliminary review of the first 682 patients showed that people with MS had reduced work and housework productivity even at an early disease state. Multiple sclerosis (MS) can significantly impair individuals’ ability to function fully at work and at home, with fatigue overwhelmingly identified as the primary contributing factor. The economic value of finding an effective treatment for MS-related fatigue is substantial, underscoring the importance of these findings for policy development, priority setting, and the strategic allocation of healthcare resources for this chronic and disabling condition.

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies.

THE 2024 REVISED McDonald Criteria for multiple sclerosis (MS) diagnosis were explained in detail during a joint session between the European Academy of Neurology (EAN) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), chaired by Bruno Stankoff, Professor of Neurology at Université Pierre et Marie Curie (UPMC), Paris, France; and Celia Oreja-Guevara, Vice Chair of Neurology and Head of Multiple Sclerosis Center at the University Hospital San Carlos, Madrid, Spain. The session highlighted significant updates to these diagnostic criteria, as well as expert insights on their potential clinical applications.

BackgroundIntegrated knowledge translation (iKT) represents an approach to optimizing health interventions research through active collaboration between researchers and knowledge users throughout the research process. To date, few studies have explored the process of engaging in iKT, particularly in the context of multiple sclerosis (MS) research. Building on a larger iKT-informed study exploring mindfulness-based interventions for people living with MS, this study explores the perspectives of iKT panellists and extended collaborators on the use of iKT in health research.MethodsThis qualitative descriptive study utilized one-on-one semi-structured interviews conducted using Zoom or Microsoft Teams. Interviews were 20–30 min in duration. An interview guide informed by the Ontario Brain Institute’s framework for patient engagement across the stages of research was used. Interviews were transcribed verbatim, coded, and analyzed using inductive thematic analysis.ResultsA total of eight iKT partners were interviewed, five were members of the iKT panel and three were extended collaborators. Five themes on the use of iKT in health interventions research on MS were identified: (1) defining iKT, (2) motivation and meaningful participation in iKT, (3) the importance of networking in iKT, (4) balancing multiple perspectives, and (5) barriers and facilitators to engaging in iKT. Within these themes, interviewees highlighted the need for further definition and operationalization of concepts. Discussion on the representativeness of iKT partners and recruitment of ‘hard to reach’ knowledge users was also salient.ConclusionThe findings from this study provide useful considerations for other teams using an iKT approach. Future research directions include finding/maximizing meaningful ways for knowledge users to participate, exploring ways in which knowledge users could lead/co-lead (rather than consult on) research activities, and examining the potential role of an iKT facilitator.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40900-025-00763-7.

Understanding the role of immune dysregulation in MS Despite significant progress in MS-related research, challenges remain. Dr Belinda Kaskow and Professor Allan G Kermode from the Perron Institute and The University of Western Australia explore the benefits of investigating the early stages of immune dysregulation in MS to enhance prevention strategies. In a landmark achievement for the global multiple sclerosis (MS) community, two MS researchers, Professor Stephen L. Hauser and Professor Alberto Ascherio, were recognised with the 2025 Breakthrough Prize in Life Sciences, often referred to as ‘Oscars® of Science’, for their pioneering work.

Multiple sclerosis (MS) research requires new, more sensitive, behavioral biomarkers that map to subtle central nervous system injury. Although gait speed, as measured using the Timed 25 Foot Walk Test, is used clinically to track MS progression, it is less useful in people with MS who do not have overt gait impairment. This study aimed to identify specific spatiotemporal gait parameters that predict corticospinal tract (CST) function in individuals with MS. We recruited consecutive patients attending a neurology clinic and evaluated CST excitatory and inhibitory function using single pulse transcranial magnetic stimulation of the primary motor cortex representation of the first dorsal interosseous muscle. We generated excitatory and inhibitory recruitment curves by calculating the area under the curve for motor-evoked potential amplitudes and cortical silent period durations, respectively, across stimulation intensities from 105 to 155% of active motor threshold in 10% increments. Spatiotemporal gait parameters were assessed using an electronic walkway. We built predictive models with gait parameters as the predictors and CST function as the outcome. We evaluated 78 individuals with MS (58 females). Longer distance of the center of pressure movement during single support was the strongest predictor of higher excitability (lower active motor threshold; accounting for 25.8% of variance, R² = 0.258), while less time in double support accounted for a smaller portion of variability in excitatory recruitment curve (13.3% variance explained, R² = 0.133). For inhibitory CST function, slower stride time (30.5% variance explained, R² = 0.305) and wider stride (6.3% variance explained, R² = 0.063) predicted greater inhibition. Notably, in all models, measures of gait stability, not gait speed, predicted CST function. Our results suggest that even among people with MS who have normal gait speed and can easily cross an urban intersection, subtle postural control impairments exist which may not be apparent to them or to their clinician.

Several epidemiological and phenotypic differences in multiple sclerosis (MS) are observed across populations. The prevalence of MS is increasing in the Middle East and North Africa (MENA) region, in part due to better access to earlier diagnosis. Many MENA countries are now considered to fall in moderate to high MS risk zones. MS in MENA populations occurs at a younger age and is more severe, specifically in North African populations. Large disparities in MS care are observed among MENA countries. Access to care remains a significant obstacle in countries with low incomes, countries with active wars, and countries with a large number of refugees. The MENA MS population could serve as participants in the evaluation of several genetic, epigenetic, and environmental risk factors for MS. Indeed, low vitamin D levels due to reduced sun exposure in hijab-wearing women might explain the striking rising prevalence in Iran after the Islamic revolution, and the prevention of MS with vitamin D could be evaluated in this community. Moreover, because immigration is part of the history of MENA populations, it can serve as an archetype for the study of the impact of immigration on MS risk and severity. Unfortunately, MENA populations are underrepresented in clinical trials, limiting our understanding of this group. However, with the creation of the Middle East and North Africa Committee for Treatment and Research in Multiple Sclerosis and the emergence of highly specialized MS centers in several countries, better access to care and collaborative research efforts are expanding.