cover image European Journal of Neurology

European Journal of Neurology

2026 - Volume 33
Issue 8 | August 2026
Previous Issue

ISSUE INFORMATION

Issue Information

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Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70640

CONSENSUS STATEMENT

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors:
Tim Van Langenhove, Sara Van Mossevelde, Marijke Miatton, Jan De Lepeleire, Rose Bruffaerts, Jean Christophe Bier, Kurt Segers, Jurn Verschraegen, Mirko Petrovic, Manfredi Ventura, Haroun Jedidi, Ingo Beyer, Eric Mormont, Rik Vandenberghe, Aline Delva, Christian Gilles, Donatienne Van Weehaeghe, Gaëtane Picard, Peter De Deyn, Mélanie Strauss, Evert Thiery, Eric Salmon, Gert Cypers, Joris Vlaemynck, Katrin Gillis, Jan Versijpt, Maria Bjerke, Anne Sieben, Bernard Hanseeuw, Sebastiaan Engelborghs and Olivier Deryck
Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70668

ORIGINAL ARTICLE

Objective

To assess awareness, attitudes, and preparedness among Italian epilepsy‐care professionals regarding the impact of climate change on epilepsy management.

Methods

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.

Results

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).

Conclusions

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.

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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 and Emilio Russo
Article first published online:
21 Aug 2026 | DOI: 10.1111/ene.70684

REVIEW ARTICLE

Background and Purpose

While the estimation of the climate change effects is dependent on the models used, there is a growing consensus that emissions of greenhouse gases (GHG) cause global warming, resulting in the acceleration of climate change. The degree to which climate change is going to affect the nervous system of healthy individuals and how it may lead to an increase in the prevalence and burden of neurological disorders is presently incompletely understood and studied. It is imperative that the neurological community increases its awareness about climate change and strives for a clear evidence‐based consensus on the relationship between climate change and the negative consequences on brain health and neurological disorders.

Methods

Part I provides a narrative overview of climate change in neurology, whereas Part II focuses on climate change action in neurology.

Results

We provide clinicians and neuroscience stakeholders with tools to understand key concepts at the interface between climate change, neurological disorders, and brain health. Moreover, this paper states priorities in this field for the European Academy of Neurology, through the work of the Environmental Influences in Neurology Task Force, presenting 10 operational areas adapted from the WHO .

Conclusion

In the frame of its Brain Health Mission, the European Academy of Neurology is committed to supporting a neurology that is able to understand the impact of climate change and become a climate‐resilient neurology to promote health in general and brain health specifically.

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Authors:
Edoardo Caronna, Sanjay M. Sisodiya, Patricia Pozo‐Rosich, Antonia Boesch, Jacques Reis, Anita Arsovska, Elisa Baldin, Cristian Falup‐Pecurariu, Thomas Foiadelli, Maria Gogou, Matilde Leonardi, Nathalie Nasr, Justyna Paprocka, Mohamed Salama, Ambra Stefani, Antonio Toscano, Claudio L. A. Bassetti, Paul Boon, Elena Moro and Ulf Kallweit
Article first published online:
21 Aug 2026 | DOI: 10.1111/ene.70687

ORIGINAL ARTICLE

Objective

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.

Methods

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).

Results

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%).

Conclusions

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.

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Authors:
Carolina Barnett‐Tapia, Kobina Quansah, Aysegul Erman, Nikhil Nath, Shane Golden, Ryan Ng, Arushi Sharma and Ari Breiner
Article first published online:
21 Aug 2026 | DOI: 10.1111/ene.70694

ORIGINAL ARTICLE

Background

Reproductive health is a critical component of care for women with multiple sclerosis (MS), yet standardized interdisciplinary approaches remain limited.

Objectives

This Delphi consensus aimed to develop an interdisciplinary, evidence‐informed care model tailored to the Italian healthcare system.

Results

A two‐round Delphi process was conducted in Italy (June–July 2025), involving MS experts (Round 1: 107, Round 2: 95), including neurologists, gynecologists, pediatricians, nurses, and patient representatives. Participants evaluated key aspects of the reproductive care pathway, from preconception counseling to postpartum follow‐up, to identify priorities and areas of agreement across disciplines. Strong consensus was achieved on the importance of early counseling, coordinated interdisciplinary management, and individualized treatment planning across the reproductive continuum. The central role of nurses in patient education was also emphasized. Divergence emerged regarding the continuation of specific therapies during pregnancy and the role of neonatal immunological monitoring following exposure to depleting agents, reflecting areas of ongoing uncertainty and limited evidence.

Conclusions

This consensus proposes the first interdisciplinary framework for reproductive care in MS within the Italian context. It emphasizes patient‐centered decision‐making, collaboration across specialties, and the integration of reproductive health into routine MS management. By identifying both shared priorities and unresolved challenges, it provides a foundation for more harmonized, evidence‐informed clinical practice and future research.

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Authors:
Emilio Portaccio, Paola Cavalla, Lucia Moiola, Francesco Patti, Luca Marozio, Paolo Palma, Martina Campobasso, Federica Balzani, Alessia Villani, Valentina Sara Barbiero, Daniela Facchinello, Raffaella Robello and Girolama Alessandra Marfia
Article first published online:
06 Aug 2026 | DOI: 10.1111/ene.70700

INVITED REVIEW

Introduction

Lack of standardised methodologies and secure processing environments for intracerebral EEG (iEEG) data creates critical barriers to international collaboration and reproducibility in clinical neuroscience. Within the framework of the Human Brain Project and EBRAINS, we have developed a specific platform, the Human Intracerebral EEG Platform (HIP), to address this challenge.

