European Journal of Neurology最新文献

{"title":"Predictors of Multiple Sclerosis After Clinically Isolated Syndrome: A Systematic Review and Meta-Analysis","authors":"María Paula Zafra-Sierra,&nbsp;Carolina Ferreira-Atuesta,&nbsp;Daniela Sofía Rodríguez,&nbsp;Jairo Gaitán,&nbsp;Susana Otero,&nbsp;Mar Tintoré,&nbsp;Fred Lublin,&nbsp;Gavin Giovannoni,&nbsp;Jaime Toro,&nbsp;Saúl Reyes","doi":"10.1111/ene.70711","DOIUrl":"https://doi.org/10.1111/ene.70711","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Most people with multiple sclerosis (MS) present with a clinically isolated syndrome (CIS); however, not all individuals with CIS are subsequently diagnosed with MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature review was conducted until December 2025. Observational studies of adults with CIS that were later diagnosed with MS were included. Odds ratios (ORs) were pooled using random-effects meta-analysis. Heterogeneity was assessed with I², sensitivity analyses with leave-one-out procedures, and publication bias with funnel plots and Egger's test. Meta-regression was performed to explore further sources of heterogeneity when appropriate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-two studies with 9915 adults were included. In the meta-analysis, younger age (OR = 1.6, <i>p</i> &lt; 0.01) and multifocal presentation (OR = 1.55, <i>p</i> = 0.02) were associated with a diagnosis of MS after a CIS. Magnetic resonance imaging findings, including a higher number of T2 lesions (OR = 7.46, <i>p</i> = 0.02), periventricular lesions (OR = 4.08, <i>p</i> &lt; 0.01), corpus callosum lesions (OR = 14.89, <i>p</i> = 0.02), infratentorial lesions (OR = 2.16, <i>p</i> = 0.03), spinal cord lesions (OR = 1.4, <i>p</i> = 0.03), and gadolinium-enhancing lesions (OR = 1.91, <i>p</i> = 0.01), as well as cerebrospinal fluid inflammatory markers such as oligoclonal bands (OR = 3.57, <i>p</i> &lt; 0.01) and pleocytosis (OR = 3.34, <i>p</i> = 0.02), were also associated with a subsequent diagnosis of MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This meta-analysis identified factors associated with an increased likelihood of MS after a CIS. These findings may help identify high-risk individuals and guide personalized treatment strategies.</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.70711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647842","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":"Sex and Gender Differences in the Association Between Physical Activity and Cryptogenic Ischemic Stroke in Young Adults","authors":"Camilla Cocchi,&nbsp;Giulia Renda,&nbsp;Sabina Gallina,&nbsp;Anna Vittoria Mattioli","doi":"10.1111/ene.70722","DOIUrl":"10.1111/ene.70722","url":null,"abstract":"&lt;p&gt;We read with great interest the article by Kutal et al., which investigated the association between physical activity and cryptogenic ischemic stroke in young adults [&lt;span&gt;1&lt;/span&gt;]. The authors should be congratulated for addressing an important and still underexplored issue in young stroke, namely the possible contribution of both insufficient and excessive physical activity to cerebrovascular risk.&lt;/p&gt;&lt;p&gt;The study provides valuable evidence that the relationship between physical activity and cryptogenic ischemic stroke may not be linear. In particular, the finding that very high levels of physical activity were independently associated with early-onset cryptogenic ischemic stroke is clinically relevant, as physical activity is generally considered protective in cardiovascular prevention [&lt;span&gt;2&lt;/span&gt;]. This observation supports the concept that, especially in young adults, the extremes of the activity spectrum may deserve careful attention.&lt;/p&gt;&lt;p&gt;An aspect that we believe deserves further discussion is the role of sex and gender differences. The authors reported sex-stratified analyses showing that women in the 75th–90th percentile of physical activity had a lower risk of cryptogenic ischemic stroke, whereas men in the top 10% of physical activity had a significantly higher risk. Moreover, sedentary behavior appeared to be more strongly associated with cryptogenic ischemic stroke in men than in women. These findings suggest that the association between physical activity, sedentary behavior, and stroke risk may differ according to sex.&lt;/p&gt;&lt;p&gt;Several biological mechanisms may contribute to these differences. In women, hormonal status, use of hormonal contraception, pregnancy-related factors, migraine with aura, and changes in endothelial function may modulate the relationship between physical activity and cerebrovascular risk [&lt;span&gt;2&lt;/span&gt;]. In men, very high-intensity or endurance exercise may be more frequently associated with specific cardiovascular adaptations, including atrial remodeling, arrhythmogenic vulnerability, blood pressure surges, prothrombotic changes, and possible interactions with undetected cardiac or vascular substrates. These mechanisms may partly explain why extreme physical activity appeared to be more strongly associated with cryptogenic ischemic stroke among men [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In addition to biological sex, gender-related factors should also be considered. Patterns of physical activity often differ between women and men in terms of intensity, type of exercise, occupational activity, training goals, social expectations, and health-seeking behavior. Similarly, sedentary behavior may reflect different occupational, domestic, and psychosocial exposures across genders [&lt;span&gt;4&lt;/span&gt;]. These dimensions are difficult to capture through total MET-minutes alone but may be highly relevant when interpreting the relationship between lifestyle behaviors and stroke risk in young adults.