Revue neurologique最新文献

{"title":"Influence of age and sex on presymptomatic phases of neurodegenerative diseases: Focus on multiple sclerosis and Alzheimer's disease","authors":"B. Zeydan ,&nbsp;K. Kantarci","doi":"10.1016/j.neurol.2025.06.015","DOIUrl":"10.1016/j.neurol.2025.06.015","url":null,"abstract":"<div><div>Neurodegenerative diseases such as multiple sclerosis (MS) and Alzheimer's dementia (AD) demonstrate an ever-evolving disease continuum. The presymptomatic phase of neurodegenerative diseases provides a window of opportunity to detect disease-specific changes and abnormalities early on and potentially intervene right away, before clinical symptoms occur. Age and sex are key modifiers of the presymptomatic phase of neurodegenerative diseases. In presymptomatic MS, younger age and male sex are main risk factors for transition to symptomatic MS, whereas older age and male sex are important predictors of the direct transition from presmyptomatic MS to primary progressive MS. In cognitively unimpaired adults, age is the strongest risk factor for AD and the lifetime AD risk after<!--> <!-->&gt;<!--> <!-->65 years is higher in women versus men. The prevalence and future disease severity of AD is further modified by factors such as apolipoprotein Eɛ4, ovarian hormones, and menopause in women. Biomarkers are instrumental in detecting and monitoring abnormalities and underlying disease mechanisms in vivo, that are already present in the presymptomatic phase. Evaluating the influence of age and sex on presymptomatic phase of neurodegenerative diseases, particularly through biomarkers, contributes to the enhanced patient selection for clinical trials, optimization and individualization of patient management and development of new therapeutics.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 829-838"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800100","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 challenging concept of preclinical Alzheimer's disease","authors":"D. Wallon ,&nbsp;A. Garnier-Crussard","doi":"10.1016/j.neurol.2025.07.016","DOIUrl":"10.1016/j.neurol.2025.07.016","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is increasingly recognized as a decades-long process that begins before any first cognitive symptoms. Neuropathology and in vivo biomarker studies have revealed a silent preclinical phase. However, its precise definition and boundaries remain debated. Elucidating the biological events and temporal sequence that characterize this stage is essential, while researchers try to identify the optimal window to prevent or postpone cognitive decline. At the same time, “preclinical AD” raises unresolved challenges in diagnosis, prognosis, therapeutic intervention and ethics. This narrative review synthesizes the current evidence, from clinical characterization to prevention trials and societal considerations, with an emphasis on original findings for amyloid, tau and neurodegeneration biomarkers. We critically contrast the two principal research frameworks that structure the field and examine how each shapes patient classification and trial design. By integrating these lines of evidence, we explore persistent gaps in prognostic modeling and in the clinical efficacy of disease-modifying strategies. The review aims to provide a concise but comprehensive overview of the preclinical concept for clinicians and researchers developing the next generation of preventive interventions for AD.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 881-892"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486255","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":"Lessons learned from 30 years of presymptomatic testing in Huntington Disease","authors":"L. Pierron ,&nbsp;M. Hébert ,&nbsp;M. Gargiulo ,&nbsp;A. Durr","doi":"10.1016/j.neurol.2025.07.009","DOIUrl":"10.1016/j.neurol.2025.07.009","url":null,"abstract":"<div><div>Presymptomatic testing allows individuals to undergo genetic testing for inherited diseases before symptoms manifest. While valuable in conditions with available preventive strategies, no therapeutic prevention currently exists for Huntington disease, making testing a personal choice rather than a medical recommendation. Available in France since 1992 – following the identification of CAG repeat expansions (&gt;<!--> <!-->35) in the huntingtin gene – presymptomatic testing is governed by guidelines emphasizing autonomy, benevolence, informed consent, confidentiality, and equity. Its implementation requires an interdisciplinary approach, including genetic counseling and psychological support, to ensure comprehensive care. One of the many lessons learned is that despite the large availability of presymptomatic testing centers, less than 20% of at-risk individuals choose to be tested, reflecting complex psychological and familial dynamics. In addition, motivations for testing vary widely, more often identified as the desire to know rather than family planning, which explains the even lower opting in for prenatal testing. Psychological support is essential, as an unfavorable result puts individuals in a