European Journal of Neurology最新文献

{"title":"Multivariate Survival Analysis of a Comprehensive Clinical Trial of Rapamycin in Amyotrophic Lateral Sclerosis Explores Prognostic Factors and Survival Patterns in C9orf72 Carriers","authors":"Alex De Nardi,&nbsp;Alessio Paris,&nbsp;Mario Lauria,&nbsp;Ilaria Martinelli,&nbsp;Elisabetta Zucchi,&nbsp;Cecilia Simonini,&nbsp;Jessica Mandrioli,&nbsp;Luca Marchetti","doi":"10.1111/ene.70756","DOIUrl":"https://doi.org/10.1111/ene.70756","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by considerable variability in survival times. This retrospective study aims to evaluate the prognostic value of a broad range of variables by conducting a comprehensive survival analysis on longitudinal data from RAP-ALS, a clinical trial investigating the effects of rapamycin in ALS patients (<i>n</i> = 63).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Covariates were classified as risk or protective factors according to their hazard ratios. Regularized Cox regression was utilized to select the best-performing multivariate models in cross-validation. Longitudinal measures were incorporated by modeling covariates as time-dependent. Survival times of treated C9orf72 mutation carriers (<i>n</i> = 6) were further investigated through log-rank tests and restricted mean survival time analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Univariate analyses confirmed several previously established prognostic factors. Multivariate regularized Cox models incorporated neurofilaments, creatinine, clinical scores, and markers of immune activation. Moreover, the inclusion of time-varying covariates allowed us to investigate late-stage risk factors, such as the neutrophil-to-lymphocyte ratio. Additionally, the analysis indicated a protective effect in treated C9orf72 mutation carriers (log-rank test, <i>p</i> = 0.026), which was confirmed after comparing this treatment subgroup with an independent C9orf72+ cohort (<i>n</i> = 40; RMST test, <i>p</i> = 0.04).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The survival analysis confirmed the role of previously identified prognostic factors, while suggesting that high-performing multivariate models should integrate multiple ALS pathological hallmarks. Moreover, the observed longer survival among C9orf72 mutation carriers contrasts with prior reports. Due to the small sample size and potential confounding factors, the observed benefits in treated C9orf72 patients should be considered exploratory, supporting evaluation in a larger, genetically stratified trial.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994298","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":"Re: “Palliative Care in Europe: Safeguarding Compassion Amidst Changing End-Of-Life Policies and Expanding Access to Medically Assisted Dying Position Statement on Behalf of the European Academy of Neurology, the European Federation of Neurological Associations and OneNeurology” by Rukavina Et al.","authors":"Eugenio Pucci,&nbsp;Alessandra Solari,&nbsp;Gianluigi Mancardi,&nbsp;Leandro Provinciali,&nbsp;Nicola Ticozzi,&nbsp;Alessandro Padovani","doi":"10.1111/ene.70758","DOIUrl":"10.1111/ene.70758","url":null,"abstract":"&lt;p&gt;We read with interest the position statement by Rukavina and colleagues [&lt;span&gt;1&lt;/span&gt;], which emphasizes that access to early, high-quality and integrated palliative care (PC) must remain an accessible option for people living with long-term neurological conditions (LTNC), irrespective of evolving legislation on medically assisted dying (MAD). We share this position.&lt;/p&gt;&lt;p&gt;We would like to extend the discussion by considering a question of particular relevance to neurological practice that is how neurologists should respond when a competent patient continues to request MAD despite receiving appropriate and comprehensive care, including PC.&lt;/p&gt;&lt;p&gt;This question cannot have a uniform European answer. Legal frameworks differ substantially across countries, and decisions concerning the permissibility and regulation of MAD remain within national legal and societal contexts.