European Journal of Neurology最新文献

{"title":"Evaluating the First CE-Marked LLM-Based Chatbot for Evidence-Based Neurology.","authors":"Patricia Kirschner, Paula Z Epping, Sven G Meuth, Marc Pawlitzki, Lars Masanneck","doi":"10.1111/ene.70736","DOIUrl":"https://doi.org/10.1111/ene.70736","url":null,"abstract":"<p><strong>Background: </strong>Large language models (LLMs) are entering clinical workflows for information retrieval and decision support, but concerns persist about factual accuracy and traceability to evidence. Prof. Valmed is the first CE-marked LLM-based tool for medical information retrieval in Europe, raising the question whether certification aligns with reliable performance in neurology. This study aims to assess the answer accuracy of Prof. Valmed on a neurology benchmark and compare its performance with previously evaluated commercial LLM tools.</p><p><strong>Methods: </strong>Prof. Valmed (V2.0.1_2.0.0) was tested on a 130-item benchmark derived from American Academy of Neurology guidelines (65 case-based, 65 knowledge-based). Each question was prompted four times. Two raters scored responses as correct, inaccurate, wrong, or refused; disagreements were adjudicated. Modal ratings per question were used for analysis. Comparative performance against 16 LLMs or configurations previously assessed using the same protocol was evaluated.</p><p><strong>Results: </strong>Prof. Valmed achieved 76.2% correct answers, 14.6% inaccurate, 6.9% wrong, and 2.3% refused. In pairwise comparisons, Prof. Valmed performed significantly better than 8 models, comparable to several retrieval- or whitelist-enabled tools, and significantly worse than one reasoning model with whitelisting of neurology sources. Overall, its performance was within the range of standard commercial tools.</p><p><strong>Conclusion: </strong>The CE-marked product demonstrated accuracy comparable to contemporary LLMs but did not outperform reasoning-enabled systems. CE marking ensures regulatory conformity rather than inherent performance advantage, and the certification process may limit the integration of rapidly evolving model architectures into approved systems. Future evaluations should examine reasoning quality, source use, and update feasibility across medical domains.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70736"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Profile of Brain-Derived Tau After Ischemic Stroke.","authors":"Karl Sjölin, Björn Röyter, Bianka Forgo, Julia Aulin, Kim Kultima, Johan Lindbäck, Jakob O Ström, Joachim Burman","doi":"10.1111/ene.70735","DOIUrl":"https://doi.org/10.1111/ene.70735","url":null,"abstract":"<p><strong>Background and aim: </strong>Brain-derived tau (BD-tau) is a predominantly CNS-derived form of tau protein detectable in blood that reflects brain injury and has emerged as a potential biomarker in ischemic stroke for assessing neuronal damage, monitoring infarct progression, and predicting functional outcome. However, its temporal profile and the optimal timing for correlation with infarct volume remain unclear.</p><p><strong>Methods: </strong>This prospective cohort study included patients with ischemic stroke, with venous blood samples collected daily during the first week and at 3 months after symptom onset. Infarct volume was assessed by MRI at 48-72 h. Plasma BD-tau concentrations were measured using a Simoa assay. Linear mixed-effects models were used to analyze changes in biomarker levels. The optimal time point for correlation between BD-tau and infarct volume was identified using a 24-h moving-window Pearson correlation analysis.</p><p><strong>Results: </strong>Fifty-four patients (median age 78 years, 50% female) contributed 285 plasma samples. Plasma levels of BD-tau followed a parabolic trajectory reaching a peak approximately 5 days after symptom onset. After 90 days, the concentration of BD-tau was lower than in the last measurement of the first week. The strongest correlation between BD-tau and infarct volume occurred at 105 h (4.4 days) (r = 0.89, 95% CI: 0.78-0.95) after symptom onset.</p><p><strong>Conclusions: </strong>Plasma BD-tau exhibits a distinct temporal profile after ischemic stroke, with peak levels and maximal correlation with infarct volume occurring around Day 4-5. These findings have important implications for interpreting BD-tau levels and optimizing sampling strategies in clinical studies.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT03812666.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70735"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombolysis in Patients With Mild Ischemic Stroke: A Comparative Effectiveness Study From the Norwegian Stroke Registry.","authors":"Elise K Kristensen, Agnethe Eltoft, Torunn Varmdal, Bent Indredavik, Ellisiv B Mathiesen","doi":"10.1111/ene.70734","DOIUrl":"10.1111/ene.70734","url":null,"abstract":"<p><strong>Background: </strong>Intravenous thrombolytic therapy (IVT) is recommended for patients with acute ischemic stroke (AIS) and disabling deficits, regardless of National Institutes of Health Stroke Scale (NIHSS) score. The benefit of IVT in patients with mild AIS was, however, not documented in recent trials. The aim of this study was to evaluate the effectiveness of IVT in mild AIS in a nationwide registry-based study.