Methods

The specifications considered to develop the HIP included: (1) secure access to sensitive datasets; (2) standardised data organisation following the BIDS for iEEG (BIDS‐iEEG) to ensure interoperability; (3) controlled access via a secure web‐based interface; (4) provision of software needed to analyse iEEG; (5) a structured governance model enabling institutional participation through formal data sharing agreements; and (6) alignment with FAIR principles.

Results

HIP was implemented as a cloud‐based Trusted Research Environment (TRE), with a first operational release in 2023. It provides private spaces for each participating institution and researchers, as well as collaborative spaces to share data. The HIP operates many software packages, including 3DSlicer, Brainstorm, HiBoP, etc., and CiCLONE, a tool specifically designed to coregister and visualise electrodes and recording leads on MRI and brain atlas. So far, the HIP hosts 34 institutions and 10 ongoing projects, including that on heartbeat potentials that show promising findings toward a better understanding of central autonomic dysfunction in persons with epilepsy.

Conclusions

The HIP addresses key barriers to large‐scale iEEG research by combining secure governance, standardised data management, and collaborative analysis within a dedicated TRE, facilitating reproducible multi‐centre research.

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Authors:
Carolina Ciumas, Florian Perrin, Florian Sipp, Nathalie Casati, Guy Spuhler, Anthony Boyer, Jonathan Haab, Viktoria Bastic Schmid, Birgit Schaffhauser, Georges Melissargos, Evan Hancock, Olivier David and Philippe Ryvlin
Article first published online:
21 Aug 2026 | DOI: 10.1111/ene.70702

ORIGINAL ARTICLE

Background

This study aimed at identifying neuropsychological sub‐phenotypes in amyotrophic lateral sclerosis (ALS) within the mild cognitive impairment (MCI) and mild behavioral impairment (MBI) frameworks.

Methods

We used individual task−/item‐level data from the cognitive and behavioral sections of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) from 901 non‐demented ALS to derive neuropsychological sub‐phenotypes pursuant to classical MCI and MBI frameworks and in accordance with an expanded version of Strong's criteria, which also addressed memory and visuo‐spatial measures.

Results

The prevalence of MCI and MBI was 39% and 37%, respectively in this retrospective review. The following MCI sub‐phenotypes were identified: dysexecutive MCI—single‐ and multiple‐domain (dMCI‐sd: 63%; dMCI‐md: 24%, respectively); non‐dysexecutive MCI—single‐ and multiple‐domain (ndMCI‐sd: 12%; ndMCI‐md: 1%, respectively). MBI was classified as follows: apathetic MBI—single‐ and multiple‐domain (aMBI‐sd: 40%; aMBI‐md: 20%, respectively); apathetic‐disinihibited/perseverative MBI—multiple domain (ad/pMBI‐md: 21%); disinihibited/perseverative MBI—multiple domain (d/pMBI‐md: 7%); psychotic MBI—single‐ and multiple‐domain (psyMBI‐sd: 2%; psyMBI‐md: 3%, respectively); unclassifiable MBI—multiple domain (uMBI‐md: 1%). 143 (16%) of patients exhibited mild cognitive and behavioral impairment (MCBI).

Conclusions

This study delivers a provisional, ECAS‐based classification for the neuropsychological sub‐phenotyping of non‐demented ALS patients, which, with further validation, might be useful for both research and clinical purposes.

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Authors:
Barbara Poletti, Edoardo Nicolò Aiello, Monica Consonni, Barbara Iazzolino, Silvia Torre, Veronica Faltracco, Alessandra Telesca, Francesca Palumbo, Beatrice Curti, Giulia De Luca, Arianna Moreschi, Francesca Frisco, Eleonora Dalla Bella, Enrica Bersano, Nilo Riva, Federico Verde, Stefano Messina, Alberto Doretti, Alessio Maranzano, Claudia Morelli, Stefano Francesco Cappa, Andrea Calvo, Michael J. Strong, Vincenzo Silani, Giuseppe Lauria, Adriano Chiò and Nicola Ticozzi
Article first published online:
03 Aug 2026 | DOI: 10.1111/ene.70706

ORIGINAL ARTICLE

Introduction

Migraine is a common neurological disorder and a non‐traditional risk factor for ischaemic stroke. Its relationship with specific stroke subtypes and post‐stroke outcomes remains unclear. We evaluated the association between migraine (with and without aura), stroke aetiology, functional outcomes, and cardiovascular risk profiles in young patients with ischaemic stroke or TIA.

Methods

Patients aged ≤ 55 years enrolled in the STROKE‐CARD long‐term follow‐up study underwent structured face‐to‐face headache interviews by headache specialists using ICHD‐3 criteria. A predefined protocol collected demographic, clinical, neuroimaging, aetiological, and cardiovascular risk data.

Results

Among 289 young stroke patients (median age 48.0 [41–52] years; 36.3% women), 92 (31.8%) had a history of migraine (51.1% with aura). Migraine was more common in women, associated with younger age at stroke onset and more frequent headache at stroke onset, but not with traditional vascular risk factors. PFO was more prevalent in patients with migraine with aura (68.9% vs. 36.9% no migraine,  < 0.001). No significant differences were observed in stroke territory or stroke pattern. Stroke severity (NIHSS) and functional outcome (mRS) at discharge were more favourable in migraineurs ( ≤ 0.001). In multivariable analysis, migraine without aura was independently associated with good functional outcome (OR 7.21, 95% CI 1.93–26.93,  = 0.003).