&lt;/p&gt;&lt;p&gt;In Italy, for example, in the absence of specific legislation, Constitutional Court Judgment no. 242/2019 identified a narrow area of non-punishability for assisted suicide under defined conditions, including decisional capacity and dependence on life-sustaining treatment. Such differences reinforce, rather than diminish, the need for neurologists to understand the clinical and ethical issues raised by these requests [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We acknowledge that individuals living with LTNC present multiple complexities. Cognitive impairment, communication difficulties, fluctuating symptoms, severe physical disability, and uncertain prognosis may complicate assessment of decisional capacity. Suffering itself may encompass physical, psychological, social, and existential dimensions. At the same time, vulnerability or disability should not in themselves be interpreted as evidence of impaired autonomy. Careful individualized assessment is therefore essential, ideally within a multidisciplinary framework. PC has a fundamental role in this process. It may relieve suffering, improve quality of life, and, in some patients, modify wishes concerning end-of-life decisions. However, even optimal PC does not remove every persistent request for MAD. Recognizing this does not place PC and MAD in opposition, nor does it imply that MAD should compensate for inadequate access to care.&lt;/p&gt;&lt;p&gt;We therefore agree with Rukavina et al. [&lt;span&gt;1&lt;/span&gt;] that neurologists require education in PC and advance care planning. We suggest that such education should also include how to recognize, explore, and manage requests for MAD, including assessment of capacity, potentially reversible causes of suffering, prognosis, and voluntariness, as well as knowledge of the applicable legal framework. This competence is relevant even where MAD is not legally available.&lt;/p&gt;&lt;p&gt;European neurological organizations cannot replace national societies or legislators in determining end-of-life policy. They should, however, provide a common clinical and ethical framework, promote education, and support rigorous evidence-b","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988827","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":"Future Prospects of Ultrasound: Role of Low-Intensity Transcranial Ultrasound Stimulation in the Treatment of Neurological and Psychiatric Disorders","authors":"Yunjie Sui,&nbsp;Mingyue Wei,&nbsp;Robert Chen,&nbsp;Xue Xia","doi":"10.1111/ene.70754","DOIUrl":"10.1111/ene.70754","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurological and psychiatric disorders pose a persistent global health burden, with conventional therapies often providing inadequate relief. Transcranial ultrasound stimulation (TUS) has attracted considerable attention as a non-invasive neuromodulation technique offering high spatial resolution and the distinctive capacity to modulate deep brain regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review synthesizes recent basic and clinical research on TUS across neurological and psychiatric disorders, and consolidates emerging evidence on its mechanisms, therapeutic applications, and safety considerations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Emerging evidence suggests that TUS may drive sustained neural remodeling—including synaptic plasticity, neurogenesis, and anti-neuroinflammatory effects—raising the possibility that TUS could eventually contribute to disease-modifying strategies. However, disease modification by TUS has not yet been demonstrated in humans; the evidence supporting this possibility is derived predominantly from preclinical studies and remains a hypothesis requiring confirmation in large-scale, controlled clinical trials. Building on these frameworks, we further propose a working hypothesis—termed mechanotransduction-to-oscillation encoding—which posits a nonlinear encoding relationship between the pulse repetition frequency of TUS and the intrinsic oscillatory properties of the stimulated region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This hypothesis remains largely speculative and is offered as a conceptual framework to generate testable predictions and guide future investigations. Together, these frameworks provide a cohesive strategy for advancing TUS from an exploratory neuromodulation technique toward a potentially clinically translatable precision intervention, while acknowledging that significant technical and clinical hurdles remain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967208","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":"Seizure Freedom Despite Piriform Cortex Sparing: Structural Connectivity Remodeling After SEEG-Guided Mesial Temporal RFTC","authors":"Stéphane Jean,&nbsp;Paul Edisie Donkor,&nbsp;Xiaoqiang Wei,&nbsp;Yihai Dai,&nbsp;Jifeng Gong,&nbsp;Qingfang Xiao,&nbsp;Weitao Chen,&nbsp;Weihong Liu,&nbsp;Xinrong Fang,&nbsp;Shiwei Song","doi":"10.1111/ene.70751","DOIUrl":"https://doi.org/10.1111/ene.70751","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate whether selective radiofrequency thermocoagulation (RFTC) targeting