&lt;/p&gt;&lt;p&gt;From a clinical perspect","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.70722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629875","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":"Nationwide Epidemiology of Motor Neuron Diseases in Latvia (2020–2024): Incidence, Prevalence, and Clinical Characteristics","authors":"Vladimirs Krutovs,&nbsp;Arta Grosmane,&nbsp;Renāte-Ruta Kažmere,&nbsp;Marija Roddate,&nbsp;Gundega Ķauķe,&nbsp;Diāna-Patrīcija Grosa,&nbsp;Signe Šetlere,&nbsp;Mikus Dīriks,&nbsp;Guntis Karelis,&nbsp;Viktorija Ķēniņa","doi":"10.1111/ene.70710","DOIUrl":"https://doi.org/10.1111/ene.70710","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Motor neuron diseases (MNDs), including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA), are rare, progressive neurodegenerative conditions. Although well-studied in Western Europe, no nationwide epidemiological data have been published from Latvia. This study aimed to assess the incidence, prevalence, and clinical characteristics of MNDs in the Latvian population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective, hospital-based analysis was performed using records from Pauls Stradiņš Clinical University Hospital, Riga East University Hospital, and the Children's Clinical University Hospital between January 2020 and December 2024. Patients were identified through relevant ICD-10 codes. Incidence and prevalence rates were calculated per 100,000 population and age-standardized to the 2013 European Standard Population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 181 prevalent MND cases were identified: 131 with ALS or related phenotypes, 10 with adult-onset SMA, 33 with pediatric SMA, and 7 with SBMA. The age-standardized incidence of ALS was 1.22 per 100,000 person-years, and the prevalence was 4.69 per 100,000. Limb weakness or paresis was the most common initial symptom (48.1%). The mean diagnostic delay was 13.4 months for ALS, 43.8 months for PLS, 206.8 months for SBMA and 17.3 months for pediatric SMA. The prevalence of pediatric SMA was 9.91 per 100,000, with type II being the most frequent subtype. All SMA and SBMA cases were genetically confirmed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This first nationwide study of MNDs in Latvia highlights diagnostic delays and possible under-recognition of adult SMA and SBMA. Genetic testing, a national registry, and equitable therapy access should be prioritized.</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.70710","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647739","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":"Biomarker-Based Diagnosis and Care Pathways for Alzheimer's Disease in the Era of Disease-Modifying Treatments: A Consensus Statement by Belgian Experts","authors":"Tim Van Langenhove,&nbsp;Sara Van Mossevelde,&nbsp;Marijke Miatton,&nbsp;Jan De Lepeleire,&nbsp;Rose Bruffaerts,&nbsp;Jean Christophe Bier,&nbsp;Kurt Segers,&nbsp;Jurn Verschraegen,&nbsp;Mirko Petrovic,&nbsp;Manfredi Ventura,&nbsp;Haroun Jedidi,&nbsp;Ingo Beyer,&nbsp;Eric Mormont,&nbsp;Rik Vandenberghe,&nbsp;Aline Delva,&nbsp;Christian Gilles,&nbsp;Donatienne Van Weehaeghe,&nbsp;Gaëtane Picard,&nbsp;Peter De Deyn,&nbsp;Mélanie Strauss,&nbsp;Evert Thiery,&nbsp;Eric Salmon,&nbsp;Gert Cypers,&nbsp;Joris Vlaemynck,&nbsp;Katrin Gillis,&nbsp;Jan Versijpt,&nbsp;Maria Bjerke,&nbsp;Anne Sieben,&nbsp;Bernard Hanseeuw,&nbsp;Sebastiaan Engelborghs,&nbsp;Olivier Deryck,&nbsp;the BeDeCo members","doi":"10.1111/ene.70668","DOIUrl":"https://doi.org/10.1111/ene.70668","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The recent approval of disease-modifying therapies (DMTs) for early Alzheimer's disease (AD) marks a major shift in clinical practice. Biomarker confirmation of amyloid pathology is now required alongside clinical assessment, and blood-based tests are improving accessibility. This creates increased demand for timely and accurate diagnosis while avoiding overdiagnosis in low-probability cases. This Belgian consensus aims to guide biomarker-based diagnosis of AD in the era of DMTs and to highlight the system adaptations required for safe and equitable implementation. Belgium, with universal healthcare but regionally organised dementia care, provides a relevant case to illustrate both opportunities and challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This consensus was developed by 31 experts in cognitive neurology, geriatrics, neuropsychology, neuroimaging, neurochemistry, and primary care, coordinated by the Belgian Dementia Council (BeDeCo). Recommendations were based on multidisciplinary discussion, current evidence, and