Conclusion

In young adults with ischaemic stroke, migraine—particularly with aura—was associated with younger age at stroke onset and a higher prevalence of PFO, while traditional vascular risk factors and stroke characteristics were similar across groups. Despite comparable stroke patterns, patients with migraine experienced more favourable short‐term outcomes.

Trial Registration

Post‐Stroke Disease Management—Stroke Card: ; Stroke Card Long‐term Follow‐Up

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Authors:
Katharina Kaltseis, Silvia Felicetti, Benjamin Dejakum, Lena Weber, Samuel Labrecque, Anel Karisik, Kurt Moelgg, Christian Boehme, Thomas Toell, Lukas Mayer‐Suess, Michael Thomas Eller, Florian Frank, Alois Schiefecker, Stefan Kiechl, Michael Knoflach, Gregor Broessner, Markus Anliker, Julia Ferrari, Martin Furtner, Andrea Griesmacher, Viktoria Hasibeder, Gerhard Klingenschmid, Stefan Krebs, Clemens Lang, Wilfried Lang, Anna Neuner, Raimund Pechlaner, Thomas Porpaczy, Gerhard Rumpold, Christoph Schmidauer, Gudrun Schoenherr, Lisa Seekircher, Martin Sojer, Christine Span, Lydia Thiemann, Lena Tschiderer, Marlies Wichtl, Johann Willeit, Karin Willeit and Peter Willeit
Article first published online:
06 Aug 2026 | DOI: 10.1111/ene.70709

ORIGINAL ARTICLE

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Authors:
Vladimirs Krutovs, Arta Grosmane, Renāte‐Ruta Kažmere, Marija Roddate, Gundega Ķauķe, Diāna‐Patrīcija Grosa, Signe Šetlere, Mikus Dīriks, Guntis Karelis and Viktorija Ķēniņa
Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70710

ORIGINAL ARTICLE

Background

Most people with multiple sclerosis (MS) present with a clinically isolated syndrome (CIS); however, not all individuals with CIS are subsequently diagnosed with MS.

Methods

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 I, 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.

Results

Seventy‐two studies with 9915 adults were included. In the meta‐analysis, younger age (OR = 1.6,  < 0.01) and multifocal presentation (OR = 1.55,  = 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,  = 0.02), periventricular lesions (OR = 4.08,  < 0.01), corpus callosum lesions (OR = 14.89,  = 0.02), infratentorial lesions (OR = 2.16,  = 0.03), spinal cord lesions (OR = 1.4,  = 0.03), and gadolinium‐enhancing lesions (OR = 1.91,  = 0.01), as well as cerebrospinal fluid inflammatory markers such as oligoclonal bands (OR = 3.57,  < 0.01) and pleocytosis (OR = 3.34,  = 0.02), were also associated with a subsequent diagnosis of MS.

Conclusions

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.

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Authors:
María Paula Zafra‐Sierra, Carolina Ferreira‐Atuesta, Daniela Sofía Rodríguez, Jairo Gaitán, Susana Otero, Mar Tintoré, Fred Lublin, Gavin Giovannoni, Jaime Toro and Saúl Reyes
Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70711

COMMENTARY

Personalised Anti‐CD20 Retreatment in Multiple Sclerosis: Precision Medicine or Precision Pharmacology?

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Authors:
Klaus Schmierer
Article first published online:
20 Aug 2026 | DOI: 10.1111/ene.70712

REVIEW ARTICLE

Introduction

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors:
Poul P. Laigaard, Fawzi W. Abla, Melika Hassani, Anna Kristina Eigenbrodt and Daniel Kondziella
Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70713

ORIGINAL ARTICLE

Background

Acute ischemic stroke is a leading cause of death and disability. Despite strong evidence supporting reperfusion therapies and Stroke Unit care, access and quality of stroke services remain heterogeneous across Europe. Although national stroke registries provide valuable real‐world data, fragmentation, limited interoperability, and data protection constraints have restricted multinational analyses and benchmarking.

Methods

The Federating European REgistries for Stroke (FERES) initiative establishes a GDPR‐compliant federated framework for secondary use of stroke registry data. FERES harmonizes heterogeneous datasets through a stroke‐specific Common Data Elements (CDE) model and performs analyses locally within each registry using the Medical Informatics Platform, sharing only aggregated, non‐identifiable outputs. To validate the framework, a predefined showcase analysis comparing anterior versus posterior circulation acute ischemic stroke was executed in both centralized and federated modes using an identical harmonized dataset.

Results

FERES connected five national registries from Austria, Greece, Ireland, Italy, and Switzerland within a unified federated infrastructure. At the time of analysis, 149,772 patient events from two registries were accessible for federated querying, with three additional registries technically integrated and in advanced onboarding. The harmonized ontology comprised 945 standardized variables spanning the stroke care pathway. Federated execution reproduced centralized pooled‐data results across descriptive statistics, hypothesis testing, effect sizes, and multivariable regression models with only minimal numerical discrepancies.

Conclusions

FERES demonstrates that large‐scale, multinational stroke research and benchmarking can be conducted in Europe using a privacy‐preserving federated approach, providing a scalable foundation for cross‐border real‐world evidence generation and quality improvement.