mesiotemporal structures, while sparing the piriform cortex (PC), can achieve seizure freedom in drug-resistant mesial temporal lobe epilepsy (MTLE), and to assess whether said seizure freedom is associated with an indirect disconnection of the PC within the epileptogenic network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was performed on 32 patients (mean age 27.81 ± 13.37 years) with drug-resistant MTLE who underwent stereoelectroencephalography (SEEG)-guided RFTC. Volumetric and structural connectivity (SC) analyses were conducted using pre- and postoperative T1-weighted (T1W) and diffusion-weighted imaging (DWI). The regions of interest (ROIs) targeted included the hippocampus, amygdala, rhinal cortex, and parahippocampal cortex, while the PC was spared. Network metrics assessed pre- and postoperative SC changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At a mean follow-up of 40.63 ± 16.36 months, 25 patients (78.1%) became seizure free (SF). SF patients had significantly greater ablation volumes in the amygdala (<i>p</i> = 0.026) and rhinal cortex (<i>p</i> = 0.023) compared to non-seizure-free (NSF) patients. SF patients showed significant postoperative reductions in SC across all mesiotemporal ROIs, including the spared PC (<i>p</i> ≤ 0.020). NSF patients exhibited no significant SC changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Seizure freedom following SEEG-guided RFTC is associated with widespread disruption of SC in mesiotemporal networks, including the spared PC. These findings support the hypothesis that seizure freedom following the ablation of key mesiotemporal ROIs can induce an indirect disconnection of the PC through its connected nodes, offering a safer therapeutic option for MTLE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70751","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942897","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":"Response Shift and Item Interpretation: Two Caveats for Using Minimal Symptom Expression as a Treatment Goal in Generalised Myasthenia Gravis","authors":"Hai-Feng Li,&nbsp;Qi Li,&nbsp;Yu-Zhou Guan,&nbsp;Huan Yang","doi":"10.1111/ene.70749","DOIUrl":"https://doi.org/10.1111/ene.70749","url":null,"abstract":"&lt;p&gt;We welcome the proposal of Minimal Symptom Expression (MSE, MG-ADL 0-1) as a patient-centric treatment goal in generalised myasthenia gravis (gMG) [&lt;span&gt;1&lt;/span&gt;]. However, its validity as a surrogate for minimal disease activity requires closer scrutiny, particularly regarding how disease duration and patient comprehension affect self-reports.&lt;/p&gt;&lt;p&gt;A key mechanism is response shift, the recalibration of internal standards due to long-term adaptation [&lt;span&gt;2&lt;/span&gt;]. Patients with longstanding MG may perceive mild ptosis as ‘normal’, reporting lower MG-ADL scores than those with recent onset despite comparable objective weakness measured by the Quantitative Myasthenia Gravis Score (QMG). This can systematically underestimate residual impairment when using patient-reported measures alone.&lt;/p&gt;&lt;p&gt;The MGTX study found a weaker correlation between QMG and MG-ADL in patients with minimal manifestation status [&lt;span&gt;3&lt;/span&gt;]. We further explored this issue in a prospective cohort of 134 patients who had achieved minimal manifestation status or better. The correlation between QMG and MG-ADL was moderate (Spearman's &lt;i&gt;ρ&lt;/i&gt; = 0.450, &lt;i&gt;p&lt;/i&gt; = 0.03). When we dichotomized MG-ADL according to the MSE definition (0–1 vs. ≥ 2) and dichotomized QMG by its sample median, the kappa coefficient for agreement between the two binary classifications was only 0.296 (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), indicating only fair agreement beyond chance. Notably, disease duration &gt; 12 months was independently associated with discordance between the two binary classifications (OR = 3.93; 95% CI: 1.09–14.19, &lt;i&gt;p&lt;/i&gt; = 0.04). Longer disease duration drives patient–clinician disagreement, most likely through response shift.