Multiple Sclerosis Research Research Articles

A quantitative multi-parameter mapping protocol standardized for clinical research in multiple sclerosis

Quantitative magnetic resonance imaging (qMRI) involves mapping microstructure in standardized units sensitive to histological properties and supplements conventional MRI, which relies on contrast weighted images where intensities have no biophysical meaning. While measuring tissue properties such as myelin, iron or water content is desired in a disease context, qMRI changes may typically reflect mixed influences from aging or pre-clinical degeneration. We used a fast multi-parameter mapping (MPM) protocol for clinical routine at 3T to reconstruct whole-brain quantitative maps of magnetization transfer saturation (MT), proton density (PD), longitudinal (R1), and transverse relaxation rate (R2*) with 1.6 mm isotropic resolution. We report reference MPM values from a healthy population with age and gender distributions typical of multiple sclerosis in whole brain white matter (WM), T2-weighted WM hyperintensities, cortical grey matter and deep grey matter regions and present post-processing optimizations including integration of lesions and normalization of PD maps against cerebrospinal fluid (CSF) for standardized research in multiple sclerosis (MS) and potentially also in related disorders. PD maps were affected by WM abnormalities in MS using WM calibration. The results acknowledge the impact of non-linear age effects on MPM and suggest using CSF calibration for future clinical application in MS.

Ozanimod in Relapsing Multiple Sclerosis: New Insights

Ozanimod is an approved treatment for relapsing forms of multiple sclerosis (RMS) that has been shown to reduce relapses, new brain lesions, and brain volume loss relative to intramuscular interferon (IFN) β-1a. This article summarizes selected data from clinical trials of ozanimod in RMS, which were presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) held in Denmark in September 2024 and the Annual Meeting of the European Charcot Foundation held in Italy in November 2024. Final safety data were presented for the completed open-label extension (OLE) study of ozanimod in adults with RMS (DAYBREAK), showing that rates of adverse events (AE) remained stable or decreased over 8 years of ozanimod treatment. These findings confirm the established safety profile of ozanimod. An analysis of brain volume changes across DAYBREAK and parent trials were also presented, demonstrating that the annualized rate of brain volume loss in participants treated with continuous ozanimod for up to 7 years was below the pathologic cutoff and was similar to those previously reported from healthy controls. Data were presented from a retrospective, observational study into the effects of switching from fingolimod to ozanimod in patients with RMS due to safety or intolerance reasons. The authors concluded that this study confirms that switching from fingolimod to ozanimod for safety reasons such as lymphopenia or hypertransaminasemia may be a good strategy to continue sphingosine-1-phosphate receptor (S1PR)-modulating drug therapy. Finally, an ad hoc interim analysis of patients with early RMS from ENLIGHTEN showed promising results, demonstrating that more than three-quarters of patients had either stable or improved cognitive processing speed after 1 year of ozanimod 0.92 mg.

How exercise shapes the anti-inflammatory environment in multiple sclerosis – a conceptual framework focusing on tryptophan-derived molecules in T cell differentiation

Abstract Multiple Sclerosis (MS) is a chronic neuroinflammatory autoimmune characterized by inflammation-induced lesion formation after immune cell infiltration into the central nervous system. T cells play an intriguing role in MS immunopathology and research over the past decade has shown that tryptophan (TRP)-derived metabolites are crucial molecules affecting T cell differentiation, also in MS, and are modulated by exercise. The aryl hydrocarbon receptor (AHR), for which TRP metabolites are well-known ligands, has been elucidated as main driver of T cell differentiation and an enhanced anti-inflammatory cellular milieu in human MS and preclinical mouse models. By integrating evidence from different research fields, the aim of this article is to summarize and critically discuss the potential of exercise to activate the AHR in T cells by modulating circulating TRP-derived metabolites and to provide a conceptual framework on potential benefits in MS immunopathology.