</p><p><strong>Methods: </strong>AIS patients from the Norwegian Stroke Registry (2016-2022) with a National Institutes of Health Stroke Scale (NIHSS) score <math><mrow><mo>≤</mo></mrow> </math> 5 at admission were included. Using 1:1 propensity score matching, 1736 IVT-treated patients were matched with 1736 controls. Primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 90 days. Secondary outcomes included mRS 0-2, a favorable mRS shift (range 0-6), and death within 28 and 90 days. Data on symptomatic intracerebral hemorrhage (sICH) were available only for the IVT group.</p><p><strong>Results: </strong>At 90 days, 68.4% of IVT-treated patients and 61.2% of controls achieved mRS 0-1 (OR 1.39; 95% CI 1.20-1.60). IVT was associated with a higher probability of achieving excellent functional outcome in patients with NIHSS 4-5 (OR 1.53; 95% CI 1.06-2.21) and NIHSS 2-3 (OR 1.64; 95% CI 1.32-2.03), but not NIHSS 0-1 (OR 1.14; 95% CI 0.89-1.44). No significant differences in overall mortality were observed. SICH occurred in 3.7% of IVT-treated patients.</p><p><strong>Conclusion: </strong>IVT was associated with favorable functional outcomes for mild AIS, but not in patients with NIHSS 0-1.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70734"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalised Anti-CD20 Retreatment in Multiple Sclerosis: Precision Medicine or Precision Pharmacology?","authors":"Klaus Schmierer","doi":"10.1111/ene.70712","DOIUrl":"https://doi.org/10.1111/ene.70712","url":null,"abstract":"","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70712"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myasthenia Gravis (MG) Resource Utilization, Epidemiology, Survival, and Treatment Patterns (MG-REST): Estimating the Clinical and Economic Burden in Ontario, Canada.","authors":"Carolina Barnett-Tapia, Kobina Quansah, Aysegul Erman, Nikhil Nath, Shane Golden, Ryan Ng, Arushi Sharma, Ari Breiner","doi":"10.1111/ene.70694","DOIUrl":"10.1111/ene.70694","url":null,"abstract":"<p><strong>Objective: </strong>The study purpose was to quantify the epidemiology, healthcare resource utilization (HCRU), costs, survival, and treatment patterns of myasthenia gravis (MG) in Canada using population-based administrative data.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using administrative data in Ontario, Canada from 2013 to 2020. MG cases were identified using a validated algorithm. Outcomes included MG incidence and prevalence, myasthenic crisis incidence and prevalence, mortality, survival, HCRU, healthcare costs, and treatment patterns (among patients receiving public drug coverage; i.e., individuals ≥ 65 years).</p><p><strong>Results: </strong>The cohort included 2601 individuals with MG (mean age 65.7 years; 46.7% female). Standardized incidence remained stable (3.2-4.0 per 100,000), while prevalence increased from 36 to 42 per 100,000 from 2013/14 to 2019/20. Myasthenic crisis occurred in 8.9% of individuals over the study, with a post-diagnosis incidence rate of 2.6 per 100 person-years and 30-day mortality of 28.1%. 5-year overall survival was 75%, declining to 39% among those with crisis. Mean annual HCRU and direct costs were highest in the first-year post-diagnosis (10.0 specialists visits and CAD $31,693), decreasing in subsequent years. Mean crisis-related costs were CAD $32,948 per person-month in the first 90 days after crisis. During the study among patients ≥ 65 years, most (77.9%) received AChE inhibitors, and excluding AChE inhibitors, corticosteroids were the most common first-line treatment (62.7%).</p><p><strong>Conclusions: </strong>MG imposes a substantial clinical and economic burden particularly among patients experiencing myasthenic crisis. These findings underscore the need for early intervention and improved access to advanced therapies to mitigate long-term morbidity and healthcare costs.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70694"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Acupuncture on the Neurovascular Unit in Migraine: A Narrative Review.","authors":"Yajie Wang, Chao Zhang, Linbo Shen, Yuanyuan Wang, Xiaocheng Wang, Linjing Song, Li Wang, Ningle Zhang, Dayong Ma, Tao Xiong","doi":"10.1111/ene.70730","DOIUrl":"10.1111/ene.70730","url":null,"abstract":"<p><strong>Objective: </strong>The neurovascular unit (NVU) is a core structural and functional entity involved in migraine pathogenesis. Acupuncture may exert therapeutic effects by protecting NVU integrity. This narrative review aims to summarize the current evidence on the mechanisms by which acupuncture protects the NVU in migraine.</p><p><strong>Methods: </strong>We reviewed and synthesized relevant literature focusing on the effects of acupuncture on neuronal excitation, blood-brain barrier (BBB) components, neuroinflammation, and energy metabolism in the context of migraine.