the organisation of dementia care in Belgium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The consensus outlines a stepwise diagnostic approach that integrates clinical assessment with biomarker confirmation using cerebrospinal fluid, amyloid-PET, and emerging blood-based tests. We review the strengths and limitations of each modality and provide guidance for use across clinical scenarios. Using Belgium as a case example, we illustrate challenges that are shared across European healthcare systems, such as limited reimbursement, unequal access to expertise, and insufficient diagnostic capacity, and formulate pragmatic recommendations to address these issues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This consensus offers practical guidance for embedding biomarker-based diagnostic strategies into clinical care. By outlining structured pathways and system-level priorities, it facilitates safe, feasible, and equitable implementation of DMTs for AD.</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.70668","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647838","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":"“Advanced ET” Is a More Appropriate Term Than “ET-Plus”","authors":"Elan D. Louis","doi":"10.1111/ene.70725","DOIUrl":"https://doi.org/10.1111/ene.70725","url":null,"abstract":"<p>Despite a remarkably high disease incidence and prevalence, there are surprisingly few prospective, longitudinal natural history studies of patients with essential tremor (ET). At a point when disease classification and nomenclature are under active discussion, such studies would provide the necessary data to effectively inform and guide such efforts. Angelini et al. [<span>1</span>] should be congratulated for undertaking a prospective natural history study and for providing high resolution phenotypic data derived from careful evaluations over three time points.</p><p>The data they present offer valuable insights into the dynamics of the ET phenotype. In presenting these data, they allow us to revisit current classification constructs. One important point that can be taken from their data is that the myriad of clinical features of ET evolve over time. Although this is not surprising, their study also underscores the point that the layering in of additional features in ET, above and beyond the core clinical feature, kinetic tremor, likely occurs as a function both of the aging process as well as disease duration (a proxy for the evolution of the underlying disease-associated pathophysiology). Furthermore, as a corollary, what has been termed “ET-plus” is likely no more than a disease stage rather than a distinct, stable, separable clinical-pathological entity. Other data firmly support this view [<span>2, 3</span>].</p><p>As a field we need to do two things. First, we need to stop using the term “ET-plus” and rather replace it with the term “advanced ET.” This preferable term captures the concepts of disease heterogeneity, the dynamic layering in of disease features over time, the concept of a continuum of features, and the concept that the addition of these features does not herald a new diagnosis, but rather simply a more advanced disease stage. Second, we need to move further along in the process of establishing a staging scheme for this common disease to order the procession of clinical features [<span>4</span>] as well as the growing catalog of postmortem cerebellar degenerative changes [<span>5</span>]. The only way to do this, and to produce a valid result, is to base such efforts on data derived from longitudinal data. The authors of this report should be commended for moving us closer to this goal.</p><p><b>Elan D. Louis:</b> conceptualization, writing – original draft.</p><p>The author declares no conflicts of interest.</p><p>Data sharing not applicable to this article as no datasets were generated or analyzed during this current study.</p>","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.70725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647836","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":"Cognitive Motor Dissociation in Disorders of Consciousness: An Individual Participant Data Meta-Analysis","authors":"Poul P. Laigaard,&nbsp;Fawzi W. Abla,&nbsp;Melika Hassani,&nbsp;Anna Kristina Eigenbrodt,&nbsp;Daniel Kondziella","doi":"10.1111/ene.70713","DOIUrl":"https://doi.org/10.1111/ene.70713","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In patients with disorders of consciousness (DoC), behavioral assessment often underestimates awareness when motor output is absent or unreliable. Cognitive motor dissociation (CMD) refers to patients who appear unresponsive but demonstrate volitional brain responses during neurodiagnostic tests. We characterized clinical and methodological factors associated with CMD detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Studies published between January 2000 and May 2026 were identified through MEDLINE, Embase, and Scopus. Individual participant data were analyzed using mixed-effects logistic regression. