Journal of Neurology最新文献

{"title":"Randomized controlled trials for multiple sclerosis: integrating pathology-driven outcomes to capture therapeutic efficacy.","authors":"Massimo Filippi, Paolo Preziosa, Maria A Rocca","doi":"10.1007/s00415-025-13141-w","DOIUrl":"https://doi.org/10.1007/s00415-025-13141-w","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"385"},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The impact of white matter hyperintensities on short-term outcomes of reperfusion therapy in patients with acute ischemic stroke.","authors":"Junying Li, Dan Yang, Rui Song, Jian Wang, Lanying He","doi":"10.1007/s00415-025-12956-x","DOIUrl":"https://doi.org/10.1007/s00415-025-12956-x","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"384"},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel strategies for targeting tau oligomers in neurodegenerative diseases.","authors":"Jing Lin, Hong Li, Lingxia Jiang, Jian Li","doi":"10.1007/s00415-025-13117-w","DOIUrl":"https://doi.org/10.1007/s00415-025-13117-w","url":null,"abstract":"<p><p>Tau protein is a soluble microtubule-associated protein enriched in neurons, is mainly distributed in the central nervous system, and is responsible for stabilizing neurons. Tau maintains nerve cell morphology and internal transport by binding to normal microtubules. In neurodegenerative diseases, such as Alzheimer's disease (AD), tau proteins undergo aberrant phosphorylation, resulting in their removal from microtubules and the formation of neurofibrillary tangles (NFTs), which are key pathological features. In contrast to the late formation of non-soluble NFTs, early, smaller, soluble tau oligomers (tauO) with disseminated toxicity are considered necessary in neurodegenerative disorders, such as the primary form of tau toxicity in the AD process. Although an increasing number of studies are focusing on tauO, there are still problems to be solved, mainly concerning the molecular and inhibitory mechanisms of tauO toxicity. In this paper, we summarize the new strategies for the molecular mechanisms of tauO toxicity, detection methods, and interventions in the last five years. An outlook on these new strategies and the challenges that may be foreseen is presented to provide new directions for future applications in the clinical treatment of neurodegenerative diseases.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"383"},"PeriodicalIF":4.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 24-week prospective, multicenter, real-world study on eptinezumab's effectiveness and safety in migraine prevention (EMBRACE II).","authors":"Piero Barbanti, Cinzia Aurilia, Gabriella Egeo, Alberto Doretti, Florindo d'Onofrio, Paola Scatena, Steno Rinalduzzi, Luisa Vinciguerra, Mattia Sansone, Rosario Vecchio, Valeria Drago, Giovanna Viticchi, Marco Bartolini, Angelo Ranieri, Monica Bandettini di Poggio, Francesco Baldisseri, Davide Mascarella, Fabio Brusaferri, Luigi Caputi, Stefano Messina, Massimo Autunno, Alessandro Valenza, Bianca Orlando, Marisa Distefano, Laura Borrello, Francesca Pistoia, Cecilia Camarda, Gennaro Saporito, Giacomo Querzola, Paola Torelli, Antonio Salerno, Francesca Gragnani, Barbara Petolicchio, Antonio Carnevale, Roberta Messina, Massimo Filippi, Sofia Tavani, Giulia Fiorentini, Stefano Bonassi, Sabina Cevoli, Alice Mannocci","doi":"10.1007/s00415-025-13095-z","DOIUrl":"https://doi.org/10.1007/s00415-025-13095-z","url":null,"abstract":"<p><strong>Introduction: </strong>We evaluated the effectiveness, tolerability, and safety of eptinezumab in preventing high-frequency episodic migraine (HFEM) and chronic migraine (CM) over 24 weeks in real-world. We also assessed its impact during the first treatment week, in patients failing monoclonal antibodies targeting the calcitonin gene-related peptide (anti-CGRP mAbs), and the effects of dose escalation to 300 mg in patients requiring enhanced control.</p><p><strong>Methods: </strong>EMBRACE II is a multicenter (n = 22), prospective, 24-week, real-world study involving consecutive patients with HFEM or CM who had failed > 3 preventive treatments. Eptinezumab (100 mg, with the option for escalation to 300 mg at week 12) was administered quarterly.</p><p><strong>Primary endpoint: </strong>change in monthly migraine days (MMD), for HFEM or monthly headache days (MHD), for CM, between weeks 21-24 and baseline. Secondary endpoints: changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates.</p><p><strong>Results: </strong>Of the 215 participants who had received ≥ 1 eptinezumab dose, 74 were treated for ≥ 24 weeks and considered for effectiveness analysis. Eptinezumab significantly (p < 0.001) reduced MMD/MHD (- 10.5), MAI (- 15.6), NRS (- 2.2), HIT-6 (- 9.9), MIDAS (- 48.7), and MIBS-4 (- 4.3). ≥ 50% responders were 69%, ≥ 75% responders 39.2%, and 100% responders 4.1%. Comparing the first week with the last baseline week, a significant reduction in migraine days was observed (- 3.7; p < 0.001). Significant improvements were seen in patients failing anti-CGRP mAbs (32.4%) and in those escalating to 300 mg (33.8%). Half of the subjects reported being \"very much improved\" or \"much improved\". The adverse events were infrequent (2.8%).