</p><p><strong>Results: </strong>Acupuncture protects the NVU through four major pathways: (1) Acupuncture inhibits pathological excitation of neurons, including activating the endogenous pain regulation system, regulating the balance of neurotransmitters and receptors, and inhibiting peripheral sensitization and inflammation; (2) Acupuncture maintains the integrity of the BBB, specifically involving improving endothelial cell function and tight junctions (TJs), regulating astrocyte reactivity, enhancing pericyte function, and inhibiting extracellular matrix (ECM) degradation; (3) Acupuncture regulates neuroinflammation mediated by microglia; (4) Acupuncture improves energy metabolism and oxidative stress.</p><p><strong>Conclusions: </strong>Acupuncture exerts multi-target, comprehensive protective effects on NVU damage in migraine. These findings provide a mechanistic basis for its clinical application and may offer new therapeutic directions for migraine management.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70730"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the Artificial Intelligence Revolution in Clinical Neurology: A New Multidisciplinary Task Force Within the European Academy of Neurology.","authors":"Alice Accorroni, Raphael Wurm, Roland Wiest, Marcello Ienca, Raphael Bernard-Valnet, Giacomo Sferruzza, Tony Marson, Giuseppe Jurman, James Teo, Elena Moro, Nathalie Nasr, Maria Chiara Malaguti","doi":"10.1111/ene.70728","DOIUrl":"https://doi.org/10.1111/ene.70728","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) is rapidly transforming clinical neurology, offering significant potential to enhance diagnosis, treatment, and disease management. Despite this transformative promise, AI adoption in neurology remains limited due to a lack of a reliable evidence base to support its use, as well as educational, ethical, methodological, and regulatory barriers. Furthermore, currently, there is no standardized educational framework for the application of AI in clinical neurology across Europe.</p><p><strong>Methods: </strong>To address this gap, the European Academy of Neurology (EAN) has established a dedicated multidisciplinary Task Force (TF) on AI in Clinical Neurology. This TF involves neurologists, neurology trainees, medical students, computer and data scientists, ethicists, patient representatives, and regulatory experts.</p><p><strong>Results: </strong>The AI TF has designed a modular curriculum covering technical AI foundations and models, clinical applications, ethical implications, and regulatory compliance. Planned educational resources include e-learning modules, podcasts, masterclasses, and interactive sessions at EAN congresses. Also, a recently conducted Europe-wide survey supported the TF in identifying current knowledge levels and educational and systemic barriers, informing the design of targeted interventions. In parallel, the TF will formulate recommendations addressing the ethical and regulatory implications of AI use in neurology, tailored to the specific needs of clinicians.</p><p><strong>Conclusions: </strong>The EAN TF on AI in Clinical Neurology represents a strategic initiative to enable responsible AI integration through multidisciplinary collaboration. By closing educational gaps, establishing clear ethical standards, and facilitating stakeholder engagement, the TF aims to empower neurologists to confidently and ethically adopt AI technologies, ultimately improving patient care across Europe.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70728"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age and Treatment Efficacy in Myasthenia Gravis: A Systematic Review, Meta-Analysis, and Meta-Regression.","authors":"Christopher Nelke, Marion Skrobol, Lukas Theissen, Francesco Sacca, Tobias Ruck","doi":"10.1111/ene.70737","DOIUrl":"10.1111/ene.70737","url":null,"abstract":"<p><strong>Background: </strong>Myasthenia gravis (MG) is increasingly concentrated in older adults, and age may shift the balance of benefit and risk for MG therapies. This study seeks to evaluate the effect of age on treatment efficacy in clinical trials of MG.</p><p><strong>Methods: </strong>PubMed and Cochrane Library were searched and clinical trials enrolling adults with MG that reported the quantitative myasthenia gravis (QMG) score and the myasthenia gravis activities of daily living (MG-ADL) scale were included. Of 2214 records identified, 18 trials met inclusion criteria. Random-effects meta-analysis was used to pool treatment effects, and random-effects meta-regression evaluated trial-level mean baseline age as a modifier of treatment efficacy.</p><p><strong>Results: </strong>Eighteen trials published from 2017 to 2025 included 1823 participants (982 assigned to treatment and 841 to control). Pooled effects favored treatment over control for the QMG (MD -2.402; 95% CI, -3.099 to -1.706; <math> <mrow><msup><mi>I</mi> <mn>2</mn></msup> </mrow> </math>  = 60.7%) and MG-ADL scores (MD, -1.591; 95% CI, -1.874 to -1.309; <math> <mrow><msup><mi>I</mi> <mn>2</mn></msup> </mrow> </math>  = 0.0%). In meta-regression, higher mean trial age was associated with attenuation of treatment benefit on the QMG scale (β per 10 years, 1.21; 95% CI, 0.02 to 2.42; p = 0.047). This effect was most pronounced for FcRn inhibitors. No association was observed for the MG-ADL score (β per 10 years, 0.08; 95% CI, -0.50 to 0.66; p = 0.779).