Journal of Neurology最新文献

{"title":"Diagnostic utility of tectal plate measures in clinical variants of progressive supranuclear palsy.","authors":"Neha Singh-Reilly, Morgan Blakey, Ryota Satoh, Farwa Ali, Nha Trang Thu Pham, Abigail Amrami, Yehkyoung C Stephens, Dennis W Dickson, Keith A Josephs, Jennifer L Whitwell","doi":"10.1007/s00415-025-13256-0","DOIUrl":"10.1007/s00415-025-13256-0","url":null,"abstract":"<p><strong>Background: </strong>The length of the tectal plate, which sits above the midbrain, is reduced in both the Richardson's syndrome (RS) and parkinsonism (P) variants of progressive supranuclear palsy (PSP). However, it is unclear whether tectal measurements could be useful biomarkers in other PSP variants or predict PSP pathology.</p><p><strong>Methods: </strong>The Neurodegenerative Research Group, Mayo Clinic, enrolled 115 PSP (including seven variants), 19 corticobasal syndrome (CBS), 21 Parkinson's disease (PD), and 50 controls. Forty-seven PSP patients had PSP at autopsy, and 15 had a non-PSP pathology. Tectal plate length and area and area of the superior/inferior colliculi were measured. Measurements were compared across clinical and pathological groups, and associations were assessed with clinical severity. Effect sizes were evaluated using the area under the receiver operator characteristic curves (AUROCs).</p><p><strong>Results: </strong>All PSP variants showed reduced tectal plate length compared to controls, with good differentiation (AUROC > 0.80). Excellent differentiation was observed for PSP-RS and PSP-P from controls (AUROC = 0.93/0.86), and PD (AUROC = 0.92/0.83), and PSP-RS showed good differentiation from CBS (AUROC = 0.80). Tectal plate and superior colliculus areas were reduced in all PSP variants, except PSP-Speech-language (SL), compared to controls. PSP-RS and PSP-P showed reduced area measurements compared to PSP-SL. No differences were observed between PSP and non-PSP pathology. Reduced tectal plate length was associated with worse clinical severity in PSP.</p><p><strong>Conclusion: </strong>Tectal plate length may have utility as a disease biomarker across PSP variants, although tectal plate measurements could not predict pathology within patients clinically diagnosed with PSP.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"541"},"PeriodicalIF":4.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731821","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":"Stroke thrombolysis for patients with intracranial aneurysms: a nationwide cohort study.","authors":"Huanwen Chen, Matthew K McIntyre, Ajay Malhotra, Dheeraj Gandhi, Marco Colasurdo","doi":"10.1007/s00415-025-13282-y","DOIUrl":"10.1007/s00415-025-13282-y","url":null,"abstract":"<p><strong>Background: </strong>The safety of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with underlying unruptured intracranial aneurysms (UIAs) is unclear. This study evaluates IVT safety and efficacy in AIS patients with UIAs in routine clinical practice.</p><p><strong>Methods: </strong>Using the 2016-2022 Nationwide Readmissions Database, we conducted a retrospective cohort study of AIS patients with National Institutes of Health Stroke Scale (NIHSS) scores ≥ 6. Patients with a diagnosis of UIA were identified. Patients with intracranial tumors and other cerebrovascular malformations were excluded. Multivariable logistic regression assessed the association between IVT and outcomes, including routine discharge, mortality, subarachnoid hemorrhage (SAH), and intraparenchymal hemorrhage (IPH). Interaction analyses compared treatment effects between UIA and non-UIA patients.</p><p><strong>Results: </strong>Of 689,285 AIS patients, 11,687 (1.7%) had UIAs; 25.0% received IVT. Among UIA patients, IVT was associated with higher rates of routine discharge [adjusted OR (aOR) 2.25 (95%CI 1.95-2.59)] and lower mortality [aOR 0.64 (95%CI 0.48-0.87)]. IVT did not increase SAH risk in UIA patients [aOR 0.97 (95%CI 0.63-1.49)]. IVT was linked to higher IPH risk for UIA patients [aOR 1.34 (95%CI 1.06-1.70)], though this association was also found among non-UIA patients with a similar magnitude (p-interaction = 0.91). Compared to IVT-treated non-UIA patients, IVT-treated UIA patients were significantly more likely to experience routine discharge [OR 1.20 (95%CI 1.02-1.40)], despite having significantly higher odds of SAH [OR 1.97 (95%CI 1.19-3.26)].</p><p><strong>Conclusions: </strong>Among AIS patients with UIAs, IVT was associated with better functional outcomes without excess risk of SAH. UIAs do not significantly alter the risk profile of IVT treatment.