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Authors:
Alexander Salerno, Georges Melissargos, Mira Katan, Michael Knoflach, Stefan Kiechl, Joseph Harbison, Leonardo Renieri, Danilo Toni, Lina Palaiodimou, Georgios Tsivigoulis, Andreas Ktenidis, Theofilos Mailis, Yannis Ioannidis, Patrik Michel and Philippe Ryvlin
Article first published online:
04 Aug 2026 | DOI: 10.1111/ene.70715

ORIGINAL ARTICLE

Background

Cerebral hypoperfusion, an acute manifestation of intracranial arterial stenosis (ICAS), is particularly concerning among older East Asian adults given its high prevalence. Systemic inflammation triggered by PM exposure has been linked to cerebrovascular diseases, yet evidence on its specific components of hypoperfusion in this vulnerable group remains limited. We explore associations between PM and its components exposure with cerebral hypoperfusion, and assess mediation by inflammatory indicators.

Methods

We analyzed 967 patients with symptomatic ICAS at the First Affiliated Hospital of Soochow University. Hypoperfusion was evaluated using multimodal CT imaging and quantified with MIStar software. Three‐year exposure to PM and its components was estimated using the TAP database. Associations were evaluated using generalized additive models and restricted cubic spline regression, while weighted quantile sum regression assessed mixture effects. Mediation analysis quantified inflammatory markers' roles in these relationships.

Results

PM was significantly association with cerebral hypoperfusion (OR = 4.344, 95% CI: 3.323–5.734), with black carbon (BC) showing the strongest association (OR = 4.396, 95% CI: 3.327–5.869), followed by sulfate (SO) (OR = 4.359), organic matter (OM) (OR = 4.278), nitrate (NO) (OR = 3.552), and ammonium (NH) (OR = 3.313). OM (44.2%) and BC (42.2%) contributed 86% of the total mixture effect. Neutrophils mediated 5.37% of the total effect between PM and cerebral hypoperfusion, whereas leukocytes (4.30%) and monocytes (2.73%) demonstrated significant mediation effects.

Conclusion

Prolonged exposure to PM and its components, particularly OM and BC, was associated with increased cerebral hypoperfusion risk, partially mediated by inflammatory responses. These findings highlight the need for component‐targeted air quality policies to reduce cerebrovascular risk in vulnerable populations.

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Authors:
Xingyan Xu, Xinyue Lu, Nan Wang, Liuyan Zheng, Jianhui Guo, Tongjin Xu, Yiming Guo, Hao Li, Yi Yang and Le Yang
Article first published online:
13 Aug 2026 | DOI: 10.1111/ene.70716

ORIGINAL ARTICLE

Background

Amyotrophic lateral sclerosis (ALS) is one of the most devastating fatal motor neuron diseases, characterized by progressive degeneration of motor neurons in the brain and spinal cord. A significant advance in ALS therapy was achieved with the recent European Medicines Agency approval of Tofersen, the first antisense oligonucleotide (ASO) specifically targeting SOD1 mRNA, a key genetic determinant of the disease. Yet, despite its clinical relevance, data on ‐ALS in Central Eastern Europe remain scarce.

Methods

Here, we present a multicentric study across six countries—Austria, Czechia, Poland, Hungary, Slovakia, and Slovenia—representing approximately 16% of the European Union's population. We report all pathogenic, likely pathogenic, and uncertain variants, along with the phenotypic features, including heritability, age, site of onset, and survival. We also assessed the availability of genetic testing, counseling, and access to Tofersen therapy across the region.

Results

Out of 1200 patients with confirmed ALS, we identified 24 distinct pathogenic variants in a total of 67 patients (median age at onset 47 [40–55] years), of whom 65.7% had familial ALS (fALS) and 34.3% had sporadic ALS (sALS). We characterized the associated phenotypes and reported that 42 patients are currently receiving Tofersen therapy.

Conclusion

This study provides the first comprehensive overview of ‐ALS in Central Eastern Europe. Our findings underscore the importance of genetic testing and counseling, as well as equitable access to targeted therapies such as Tofersen to advance patient‐specific care in this region.

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Authors:
Magui Khazaal, Paula Stretavská, Magdalena Kuźma‐Kozakiewicz, Krzysztof Nieporęcki, Adam Betík, Eva Vlčková, Monika Turčanová Koprušáková, Robert Petrovic, Hakan Cetin, Omar Keritam, Wolfgang Löscher, Christian Eggers, Stephan Iglseder, Radoslav Orenčák, Mária Judit Molnár, Zoltán Grosz, Tamás Szlepák, Blaž Koritnik, Magdalena Anna Koszewicz, Daniel Baumgartner and Lenka Slachtova
Article first published online:
19 Aug 2026 | DOI: 10.1111/ene.70717

ORIGINAL ARTICLE

Background

Neuro‐Behçet syndrome (NBS) is a heterogeneous inflammatory disorder in which venous involvement is well recognized, while intracranial arterial pathology remains insufficiently characterized. Conventional luminal imaging methods are limited in detecting early or isolated arterial wall abnormalities. Vessel wall imaging (VWI) may provide additional insights into arterial involvement in NBS.

