Revue neurologique最新文献

Magnetic resonance imaging (MRI) is central to the diagnosis and monitoring of multiple sclerosis (MS). While conventional MRI (1.5 or 3T) is sufficient in clinical practice for detecting and monitoring lesions, it fails to provide a comprehensive and sensitive assessment of the pathology across the entire central nervous system. This limitation has fueled growing interest in the use of 7T MRI systems to gain deeper insight into MS pathophysiological mechanisms. 7T MRI of the brain has already been shown to be transformative , with improved detection of cortical lesions, central vein sign and paramagnetic rim. Although not yet as advanced as for the brain in MS, spinal cord 7T MRI is also increasingly demonstrating its potential. Key advances to date include assessement of increased lesion burden and characterization of refined tissue in both white and gray matter substructures with anatomical MRI, refined atrophy measurements with higher spatial resolutions, enhanced susceptibility-based contrasts, as well as subregional quantitative and functional MRI. Such methods are opening opportunities to facilitate neuroradiological assessment, to better describe gray matter pathological involvement, and to identify potential myelin-related or vascular biomarkers, that can be used for disability risk stratification, monitoring and therapeutic decision-making. Yet, beyond the mere availability of 7T MRI systems in clinical practice and across sites worldwide, 7T SC MRI remains limited by technical challenges, radio frequency coil availability, regulatory constraints, and the need for standardized protocols. This review summarizes the techniques, together with the main findings, that have been applied so far for the study of MS. Most of them being exploratory, we discuss their potential use in clinical practice, perspectives, challenges and remaining unmet needs.

A growing body of evidence positions Epstein-Barr virus (EBV) as a central agent in the etiopathogenesis of multiple sclerosis (MS). Compelling epidemiological studies now demonstrate that EBV infection precedes MS onset and is a necessary precondition for disease development. This is supported by pathology findings revealing EBV-infected B cells within CNS lesions and immunogenetic data linking viral and human genetic susceptibility to MS risk. Mechanistically, EBV appears to act as an upstream trigger that reshapes B cell function, promotes molecular mimicry with CNS antigens, and drives compartmentalized neuroinflammation. In this Review, we synthesize epidemiological, pathological, immunogenetic, and clinical-therapeutic evidence to construct a coherent model of EBV-driven MS pathogenesis. We examine how current MS therapies intersect with EBV biology and discuss the challenges and opportunities in developing EBV-targeted strategies, including vaccines and antivirals, for disease prevention and early intervention. Finally, we highlight key unresolved questions and outline a translational research agenda aimed at intercepting MS through virologically informed approaches.

Multiple sclerosis (MS) is the leading cause of non-traumatic disability in young adults, characterized by autoimmune demyelination and neurodegeneration. While high-efficacy therapies have transformed relapsing MS management, disability progression remains an unmet need. Emerging evidence implicates compartmentalized central nervous system (CNS) inflammation, including microglial activation, in disease pathogenesis, necessitating novel immunotherapeutic strategies that target both peripheral and CNS-resident immune cells. This review synthesizes recent preclinical and clinical data on emerging MS immunotherapies offering promise for halting disability progression in MS. Their clinical integration will depend on balancing efficacy with safety, particularly in progressive phenotypes where therapeutic options remain limited.

Objective: Amyotrophic lateral sclerosis (ALS) is a severe, progressive disease, associated with high clinical burden. The aim of this study was to estimate ALS-related healthcare resource utilization (HCRU), associated direct costs and their determinants in France.

Methods: A retrospective cohort study was conducted among newly diagnosed patients with ALS identified between 2012 and 2022 (11 years) in the French National Health Data System (SNDS) through a validated algorithm. This incident population was compared with non-ALS controls (1:2) matched on age, sex, and region. Direct all-cause healthcare reimbursable costs were estimated. Survival, HCRU and direct costs were analyzed over the first five years after diagnostic.

Results: A total of 16,814 newly diagnosed ALS patients were identified who could be matched with 33,628 non-ALS controls. The median age was 68.0 year and 55.3% were males. Over the first year after diagnosis, the direct all-cause medical cost per patient was €19,497 of which 47.2% was related to inpatient care, compared to €4,921 for controls which led to an ALS-attributable cost of €14,474 per patient per year. ALS patients had significantly (P<0.0001) higher HCRU than controls in all items of inpatient and outpatient care but especially for utilization of medical devices, frequencies of nurse and physiotherapist visits and acute care hospitalizations. The annual direct cost per patient who survived the successive annual period after diagnosis increased during the second, third and fourth year to €22,358, €22,276 and €21,372 respectively and then declined in year 5 to €19,720. These results largely underestimated the real cost of the management of ALS by not considering the out-of-pocket expenses associated with informal care and home renovation as well as productivity loss.

Conclusions: Patients with ALS had higher HCRU and direct medical cost, compared with controls. The economic burden of ALS was substantial even when restricted to the medical costs covered by the public health insurance system. There is an important need for novel therapies that might lower disease progression in early disease stages.