&lt;/p&gt;&lt;p&gt;Beyond response shift, a more fundamental issue exists. The MG-ADL assumes that all respondents interpret its wording uniformly. Even though acceptable concordance between patient- and physician-rated MG-ADL has been reported [&lt;span&gt;4&lt;/span&gt;], this does not guarantee uniform understanding among patients. Terms such as ‘intermittent’, ‘extra effort’, and ‘mild’ lack objective anchors; different patients may apply them based on their own experience and coping strategies. Moreover, the available detailed item descriptions provided in the instructions are often not read by patients in routine practice or even in trial settings. Instead, patients tend to answer based on their intuitive understanding of the wording, introducing additional variability in responses. Brief instruction or interview-based assessment may reduce this bias, but qualitative evidence on how patients actually arrive at their answers, whether they read the descriptions, how they interpret key terms, and which internal shortcuts they rely on remains lacking [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We therefore suggest: (1) Qualitative studies should explore how patients interpret MG-ADL items to establish content validity and identify sources of misinterpretation. (2) Disease duration should be incorporated ","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943016","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":"TUBA4A Pathogenic Variant Manifesting With Adulthood-Onset Genetic Myasthenic Syndrome, Myopathy, and Infertility","authors":"Margherita Milone,&nbsp;Stefan Nicolau,&nbsp;Zhiyv Niu,&nbsp;Teerin Liewluck,&nbsp;Eric J. Sorenson,&nbsp;Xin-Ming Shen,&nbsp;C. Michael Harper,&nbsp;William J. Litchy","doi":"10.1111/ene.70753","DOIUrl":"https://doi.org/10.1111/ene.70753","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p><i>TUBA4A</i> pathogenic variants are associated with ALS, frontotemporal dementia, spastic ataxia, spasticity, ataxia, Parkinson's disease, female infertility, macrothrombocytopenia, and myopathy. Four recently reported patients with <i>TUBA4A</i> neonatal/childhood onset myopathy had also a decrement on repetitive nerve stimulation (RNS), but such a finding was not further characterized. We describe a patient with a <i>TUBA4A</i> pathogenic variant with adulthood-onset genetic myasthenic syndrome accompanied by myopathy and infertility to highlight the neuromuscular junction defect as the main feature of the patient's phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We reviewed the patient's clinical and laboratory findings and performed transcriptomic analysis on the patient's muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A 53-year-old woman with infertility of unknown etiology manifested fatigability and proximal upper limb muscle weakness in her mid-30s, followed by lower limb involvement. Her examination showed proximal muscle weakness and fatigability but spared facial muscles. CK values were mildly elevated. Anti-AChR, MuSK, P/Q-type calcium channel, and LRP4 antibodies were absent. 2 Hz RNS showed decrement (−14% to −48%) in limb muscles that improved with 3,4-dyaminopyridine (3,4-DAP). Facilitation (231%) occurred in the trapezius. Muscle biopsy showed patchy loss of oxidative enzyme reactivity and no C5b9 or IgG at neuromuscular junctions. Whole genome sequencing identified a heterozygous known <i>TUBA4A</i> pathogenic variant (c.850G&gt;A, p.Glu284Lys). Patient improved with 3,4-DAP and albuterol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>TUBA4A p.Glu284Lys can lead to treatable myasthenic syndrome with postsynaptic and likely presynaptic involvement, as suggested by the patient's electrophysiological findings and response to therapy. This patient expands the <i>TUBA4A</i>-disorder spectrum to include overlapping myasthenic syndrome-myopathy and shows that neuromuscular disease and infertility can occur within the same patient.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70753","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942893","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":"Cervical Atrophy Following Complete Thoracic Spinal Cord Injury: Insights From a Multinational Cohort","authors":"Yann Quidé,&nbsp;Negin Hesam-Shariati,&nbsp;Zina Trost,&nbsp;Thiago Folly de Campos,&nbsp;William R. Willoughby,&nbsp;Mark Bolding,&nbsp;Rachel E. Cowan,&nbsp;Pauline Zahara,&nbsp;Sylvia M. Gustin","doi":"10.1111/ene.70750","DOIUrl":"10.1111/ene.70750","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord injury (SCI) results in neurodegeneration both at and above the lesion site. While cervical cord atrophy is well characterised in populations of mixed cervical, thoracic and/or lumbar injuries, the remote morphological changes in cervical cord following thoracic SCI remain unclear. The present study aimed to quantify cervical spinal cord morphology at C2–C3 in individuals with complete thoracic SCI and compare these metrics to matched controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were 52 adults with complete thoracic SCI and 55 neurologically healthy, able-bodied controls matched for age and sex. Extracted cervical metrics included mean