Methods

Thirty‐nine NBS patients (27 men, 12 women; mean age 38.52 ± 9.54 years) underwent intracranial VWI; 16 were imaged during the attack period and 23 during the attack‐free period. A total of 1170 artery segments were systematically evaluated for wall thickening patterns and contrast enhancement. VWI findings were analyzed in relation to imaging timing, radiological subtype, MR angiography findings, and EDSS.

Results

Vessel wall involvement was found in 16 patients (41%), mainly in the posterior circulation (81%). Concentric wall thickening without enhancement was the most common pattern (80.48%). Vessel wall involvement was significantly more frequent in patients imaged during the attack period compared with those imaged in the attack‐free period (68.8% vs. 21.7%;  = 0.007). Vessel wall enhancement was present only in the attack period ( = 0.022). Notably, higher EDSS scores were significantly associated with multisegmental posterior circulation involvement, particularly when ≥ 3 segments were affected ( = 0.015;  = 0.024).

Conclusion

Intracranial arterial wall involvement is detectable by VWI in a substantial proportion of NBS patients, predominantly in the posterior circulation with a concentric thickening pattern. These findings suggest that arterial wall pathology may be more common than previously recognized and that VWI provides complementary diagnostic information beyond conventional luminal imaging.

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Authors:
Esra Kochan Kizilkilic, Bora Korkmazer, Nursena Erener, Ahmet Kursat Karaman, Abdullah Arcan, Serdar Arslan, Aksel Siva, Emire Seyahi, Ugur Uygunoglu and Osman Kizilkilic
Article first published online:
07 Aug 2026 | DOI: 10.1111/ene.70718

ORIGINAL ARTICLE

Background

Differentiating myogenic from neurogenic neuromuscular diseases (NMDs) can be clinically challenging. While quantitative muscle MRI (qMRI) with proton density fat fraction (PDFF,%) quantifies fat replacement, it misses micro‐spatial patterns linked to underlying pathology. This study investigates whether qMRI with 3D radiomic texture analysis (TA) might improve differentiation between myogenic and neurogenic diseases, using myotonic dystrophy type 1 (DM1) and Charcot–Marie‐Tooth neuropathy type 1A (CMT1A) as proof‐of‐concept models.

Methods

Thirty‐three adults with DM1, 33 with CMT1A, and 33 matched healthy controls were included. qMRI on a 3T Philips Achieva system using a 6‐point Dixon sequence generated PDFF(%) maps of the lower limbs, and a convolutional neural network performed 3D segmentation of 28 lower limb muscles. We extracted macroscopic features, including muscle volume, asymmetry, and disto‐proximal gradients, alongside micro‐spatial radiomic features (entropy, contrast, homogeneity) to quantify tissue heterogeneity.

Results

Both patient cohorts exhibited higher PDFF(%) in all lower limb muscles compared to controls ( < 0.001). DM1 predominantly involved the posterior compartment, while CMT1A targeted the anterolateral compartment with significantly steeper disto‐proximal fat gradients ( < 0.05). TA revealed higher entropy and contrast, and lower homogeneity in CMT1A compared to DM1, reflecting a more reticular pattern of fat infiltration vs. the confluent pattern in DM1.

Conclusion

In this proof‐of‐concept study, 3D radiomic texture analysis of PDFF(%) maps revealed distinct spatial patterns of fat replacement in DM1 and CMT1A. Integrating radiomic and conventional qMRI features may enhance the non‐invasive distinction between DM1 and CMT1A and warrants further investigation in a broader range of NMDs.

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Authors:
Louise Iterbeke, Lotte Huysmans, Kobe Bamps, Ronald Peeters, Veerle Goosens, Frederik Maes, Patrick Dupont and Kristl G. Claeys
Article first published online:
01 Aug 2026 | DOI: 10.1111/ene.70719

ORIGINAL ARTICLE

Objective

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).

Methods

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.

Results

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.

Interpretation

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.

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Authors:
Andrea Calvo, Cristina Moglia, Antonio Canosa, Umberto Manera, Rosario Vasta, Enrico Matteoni, Alessandra Maccabeo, Sara Cabras, Giorgio Pellegrino, Emilio Minerva, Anastasia Dei Giudici, Vita Passidomo, Francesca Palumbo, Barbara Iazzolino, Gabriele Mora and Adriano Chiò
Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70720

ORIGINAL ARTICLE

Background

Long‐term health effects of thymectomy in adults remain uncertain. Previous reports suggested associations with increased mortality, cancer incidence, and autoimmune disease, although these findings may reflect differences in patient selection, surgical indication, or follow‐up duration. We aimed to examine long‐term outcomes following adult thymectomy.

Methods

We performed a propensity score‐matched retrospective study of patients who underwent thymectomy or comparator cardiothoracic procedures, with follow‐up extending to 10 years. Primary outcomes were all‐cause mortality, new‐onset malignancy, and autoimmune disease. Findings were compared with those reported in a recent study that has raised caution regarding thymic excision.

Results

We identified 425 patients who underwent thymectomy and 5401 controls who underwent coronary artery bypass or valve surgery. After matching, 398 patients remained in each group. Thymectomy was not associated with increased mortality at 5 years (HR = 0.63; 95% CI, 0.38–1.04) or 10 years (HR = 0.78; 95% CI, 0.54–1.13). Excluding reclassified thymic cancers, 5‐year extrathymic malignancy incidence was 2.3% versus 1.8% ( = 0.54); no significant differences were observed in immune‐related disease. Mortality was higher among patients with thymic malignancy. Among MG patients, only one event occurred, precluding reliable estimation.