prolonged liminal state, waiting for disease onset. Favorable results are the happy ending of testing, but can, in some instances, also trigger complex emotional responses, such as survivor's guilt. Involving presymptomatic carriers in research programs has offered important scientific benefits and also a sense of agency and meaning for participants. Our experience with presymptomatic testing in Huntington disease has established a paradigm for predictive genetic medicine, highlighting the importance of interdisciplinary care and ethical considerations. As genomic medicine advances, the core principles of presymptomatic testing remain relevant, ensuring the protection and consent of individuals and their families. These lessons help to disseminate information about the utility of genetic counseling and call for an informed approach to presymptomatic testing in neurogenetics.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 852-862"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486263","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":"Presymptomatic late-onset Pompe disease: Optimizing the timing of treatment","authors":"C. Guémy ,&nbsp;C. Lefeuvre ,&nbsp;E. Berling ,&nbsp;A. Rouyer ,&nbsp;G. Nicolas ,&nbsp;P. Laforêt","doi":"10.1016/j.neurol.2025.09.001","DOIUrl":"10.1016/j.neurol.2025.09.001","url":null,"abstract":"<div><div>Late-onset Pompe disease (LOPD) is a genetic myopathy causing severe limb girdle and diaphragmatic weakness. Pre-symptomatic diagnosis of LOPD is increasing. Enzyme replacement therapy (ERT) has shown dramatic efficacy in infantile-onset forms of the disease, supporting early diagnosis and treatment initiation, whereas the benefit of ERT on muscle weakness and respiratory insufficiency is moderate and not sustained over time in LOPD, raising questions about presymptomatic screening. Here, we present three presymptomatic cases of LOPD, showing that clinical symptoms can occur long after the diagnosis, resulting in a close monitoring without the need for treatment over several years. Several tests, such as walking tests, pulmonary function tests or whole-body muscle magnetic resonance imaging are sensitive for detecting early disease progression. Current guidelines provide no clear recommendations regarding the optimal timing of treatment initiation in presymptomatic patients. Nevertheless, in the context of a disease with a highly variable course, regular clinical, physiological and radiological assessments of each patient may allow for early detection of disease progression and support the decision to initiate treatment.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 922-928"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486175","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":"Digital health in presymptomatic diseases","authors":"M. Cohen","doi":"10.1016/j.neurol.2025.06.017","DOIUrl":"10.1016/j.neurol.2025.06.017","url":null,"abstract":"<div><div>Most of widely available consumer devices like smartphones and tablets are equipped with various sensors that allow for detection of subtle and undetectable neurological impairment of various neurological functions like motricity, coordination, cognition, visual function or eye movements. This opens the perspective of earlier diagnosis of neurological diseases, even at the preclinical stage, which could allow for earlier therapeutic intervention and improved long term outcomes. In this article, we review how technology can enhance the clinician's examination skills and the current level of evidence in the field of preclinical diseases detection, in diseases like Parkinson's disease, Alzheimer's disease or multiple sclerosis. Many studies reported subtle impairment regarding fine motricity, eye movements, cognition, voice features and speech. We will also discuss current limitations regarding scientific evidence and practical implementation in the daily practice, as well as future perspectives.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 937-943"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486257","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":"Artificial intelligence in presymptomatic neurological diseases: Bridging normal variation and prodromal signatures","authors":"T. Soulier ,&nbsp;N. Burgos ,&nbsp;R. Hassanaly ,&nbsp;M. Pitombeira ,&nbsp;M. Solal ,&nbsp;H. Roy ,&nbsp;M. Hamzaoui ,&nbsp;A. Yazdan-Panah ,&nbsp;D. de Paula Faria ,&nbsp;C. Louapre ,&nbsp;B. Bodini ,&nbsp;M. Bottlaender ,&nbsp;N. Ayache ,&nbsp;O. Colliot ,&nbsp;B. Stankoff","doi":"10.1016/j.neurol.2025.07.011","DOIUrl":"10.1016/j.neurol.2025.07.011","url":null,"abstract":"<div><div>Presymptomatic neurological diseases are marked by early pathological changes that occur before overt clinical symptoms. These stages, which include prodromes such as REM sleep behavior disorder in Parkinson's or mild cognitive impairment in Alzheimer's, offer critical opportunities for early intervention. However, their detection remains challenging due to the subtlety of changes and the overlap with normal interindividual variability. Artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), offers