Disrupted working memory event-related network dynamics in multiple sclerosis

In multiple sclerosis (MS), working memory (WM) impairment can occur soon after disease onset and significantly affects the patient’s quality of life. Functional imaging research in MS aims to investigate the neurophysiological underpinnings of WM impairment. In this context, we utilize a data-driven technique, the time delay embedded-hidden Markov model, to extract spectrally defined functional networks in magnetoencephalographic (MEG) data acquired during a WM visual-verbal n-back task. Here, we show that the activation of two networks is altered in relapsing remitting-MS patients. First, the activation of an early theta prefrontal network linked to stimulus encoding and attentional control significantly decreases in MS compared to HC. This diminished activation correlates with reduced accuracy and higher reaction time, suggesting that impaired attention control impacts task performance in MS patients. Secondly, a frontoparietal network characterized by beta coupling is activated between 300 and 600 ms post-stimulus, resembling the event-related P300, a cognitive marker extensively explored in EEG studies. The activation of this network is amplified in patients treated with benzodiazepine, in line with the well-known benzodiazepine-induced beta enhancement. Altogether, the TDE-HMM technique extracts task-relevant functional networks showing disease-specific and treatment-related alterations, revealing potential new markers to assess and track WM impairment in MS.

The impact of social and environmental factors on triggering multiple sclerosis onset, before and during the COVID-19 pandemic: a retrospective study from Iran

BackgroundMultiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. The first presentation’s possible triggers are still controversial among scientists. The objective of this study is to investigate and compare the potential social, environmental, and physical factors that may have contributed to the onset of MS before and during the Coronavirus Disease 2019 (COVID-19) pandemic.MethodsA questionnaire was designed in the MS research center of Sina Hospital and also distributed as an online Google Form on social media among Iranian MS patients. Demographic information, MS disease-related data, and possible patients reported MS triggers were recorded. They were containing stressful life events, COVID-19 and other infections, COVID-19 and other vaccines, pregnancy or labor, head trauma, surgery, and weight loss. Patients were divided into two groups regarding the time of MS diagnosis (before and during the COVID-19 pandemic).ResultsOf 920 participants, 670 (72.8%) were female, and the mean age ± SD was 35.63 ± 8.1. The majority of patients (69.2%) had non-progressive forms of MS, and only 7.6% needed assistance for ambulation. 69% of participants were diagnosed with MS before the onset of the COVID-19 pandemic. There was a statistically significant difference between the most common first MS symptom before and after the beginning of the pandemic (visual type (n: 317 (49.9%)) before and sensory type (n: 170 (59.6%)) after the COVID-19 pandemic). A stressful life event was the most common patient-reported trigger of MS first presentation in both groups. (56.1% before and 54% after the COVID-19 pandemic). Comparing two groups, economic problems (AOR: 1.81; 95% ACI: 1.23–2.65) and job losses (AOR: 2.89; 95% ACI: 1.37–6.08) were significantly more common triggers for the initial presentation of MS after the pandemic, while the stress of occupational or educational exams (AOR: 0.52; 95% ACI: 0.34–0.79) was more prevalent before the pandemic.ConclusionPatients believe that stressful life events are closely linked to triggering their first MS symptoms. Since the beginning of the COVID-19 pandemic, economic problems and job losses have increased; however, occupational or educational exams stress decreased. Caring for social stress by societies may affect MS development or delay MS onset.

MS Australia: Progress in MS Research Conference 2023

MS Australia: Progress in MS Research Conference 2023

The arisal of data spaces: why I am excited and worried.

This paper explores the significant role of real-world data (RWD) in advancing our understanding and management of Multiple Sclerosis (MS). RWD has proven invaluable in MS research and care, offering insights from larger and diverse patient populations. A key focus of the paper is the European Health Data Space (EHDS), a significant development that promises to change how healthcare data is managed across Europe. This initiative is particularly relevant to the MS community. The paper highlights various data initiatives, discussing their importance for those affected by MS. Despite the potential benefits, there are challenges and concerns, especially about ensuring that the growth of various data platforms remains beneficial for MS patients. The paper suggests practical actions for the global MS community to consider, aimed at optimizing the use of RWD. The emphasis of this discussion is on the secondary use of health data, particularly in the European context. The content is based on the author's own experiences and interpretations, offering a personal yet informed view on using RWD to improve MS research and patient care.

Impact of Lifestyle Interventions on Multiple Sclerosis: Focus on Adipose Tissue.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination in the central nervous system (CNS), affecting individuals globally. The pathological mechanisms underlying MS remain unclear, but current evidence suggests that inflammation and immune dysfunction play a critical role in the pathogenesis of MS disease. Adipose tissue (AT) is a dynamic multifunctional organ involved in various immune diseases, including MS, due to its endocrine function and the secretion of adipokines, which can influence inflammation and immune responses. Physical activity represents an efficacious non-pharmacological strategy for the management of a spectrum of conditions that not only improves inflammatory and immune functions but also directly affects the status and function of AT. Additionally, the exploration of nutritional supplementation represents an important field of MS research aimed at enhancing clinical symptoms and is closely tied to the regulation of metabolic responses, including adipokine secretion. This review, therefore, aims to elucidate the intricate relationship between lifestyle and MS by providing an overview of the latest published data about the involvement of AT and the main adipokines, such as adiponectin, leptin, and tumor necrosis factor α (TNFα) in the pathogenesis of MS. Furthermore, we explore whether physical activity and dietary management could serve as useful strategies to improve the quality of life of MS patients.