Conclusions

Thymectomy was not associated with excess mortality or malignancy at 10 years compared with matched cardiothoracic controls. Indication‐stratified analyses within the thymectomy cohort showed higher mortality for thymic malignancy, with insufficient events to assess outcomes in MG patients. These findings do not support a generalized survival penalty from thymectomy, though caution is warranted for incidental thymic removal.

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Authors:
Shahar Shelly, Mor Ani, Christopher Klein, Yuebing Li, Henry Kaminski, Gil I. Wolfe, Keren Miron and Roni Ramon‐Gonen
Article first published online:
01 Aug 2026 | DOI: 10.1111/ene.70721

LETTER TO THE EDITOR

Sex and Gender Differences in the Association Between Physical Activity and Cryptogenic Ischemic Stroke in Young Adults

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Authors:
Camilla Cocchi, Giulia Renda, Sabina Gallina and Anna Vittoria Mattioli
Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70722

ORIGINAL ARTICLE

Background

Acquired demyelinating syndromes (ADS) in children include multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), aquaporin 4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD), and other seronegative disorders. We previously reported an increased incidence of overall paediatric ADS and MS between 2007 to 2010 and 2011–2016 (from 0.66 to 0.80 and 0.15 to 0.26 per 100,000 person‐years, respectively). Environmental factors, including viral exposure, may influence these rates. Comparing a recent period that includes the COVID‐19 pandemic provides an opportunity to study temporal patterns.

Methods

Children < 18 years with a first demyelinating event between January 2017 and June 2025 were prospectively included in the nationwide PROUDkids 2.0 study or referred to the Dutch Paediatric MS Centre. Diagnoses followed international criteria, and incidence rates were calculated using national population data.

Results

Among 257 included children, 111 (43%) had MS, 93 (36%) MOGAD, 5 (2%) AQP4+ NMOSD, and 48 (19%) seronegative ADS. Overall ADS incidence was 0.91 per 100,000 person‐years, with MS 0.40, MOGAD 0.33, AQP4+ NMOSD 0.02, and seronegative ADS 0.16 per 100,000 person‐years. Compared with 2011–2016 (0.26 per 100,000), MS incidence increased, whereas other ADS rates remained stable. MS incidence declined after COVID‐19 restrictions, particularly among adolescents, while MOGAD incidence rose modestly in younger children during the COVID restrictions.

Conclusions

Paediatric MS incidence continues to rise in the Netherlands, whereas the incidence of other ADS remains stable. Temporal variations in the incidence of MS and MOGAD during and after the COVID‐19 pandemic may reflect the influence of viral exposure in their pathogenesis.

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Authors:
Sandy Molenaar, Michiel S. J. Buijze, Arlette L. Bruijstens, Yu Yi M. Wong, Maud A. Quist, C. Louk de Mol, Beatrijs H. A. Wokke and Rinze F. Neuteboom
Article first published online:
03 Aug 2026 | DOI: 10.1111/ene.70723

ORIGINAL ARTICLE

Background

Lewy body diseases (LBDs) are heterogeneous, and this variability is already evident in the prodromal phase. Several frameworks propose that prodromal heterogeneity reflects distinct phenotypic and biological subtypes, supported by differences in clinical profiles, imaging, and α‐synuclein biomarkers. We provide a detailed clinical characterization of two enriched prodromal cohorts: isolated REM Sleep Behavior Disorder (iRBD) and Hyposmia with Dopamine Transporter Deficit.

Methods

This cross‐sectional study included 360 participants with iRBD, 1101 with hyposmia and abnormal dopamine transporter imaging and 283 healthy controls from the Parkinson's Progression Markers Initiative. Using the earliest assessments available, we compared the Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease Autonomic Dysfunction (SCOPA‐AUT) and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Parts I‐III. Group differences were assessed using age and sex‐adjusted permutation testing. Secondary descriptive analysis identified the individual items contributing most to between‐group differences.

Results

Both prodromal cohorts had significantly worse scores than healthy controls in all assessments. Compared with hyposmia, iRBD was associated with higher SCOPA‐AUT and MDS‐UPDRS Part I scores, driven mainly by constipation and urinary symptoms.

Conclusion

In prodromal Lewy body disease, iRBD is associated with a statistically significant excess of autonomic symptom burden compared with hyposmia with dopamine transporter deficit, with the largest item‐level differences in urinary and constipation measures.

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Authors:
Luke Vikram Banerjee, Jacopo Pasquini, Robin Henderson, Nicola Pavese and Kirstie N. Anderson
Article first published online:
06 Aug 2026 | DOI: 10.1111/ene.70724

LETTER TO THE EDITOR

“Advanced ET” Is a More Appropriate Term Than “ET‐Plus”

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Authors:
Elan D. Louis
Article first published online:
31 Jul 2026 | DOI: 10.1111/ene.70725

ORIGINAL ARTICLE

Background

Diagnosing chronic inflammatory demyelinating polyneuropathy (CIDP) relies on clinical and electrodiagnostic features. In 2021, the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) revised the CIDP guideline, superseding the 2010 European Federation of Neurological Societies (EFNS)/PNS guideline. This study compares the diagnostic accuracy of both guidelines and evaluates the impact of specific criterion changes and nerve conduction study (NCS) extensiveness.

