European Journal of Neurology最新文献

{"title":"Harmonized Acquisition of Connectome MRI and Clinical Data for Stroke, Parkinson's Disease and Glioma: Delphi-Derived Protocol Recommendations by the European Academy of Neurology","authors":"Thomas Berger,&nbsp;Lorenzo Pini,&nbsp;Alessandro Salvalaggio,&nbsp;Simone Cauzzo,&nbsp;Christine Klein,&nbsp;Maria Lolich,&nbsp;Alberto Picca,&nbsp;Dauren Ramankulov,&nbsp;Maria A. Rocca,&nbsp;Roberta Rudà,&nbsp;Alessandro Sodero,&nbsp;Alessandro Tessitore,&nbsp;Thomas Truelsen,&nbsp;Roland Wiest,&nbsp;Gereon R. Fink,&nbsp;Elena Moro,&nbsp;Philippe Ryvlin,&nbsp;Maurizio Corbetta","doi":"10.1111/ene.70708","DOIUrl":"10.1111/ene.70708","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction and Aims</h3>\u0000 \u0000 <p>The European Academy of Neurology (EAN) joined the Horizon Europe EBRAINS 2.0 research consortium to co-develop recommendations for prospective acquisition and integration of clinical and research core multi-scale human datasets for connectome analysis in stroke, Parkinson's disease (PD), and glioma (GBM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using an online Delphi survey method, expert consensus was sought on 28 statements for each of the following protocols in stroke, PD and GBM: clinical core/research brain MRI, minimum/extended clinical outcomes, minimum/extended cognition assessments, case report forms (CRF). The level of agreement for each statement was predefined as ≥ 80%. 536 experts from four EAN Scientific Panels (SP) (SP Neuro-oncology [<i>n</i> = 70], SP Movement Disorders [<i>n</i> = 206], SP Neuroimaging [<i>n</i> = 112], SP Stroke [<i>n</i> = 148]) were invited to participate in this Delphi process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two Delphi voting rounds were conducted to reach the predefined level of agreement (≥ 80%; range: 80.49%–100%) for all items to establish consensus on protocol recommendations for stroke, PD and GBM. Cumulative response rate from SP experts was 25% (<i>n</i> = 135 from 30 European countries) for the first, and 32% (<i>n</i> = 173 from 35 European countries) for the second Delphi voting round.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>These consented protocols provide a pragmatic framework for harmonizing multi-scale data acquisition for connectome analyses in stroke, PD, and GBM. Further, these protocols allow future modular extensions for other datasets, e.g., neurophysiological data or non-imaging biomarkers, and serve as a role model for brain network analyses in other neurological disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911208","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":"Tear Fluid Calcitonin Gene-Related Peptide Levels Are Elevated in Glycerol Trinitrate-Induced Cluster Headache Attacks: Results From an Exploratory Study","authors":"Katharina Kamm,&nbsp;Maria Angelhuber,&nbsp;Adrian Marius Le Prince,&nbsp;Andreas Straube,&nbsp;Ruth Ruscheweyh","doi":"10.1111/ene.70745","DOIUrl":"10.1111/ene.70745","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cluster headache (CH) is a primary headache disorder characterized by severe, unilateral headache attacks accompanied by trigemino-autonomic symptoms. Calcitonin gene-related peptide (CGRP) is thought to be released during CH attacks, although the role of CGRP has been questioned. In this exploratory study, we investigated tear fluid CGRP levels during experimentally induced CH attacks using glycerol trinitrate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Active episodic and chronic CH patients were screened at study Day 1 and eligible patients received sublingual glycerol trinitrate 0.9 mg at study Day 2. Headache characteristics and tear fluid were sampled before and after intake of GTN. Tear fluid CGRP levels were analyzed using a commercial CGRP ELISA (Cusabio, Wuhan, China).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>89 episodic (eCH) and chronic cluster headache (cCH) patients were screened. Of these, 18 CH patients (eCH <i>n</i> = 11, 42.6 ± 10.0 years) were included in the analysis. Of 16 CH patients reported an experimentally induced CH attack, tear fluid CGRP levels significantly increased from “baseline” to “headache” (“baseline”: 2.34 ± 3.22 ng/mL, “headache”: 3.70 ± 5.60 ng/mL; <i>p</i> = 0.019). Tear fluid CGRP levels increased significantly more in participants with an intense headache attack (NRS ≥ 5: +2.65 ± 3.51 ng/mL) compared to participants with a mild intensity (NRS &lt; 5: +0.07 ± 0.83 ng/mL, <i>p</i> = 0.015).