cross-sectional area (CSA), antero-posterior (AP) and right–left (RL) diameters, eccentricity, solidity, orientation and cord length. Group differences were assessed using linear mixed models adjusted for age, sex and scanning sites. Impacts of experiencing SCI-related chronic neuropathic pain on these metrics were explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to controls, the thoracic SCI group showed significantly reduced cervical CSA and AP/RL diameters, consistent with remote atrophy, and increased eccentricity, indicating a more flattened cord profile. Solidity, orientation and cord length showed no group differences, supporting metric reliability and absence of segmentation artefacts. Although no difference was evident among the SCI groups, those experiencing chronic neuropathic pain had larger eccentricity than controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Complete thoracic SCI is associated with significant remote cervical cord degeneration, even in the absence of direct cervical injury. Results highlight that neurodegenerative processes propagate along ascending and descending spinal pathways. Cervical morphometry metrics, particularly CSA and eccentricity, may represent biomarkers of distal neurodegeneration following thoracic SCI and inform future therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918798","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":"Pathways of Patients With Neurological Emergencies at Pediatric Emergency Department: A Process-Based Data Mining Study","authors":"Henna Aro,&nbsp;Tuomo Antikainen,&nbsp;Mari Videman,&nbsp;Elina Wärnhjelm,&nbsp;Erika Ignatius,&nbsp;Pirjo Isohanni,&nbsp;Miika Koskinen","doi":"10.1111/ene.70743","DOIUrl":"10.1111/ene.70743","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurological patients represent a small yet resource-demanding group in pediatric emergency departments (PEDs). Their pathways and resource needs remain poorly understood. This population-based real-world data study aims to bridge this gap.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed neurological visits from 2021 to 2023 at the sole PED serving 300,000 children using process mining and statistical analysis. Neurological visits included patients triaged for neurologist evaluation and those with neurological complaints and/or diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 4854 neurological visits, constituting 5% of PED visits. Seizure and headache comprised 64% of the chief complaints; seizures dominated the highest acuity visits, while headache was linked to visits with lower acuity. Neurological patients had a nearly fivefold increased risk of requiring immediate lifesaving interventions compared to non-neurological patients. Half of the highest acuity patients were 1–5 years old. Patient disposition was most strongly associated with acuity: 81% of highest acuity patients were admitted and 15% of them to the pediatric intensive care or surgical unit, whereas only 18% of stable patients were hospitalized. Variability of patient pathways was moderate. 87% of patients adhered to one of four most common pathways where disposition decision was made without advanced testing. Over 30 pathways were identified for patients needing advanced tests. These patients presented with higher acuity, non-seizure complaints and increased admissions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This population-based study pioneers process mining for analyzing patient care processes and resource utilization of neurological patients at the PED. It highlights the critical nature of pediatric neurological emergencies and uncovers the variability of patient needs and pathways.</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://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911287","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":"Practical Guidance on Initiating and Switching Targeted Immunotherapies in Generalised Myasthenia Gravis: A German–Austrian Expert Opinion Paper","authors":"Andreas Meisel,&nbsp;Adela Della Marina,&nbsp;Paolo Doksani,&nbsp;Tim Hagenacker,&nbsp;Christoph Kleinschnitz,&nbsp;Heidrun H. Krämer,&nbsp;Jan D. Lünemann,&nbsp;Sven G. Meuth,&nbsp;Tobias Ruck,&nbsp;Ulrike Schara-Schmidt,&nbsp;Christiane Schneider-Gold,&nbsp;Benedikt Schoser,&nbsp;Michael Schroeter,&nbsp;Charlotte Schubert,&nbsp;Jörn Peter Sieb,&nbsp;Fritz Zimprich,&nbsp;Jana Zschüntzsch,&nbsp;Sarah Hoffmann","doi":"10.1111/ene.70747","DOIUrl":"10.1111/ene.70747","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The therapeutic landscape of generalised myasthenia gravis (gMG) has evolved substantially with the approval of