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-six studies with 1248 patients (mean age 45.5 years; 66.1% male; 44.5% unresponsive wakefulness syndrome [UWS]) were included. In unadjusted analyses, CMD detection was lower in anoxic (OR 0.43, 95% CI 0.29–0.66) and cerebrovascular (OR 0.59, 95% CI 0.37–0.98) compared to traumatic brain injury, and higher in minimally conscious state minus (MCS−) compared to UWS (OR 1.64, 95% CI 1.14–2.35). In multivariable models, anoxic (OR 0.35, 95% CI 0.23–0.55) and cerebrovascular (OR 0.51, 95% CI 0.32–0.84) etiologies remained independently associated with lower CMD detection, while MCS− remained associated with higher detection (OR 1.50, 95% CI 1.02–2.23). Time since injury, diagnostic modality and task paradigms were not independently associated with CMD detection. Overall, the studies showed a relatively low risk of bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CMD is common but varies by etiology and clinical state. Its detection appears to be independent of the time of injury, the task paradigm, and the diagnostic modality, highlighting the importance of standardized protocols and longitudinal studies.</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.70713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647837","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":"Corticospinal Subfiber Neurite Density Index Detects Upper Motor Neuron Degeneration in Prediagnostic Patients With Sporadic Amyotrophic Lateral Sclerosis","authors":"Ninglu Gao,&nbsp;Bo Cui,&nbsp;Yan Yun,&nbsp;Wenfei Yu,&nbsp;Xianlei Gao,&nbsp;Xiaohan Sun,&nbsp;Kai Shao,&nbsp;Pengfei Lin,&nbsp;Fuchen Liu,&nbsp;Wei Li,&nbsp;Yuying Zhao,&nbsp;Dexin Yu,&nbsp;Chuanzhu Yan,&nbsp;Shuangwu Liu,&nbsp;Jianwei Lou","doi":"10.1111/ene.70703","DOIUrl":"https://doi.org/10.1111/ene.70703","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Using multi-shell diffusion MRI, we aimed to identify whether corticospinal tract (CST) subfiber damage can be detected in prediagnostic amyotrophic lateral sclerosis (ALS) patients. We also explored whether the combination of serum neurofilament light chain (NfL) levels and CST subfiber abnormalities may provide better diagnostic performance in differentiating prediagnostic ALS patients from disease controls (DCs) and healthy controls (HCs) than single markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective study, prediagnostic ALS was used as an operational term for patients who presented at baseline with chronic progressive limb weakness or bulbar symptoms, had no clinically evident typical UMN signs, and were subsequently confirmed to have sporadic ALS according to the Awaji criteria during longitudinal follow-up. Patients whose final diagnosis was not ALS after follow-up were classified as disease controls. Probabilistic tractography was performed on baseline MRI data to assess CST subfiber damage in 47 ALS patients, 20 DCs, and 51 HCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with Controls, ALS patients had significantly lower neurite density index (NDI) values of CST subfibers, particularly those originating from the primary and supplementary motor cortex. The diagnostic performance of the combined model incorporating serum NfL and CST subfiber NDI values in differentiating prediagnostic ALS patients from HCs and DCs was 0.925 and 0.928, respectively, which was better than that of single markers (0.634–0.886 and 0.699–0.856, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that CST subfibers NDI values are promising neuroimaging markers for detecting in vivo UMN degeneration in prediagnostic ALS. Moreover, combining blood and neuroimaging markers may further improve early diagnostic performance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467119","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":"Vascular–Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood–Brain Barrier Dysfunction","authors":"Carlangelo Carrese,&nbsp;Chiara Giuseppina Bonomi,&nbsp;Francesca Bernocchi,&nbsp;Martina Gaia Di Donna,&nbsp;Martina Poli,&nbsp;Guido Greco,&nbsp;Nicola Biagio Mercuri,&nbsp;Alessandro Martorana,&nbsp;Caterina Motta","doi":"10.1111/ene.70679","DOIUrl":"10.1111/ene.70679","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Blood–brain barrier (BBB) dysfunction is an early feature of Alzheimer's disease (AD), influenced by amyloid pathology, astrocyte activation, and vasoactive mediators such as endothelin-1 (ET-1). ET-1 has been implicated in apoptosis and vascular senescence through induction of p53, a pro-apoptotic factor, whereas BCL-X exerts antiapoptotic effects. We investigated the interplay between ET-1, p53, and BCL-X in AD and their contribution to BBB permeability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied 101 individuals (70 AD, 31 controls) who underwent cerebrospinal fluid (CSF) analysis for Aβ42, p-tau, ET-1, p53, BCL-X, and the CSF/serum albumin quotient (QAlb), an index of BBB permeability. Correlations between biomarkers were explored, followed by multiple regression and mediation analysis to assess whether p53 mediated the ET-1–BBB relationship.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No absolute differences in ET-1, p53, or BCL-X were found between AD and controls. However, in AD, ET-1 correlated positively with p53 and negatively with BCL-X, whereas no such associations were seen in controls. None of these biomarkers related to the p-tau/Aβ42 ratio. Regression analysis identified both ET-1 and p53 as independent predictors of BBB permeability. Mediation analysis further revealed that ET-1 influenced BBB permeability both directly and indirectly through p53.