Progressive multiple sclerosis: A bibliometric analysis.

Progressive multiple sclerosis (MS) is a chronic immune-mediated disease with a poorly understood pathophysiology. This bibliometric analysis of the literature aims to gain an overview of the current state of research on progressive MS. The Scopus database was searched using the terms "progressive" and "multiple sclerosis" in the title. The search was done till the 7th of January 2023. We analyzed annual trends, countries, institutions, authors, journals, articles, and keywords based primarily on the citation count. One thousand nine hundred ninety-one studies out of 1993 search results were included. The included studies had 65,788 citations with a mean of 33 citations per study. Most studies were published between the years 2016 and 2020 (n = 607) with a mean number of 20 citations. The United States of America had the highest number of publications (n = 547) and citations (n = 24,921). The top 3 authors were Thompson A.J., Miller D.H., and Filippi M., and Multiple Sclerosis Journal had the most publications (n = 227) and citations (n = 6849). To our knowledge, this is the first bibliometric study to address the topic of progressive MS in particular and potentially emphasize the direction of progressive MS research.

The use of 7T MRI in multiple sclerosis: review and consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

The use of ultra-high-field 7-Tesla (7T) MRI in multiple sclerosis (MS) research has grown significantly over the past two decades. With recent regulatory approvals of 7T scanners for clinical use in 2017 and 2020, the use of this technology for routine care is poised to continue to increase in the coming years. In this context, the North American Imaging in MS Cooperative (NAIMS) convened a workshop in February 2023 to review the previous and current use of 7T technology for MS research and potential future research and clinical applications. In this workshop, experts were tasked with reviewing the current literature and proposing a series of consensus statements, which were reviewed and approved by the NAIMS. In this review and consensus paper, we provide background on the use of 7T MRI in MS research, highlighting this technology's promise for identification and quantification of aspects of MS pathology that are more difficult to visualize with lower-field MRI, such as grey matter lesions, paramagnetic rim lesions, leptomeningeal enhancement and the central vein sign. We also review the promise of 7T MRI to study metabolic and functional changes to the brain in MS. The NAIMS provides a series of consensus statements regarding what is currently known about the use of 7T MRI in MS, and additional statements intended to provide guidance as to what work is necessary going forward to accelerate 7T MRI research in MS and translate this technology for use in clinical practice and clinical trials. This includes guidance on technical development, proposals for a universal acquisition protocol and suggestions for research geared towards assessing the utility of 7T MRI to improve MS diagnostics, prognostics and therapeutic efficacy monitoring. The NAIMS expects that this article will provide a roadmap for future use of 7T MRI in MS.

The role of vitamin D in multiple sclerosis and its mechanisms of action

Introduction and Purpose: Multiple sclerosis (MS) is a prevalent autoimmune disease affecting the central nervous system, particularly in young people. Characterized by neurodegenerative and demyelinating processes, MS is influenced by genetic and environmental factors. Research indicates that sufficient levels of vitamin D can reduce the risk of developing MS. Studies show that higher sun exposure and dietary vitamin D intake are associated with a lower incidence of MS. Moreover, vitamin D supplementation may benefit those already diagnosed by alleviating symptoms and improving their quality of life. This review explores the potential benefits of vitamin D and its neuroprotective mechanisms in MS. State of Knowledge: MS research and treatments have focused on immunomodulation, with less emphasis on neuroprotection, including the role of vitamin D. It is well-established that vitamin D has anti-inflammatory effects on the immune system in MS. It influences the proliferation and differentiation of neural stem cells and oligodendrocytes, enhances neurotrophin expression, reduces reactive astrogliosis, decreases oxidative stress, and stabilizes the blood-brain barrier. Research suggests that adequate vitamin D levels and supplementation might improve MS outcomes. Conclusion: New diagnostic tools and therapeutic strategies are urgently needed to address the complex nature of MS, which includes inflammation, neuronal death, demyelination, and oxidative stress. Promoting vitamin D sufficiency and supplementation, alongside developing new neuroprotective agents, remains a valuable approach in combating MS. Understanding the mechanisms of MS and the effects of vitamin D could lead to better management strategies and enhanced quality of life for patients.