new tools to uncover hidden signatures in complex biomedical data. First, we explore how supervised ML models can detect known prodromal patterns across diverse modalities, including EEG, cognitive scores, and structural imaging. Depending on the input, various model types — such as tree-based algorithms for structured data and convolutional or transformer networks for images and signals — can extract predictive features of early neurodegeneration. These approaches have demonstrated success in identifying at-risk individuals before clinical thresholds are reached. Yet, detecting only known patterns limits the scope of early intervention. Many individuals who will go on to develop neurological disease may not yet exhibit any recognized prodromal syndrome. Bridging this gap requires moving beyond predefined labels toward models capable of identifying subtle, unknown anomalies in individuals still considered healthy. Second, we address the detection of latent anomalies among individuals not yet considered at risk without identifiable known prodromal patterns. By mining clinical records, free-text medical notes, and population-level health databases (e.g., UK Biobank, EDS-AP–HP), and by analyzing sensor data from smartphones or wearables, AI can flag deviations from healthy patterns long before symptom onset or formal diagnosis. This approach holds promise for scalable, low-burden, ecological screening. Finally, we introduce the concept of pseudo-healthy twins — synthetic, personalized baselines generated from structural data such as MRI, to improve anomaly detection. These models predict a patient's expected healthy signal in another modality, such as PET, enabling the subtraction of normal anatomical and physiological variability to isolate disease-specific effects. Generative models like GANs and VAEs have shown promise in producing these cross-modal references, enhancing early anomaly detection in diseases like Alzheimer's and multiple sclerosis. Together, these approaches show how AI can bridge the gap between normal variation and early pathology, enabling more sensitive, personalized, and population-scalable detection of presymptomatic neurological disease.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 944-950"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486258","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":"Prodromal Parkinson's disease","authors":"L. Grass ,&nbsp;S. Grimaldi ,&nbsp;P. Damier","doi":"10.1016/j.neurol.2025.06.012","DOIUrl":"10.1016/j.neurol.2025.06.012","url":null,"abstract":"<div><div>The neurodegenerative process responsible for Parkinson's disease (PD) begins years before the level of dopamine denervation of the basal ganglia leads to the characteristic clinical phenotype of the disease. During the past 20<!--> <!-->years, numerous symptoms that may occur during the prodromal stage of the disease have been identified: subtle motor symptoms, psychocognitive disorders, sleep disorders, sensorial dysfunction, and dysautonomia. Among them, rapid eye movement sleep behaviour disorder (RBD) is one of the most specific. The follow-up of cohorts of subjects affected by this disorder has provided valuable information about the prodromal stage, including evidence of various biological or imaging biomarkers associated with the pre-clinical stage of the disease. From all the knowledge acquired about this stage of the disease, criteria for diagnosing prodromal PD have been proposed and have progressively improved in sensitivity and specificity. The strong focus on the RBD-associated prodromal stage has, however, tended to conceal other, less florid forms of prodromal PD, such as those beginning with mild cognitive impairment or mild motor symptoms, which affected subjects are less likely to notice. Here, we review the various symptoms observed in the prodromal stage of PD, progress on identifying relevant imaging and biological biomarkers, and recent insights into the pathogenesis of a disease having such a wide spectrum of presentation and progression. Advances in knowledge about prodromal PD will lead to earlier diagnosis and better identification of prognostic factors, and, subsequently, to the capacity to initiate personalized treatment and potentially slow down the degenerative process.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 863-880"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486264","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":"Tracing Neurological Diseases in the presymptomatic phase: moving forward a detection panel","authors":"M. Rival ,&nbsp;E. Thouvenot","doi":"10.1016/j.neurol.2025.08.004","DOIUrl":"10.1016/j.neurol.2025.08.004","url":null,"abstract":"<div><div>Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) often exhibit a prolonged presymptomatic phase during which neuropathological changes silently progress. Recent advances in biomarker research have revealed molecular and imaging signatures that precede clinical onset by years, offering a critical window for early intervention. This review synthesizes current knowledge on the most promising