Revue neurologique最新文献

{"title":"The genetic architecture of multiple sclerosis in 2026: From susceptibility to disease progression.","authors":"S Bourguiba-Hachemi, J Paris, P-A Gourraud, N Vince","doi":"10.1016/j.neurol.2026.03.006","DOIUrl":"https://doi.org/10.1016/j.neurol.2026.03.006","url":null,"abstract":"<p><p>The genetics of multiple sclerosis (MS) has advanced dramatically through the combined impact of high-throughput genotyping, large biobank resources, worldwide collaborations, and powerful computational analyses. Over the past two decades, genome-wide association studies (GWAS) have significantly reshaped our understanding of the genetic architecture of complex multifactorial diseases such as MS. The number of MS susceptibility-associated genomic regions is now more than 200, underscoring its highly polygenic nature. Within the major histocompatibility complex (MHC), the HLA-DRB1*15:01 allele and its extended haplotypes remain the most robust and reproducible risk factors. This historical association reflects a long-standing link between antigen presentation, immune regulation, and central nervous system autoimmunity. Beyond the MHC, common non-HLA loci implicate a wide network of immune pathways involving T-cell and B-cell activation, cytokine signaling, and antigen presentation. Moreover, rare variant analyses and family-based designs, although limited in power, have uncovered additional susceptibility genes, such as PRF1, CYP27B1, and NLRP1, shedding light on distinct mechanisms of immune modulation and metabolic regulation. The step forward will be now to explore diverse genetic ancestry populations, bearing differences in risk allele frequencies; multi-ethnic and family-based designs are needed to disentangle true genetic effects from environmental confounders. In parallel, progress has been made toward MS progression, as variants potentially influencing disability accumulation and neurodegeneration were identified. These findings have deepened our understanding of MS pathophysiology. They now provide a foundation for future integrative models that combine genetics, environment, and multi-omics data to elucidate disease heterogeneity and guide personalized therapeutic strategies.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMOSD and MOGAD: Updates on diagnostic criteria.","authors":"R Marignier, M Leal Rato","doi":"10.1016/j.neurol.2026.01.270","DOIUrl":"https://doi.org/10.1016/j.neurol.2026.01.270","url":null,"abstract":"<p><p>Recently, diagnostic criteria for demyelinating diseases, including multiple sclerosis, have been updated with a focus on imaging and fluid markers. The upcoming criteria for neuromyelitis optica (NMO) introduce several clinico-radiological updates, and highlight the need for accurate determination of AQP4-IgG status. Furthermore, seronegative NMO is now considered a syndrome distinct from AQP4-IgG disease. The MOG-antibody associated disease (MOGAD) criteria have been validated in different populations, and a clear role for case-by-case expert review has emerged in light of some limitations to clinical application of the criteria. The impact and the limitations of these criteria will be discussed in this mini-review.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target trial emulation for causal inference using observational data in neurology.","authors":"A Gavoille, M Nourredine, F Subtil, T Kalincik, S Vukusic","doi":"10.1016/j.neurol.2026.03.001","DOIUrl":"https://doi.org/10.1016/j.neurol.2026.03.001","url":null,"abstract":"<p><p>Most clinical questions in neurology are inherently causal, yet observational studies have long been interpreted in terms of associations rather than causal effects of well-defined interventions. This limitation has contributed to persistent biases in neurology research, including inappropriate covariate adjustment, temporal misalignment, immortal-time bias, and susceptible depletion. Recent developments in causal inference offer a formal framework to overcome these issues through counterfactual reasoning, causal diagrams, and g-methods. The target trial emulation approach translates these concepts into a practical strategy: investigators first specify the protocol of the randomized trial that would ideally address their question, and then emulate this protocol using observational data. This requires explicit definition of eligibility, treatment strategies, assignment procedures, time zero, follow-up, outcomes, causal contrasts, and handling of intercurrent events, together with prespecified causal assumptions and an appropriate analysis plan. By aligning the design of observational studies with the structure of randomized trials, target trial emulation reduces design-related bias, clarifies the causal question, and provides a transparent foundation for real-world evidence generation. Validation studies, including recent work in multiple sclerosis, have demonstrated good concordance between emulated trials using observational data and randomized controlled trials. Target trial emulation therefore represents an essential complement to randomized evidence, particularly for questions that are difficult or impossible to address through randomization, and has the potential to substantially improve causal inference in neurology.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple sclerosis disability progression and predictors: A retrospective cohort study over five decades from a Canadian registry","authors":"T. Quevillon ,&nbsp;P.