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that AD is characterized less by absolute biomarker changes and more by altered interrelationships linking ET-1, apoptosis, and BBB integrity. ET-1 may promote BBB dysfunction partly via p53, which is consistent with the mechanisms of vascular senescence. These results highlight apoptosis–vascular interactions as potential drivers of BBB impairment in AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435700","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":"Speech-In-Noise Perception in Alzheimer's Disease and Primary Progressive Aphasia","authors":"Sophie A. Froud,&nbsp;Benjamin A. Levett,&nbsp;Jessica Jiang,&nbsp;Lucy B. Core,&nbsp;Nehzat Koohi,&nbsp;Madison Tutton,&nbsp;Tim Green,&nbsp;Doris-Eva Bamiou,&nbsp;Charles R. Marshall,&nbsp;Chris J. D. Hardy,&nbsp;Jason D. Warren","doi":"10.1111/ene.70701","DOIUrl":"10.1111/ene.70701","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Understanding speech despite background noise is essential for everyday communication, but makes heavy neural processing demands. It is therefore potentially vulnerable to neurodegenerative diseases, particularly those led by communication deficits (primary progressive aphasia). However, how speech-in-noise perception is affected in these diseases is poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here we addressed this in 59 patients representing typical Alzheimer's disease and canonical logopenic, nonfluent/agrammatic and semantic variant syndromes of primary progressive aphasia, compared with 24 cognitively-well, older controls. We administered a digit triplet test of speech-in-noise perception based on the task used in the UK Biobank study, alongside pure tone audiometry and a general neuropsychological assessment. Voxel-based morphometry of patients' brain MRI scans was used to identify structural neuroanatomical associations of speech-in-noise perception.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After adjusting for age, peripheral hearing and general cognitive function, the Alzheimer's, logopenic and nonfluent primary progressive aphasia groups performed significantly worse on speech-in-noise perception than controls. The nonfluent primary progressive aphasia and Alzheimer groups additionally had significantly worse peripheral hearing function than controls. Speech-in-noise perceptual performance correlated with grey matter atrophy in the right supramarginal gyrus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Profiles of central (brain) and peripheral hearing impairment stratify major dementias, with implications for diagnosis and development of interventions to improve real-world communication in people living with dementia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435691","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":"Comorbidities and Complications in Parkinson’s Disease in Primary Care","authors":"Olaitan Okunoye,&nbsp;Laura Horsfall,&nbsp;Louise Marston,&nbsp;Kate Walters,&nbsp;Anette Schrag","doi":"10.1111/ene.70697","DOIUrl":"10.1111/ene.70697","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is associated with an increased rate of mortality. It is unclear whether this is due to complications and comorbidities associated with the disease or the disease process of PD itself.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We undertook a cohort study in patients with PD in an electronic primary care record database. Mortality rate ratios and risk differences per 1000 person-years were calculated for each complication and comorbidity using multivariable Poisson regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 10,104 patients with incident PD and 55,664 controls. The rate of falls, dementia, hallucinations, postural hypotension, stroke, depression, anxiety, sleep disorders, gastrointestinal and urinary disorders, headaches, epilepsy, and myocardial infarction was higher in individuals with PD compared to controls. Conversely, the rates of chronic obstructive pulmonary disease (COPD), congestive heart failure, and gout were lower. In the PD group, the comorbidities of dementia, falls, stroke, cancer, chronic heart failure, COPD, myocardial infarction, and gastrointestinal disorders were associated with higher mortality rates. However, for all comorbidities, the increase in mortality rate was similar to or lower in the PD group compared to people without PD, except for falls which tended to be associated with higher mortality in the PD group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides data on the increased rate of mortality associated with different complications and comorbidities in PD. The mortality associated with these alone, however, does not explain the increased mortality in PD. This underscores the need for treatments to slow the underlying disease process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435648","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}