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study results support the role of CGRP in the pathophysiology of CH. Further studies with a larger study sample and investigation of other neuropeptides are needed to better understand the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905437","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":"Artificial Intelligence for Improving the Management of People With Epilepsy in Low-and-Middle Income Countries","authors":"Philippe Ryvlin,&nbsp;Sándor Beniczky,&nbsp;Harald Aurlien,&nbsp;Adriano Bernini,&nbsp;Gabriel Davis Jones,&nbsp;Symon M. Kariuki,&nbsp;Antoine Spahr,&nbsp;Jesper Tveit,&nbsp;Arjune Sen","doi":"10.1111/ene.70740","DOIUrl":"10.1111/ene.70740","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>About 80% of people with epilepsy live in low-and-middle-income countries (LMICs) where the treatment gap is high. Limited access to neurologists, diagnostic tools, and antiseizure medications, combined with persistent stigma, contribute to poor outcomes, including premature mortality. Artificial intelligence (AI) offers potential to address these gaps through scalable, low-cost solutions for diagnosis, investigation, management, and monitoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review examines three recent and complementary AI applications in epilepsy care for LMICs: a smartphone-based diagnostic tool for convulsive epilepsy developed using population-based data from five sub-Saharan African countries; an automated EEG interpretation system based on a deep learning model (SCORE-AI) validated across multicenter datasets; and a wearable-based deep learning model for detecting generalized convulsive seizures using low-cost smartwatches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The smartphone diagnostic tool achieved area under the curve (AUC) 0.92–0.95 with sensitivity 85.0%–97.5% for identifying epilepsy with convulsive seizures using eight binary clinical features. SCORE-AI demonstrated expert-level performance (AUC 0.89–0.96, accuracy 85%–92%) for automated EEG classification across multiple validation datasets. The wearable seizure detection algorithm achieved 96% sensitivity with approximately one false alarm per 8 days. All three solutions were designed for deployment on widely accessible platforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AI-driven approaches demonstrate feasibility for addressing diagnostic and monitoring gaps in resource-limited settings. However, implementation faces substantial challenges including infrastructure constraints, limited digital literacy, ethical considerations, and sociocultural factors. Successful deployment requires validation with large locally relevant datasets, context-adapted solutions, task-sharing strategies, implementation research, appropriate regulatory frameworks/certification, and community engagement to reduce the global epilepsy care gap.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905433","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":"Asymptomatic Carrier Neurologic Assessment: A Tool for Early Detection of Symptomatic Transition in Pathogenic TTR Gene Variant Carriers","authors":"Isabel Conceição,&nbsp;Juan González-Moreno,&nbsp;Andoni Echaniz-Laguna,&nbsp;Kuangnan Xiong,&nbsp;Adam Castaño,&nbsp;Jonathan C. Fox,&nbsp;Julian D. Gillmore,&nbsp;Pablo Garcia-Pavia,&nbsp;Mary M. Reilly","doi":"10.1111/ene.70729","DOIUrl":"10.1111/ene.70729","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary variant transthyretin amyloidosis (ATTRv) is caused by &gt; 140 pathogenic <i>TTR</i> gene variants. The heterogeneous presentation of ATTRv clinical phenotypes complicates diagnosis and staging of patients. Tools that improve early detection of ATTRv symptoms and signs and identify risk of transition to clinically detectable disease are needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective, multicenter study at amyloid centers in France, Spain, Portugal, and the United Kingdom (December 2023–December 2024) assessed asymptomatic carriers (ACs) and ACs who transitioned to symptomatic disease within the previous 2 years (newly symptomatic carriers [NSCs]). A new 23-question asymptomatic carrier neurologic assessment (ACNA) was developed to screen for the potential transition to clinically detectable ATTRv-polyneuropathy (PN). Question topics spanned sensory, autonomic, and systemic signs and symptoms. Fisher's exact tests were conducted to evaluate the association between each individual question and disease status (i.e., NSC vs. AC). Logistic regression models with a Firth correction were used to estimate odds ratios and corresponding 95% confidence intervals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 217 carriers (AC, <i>n</i> = 128; NSC, <i>n</i> = 89) with 18 unique transthyretin variants; 166 (76.5%) had p.Val50Met. Of 23 ACNA questions, 17 were significantly associated with transition to symptomatic disease for all patients. The pattern of neurologic signs and symptoms found to be associated with p.Val50Met and other common variants reflected what is known about variant-specific symptomatology. Confounding factors included age, medical center of treatment, and variant type.