Methods

Patients with CIDP were included if they fulfilled the 2010 EFNS/PNS electrodiagnostic criteria for at least possible CIDP or had a presumptive clinical CIDP diagnosis with objective treatment response. Matched controls were patients with suspected chronic immune‐mediated neuropathy who received a diagnosis other than CIDP. Diagnostic accuracy was evaluated using two thresholds: one including possible CIDP and one restricted to (probable/definite) CIDP. The impact of electrodiagnostic criteria changes and NCS extensiveness on diagnostic performance was assessed.

Results

We included 339 patients and 339 matched controls. Sensitivity of the 2010 EFNS/PNS guideline was 92% when including possible CIDP and 91% for probable/definite CIDP, with specificities of 67% and 78%, respectively. For the 2021 EAN/PNS guideline, sensitivity was 94% when including possible CIDP and 83% for CIDP, with specificities of 66% and 86%, respectively. Differences were due to sensory criteria and changes in conduction block criteria. Unilateral NCS would miss 77 possible CIDP diagnoses.

Conclusion

Sensitivity and specificity were comparable when including possible CIDP, but the 2021 EAN/PNS guideline showed lower sensitivity and higher specificity for CIDP alone. Modifying criteria, including removal of sensory abnormalities, and more extensive NCS enhanced accuracy.

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Authors:
Iris N. van Doorn, Adája E. Baars, Luuk Wieske, Bart C. Jacobs, Krista Kuitwaard, W. Ludo van der Pol, Pieter A. van Doorn, Ivo N. van Schaik, Filip Eftimov, H. Stephan Goedee, Judith Drenthen and Camiel Verhamme
Article first published online:
04 Aug 2026 | DOI: 10.1111/ene.70726

LETTER TO THE EDITOR

A Network Meta‐Analysis of Hereditary Transthyretin Amyloidosis With Polyneuropathy Supports a Class Effect, Not a Ranking of Individual Drugs

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Authors:
Nicholas Streicher, Michelle Mezei and Marco Luigetti
Article first published online:
04 Aug 2026 | DOI: 10.1111/ene.70727

EAN CORNER

Abstract

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.

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Authors:
Alice Accorroni, Raphael Wurm, Roland Wiest, Marcello Ienca, Raphael Bernard‐Valnet, Giacomo Sferruzza, Tony Marson, Giuseppe Jurman, James Teo, Elena Moro, Nathalie Nasr and Maria Chiara Malaguti
Article first published online:
21 Aug 2026 | DOI: 10.1111/ene.70728

REVIEW ARTICLE

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors:
Yajie Wang, Chao Zhang, Linbo Shen, Yuanyuan Wang, Xiaocheng Wang, Linjing Song, Li Wang, Ningle Zhang, Dayong Ma and Tao Xiong
Article first published online:
23 Aug 2026 | DOI: 10.1111/ene.70730

ORIGINAL ARTICLE

Background

CVT‐301 (Inbrija) has demonstrated its effectiveness in treating OFF periods in people with Parkinson's disease (PwP). However, its effect on non‐motor symptoms (NMS) and quality of life has not been researched yet. Our aim was to analyze the change observed in health‐related quality of life (HRQoL) and, as a secondary exploratory analysis, NMS associated with OFF episodes in PwP treated with CVT‐301.

Methods

INLEVO‐LIFE PD (an open‐label study of the effect of INhaled LEVOdopa on quality of LIFE and non‐motor symptoms in Parkinson's Disease) is a prospective open‐label study conducted in five centers in Spain. The change from baseline (V0) to the end of the observational period (12 ± 2 weeks) (V12w) in the 39‐item Parkinson's Disease Quality of Life Questionnaire (PDQ‐39) total score was the primary efficacy measure.

Results

Forty PD patients (age 62.3 ± 9.2 years; 55% males) were included between March/2024 and November/2025. At 12 weeks, 34 patients were using CVT‐301 and completed the follow‐up (85%). The PDQ39 total score decreased from 43.6 ± 24.2 at V0 to 31.4 ± 20.6 at V12w ( < 0.0001). A significant decrease was observed in the mean score of 4 domains of the PDQ39. NMS burden was reduced at v12w from the OFF state to 30, 60, and 90 min after using CVT‐301 ( < 0.0001). Mean daily OFF time decreased by 1.6 ± 1.9 h ( < 0.0001). Adverse events related to CVT‐301 were reported in 35% of the patients.

Conclusion

HRQoL and NMS associated with OFF episodes improved in PwP after 12 weeks using CVT‐301.

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Authors:
Diego Santos García, María Cerdán Sánchez, Rosa Yáñez Baña, Iria Cabo and Maria Icíar Cimas Hernando
Article first published online:
06 Aug 2026 | DOI: 10.1111/ene.70731

LETTER TO THE EDITOR

Reply to: “A Network Meta‐Analysis of Hereditary Transthyretin Amyloidosis With Polyneuropathy Supports a Class Effect, Not a Ranking of Individual Drugs”

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Authors:
Gonçalo Nuno da Silva Duarte, Tiago Luís Gonçalves Neves Machado, Filipe André Brogueira Rodrigues, Isabel Conceição, Davide Pareyson and João Nuno Marques Parracho Guerra da Costa
Article first published online:
09 Aug 2026 | DOI: 10.1111/ene.70732

ORIGINAL ARTICLE

Background

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.

Methods

AIS patients from the Norwegian Stroke Registry (2016–2022) with a National Institutes of Health Stroke Scale (NIHSS) score 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.