-O. Despault ,&nbsp;P. Duquette ,&nbsp;M. Girard ,&nbsp;A. Prat ,&nbsp;C. Larochelle ,&nbsp;G. Macaron ,&nbsp;A. Cusson ,&nbsp;T. Ducruet","doi":"10.1016/j.neurol.2026.02.154","DOIUrl":"10.1016/j.neurol.2026.02.154","url":null,"abstract":"<div><h3>Background</h3><div>Long-term disability progression data from Canadian multiple sclerosis (MS) populations remain limited. We examined disability progression patterns and prognostic factors in a large Canadian MS registry while assessing the robustness of findings across different analytical approaches.</div></div><div><h3>Methods</h3><div>We analyzed 2,769 patients from the CHUM MS registry (1976–2020) with relapsing-remitting, secondary-progressive MS (SPMS), or clinically isolated syndrome. Primary outcomes were time to EDSS milestones 3, 4, 6, 8, and to SPMS from disease onset. Cox hazards models examined associations with sex, age at onset, calendar period, relapse frequency, pregnancy, and treatment timing. Sensitivity analyses used additional severity adjustments and alternative time origins to distinguish robust biological associations from methodology-sensitive findings.</div></div><div><h3>Results</h3><div>The cohort included 2,101 women and 668 men with median age at onset of 29.9 years and median follow-up of 24.6 years. Median time from disease onset to EDSS 3 was 21.3 years (95% CI: 20.1–22.4), to EDSS 4 was 26.1 years (24.7–27.8), to EDSS 6 was 34.1 years (31.8–35.8), and to SPMS was 36.4 years (35.5–38.1). Male sex consistently predicted faster progression across all milestones (HR 1.50–1.71, <em>P</em> <!-->&lt;<!--> <!-->0.001). Age<!--> <!-->≥<!--> <!-->30 years at onset was associated with faster progression to earlier milestones. Pregnancy after disease onset was associated with slower progression (HR 0.70-0.86). High relapse frequency and treatment-timing effects varied markedly depending on analytical approach.</div></div><div><h3>Conclusion</h3><div>This cohort demonstrates progression times comparable to international registries. Male sex emerged as the most robust prognostic factor, while other associations showed varying methodological sensitivity, highlighting complexity in interpreting observational MS research.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"182 4","pages":"Pages 301-311"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolutionary origins of multiple sclerosis.","authors":"W Barrie","doi":"10.1016/j.neurol.2026.03.004","DOIUrl":"https://doi.org/10.1016/j.neurol.2026.03.004","url":null,"abstract":"<p><p>There are two main evolutionary theories for why modern humans develop multiple sclerosis (MS). The first, antagonistic pleiotropy, argues that genetic variants that predispose people to MS are protective against infections; this explains why these genetic variants persist at high frequency. The second, the Old Friends hypothesis, argues that reduced exposure to ancient, co-evolved micro-organisms like helminths results in immune dysregulation and overreactions to harmless infections and substances; this explains why MS prevalence increases with sanitation. Here, I assess these theories in the light of recent ancient DNA (aDNA) studies. These suggest that populations from the Pontic-Caspian Steppe which migrated across Eurasia in the Bronze Age evolved a strong pro-inflammatory immune response due to increased zoonotic infections resulting from their pastoralist lifestyle. It is possible that this may have occurred in a context of high levels of anti-inflammatory helminth infections, which resulted in a balanced pro- and anti- inflammatory response. In the modern sanitary world, with a lower helminth burden, the immune system 'overshoots' the level of inflammation required. This explains why genetic risk for MS is higher in northern Europe where people have higher genetic ancestry from the ancient Steppe population, and why disease penetrance is increasing.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolated medial temporal lobe amnesia (MTLA): Predictor of cerebral amyloidosis or marker of phenotype-specific vulnerability?","authors":"G. Pin ,&nbsp;T. Horowitz ,&nbsp;E. Guedj ,&nbsp;O. Felician ,&nbsp;M. Ceccaldi ,&nbsp;L. Koric","doi":"10.1016/j.neurol.2026.02.149","DOIUrl":"10.1016/j.neurol.2026.02.149","url":null,"abstract":"<div><h3>Background</h3><div>Medial temporal lobe amnestic syndrome (MTLA) is classically considered a hallmark of Alzheimer's disease (AD). However, emerging evidence suggests etiological heterogeneity, challenging the assumption that MTLA universally reflects AD pathology.</div></div><div><h3>Objective</h3><div>To determine the prevalence of amyloid pathology in isolated MTLA, identify phenotypic and genetic risk factors, and characterize associated network vulnerabilities in amnestic mild cognitive impairment (aMCI).</div></div><div><h3>Method</h3><div>This retrospective observational study analyzed 55 patients with isolated MTLA at the aMCI stage. Participants underwent neuropsychological testing, cerebrospinal fluid (CSF) biomarker analysis, amyloid PET, and 18FDG-PET. Patients were stratified by amyloid status (positive/negative) and compared for <em>APOE</em> genotype, clinical features, and metabolic patterns. Statistical analyses included the Kruskal-Wallis test for non-parametric group comparisons and chi-square tests for categorical genetic associations.