Initial Evaluation of lncRNA A2M-AS1 Gene Expression in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is one of the three leading neurodegenerative diseases worldwide. Gene expression profile studies play an important role in recognizing and preventing disease. Considering the inherent ability of biomarkers to diagnose and prognose the occurrence of a disease, with the aim of gene therapy and changing gene expression, it can be helped to treat it. In this study, by examining the gene interaction and expression of non-coding genes in patients with MS, using bioinformatics analyses, laboratory research and potential non-coding diagnostic biomarkers of MS were selected for further investigations. First, by using micro-array data analysis of the GEO database, the expression status of the long non-coding ribonucleic acid (RNA) (lncRNA) A2M-AS1 gene was investigated in patients with MS. lncRNA-mRNA interaction analysis was performed in the lncRRisearch database. After sample collection, the total RNA extracted using the RNA extraction kit from 20 patient samples and 20 healthy samples was synthesized into cDNA with the synthesis kit. The quantitative reverse transcriptase polymerase chain reaction experiment was performed for the final validation of expression change. Based on bioinformatic and laboratory analysis, the expression of the A2M-AS1 gene in MS samples showed a significant decrease in expression compared to healthy samples. Also, based on the receiver operating characteristic analysis, lncRNA A2M-AS1 can be introduced as an acceptable diagnostic biomarker to distinguish MS samples from healthy samples. lncRNA A2M-AS1, by reducing its expression as an acceptable diagnostic biomarker, can increase the risk of developing MS.

Recent Advances in Understanding and Treating Multiple Sclerosis

MS, often known as multiple sclerosis, is a chronic autoimmune illness that is characterised by inflammation, demyelination, and neurodegeneration in the central nervous system (CNS). This review provides a comprehensive summary of current achievements in multiple sclerosis (MS) research, focusing on substantial advancements in understanding the biology of the disease, improving diagnostic tools, and developing a variety of treatment strategies. Multiple Sclerosis (MS) is characterised by an attack by the immune system on myelin, which is the protective sheath that surrounds nerve fibres. This attack results in a wide variety of neurological symptoms. Genetic factors, such as polymorphisms in the HLA-DRB1 gene, as well as environmental variables, such as a lack of vitamin D and viral infections, have been identified as contributors to disease susceptibility. However, the exact cause of multiple sclerosis (MS) is still unknown. Among the advancements in diagnostics are the utilisation of more sophisticated magnetic resonance imaging (MRI) techniques and the investigation of novel biomarkers in cerebrospinal fluid (CSF) and clinical blood. Beyond the standard disease-modifying treatments (DMTs), there are now additional treatment alternatives available, which include more recent medications that have mechanisms of action that are more specifically targeted. Treatments that are only coming into existence, such as monoclonal antibodies and cell-based therapies, provide the possibility of progress in the management of diseases. The purpose of this review is to provide a summary of the most important discoveries, identify trends in research, and explore the significance of current developments for MS care as well as future research directions.

Quality of reporting health behaviors for multiple sclerosis (QuoRH-MS): A scoping review to inform intervention planning and improve consistency of reporting.

Multiple sclerosis (MS) is a neurological condition that necessitates a multidisciplinary approach to aid those living with MS in managing their disease. Health behavior, or lifestyle modification, is an emerging approach to MS self-management. MS researchers utilize measurement tools to ensure that interventions are best suited to the outcomes, thereby potentially influencing practice. The aim of this study was to investigate which tools are being used for health behavior management studies in people living with MS and develop an aid for tool selection. A scoping review guided by the PRISMA-Sc checklist and the JBI manual for evidence synthesis was employed with a systematic search strategy executed across four scientific databases: Medline, PubMed, CINAHL, and Cochrane Libraries. The types of assessment tools used were extracted from the included studies. Each tool was categorized into the health behavior intervention discipline (nutrition, exercise, and psychology) and then subcategorized by the tool's purpose. The frequency of use was determined for each tool. Reporting of validation of the assessment tools were collated to inform a tool selection checklist. The review identified a total of 248 tools (12 nutrition, 55 exercise, and 119 psychology unique reports) from 166 studies. Seventy-seven multidimensional tools were identified including measures of quality of life, fatigue, and functional scales. Only 88 studies (53%) referred to the validity of the tools. The most commonly reported tools were the dietary habits questionnaire (n=4, nutrition), 6-minute walk test (n=17, exercise), Symbol Digits and Modalities Test, and Hospital Anxiety and Depression Scale (n=15 each, psychology) with the Expanded Disability Status Scale reported 43 times. Evidence from interventions may inform practice for health professionals. This review provides insights into the range of tools reported across health behavior intervention studies for MS and offers a guide toward more consistent reporting of study methods.