presymptomatic biomarkers across these conditions, highlighting their biological origins, diagnostic performance, and clinical utility. Particular emphasis is placed on the development and validation of biomarker panels, which combine multiple markers to enhance diagnostic sensitivity and specificity, enabling more accurate detection of disease in its earliest stages. Minimally invasive approaches, such as blood-based assays, are also discussed for their potential to facilitate widespread screening and longitudinal monitoring. As these biomarkers begin to integrate into clinical workflows, particularly in AD and MS, international collaboration will be essential to standardize methodologies and ensure equitable implementation. Ultimately, presymptomatic biomarkers hold transformative potential for shifting neurology toward a proactive and precision-based paradigm.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 9","pages":"Pages 821-828"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486261","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":"Amyloid PET imaging in France: One-year experience and perspectives","authors":"A. Verger ,&nbsp;P. Payoux ,&nbsp;S. Heyer ,&nbsp;M.O. Habert ,&nbsp;A. Flaus ,&nbsp;M. Ribeiro ,&nbsp;N. De Leiris ,&nbsp;J. Pariente ,&nbsp;D. Wallon ,&nbsp;M. Ceccaldi ,&nbsp;S. Bombois ,&nbsp;E. Guedj ,&nbsp;Groupe de travail « neurologie » de la Société française de médecine nucléaire (GT neurologie SFMN)","doi":"10.1016/j.neurol.2025.08.001","DOIUrl":"10.1016/j.neurol.2025.08.001","url":null,"abstract":"","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 8","pages":"Pages 699-702"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856180","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":"Clinical presentation and natural history of RAVINE leukoencephalopathy in Reunion Island","authors":"M. Renouil ,&nbsp;I.I. Grigorashvili-Coin ,&nbsp;M.-L. Jacquemont ,&nbsp;A. Gelot ,&nbsp;V. Trommsdorff ,&nbsp;A. Pervillé ,&nbsp;F. Darcel ,&nbsp;M. Bintner ,&nbsp;A. Choumert","doi":"10.1016/j.neurol.2025.06.014","DOIUrl":"10.1016/j.neurol.2025.06.014","url":null,"abstract":"<div><h3>Introduction</h3><div>RAVINE leukoencephalopathy (RLE) is a hereditary autosomal recessive disease characterized by typical clinical and radiological signs that has so far been observed only in patients of Reunionese origin. The term RAVINE is a French acronym for the main clinical features of the disease: <em>Réunion, Anorexie, Vomissements Incoercibles, signes NEurologiques</em> (Reunion, Anorexia, Intractable Vomiting, NEurological signs). Patients with RLE carry the IVS1-1778A&gt;G mutation of the <em>SLC7A2</em> gene in the homozygous state. Here we present the first complete clinical description and natural history of RLE.</div></div><div><h3>Material and methods</h3><div>The medical records of all patients born to Reunionese parents and presenting with suspected RLE were reviewed. The diagnosis of RLE was confirmed by detection of the homozygous mutation IVS1-1178A&gt;G of the <em>SLC7A2</em> gene. The clinical and paraclinical data of patients with genetically confirmed RLE were retrospectively analyzed to determine the clinical presentation and natural history of the disease.</div></div><div><h3>Results</h3><div>Our retrospective analysis of the clinical and paraclinical data of 40 patients with genetically confirmed RLE distinguished 3 types of the disease based on the evolution of symptoms. Symptoms were classified into 4 stages of development: stage A, or digestive-like stage, characterized by digestive symptoms and to a lesser extent by neurological symptoms; stage B, or clinically latent stage; stage C, or exacerbation stage, marked by attacks of neurological symptoms; and stage D, or decline stage, characterized by loss of walking ability and progression towards death. Patients with type I RLE (37.5%), or monophasic RLE, experience only the severe stage A. Death occurs before the age of 28<!--> <!-->months in a very narrow time window (23.0<!--> <!-->±<!--> <!-->2.2<!--> <!-->months). Patients with type II RLE (16.7%), or biphasic RLE, move directly from stage A to stage D. Patients with type III RLE (45.8%), or multiphasic RLE, experience all 4 stages with varying degrees of symptom severity. This is the most frequent type of RLE. The joint occurrence of central apnea and vocal cord paralysis during stage A is indicative of unfavorable prognosis. Corticosteroid therapy seems to be effective during stage A and in some cases during stage C.</div></div><div><h3>Discussion</h3><div>This retrospective study provides the first complete clinical description and natural history of RLE. Three types of the disease were distinguished based on the evolution of symptoms. The diagnosis of RLE can be established outside of Reunion Island as many Reunionese couples have emigrated to other parts of the world.</div></div>","PeriodicalId":21321,"journal":{"name":"Revue neurologique","volume":"181 8","pages":"Pages 775-789"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134922","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}