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The ACNA questionnaire may be a clinically valuable tool to screen ACs for risk of transition to symptomatic ATTRv-PN but requires validation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900354","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":"Protein Biomarkers in Risk and Prognosis of Amyotrophic Lateral Sclerosis","authors":"Lu Pan,&nbsp;Can Hou,&nbsp;Christina Seitz,&nbsp;Caroline Ingre,&nbsp;Åsa K. Hedman,&nbsp;Jose Laffita,&nbsp;Trung Nghia Vu,&nbsp;Yudi Pawitan,&nbsp;Abbe Ullgren,&nbsp;Solmaz Yazdani,&nbsp;John Andersson,&nbsp;Emily E. Joyce,&nbsp;Charilaos Chourpiliadis,&nbsp;Anikó Lovik,&nbsp;Yan Chen,&nbsp;Sebastian A. Lewandowski,&nbsp;Oscar Fernandez-Capetillo,&nbsp;Myriam Barz,&nbsp;Kristin Samuelsson,&nbsp;Rayomand Press,&nbsp;Fredrik Piehl,&nbsp;Caroline Graff,&nbsp;Anders Mälarstig,&nbsp;Fang Fang","doi":"10.1111/ene.70741","DOIUrl":"10.1111/ene.70741","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Plasma and cerebrospinal fluid (CSF) protein biomarkers in amyotrophic lateral sclerosis (ALS) may provide insight into disease mechanisms and yield clinically useful biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Overall, 363 proteins in plasma and CSF from 198 patients with ALS and 125 matched controls were profiled using Olink assays. Associations with disease status, survival, and functional decline, as well as longitudinal biomarker stability across the disease course were assessed, together with network and enrichment analyses. ALS risk-associated biomarkers were externally validated in the UK Biobank (UKB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 125 proteins were significantly associated with at least one outcome (i.e., case status, risk, survival, or functional decline), and 21 were associated with three or more outcomes. NEFL was the most robust biomarker in plasma and CSF, alongside TNFRSF12A in plasma and CSF, EDA2R in plasma, and FABP4 in plasma and CSF. Most biomarkers remained stable longitudinally across the disease course. ALS risk-associated biomarkers were replicated in UKB, in which &gt; 3000 plasma proteins were measured in 52,990 participants, including 298 with ALS. Network and enrichment analyses highlighted their roles in immune response and extracellular-matrix remodeling, and their enrichments in the brain and T-cell subsets. Construction of an ALS risk-prediction model achieved an ROC-AUC of 0.72 in the UKB validation cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest candidate protein biomarkers for ALS risk stratification, early detection, and clinical therapeutic monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891157","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":"Correction to “A Population-Based Study of Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome During Pregnancy and Puerperium”","authors":"","doi":"10.1111/ene.70748","DOIUrl":"10.1111/ene.70748","url":null,"abstract":"<p>\u0000 <span>V. Teresa</span>, <span>V. Liisa</span>, <span>R. Kirsi</span>, et al., “ <span>A Population-Based Study of Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome During Pregnancy and Puerperium</span>,” <i>European Journal of Neurology</i> <span>33</span>, no. <span>5</span> (<span>2026</span>): e70615, https://doi.org/10.1111/ene.70615.\u0000 </p><p>We have identified several errors in our article.</p><p>First, in the “Discussion” section (paragraph 2), we state: “Moreover, the incidence of PRES was 30 per 100,000 among eclamptic women in another study [12].” This statement is incorrect. The sentence should read: “Moreover, the incidence of eclampsia-associated PRES was 0.03% (30 per 100,000 deliveries) in a previous study [12].”</p><p>Second, in Figure 1, the exclusion number “459” is incorrect and should be corrected to “377.” In addition, we suggest correcting minor grammatical errors ( e.g., replacing “associated to pregnancy” with “associated with pregnancy”).</p><p>Third, Figure 2 contains incorrectly labeled time periods. The period 1997–2002 should be revised to 1997–2001, and 2003–2006 should be revised to 2002–2006, reflecting the intended 5-year intervals.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891236","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":"Intrathecal Plasma Cell Activity as Measured by the Kappa Free Light Chain Index Is Associated With Retinal Layer Atrophy in Early Multiple Sclerosis.","authors":"Klaus Berek, Martin Schmidauer, Fabian Föttinger, Michael Auer, Thomas Berger, Franziska Di Pauli, Luisa Velez Escola, Thomas Hofer, Barnabas Kremser, Stephanie Mangesius, Jan P Nolte, Marie-Christine Pali, Berthold Pemp, Katharina Stock, Markus Tiefenthaler, Janette Walde, Anne Zinganell, Florian Deisenhammer, Gabriel Bsteh, Harald Hegen","doi":"10.1111/ene.70759","DOIUrl":"10.1111/ene.70759","url":null,"abstract":"<p><strong>Background: </strong>The relationship between intrathecal kappa free light chain (κ-FLC) synthesis and retinal layer atrophy in multiple sclerosis (MS) is unknown.