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"540"},"PeriodicalIF":4.6,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731769","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":"Saccadic eye movements in neurological disease: cognitive mechanisms and clinical applications.","authors":"Yong Lin Wang, Mahima Kapoor, Joanne Fielding, Stephen Reddel, Chao Zhu, Meaghan Clough, Mina Botrous, Mastura Monif, Anneke van der Walt","doi":"10.1007/s00415-025-13275-x","DOIUrl":"10.1007/s00415-025-13275-x","url":null,"abstract":"<p><p>Saccadic eye movements are rapid, precisely coordinated shifts that centre the fovea on a visual target. Their control relies on the integration of cognitive processes spanning multiple brain regions. High-resolution video-oculography enables precise measurement of saccadic dynamics, offering a window into disruptions affecting these networks. This review examines the neuroanatomy and physiology of saccadic eye movements, emphasising the cognitive mechanisms underlying their control and the methodologies used for their assessment. We synthesise evidence from saccadic eye movement testing across a spectrum of neurological diseases, highlighting its potential as an early and sensitive biomarker for detecting subclinical disease impact. While current findings underscore its promise as a non-invasive, objective tool for tracking neuropsychological dysfunction in these various diseases, we also address existing limitations and critical directions for future research towards improving clinical utility.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"539"},"PeriodicalIF":4.6,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731823","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":"Lung function and the risk of Parkinson's disease: a population-based cohort study.","authors":"Jiyong Liu, Shichan Wang, Xiaoting Zheng, Sirui Zhang, Qirui Jiang, Chunyu Li, Huifang Shang","doi":"10.1007/s00415-025-13274-y","DOIUrl":"10.1007/s00415-025-13274-y","url":null,"abstract":"<p><strong>Objective: </strong>Some researchers have noted a faster decline in lung function among Parkinson's disease (PD) patients compared to healthy individuals. However, the relationship between lung function and the risk of developing PD remains unknown. This study aims to explore the association between lung function and the risk to develop PD.</p><p><strong>Method: </strong>Based on the UK Biobank, Cox proportional hazards models were used to investigate the relationship between lung function measurements, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF), and FEV1/FVC, and the risk of PD. Furthermore, this study constructed a lung function score and explore the relationship between the lung function score and PD risk. This study also conducted mediation analysis using blood inflammatory markers and metabolic indicators as mediators.</p><p><strong>Result: </strong>This study included a total of 322,731 participants. We identified a correlation between lower lung function measures, particularly PEF and the lung function score we generated, and an increased risk of PD. Our mediation analysis highlighted several inflammatory markers, such as eosinophil, lymphocyte, monocyte, neutrophil, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammatory index, and reticulocyte, as mediators in the relationship between PEF and PD.</p><p><strong>Conclusion: </strong>Declining lung function, especially PEF and the lung function score we generated, could serve as a potential indicator for predicting the risk of PD. Inflammatory changes play a crucial role in the association, highlighting the significance of inflammatory alterations in the pathophysiology of PD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"538"},"PeriodicalIF":4.6,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717970","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":"Neurofilament light chain reference values in serum and cerebrospinal fluid: a bi-compartmental analysis in neurological diseases.","authors":"Steffen Halbgebauer, Veronika Klose, Badrieh Fazeli, Paula Klassen, Christoforos Alexudis, Gabriele Nagel, Angela Rosenbohm, Dietrich Rothenbacher, Nerea Gomez de San Jose, Simon Witzel, Zeynep Elmas, Maximilian Wiesenfarth, Joachim Schuster, Johannes Dorst, Andre Huss, Franziska Bachhuber, Markus Otto, G Bernhard Landwehrmeyer, Albert C Ludolph, Hayrettin Tumani","doi":"10.1007/s00415-025-13271-1","DOIUrl":"10.1007/s00415-025-13271-1","url":null,"abstract":"<p><strong>Background: </strong>Concentrations of neurofilament light chain (NfL), a neuroaxonal damage marker, increase with age. Therefore, age-dependent reference values are important in clinical practice. However, so far these have only been established with a bead-based system and age-dependent z-scores for CSF are missing. In addition, we here propose how the combined analysis of CSF and serum NfL could help in the discrimination between central (CNS) and peripheral nervous system (PNS) axonal degeneration.