The first global landscape analysis of multiple sclerosis research funding

Introduction: Multiple sclerosis (MS) is an immune-mediated central nervous system disorder and a growing global health challenge affecting nearly 3 million people worldwide. Incidence and prevalence continue to increase with no known cause or cure. Globally governments and non-profit organizations fund research toward better understanding of and treatments for multiple sclerosis. Methods: This study identified MS research projects funded between 2021 and 2023 by government and non-profit organization sources. Projects were described by type of scientific approach, Pathways to Cure research category (i.e. Stop, Restore, End), and other key characteristics. Results: Over 2,300 MS research projects were identified through 16 non-profit MS organizations and 18 government databases. The overall global portfolio of these projects is valued at nearly one and a half billion Euros. The majority of projects were classified in the Stop category (60%). Research collaboration occurs in many forms among the research community; around 272 projects were reported to be co-funded. Conclusion: Global MS research collaboration will accelerate progress toward increased knowledge, effective treatments, improved health outcomes, and ultimately cures for MS. This landscape analysis highlights the current distribution of MS research investment between topics and begins to suggest where the MS community should focus to increase potential impact for current and future endeavors.

A preclinical mice model of multiple sclerosis based on the toxin-induced double-site demyelination of callosal and cerebellar fibers

BackgroundMultiple sclerosis (MS) is an irreversible progressive CNS pathology characterized by the loss of myelin (i.e. demyelination). The lack of myelin is followed by a progressive neurodegeneration triggering symptoms as diverse as fatigue, motor, locomotor and sensory impairments and/or bladder, cardiac and respiratory dysfunction. Even though there are more than fourteen approved treatments for reducing MS progression, there are still no cure for the disease. Thus, MS research is a very active field and therefore we count with different experimental animal models for studying mechanisms of demyelination and myelin repair, however, we still lack a preclinical MS model assembling demyelination mechanisms with relevant clinical-like signs.ResultsHere, by inducing the simultaneous demyelination of both callosal and cerebellar white matter fibers by the double-site injection of lysolecithin (LPC), we were able to reproduce CNS demyelination, astrocyte recruitment and increases levels of proinflammatory cytokines levels along with motor, locomotor and urinary impairment, as well as cardiac and respiratory dysfunction, in the same animal model. Single site LPC-injections either in corpus callosum or cerebellum only, fails in to reproduce such a complete range of MS-like signs.ConclusionWe here report that the double-site LPC injections treatment evoke a complex MS-like mice model. We hope that this experimental approach will help to deepen our knowledge about the mechanisms of demyelinated diseases such as MS.

Cladribine effects on patient-reported outcomes and their clinical and biometric correlates in highly active relapsing multiple sclerosis at first switch: the observational, multicenter, prospective, phase IV CLADFIT-MS study.

Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients' lives; they play an important role in multiple sclerosis (MS) research and practice. We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient's experience and self-assessed impact of treatment on daily life.

Rule-Based DSL for Continuous Features and ML Models Selection in Multiple Sclerosis Research

Machine learning (ML) has emerged as a powerful tool in multiple sclerosis (MS) research, enabling more accurate diagnosis, prognosis prediction, and treatment optimization. However, the complexity of developing and deploying ML models poses challenges for domain experts without extensive programming knowledge. We propose a novel domain-specific language (DSL) that simplifies the process of selecting features, choosing appropriate ML models, and defining training rules for MS research. The DSL offers three approaches: AutoML for automated model and feature selection, manual selection for expert-guided customization, and a customizable mode allowing for fine-grained control. The DSL was implemented and evaluated using real-world MS data. By establishing task-specific DSLs, we have successfully identified workflows that enhance the filtering of ML models and features. This method is crucial in determining the T2-related MRI features that accurately predict both process speed time and walk speed. We assess the effectiveness of using our DSL to enhance ML models and identify feature importance within our private data, aiming to reveal the relationships between features. The proposed DSL empowers domain experts to leverage ML in MS research without extensive programming knowledge. By integrating MLOps practices, it streamlines the ML lifecycle, promoting trustworthy AI through explainability, interpretability, and collaboration. This work demonstrates the potential of DSLs in democratizing ML in MS and paves the way for future research in adaptive and evolving DSL architectures.