Despite major advances in therapy for multiple sclerosis (MS) patients, substantial unmet needs remain, particularly regarding the prevention of disability progression and the treatment of progressive and aggressive forms of the disease. While early use of high-efficacy therapies has improved inflammatory disease control, their impact on long-term neurodegeneration is limited, and therapeutic options for progressive MS remain scarce. Autologous hematopoietic stem cell transplantation (AHSCT) has emerged as a highly effective escalation strategy for selected patients with aggressive, inflammatory MS. Randomized trials and large observational cohorts demonstrate sustained suppression of inflammatory activity and high rates of no evidence of disease activity, with markedly improved safety profiles over time. Current consensus recommendations support AHSCT for highly active MS refractory to high-efficacy DMTs, while its use in non-inflammatory progressive MS remains debatable. Chimeric antigen receptor (CAR) T-cell therapies represent a novel approach targeting compartmentalized B-cell - driven pathology. Early clinical reports using CD19- and BCMA-directed CAR-T cells in progressive MS demonstrate CNS penetration, manageable toxicity, and preliminary signals of clinical improvement, warranting further investigation in controlled trials. Mesenchymal stromal cells (MSCs) offer immunomodulatory and neurotrophic properties with a favorable safety profile. Clinical studies suggest potential benefits, particularly with intrathecal administration, though efficacy remains inconsistent due to heterogeneous study designs, patient populations, and outcome measures. Overall, cell-based therapies hold promise for addressing unmet needs in MS, but robust randomized trials, optimized delivery strategies, and appropriate patient selection are essential to define their therapeutic role.

The development of remyelinating therapies is becoming an increasingly important strategy in the treatment of diseases such as multiple sclerosis. In this context, reliable measurement of myelin content is essential for the objective assessment of therapeutic efficacy. Over the past two decades, quantitative MRI has emerged as a method of choice for this purpose, supported by several postmortem validation studies that combine MRI with histology, the latter serving as the reference standard. In this review, we summarize the most relevant quantitative MRI contrasts sensitive to myelin changes and describe the mechanisms by which each contrast provides an estimate of myelin content. In addition, we outline the key steps involved in histological myelin quantification, highlighting the different methodological approaches as well as their limitations and potential pitfalls.

The trajectory of multiple sclerosis (MS) is shaped by complex interactions between genetic susceptibility and environmental factors. This review examines modifiable non-infectious determinants across the life course and proposes integrated prevention strategies. Key factors include vitamin D deficiency, low UV exposure, smoking, adolescent obesity, air pollution, and chemical environmental exposures. Mendelian randomization studies support the causality of several determinants, particularly low vitamin D and high BMI. Adolescence emerges as a critical susceptibility window where the maturing immune system is uniquely sensitive to metabolic and environmental triggers. Among validated interventions, vitamin D supplementation stands out for its ability to reduce disease activity in early MS. Effective prevention requires both individual actions and structural public health policies, such as air quality regulations and urban "walkability". Future efforts should prioritize multimodal strategies targeting high-risk youths through the educational system (physical activity, weight management, and smoking prevention). These holistic approaches offer broad-spectrum benefits, reducing the burden of MS while preventing comorbidities, including cardiovascular, metabolic but also cancer.

Multiple sclerosis disease-modifying treatments have reduced inflammatory activity but have limited impact on progressive neurodegeneration. In this context, remyelination and neuroprotection appear as key therapeutic goals. The visual pathway offers an attractive translational model, as optic neuritis recapitulates the demyelinating and neurodegenerative features of multiple sclerosis while providing accessible functional and structural readouts through visual evoked potentials and optical coherence tomography. Over the past two decades, several clinical trials have evaluated remyelinating and neuroprotective agents using optic neuritis as a model. However, so far, no phase 3 trial has met its primary endpoint for either indication. This review synthesises the preclinical rationale, clinical trial evidence, and methodological lessons from these studies. Key challenges include the timing of intervention, heterogeneity in baseline damage, variability of electrophysiological assessments, and uncertain clinical impact of surrogate markers. Addressing these limitations through refined trial design, outcome measure harmonisation, and combined therapeutic strategies will be essential for future translational success.

Multiple sclerosis (MS) is characterized by substantial clinical heterogeneity, yet the factors governing long-term outcomes remain poorly understood. Over the past two decades, genome-wide association studies have identified an increasing number of genetic variants influencing MS susceptibility, predominantly implicating immune pathways. Whether these same variants also shape disease course after onset is a question with direct implications for risk prediction, causal inference, and drug development in patients with established disease. This review examines the relationship between MS susceptibility genetics and disease outcomes, synthesizes emerging efforts to identify genetic determinants of severity, neuroimaging phenotypes, and treatment response, and considers how these findings inform our understanding of the mechanisms driving disease heterogeneity.

Multiple sclerosis (MS) features extensive neurodegenerative pathology, in addition to the well-known neuro-inflammatory lesions. Recent breakthroughs highlight the importance of slow physical and cognitive progression in MS, which can continue despite effective slowing of lesion formation through high efficacy treatment. These types of progression seem driven to a large extent by neurodegenerative changes in MS, highlighting the need for more research to achieve clinical implementation with clear cut-off scores and monitoring strategies. This mini review outlines possible mechanisms underlying neurodegeneration, how to measure these processes on MRI and how we can move towards implementation.