</p><p><strong>Objective: </strong>To investigate whether the κ-FLC index is associated with peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIPL) thickness.</p><p><strong>Methods: </strong>Patients with newly diagnosed clinically isolated syndrome or relapsing MS and available cerebrospinal fluid (CSF) analysis and optical coherence tomography (OCT) were included. Clinical and magnetic resonance imaging (MRI) data were also assessed. κ-FLC concentrations were measured by nephelometry, and the κ-FLC index was calculated as (CSF κ-FLC/serum κ-FLC)/albumin quotient.</p><p><strong>Results: </strong>A total of 100 patients at a median age of 33 (25th-75th percentile: 25-39) years and a female predominance (58%) were included. In multivariable linear regression analysis adjusted for age, sex, disease duration, number of T2-hyperintense and number of contrast-enhancing MRI lesions, the κ-FLC index was associated with pRNFL (log-transformed κ-FLC index: β: -2.51; 95% confidence interval [CI]: -4.01, -1.01; p = 0.001) and GCIPL thinning (log-transformed κ-FLC index: β: -1.24, 95% CI: -2.32, -0.17; p = 0.024).</p><p><strong>Conclusions: </strong>Intrathecal plasma cell activity, as measured by the κ-FLC index, is associated with neuroaxonal damage, as reflected by pRNFL and GCIPL atrophy.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":"e70759"},"PeriodicalIF":4.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001455","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":"Association of Time of Day With Functional Outcome in Intracerebral Hemorrhage.","authors":"Franziska Lieschke, Eng H Lo, Emiri T Mandeville, Christian Foerch, Elizabeth B Klerman, Jeffrey L Saver, Erik Maronde, Jan Hendrik Schaefer, Ferdinand O Bohmann, Thorsten Steiner, Marco Stein, Björn Misselwitz, Daniel T Marggrander","doi":"10.1111/ene.70762","DOIUrl":"10.1111/ene.70762","url":null,"abstract":"<p><strong>Background: </strong>The timing of ischemic stroke and intracerebral hemorrhage (ICH) onsets follow distinct daily patterns, but it remains unclear whether these patterns influence ICH outcomes.</p><p><strong>Methods: </strong>Consecutive data were obtained from the prospective stroke inpatient quality assurance registry of Hesse, Germany from 2015 to 2023. Patients with ICH were grouped according to the time of symptom onset: morning (5:00 AM to 10:59 AM), midday (11:00 AM to 4:59 PM), evening (5:00 PM to 10:59 PM), and night (11:00 PM to 4:59 AM). The primary outcome was global disability at discharge, analyzed using ordinal logistic regression. Secondary outcomes included mortality and complications during hospitalization. To account for potential confounding, the analysis incorporated both inverse probability weighting (IPW) and propensity score matching (PSM) based on baseline characteristics.</p><p><strong>Results: </strong>After exclusions, 5665 patients underwent final analysis. Peak ICH incidences occurred around 8:30 AM and 5:00 PM with a minimum at approximately midnight. Patients experiencing ICH during the evening and particularly at night had higher discharge disability, compared to those with symptom onset in the morning or midday. Unadjusted analyses found daily variations in mortality and in-hospital complications that were no longer significant after adjustment by PSM or IPW.</p><p><strong>Conclusion: </strong>Our study confirms the daily pattern previously observed in ICH onset, with peak onset during daytime. Functional outcomes were worse in evening and night onset ICH patients. These findings underscore the potential for chronobiologically informed prevention and treatment strategies and the need for further research into time-dependent pathophysiology and care delivery.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":"e70762"},"PeriodicalIF":4.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001460","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":"Migraine and Work-Disability: New Treatments Reduce Work-Related Burden Among Migraine Population","authors":"Danilo Antonio Montisano,&nbsp;Gloria Vaghi,&nbsp;Claudia Altamura,&nbsp;Alessandra Parisi,&nbsp;Roberto De Icco,&nbsp;Marilena Marcosano,&nbsp;Alessia Marcassoli,&nbsp;Erika Guastafierro,&nbsp;Michele Corrado,&nbsp;Domenico D'Amico,&nbsp;Grazia Sances,&nbsp;Fabrizio Vernieri,&nbsp;Cristina Tassorelli,&nbsp;Alberto Raggi,&nbsp;Licia Grazzi","doi":"10.1111/ene.70738","DOIUrl":"10.1111/ene.70738","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Migraine's economic burden is mostly due to reduced work productivity, which is underestimated by commonly used patient-reported outcome measures (PROMs). In this prospective, multicentric, real-world study, we used the HEADWORK questionnaire (HWq), a disease-specific work-related PROM, to assess the impact of anti-calcitonin gene receptor peptide (anti-CGRP) monoclonal antibodies (mAbs) on work-related limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Migraine patients eligible for treatment with anti-CGRP mAbs were enrolled from three headache centers: IRCCS C.Besta, Mondino Foundation and Policlinico Campus Bio-Medico. Migraine days per month (MMDs), monthly acute medications (MAMs), and HWq were collected every 3 months up to 12 months of follow-up. A GLM design was used to address change in HWq scales' score (primary endpoint), MAMs and MMDs; we also tested whether change in HWq differed across responders' group and defined minimum clinically important difference (MCID) for HWq.