An Overview of Multiple Sclerosis In Vitro Models.

Multiple sclerosis (MS) still poses a challenge in terms of complex etiology, not fully effective methods of treatment, and lack of healing agents. This neurodegenerative condition considerably affects the comfort of life by causing difficulties with movement and worsening cognition. Neuron, astrocyte, microglia, and oligodendrocyte activity is engaged in multiple pathogenic processes associated with MS. These cells are also utilized in creating in vitro cellular models for investigations focusing on MS. In this article, we present and discuss a summary of different in vitro models useful for MS research and describe their development. We discuss cellular models derived from animals or humans and present in the form of primary cell lines or immortalized cell lines. In addition, we characterize cell cultures developed from induced pluripotent stem cells (iPSCs). Culture conditions (2D and 3D cultures) are also discussed.

P-377 Understanding the interplay between multiple sclerosis patterns and ovarian reserve, which influences the other?

Abstract Study question Is multiple sclerosis (MS) associated with diminished ovarian reserve in women? Does ovarian reserve influence multiple sclerosis progression patterns? Summary answer AntiMüllerian Hormone (AMH) is not diminished in MS patients compared to healthy matched controls. Ovarian reserve predicts multiple sclerosis patterns independently from chronological age. What is known already Population registries indicate increased childlessness in individuals with MS, but the influence of MS on ovarian reserve and the need for fertility preservation counseling are topics of ongoing debate. Notably, MS research highlights the concept of immunosenescence: with age the disease shifts from high relapse rates to disability accumulation and fewer relapses. It is uncertain whether ovarian aging, assessed through AMH, could serve as a marker of immunosenescence, offering more precise predictions of MS patterns compared to chronological age alone. Study design, size, duration This prospective observational study enrolled all female MS patients aged 18 to 50 presenting to the neurology service between June and November 2023, matching them in a 1:2 ratio with controls of similar age and BMI. The controls were healthy females, without known causes of female infertility. Exclusion criteria were: postmenopausal state, prior neoplasm requiring gonadotoxic therapy or prior hematopoietic stem cell transplantation. Participants/materials, setting, methods The study was conducted in an academic hospital, regional referral for neurology and fertility preservation. Detailed neurological and gynecological anamnesis was collected for 73 patients and 146 controls. AMH measurements were performed by the same laboratory with the Roche Elecsys AMH system. Multiple generalized linear models were carried out to explore the correlation between AMH and neurological data. All results were adjusted for age and use of hormonal contraception. Bonferroni corrected post-hoc analyses were performed. Main results and the role of chance Cases and controls were matched for age (33.6±6.1 vs. 34.4±4.5 years) and BMI (22.3±3.4 vs. 22.2±3.5 Kg/m2). The AMH values were not significantly different between cases and controls (2.7±3.5 vs. 2.7±1.6 ng/ml, p = 0.7) and showed no correlation with MS duration (p = 0.3) and disability measured with EDSS score (p = 0.9). Interestingly, higher AMH levels correlated with both having relapsed in the prior year (yes: 4.9±5.3 vs. no: 1.7±1.6 p = 0.008) and with the number of relapses in the 2 previous years (zero: 1.9±1.8, one: 2.3±2.9, more than 2: 5.8±6.2 ng/ml, p = 0.02). Consequently, patients with “No Evidence of Disease Activity”(NEDA) in the previous year showed lower AMH levels (1.68±1.3 vs. 4.1±4.7 ng/ml, p = 0.01), since absence of relapses is one of the components to define NEDA. In summary, patients with higher ovarian reserve showed a MS pattern typical of young age (higher relapse rates) independently from the actual chronological age. Limitations, reasons for caution The results should be confirmed by larger/multicenter datasets, powered to properly assess the possible influence of the different disease modifying therapies. Further research is warranted to understand the biological link behind the observed results. Wider implications of the findings Ovarian aging, measured through AMH, may provide a better indicator of a patient’s biological age than chronological age only. This may help neurologists in predicting MS patterns and treating it accordingly, providing a unique perspective on the mechanisms that link immunosenescence to the ovarian reserve reduction. Trial registration number Not Applicable