</p><p><strong>Conclusions: </strong>This real-world study documents that 24-week eptinezumab treatment is rapidly effective and well tolerated in migraine patients with multiple therapeutic failures (including anti-CGRP mAbs). One-third of patients escalated to 300 mg at week 12, achieving further significant migraine-related disability reduction.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"382"},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988680","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":"FDA vs. EMA: evaluating donanemab and the global debate on accelerated approvals.","authors":"Prakriti Pokhrel, Aakriti Jindal, Qadeer Ahmed","doi":"10.1007/s00415-025-13131-y","DOIUrl":"https://doi.org/10.1007/s00415-025-13131-y","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"378"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Need for awareness and surveillance of long-term post-COVID neurodegenerative disorders. A position paper from the neuroCOVID-19 task force of the European Academy of Neurology.","authors":"Dániel Bereczki, Ádám Dénes, Filippo M Boneschi, Tamar Akhvlediani, Francesco Cavallieri, Alessandra Fanciulli, Saša R Filipović, Alla Guekht, Raimund Helbok, Sonja Hochmeister, Tim J von Oertzen, Serefnur Özturk, Alberto Priori, Martin Rakusa, Barbara Willekens, Elena Moro, Johann Sellner","doi":"10.1007/s00415-025-13110-3","DOIUrl":"https://doi.org/10.1007/s00415-025-13110-3","url":null,"abstract":"<p><strong>Background: </strong>Neuropathological and clinical studies suggest that infection with SARS-CoV-2 may increase the long-term risk of neurodegeneration.</p><p><strong>Methods: </strong>We provide a narrative overview of pathological and clinical observations justifying the implementation of a surveillance program to monitor changes in the incidence of neurodegenerative disorders in the years after COVID-19.</p><p><strong>Results: </strong>Autopsy studies revealed diverse changes in the brain, including loss of vascular integrity, microthromboses, gliosis, demyelination, and neuronal- and glial injury and cell death, in both unvaccinated and vaccinated individuals irrespective of the severity of COVID-19. Recent data suggest that microglia play an important role in sustained COVID-19-related inflammation, which contributes to the etiology initiating a neurodegenerative cascade, to the worsening of pre-existing neurodegenerative disease or to the acceleration of neurodegenerative processes. Histopathological data have been supported by neuroimaging, and epidemiological studies also suggested a higher risk for neurodegenerative diseases after COVID-19.</p><p><strong>Conclusions: </strong>Due to the high prevalence of COVID-19 during the pandemic, healthcare systems should be aware of, and be prepared for a potential increase in the incidence of neurodegenerative diseases in the upcoming years. Strategies may include follow-up of well-described cohorts, analyses of outcomes in COVID-19-registries, nationwide surveillance programs using record-linkage of ICD-10 diagnoses, and comparing the incidence of neurodegenerative disorders in the post-pandemic periods to values of the pre-pandemic years. Awareness and active surveillance are particularly needed, because diverse clinical manifestations due to earlier SARS-CoV-2 infections may no longer be quoted as post-COVID-19 symptoms, and hence, increasing incidence of neurodegenerative pathologies at the community level may remain unnoticed.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"380"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023655","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":"The intersection of delirium and long-term cognition in older adults: the critical role of delirium prevention.","authors":"Zhongyuan Lu, Xiaoling Wang, Jiao Wang, Liang Zhao, Yichen Wu, Mingyang Sun, Jiaqiang Zhang","doi":"10.1007/s00415-025-13104-1","DOIUrl":"https://doi.org/10.1007/s00415-025-13104-1","url":null,"abstract":"<p><p>Delirium, a neuropsychiatric syndrome characterized by an acute and usually reversible state of confusion, while dementia is a chronic, acquired cognitive impairment that significantly reduces a patient's ability to perform daily tasks, learn, work, and engage in social interactions. Previous studies indicates that individuals with dementia are more susceptible to delirium than the general population, and that delirium serves as an independent risk factor for the subsequent onset of dementia. However, a major controversy in this field concerns whether delirium is merely a marker of vulnerability to dementia, or whether delirium-induced adverse outcomes such as falls and functional decline contribute to dementia, or whether delirium directly causes permanent neuronal damage and lead to dementia. It is possible that all these hypotheses hold some truth. In this review, we examine the shared and distinct mechanisms of delirium and dementia by reviewing their clinical features, epidemiology, clinicopathological, biomarkers, neuroimaging, and recent experimental studies, and we discuss the importance of targeting delirium to explore new preventive and therapeutic strategies for reducing long-term cognitive impairment.