targeted immunotherapies, including complement C5 inhibitors (C5-I) and neonatal Fc receptor inhibitors (FcRn-I). While pivotal trials have demonstrated marked efficacy in defined subgroups, real-world experience reveals more heterogeneous outcomes and raises questions about optimal patient selection, therapy sequencing and integration into clinical practice. In Germany and Austria, early access following regulatory approval has facilitated clinical experience over recent years. This expert opinion paper aims to combine current evidence with clinical experience to guide the use of C5-I and FcRn-I in everyday care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A panel of 18 neurologists from Germany and Austria, including two paediatric neurologists, evaluated study data and real-world experiences. Through structured discussion and a consensus process, they developed evidence- and experience-based recommendations on integrating targeted immunotherapies into existing treatment algorithms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The panel provides practical recommendations for managing (highly) active gMG in adults, focusing on C5-I (eculizumab, ravulizumab, zilucoplan) and FcRn-I (efgartigimod, rozanolixizumab). The statements cover initiation criteria, sequencing and switching within and between drug classes and transitions to intensified immunomodulatory therapies (rituximab, apheresis, intravenous or subcutaneous immunoglobulin), as well as special considerations for juvenile MG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This expert statement provides a practice-oriented framework integrating current evidence and clinical experience to support individualised therapeutic decision-making in gMG.</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.70747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918866","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":"Dopaminergic- and Cholinergic-Related Structural MRI Patterns Across Cognitive Subtypes of Parkinson's Disease With Mild Cognitive Impairment","authors":"Xueqin Bai,&nbsp;Haoxin Chen,&nbsp;Qiuyue Li,&nbsp;Shiwei Zhang,&nbsp;Shuangli Chen,&nbsp;Andan Qian,&nbsp;Ronghui Zhou,&nbsp;Yitong Cheng,&nbsp;Chenglong Xie,&nbsp;Zhen Wang,&nbsp;Yunjun Yang,&nbsp;Meihao Wang","doi":"10.1111/ene.70746","DOIUrl":"10.1111/ene.70746","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The dual syndrome hypothesis distinguishes frontostriatal and posterior cortical cognitive subtypes in Parkinson's disease with mild cognitive impairment (PD-MCI), which are associated with distinct cognitive profiles and different risks of dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To characterize dopaminergic- and cholinergic-related structural MRI patterns across cognitive subtypes of PD-MCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 182 non-demented patients with Parkinson's disease (PD) and 38 healthy controls (HC) were included. Based on comprehensive neuropsychological assessments, PD patients were classified as having normal cognition (PD-NC, <i>n</i> = 112), PD-MCI with frontostriatal deficits (<i>n</i> = 20), posterior cortical deficits (<i>n</i> = 28), or mixed deficits (<i>n</i> = 22). All participants underwent T1-weighted MRI. Normalized volumetric measures of subcortical nuclei (caudate, putamen, globus pallidus, and thalamus) and the basal forebrain were obtained.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Distinct subtype-specific patterns of subcortical and basal forebrain atrophy were observed. PD-MCI patients with posterior cortical deficits showed significant atrophy of cholinergic nucleus 4 (Ch4) compared with HC and PD-MCI patients with frontostriatal deficits. In contrast, PD-MCI patients with frontostriatal deficits exhibited atrophy of the caudate nucleus and putamen relative to HC. The mixed deficits subtype showed putamen and thalamic atrophy compared with HC. In addition, basal forebrain Ch4 volume was significantly associated with visuospatial performance in PD-MCI patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Different PD-MCI subtypes exhibit distinct patterns of dopaminergic- and cholinergic-related structural alterations on MRI. Posterior cortical deficits are predominantly associated with cholinergic basal forebrain degeneration, whereas frontostriatal deficits are linked to dopaminergic involvement. These findings support the neural heterogeneity underlying cognitive impairment in PD.</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.70746","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918900","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}