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 175 patients (130 females, mean age 48.9 ± 8.8) 152 completed the study. Among them: 37 (24.3%) were non-responders, 69 (45.4%) were responders, and 46 (30.3%) were super-responders. A reduction in all endpoints was observed since the first 3 months of treatment and maintained up to 12-month follow-up. Time*group interaction showed a superior effect, both in HWq scales and MAMs, with super-responders achieving the best outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A significant reduction in MMDs and MAMs and an improvement in both HWq scales in patients under mAbs treatment was found from the 3-month follow-up onwards. The positive impact on work-related disability should be taken into consideration in planning cost-effectiveness evaluations and drug policy strategy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863916","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":"Letter to the Editor in Reply to: “Advanced ET” Is a More Appropriate Term Than “ET-Plus”","authors":"Luca Angelini,&nbsp;Matteo Bologna","doi":"10.1111/ene.70744","DOIUrl":"https://doi.org/10.1111/ene.70744","url":null,"abstract":"&lt;p&gt;We sincerely thank the author for his thoughtful comments [&lt;span&gt;1&lt;/span&gt;] and for his generous appraisal of our longitudinal study. We are particularly encouraged that our work [&lt;span&gt;2&lt;/span&gt;] is viewed as contributing to the ongoing discussion on the natural history, heterogeneity, and classification of essential tremor (ET). We fully agree that prospective longitudinal studies are essential to better understand disease evolution and ultimately develop a biologically meaningful staging system.&lt;/p&gt;&lt;p&gt;Indeed, we believe that one of the main messages of our study is that ET is a dynamic disorder, in which both motor and non-motor manifestations evolve over time [&lt;span&gt;2, 3&lt;/span&gt;]. Our findings support the concept that, in many patients, additional neurological features progressively emerge due to the combined effects of disease evolution and aging phenomena per se. In this respect, we agree that some manifestations currently included within the ET-plus construct may represent later stages of ET rather than a separate disease entity.&lt;/p&gt;&lt;p&gt;At the same time, we believe that the currently available evidence does not yet allow ET-plus to be considered synonymous with “advanced ET.” While this remains an attractive and plausible hypothesis, it has not yet been validated longitudinally. A staging framework requires that stage-defining features show relatively consistent longitudinal trajectories. However, the ET-plus construct encompasses a heterogeneous spectrum of soft signs that may differ in their biological significance and temporal evolution.&lt;/p&gt;&lt;p&gt;Importantly, the diagnosis of ET-plus is longitudinally unstable, with patients moving between ET and ET-plus during prospective follow-up [&lt;span&gt;4&lt;/span&gt;]. This suggests that at least some soft signs may not behave as stable stage-defining features and reinforces the need to better understand their natural history before incorporating them into a staging model. Rather than viewing these observations as arguments against disease staging, we believe they highlight an important intermediate step. Staging and phenotyping may represent complementary rather than competing approaches.&lt;/p&gt;&lt;p&gt;Future studies may instead characterize individual soft-sign phenotypes, as previously proposed [&lt;span&gt;5&lt;/span&gt;], since parkinsonian, dystonic, cerebellar, gait-related, and cognitive features may differ in longitudinal stability, biological substrate, and prognostic significance. Some of these phenotypes may reflect disease progression, whereas others may identify distinct or overlapping biological trajectories.&lt;/p&gt;&lt;p&gt;We therefore share the author's view that longitudinal studies are fundamental for refining the classification of ET and for developing a clinically meaningful staging system. However, we believe that an important prerequisite is to determine the longitudinal significance of individual soft signs, that is, which consistently reflect disease progression and which instead identify distinct biological traj","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816524","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}