</p><p><strong>Conclusions: </strong>In this meta-analysis, older trial populations showed smaller treatment-related improvements in the QMG but not in the MG-ADL score. These findings suggest that age may contribute to differences in treatment effects across MG trials.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70737"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Climate Change: A National Survey on Viewpoints of Italian Epilepsy-Care Professionals.","authors":"Emanuele Bartolini, Simona Balestrini, Giulia Battaglia, Pia Bernardo, Giovanni Falcicchio, Francesco Fortunato, Manuela Lo Bianco, Silvia Pradella, Teresa Ravizza, Alessandra Rossi, Leila Zummo, Annamaria Vezzani, Emilio Russo","doi":"10.1111/ene.70684","DOIUrl":"10.1111/ene.70684","url":null,"abstract":"<p><strong>Objective: </strong>To assess awareness, attitudes, and preparedness among Italian epilepsy-care professionals regarding the impact of climate change on epilepsy management.</p><p><strong>Methods: </strong>We conducted a national, anonymous Italian-language online survey distributed through professional networks and scientific societies (LICE, SNO). The questionnaire included Likert-scale items, closed-ended responses were summarized descriptively.</p><p><strong>Results: </strong>We collected 167 responses from a heterogeneous sample by professional role and geographical area. All respondents acknowledged that global warming is occurring; 100% rated its impact on future generations as moderate-to-severe, and 84.3% reported moderate-to-severe concern for their patients. Support was high for continuing professional education on climate and health (99.4%), patient educational materials (88.6%), and workplace sustainability guidelines (97%). Individual mitigation actions were common (e.g., 93.3% reported recycling more frequently), whereas institutional initiatives were less consistently reported (e.g., 46.1% reported telemedicine use and 42.6% reported no transportation-related initiatives).</p><p><strong>Conclusions: </strong>Italian epilepsy-care professionals demonstrate high awareness and concern regarding climate change and its impact on patients. While support for education and sustainability initiatives is strong, translation into institutional and research practices remains limited, highlighting the need for targeted policies and infrastructure.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":"e70684"},"PeriodicalIF":4.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Cognitive and Behavioral Changes in Primary Lateral Sclerosis: A Population-Based Study","authors":"Andrea Calvo,&nbsp;Cristina Moglia,&nbsp;Antonio Canosa,&nbsp;Umberto Manera,&nbsp;Rosario Vasta,&nbsp;Enrico Matteoni,&nbsp;Alessandra Maccabeo,&nbsp;Sara Cabras,&nbsp;Giorgio Pellegrino,&nbsp;Emilio Minerva,&nbsp;Anastasia Dei Giudici,&nbsp;Vita Passidomo,&nbsp;Francesca Palumbo,&nbsp;Barbara Iazzolino,&nbsp;Gabriele Mora,&nbsp;Adriano Chiò","doi":"10.1111/ene.70720","DOIUrl":"https://doi.org/10.1111/ene.70720","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Primary lateral sclerosis (PLS) is a rare upper motor neuron neurodegenerative disorder whose cognitive profile, particularly at early stages, remains incompletely defined. We aimed to characterize cognitive and behavioral features of PLS at diagnosis and compare them with predominant upper motor neuron amyotrophic lateral sclerosis (PUMN-ALS) and healthy controls (HCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients diagnosed with PLS between 2007 and 2021 were identified from the population-based Piemonte and Valle d'Aosta ALS Register. Diagnoses were established according to consensus criteria, including early, probable, and definite PLS. All patients underwent comprehensive neuropsychological and behavioral assessment within 3 months of their first ALS center visit. Cognitive–behavioral status was classified using ALS–frontotemporal dementia (FTD) consensus criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-two PLS patients were included (mean disease duration, 25 months). Cognitive and/or behavioral impairment was identified in 29.3% of patients, most commonly affecting executive function, memory, and social cognition, including 21.1% early PLS. Compared with HCs, PLS patients showed poorer performance across several cognitive domains and higher anxiety and depression scores. Compared with matched PUMN-ALS patients, PLS patients demonstrated slightly worse executive performance, while the overall frequency of cognitive–behavioral impairment was similar. Behavioral profiles differed qualitatively, with apathy more frequent in PUMN-ALS. No PLS patient met criteria for frontotemporal dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Cognitive and behavioral impairments are already detectable at the time of diagnosis in a substantial proportion of patients with PLS, including early PLS, supporting the view of PLS as a multidimensional neurodegenerative disorder with early extramotor involvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}