</p><p><strong>Methods: </strong>For the calculation of age reference values, serum and CSF NfL concentrations from 1,514 control subjects, measured using the microfluidic Ella system, were applied.</p><p><strong>Results: </strong>Age-dependent NfL levels were calculated with additive quantile regression and presented with percentiles and z-scores. We observed a non-linear increase of NfL in serum and CSF. The spearman r of the association with age was 0.81 (95% CI 0.78-0.83), p < 0.0001 and 0.82 (95% CI 0.79-0.85), p < 0.0001 for serum and CSF NfL, respectively. Serum and CSF NfL levels were also associated with each other (r = 0.68 (95%CI 0.62-0.73), p < 0.0001). Furthermore, we used this association to establish a bi-compartmental CSF and serum NfL model allowing to differentiate between peripheral or central origin of neurodegeneration.</p><p><strong>Conclusions: </strong>The age reference curves corroborate findings of an exponential elevation of NfL in serum and CSF with increasing age. As NfL values from different platforms are not interchangeable, this is of additional high relevance. Moreover, the association between CSF and serum NfL values could be applied for clinical use regarding overlapping symptoms of CNS and PNS-based neurological diseases.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"535"},"PeriodicalIF":4.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707816","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":"Comprehensive observations and multidisciplinary approaches (COMA) in the management of unconscious patients: a prospective high fidelity simulation study.","authors":"Nüesch Liliane, Kai Tisljar, Sebastian Berger, Gian Marco De Marchis, Tolga D Dittrich, Stefano Bassetti, Roland Bingisser, Sabina Hunziker, Stephan Marsch, Raoul Sutter","doi":"10.1007/s00415-025-13228-4","DOIUrl":"10.1007/s00415-025-13228-4","url":null,"abstract":"<p><strong>Background: </strong>Managing patients with coma of unknown etiology presents a challenge requiring rapid, structured assessment. We aimed to examine how physicians from different specialties manage patients with coma of unknown etiology and adhere to recommendations in a highly standardized scenario.</p><p><strong>Methods: </strong>Prospective high-fidelity simulation study conducted at an academic simulation center involving 50 physicians from acute care (38%), internal medicine (36%), and neurology (26%). Participants were confronted with a standardized coma scenario. Performance was assessed for adherence to expert-recommended clinical assessments (primary endpoints) and timing of interventions, such as airway protection, oxygen administration, toxicological screening, and self-evaluation (secondary endpoints).</p><p><strong>Results: </strong>All participants recognized coma; 80% assessed the Glasgow Coma Scale, with 40% quantifying it correctly. 20% completed ABCDE assessments, with 66% performing head-to-toe examinations. Airway inspection was conducted by 89% of acute care physicians, 70% of neurologists, and 60% of internists. A median of 4 ancillary tests were ordered, mostly neuroimaging (98%) and toxicological screening (86%), while rare toxin screening (2%) and EEG (12%) were scarce. Oxygen was universally administered (100%), but treatment response was rarely checked (8%). Side-positioning for airway protection was infrequent (21% acute care, 15% neurology, 6% internal medicine), while intubation was more commonly ordered by internists (17%). Prior simulator training improved side-positioning rates (27% vs. 4%, p = 0.047). Self-evaluations showed high motivation (median 8/10) but moderate confidence (5/10).</p><p><strong>Conclusions: </strong>This study highlights specialty-specific differences, misconceptions, and gaps in managing coma of unknown etiology, including inconsistent diagnostic workup and missed treatments, emphasizing the need for guidelines, standardized care and training.</p><p><strong>Registration: </strong>ClinicalTrials.gov registry (ID NCT06265168).</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"537"},"PeriodicalIF":4.