Results

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.

Conclusion

IVT was associated with favorable functional outcomes for mild AIS, but not in patients with NIHSS 0–1.

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Authors:
Elise K. Kristensen, Agnethe Eltoft, Torunn Varmdal, Bent Indredavik and Ellisiv B. Mathiesen
Article first published online:
12 Aug 2026 | DOI: 10.1111/ene.70734

SHORT COMMUNICATION

Background and Aim

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.

Methods

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.

Results

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) ( = 0.89, 95% CI: 0.78–0.95) after symptom onset.

Conclusions

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.

Trial Registration

NCT03812666

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Authors:
Karl Sjölin, Björn Röyter, Bianka Forgo, Julia Aulin, Kim Kultima, Johan Lindbäck, Jakob O. Ström and Joachim Burman
Article first published online:
19 Aug 2026 | DOI: 10.1111/ene.70735

ORIGINAL ARTICLE

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Authors:
Patricia Kirschner, Paula Z. Epping, Sven G. Meuth, Marc Pawlitzki and Lars Masanneck
Article first published online:
18 Aug 2026 | DOI: 10.1111/ene.70736

ORIGINAL ARTICLE

Background

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.

Methods

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.

Results

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;  = 60.7%) and MG‐ADL scores (MD, −1.591; 95% CI, −1.874 to −1.309;  = 0.0%). In meta‐regression, higher mean trial age was associated with attenuation of treatment benefit on the QMG scale ( per 10 years, 1.21; 95% CI, 0.02 to 2.42;  = 0.047). This effect was most pronounced for FcRn inhibitors. No association was observed for the MG‐ADL score ( per 10 years, 0.08; 95% CI, −0.50 to 0.66;  = 0.779).

Conclusions

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.

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Authors:
Christopher Nelke, Marion Skrobol, Lukas Theissen, Francesco Sacca and Tobias Ruck
Article first published online:
12 Aug 2026 | DOI: 10.1111/ene.70737

ORIGINAL ARTICLE

Background

The definition of motor conduction block (CB) and proximal temporal dispersion (TD) for the diagnosis of CIDP and MMN remains debated, particularly regarding whether CB should be based on amplitude or area reduction, and whether proximal TD is best assessed using negative peak or total CMAP duration.

Methods

Nerve conduction waveforms from 106 CIDP, 87 MMN, and 234 controls were analyzed. Motor CB was defined by ≥ 30%, ≥ 40%, or ≥ 50% amplitude or area reduction. Proximal TD was defined as a ≥ 30% increase in negative peak duration, total CMAP duration, or either criterion. Sensitivity, specificity, and inter‐rater reliability were analyzed.

Results

Across both CIDP and MMN, a ≥ 30% reduction in CMAP amplitude showed diagnostic performance comparable to area‐based CB definitions and outperformed higher cutoff values. Requiring CB in multiple nerves increased specificity but reduced sensitivity. For proximal TD, negative peak duration was the most robust single parameter. Total CMAP duration identified additional abnormalities and, when combined with negative peak duration, improved diagnostic sensitivity in both disorders while maintaining high specificity. Total CMAP duration demonstrated good inter‐rater agreement at the patient level. CMAP morphology showed substantial overlap between CIDP and MMN and limited discriminatory value.

Conclusions

A ≥ 30% reduction in CMAP amplitude can be used as a universal definition of motor CB in both CIDP and MMN, providing diagnostic performance comparable to area‐based criteria with greater simplicity. In addition, proximal TD assessed using total CMAP duration may represent a complementary electrophysiological criterion in both disorders.

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Authors:
Chiara Gallo, Carla Fasano, Angelo Fonseca, Yuri Falzone, Dario Cocito, Fiore Manganelli, Sabrina Matà, Giuseppe Cosentino, Vincenzo Di Stefano, Massimiliano Filosto, Luca Leonardi, Dario Ricciardi, Anna Mazzeo, Luana Benedetti, Marco Luigetti, Paolo Solla, Maurizio Inghilleri, Francesco Habetswallner, Alessandro Barilaro, Fabrizio Canale, Alberto De Lorenzo, Adele Ratti, Emanuele Cassano, Maddalena Spalletti, Elisa Vegezzi, Filippo Brighina, Barbara Risi, Francesca Forcina, Alessandra Fasolino, Luca Gentile, Giacomo Iabichella, Alessandro Beronio, Francesca Vitali, Federica Moret, Stefano Gazzina, Corrado Cabona, Vincenzo Todisco, Eduardo Nobile‐Orazio, Pietro Emiliano Doneddu, Benedetta Sorrenti, Giuseppe Lauria Pinter, Eleonora Dalla Bella, Marinella Carpo, Chiara Briani, Alessandro Salvalaggio, Girolama Alessandra Marfia, Giorgia Mataluni, Angelo Schenone, Giovanni Antonini, Matteo Tagliapietra, Sara Mariotto, Gabriele Siciliano, Erika Schirinzi, Tiziana Rosso, Teresa Cantisani, Lucia Farotti, Francesca Notturno, Stefano Sotgiu, Maria Margherita Sechi, Alessandra Carta, Vincenzo Donadio, Alessandro Furia, Rita Rinaldi, Simone Rossi, Roberta Brusa, Alessandro Cesare Prelle, Chiara Dalla Torre and Lorenzo Verriello
Article first published online:
18 Aug 2026 | DOI: 10.1111/ene.70739