</div></div><div><h3>Results</h3><div>Amyloid pathology was observed in only 67% (37/55) of MTLA patients, dissociating the syndrome from AD in one-third of cases. Amyloid-positive patients demonstrated a significantly higher <em>APOE ɛ4</em> carrier rate compared to amyloid-negative peers (χ² <!-->=<!--> <!-->7.02, df<!--> <!-->=<!--> <!-->2, <em>P</em> <!-->=<!--> <!-->0.030), while 18FDG-PET revealed inferotemporal hypometabolism in amyloid-positive cases, marking early decontextualized memory impairment.</div></div><div><h3>Conclusion</h3><div>MTLA syndrome is not homogeneous on the biological level and amyloid pathology and <em>APOE ɛ4</em> genotype stratify patients into distinct subgroups. Amyloid-positive cases demonstrate inferotemporal hypometabolism, suggesting AD-related network vulnerability. By contrast, amyloid-negative MTLA group shows no systemic brain network vulnerabilities, likely due to its heterogeneous etiological origins. These findings advocate for a precision medicine framework integrating biomarkers to guide therapeutic strategies, moving beyond syndromic diagnoses to target underlying mechanisms.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"182 4","pages":"Pages 290-300"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balint syndrome as the initial presentation of neuromyelitis optica spectrum disorder","authors":"N. Billet ,&nbsp;S. Donat ,&nbsp;C. Grosset-Janin ,&nbsp;G. Androdias ,&nbsp;J. Pique ,&nbsp;R. Marignier ,&nbsp;P. Nicolas","doi":"10.1016/j.neurol.2026.02.157","DOIUrl":"10.1016/j.neurol.2026.02.157","url":null,"abstract":"","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"182 4","pages":"Pages 313-315"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consciousness, awareness, and wakefulness in epilepsy: Clarifying concepts in the 2025 ILAE classification","authors":"F. Bartolomei ,&nbsp;L. Naccache","doi":"10.1016/j.neurol.2026.02.146","DOIUrl":"10.1016/j.neurol.2026.02.146","url":null,"abstract":"","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"182 4","pages":"Pages 316-318"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving MS diagnostic criteria: Progress and challenges.","authors":"Christine Lebrun-Frenay","doi":"10.1016/j.neurol.2025.12.010","DOIUrl":"https://doi.org/10.1016/j.neurol.2025.12.010","url":null,"abstract":"<p><p>The 2024 update to the McDonald criteria for multiple sclerosis aims to be more inclusive, covering paediatric and elderly patients, as well as those with atypical symptoms or comorbidities. These criteria emphasise objective evidence of central nervous system involvement through clinical signs and biomarkers from fluid analysis or imaging. Several new biomarkers have been added, although some are not yet widely accessible but are expected to be implemented soon: kappa-free light chains in cerebrospinal fluid, which are more reproducible and cost-effective than oligoclonal bands, along with advanced imaging techniques such as the central vein sign and paramagnetic rim lesions on susceptibility-weighted imaging. Cases with incidental magnetic resonance imaging hyperintensities, identified as radiologically isolated syndrome (RIS), may also be classified as preclinical MS if they show T2 lesions in at least two typical locations and meet other specific biomarker criteria. Careful, step-by-step evaluation is essential to prevent misdiagnosis, especially in paediatric and late-onset MS, and in cases with comorbidities. The inclusion of RIS individuals or those with atypical presentations marks a crucial shift in the MS spectrum, requiring expertise and the use of specific biomarkers.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic updates in NMOSD and MOGAD: From present practice to future promise.","authors":"I Elosua-Bayés, A Cobo-Calvo","doi":"10.1016/j.neurol.2026.02.158","DOIUrl":"https://doi.org/10.1016/j.neurol.2026.02.158","url":null,"abstract":"<p><p>Aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare, antibody-mediated inflammatory disorders of the central nervous system (CNS). Although historically grouped under the umbrella of multiple sclerosis, both entities differ markedly in pathophysiology, clinical course, prognosis and therapeutic requirements. The identification of disease-specific autoantibodies has not only refined diagnostic accuracy but has also highlighted fundamental differences in therapeutic strategy, particularly regarding the need for and choice of long-term immunosuppression. While acute management of both conditions relies on similar approaches, the long-term treatment paradigms diverge. Sustained immunosuppression may not be required for all patients with MOGAD, whereas AQP4+NMOSD typically demands continuous therapy, in which agents directed against complement activation, IL-6 signaling, and B-cell-mediated pathways form the cornerstone of relapse prevention. The rarity of these disorders continues to challenge the conduct of large, rigorous therapeutic trials. Nonetheless, innovative targeted therapies have already been developed and transformed the therapeutic landscape in NMOSD while more off-label approaches are being investigating in MOGAD. This review synthesizes current evidence on established and investigational therapies in NMOSD and MOGAD, providing an updated framework to inform clinical practice and guide future research in these complex, antibody-mediated CNS disorders.</p>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}