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"381"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein-a and white matter abnormalities: predicting small vessel disease in young patients with ischemic cerebrovascular events.","authors":"Paola Caruso, Marco Liccari, Gabriele Prandin, Pierandrea Vinci, Federica Pellicori, Nicola Fiotti, Emiliano Panizon, Giovanni Furlanis, Marcello Naccarato, Gianni Biolo, Paolo Manganotti","doi":"10.1007/s00415-025-13111-2","DOIUrl":"https://doi.org/10.1007/s00415-025-13111-2","url":null,"abstract":"<p><strong>Introduction: </strong>Post-stroke cognitive impairment (PSCI) affects 15-70% of ischemic stroke survivors, with vascular dementia contributing significantly to long-term disability. Lipoprotein(a) [Lp(a)] has emerged as a key risk factor for cardiovascular and cerebrovascular diseases, but its role in cerebral small vessel disease (cSVD) remains unclear. This study investigates the association between elevated Lp(a) levels and Fazekas scores (≥ 2), a marker of white matter hyperintensities (WMHs) indicative of cSVD, in young patients (< 65 years) with ischemic stroke or transient ischemic attack (TIA).</p><p><strong>Methods: </strong>We retrospectively analysed data of 217 patients with ischemic stroke/TIA, age 18-65, and Lp(a) measurement within four weeks of the event. Data included clinical history, imaging (MRI Fazekas scores), and Lp(a) levels (> 50 mg/dL). Multivariable logistic regression and ROC analysis were performed to identify predictors of higher Fazekas scores.</p><p><strong>Results: </strong>Elevated Lp(a) levels were independently associated with Fazekas scores ≥ 2 (OR 2.83, 95% CI 1.13-7.10, p = 0.03) alongside older age, hypertension, prior stroke/TIA, and elevated non-HDL cholesterol. The predictive model demonstrated high accuracy (AUC = 0.81). Patients with elevated Lp(a) exhibited greater WMH burden, indicating advanced small vessel damage.</p><p><strong>Conclusions: </strong>Elevated Lp(a) levels are a significant biomarker for WMHs and cSVD in young stroke patients, offering prognostic value beyond traditional risk factors. Incorporating Lp(a) testing into routine stroke evaluations could enable early identification and tailored management strategies to mitigate further vascular damage and cognitive decline.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"379"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030909","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":"Core diagnostic features of stiff person syndrome: insights from a case-control study.","authors":"Shuvro Roy, Yishang Huang, Chen Hu, Kathryn C Fitzgerald, Yujie Wang, Scott D Newsome","doi":"10.1007/s00415-025-13103-2","DOIUrl":"10.1007/s00415-025-13103-2","url":null,"abstract":"<p><strong>Background: </strong>Stiff person syndrome spectrum disorders (SPSD) are rare, disabling neuroimmunological conditions with no consensus diagnostic criteria, making diagnosis challenging. Misdiagnosis often occurs due to the limited awareness of atypical symptoms and presentations. This study aimed to identify key clinical and paraclinical features most predictive of classic SPS and SPS-plus diagnosis and misdiagnosis patterns.</p><p><strong>Methods: </strong>We conducted a retrospective case-control study at Johns Hopkins SPS center, analyzing patient data from 1997-2021. A total of 154 classic SPS, 45 SPS-plus, and 66 control patients (evaluated for SPSD but given an alternative diagnosis) were included. Clinical assessments, autoantibody testing, electromyography (EMG), and other diagnostic studies were reviewed. Sensitivity, specificity, and diagnostic odds ratios were calculated, with logistic regression identifying the strongest diagnostic indicators of the SPS phenotypes.</p><p><strong>Results: </strong>Torso/lower extremity symptoms, hypersensitivity triggers, paravertebral stiffness, and gait dysfunction were common in both phenotypes. Classic SPS was most specifically associated with high-titer GAD65 antibodies (98%), cerebrospinal fluid GAD65 positivity (100%), characteristic EMG abnormalities (> 90%), and hyperlordosis (87%). SPS-plus specificity was highest for cerebellar (98.5%) and brainstem (100%) signs/symptoms. High-titer GAD65 antibodies were the strongest independent diagnostic factor for both phenotypes. Misdiagnosis was most common in patients presenting with upper extremity, brainstem, or cerebellar involvement.</p><p><strong>Conclusions: </strong>Recognizing key diagnostic and misdiagnosis patterns may help clinicians make accurate and timely diagnoses of SPSD. This could help prevent misdiagnosis/overdiagnosis, ensure timely treatment, and assure appropriate patient populations are included in future interventional SPS clinical trials. Further studies are needed to validate these findings and refine diagnostic criteria.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 5","pages":"377"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024517","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":"William Henry Broadbent (1835-1907).","authors":"Andrew J Larner","doi":"10.1007/s00415-025-13119-8","DOIUrl":"https://doi.org/10.1007/s00415-025-13119-8","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 5","pages":"376"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}