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707808","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":"Learning as a digital hallmark of cognition in multiple sclerosis: lessons from a digital symbol digit modalities test.","authors":"Michelangelo Dini, Marta Tacchini, Giulia Gamberini, Angela Boschetti, Alessandra Caporali, Luca Chiveri, Mariaemma Rodegher, Letizia Turchi, Giancarlo Comi, Letizia Leocani","doi":"10.1007/s00415-025-13270-2","DOIUrl":"10.1007/s00415-025-13270-2","url":null,"abstract":"<p><strong>Background: </strong>Multiple Sclerosis (MS) often causes cognitive impairment that significantly impacts functional independence. The Symbol Digit Modalities Test (SDMT) is the gold standard for screening and monitoring cognitive functioning in people with MS (pwMS). Electronic SDMT (eSDMT) adaptations offer potential for remote monitoring and capturing more detailed performance metrics, compared to conventional pen-and-paper administration.</p><p><strong>Objectives: </strong>This study aimed to evaluate novel metrics derived from a validated eSDMT to enhance cognitive assessment and detect cognitive impairment in pwMS.</p><p><strong>Methods: </strong>We included 93 pwMS who performed an eSDMT which enables automatic collection of single-stimulus reaction times (RTs) and accuracy of responses. We investigated Performance Index-a scoring metric based on speed and accuracy-and the slope of individual RTs during the eSDMT task, which reflects response speed changes. We assessed the concurrent validity and test-retest reliability of Performance Index, as well as the impact of sociodemographic variables. Correlations with gold-standard cognitive tests of learning (California Verbal Learning Test, Brief Visuospatial Memory Test) were also explored. Hierarchical linear and logistic regression analyses were used to predict oral SDMT scores and broader cognitive impairment, respectively.</p><p><strong>Results: </strong>Participants exhibited improving RTs as the eSDMT progressed, reflecting generalized intra-trial learning. eSDMT Performance Index showed excellent concurrent validity with oral SDMT score, good-to-excellent test-retest reliability for remote administration, and excellent discriminant validity in detecting cognitive impairment. Including response speed trends further improved oral SDMT score prediction and detection of cognitive impairment. Response speed improvements correlated with higher scores at gold-standard neuropsychological tests of learning.</p><p><strong>Conclusions: </strong>Intra-trial learning metrics can enhance the validity of digital cognitive testing in pwMS. Future research should explore the predictive value of these metrics, particularly in remote and autonomous scenarios. The ability to collect reliable information on multiple cognitive processes in a cost- and time-effective manner via digital testing could significantly improve both clinical care and research.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"536"},"PeriodicalIF":4.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707815","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":"Variation in the reported prevalence of Huntington's disease: a systematic review and guide to interpretation.","authors":"Alexander Thompson, Oliver Quarrell, Mark Strong","doi":"10.1007/s00415-025-13255-1","DOIUrl":"10.1007/s00415-025-13255-1","url":null,"abstract":"<p><p>There is significant variation in the reported estimates of Huntington's disease (HD) prevalence in different settings. This systematic review was undertaken to describe and assess the sources of heterogeneity in estimated prevalence values, and to consider the role of quantitative synthesis in the context of such heterogeneity. Observational studies from which a prevalence estimate (point or period) or cumulative incidence of HD could be calculated between 1993 and 2024 were sought from Medline and Embase databases. The study features are described and the sources of heterogeneity are discussed. A meta-regression was conducted including predictor variables: continent, median age of population, number of years since 1993, case ascertainment method, and Healthcare Access and Quality Index score. 43 studies met the inclusion criteria. Significant clinical and methodological heterogeneity between studies is described, including differences in case definitions and ascertainment methods, and in the estimates of disease burden calculated. There were differences in the estimated point prevalence between regions and populations within regions, while the estimated point prevalence was shown to be increasing since 1993. Wide prediction intervals in the overall pooled point prevalence (95% prediction interval: 0.32-37.55 cases per 100,000), and the European pooled point prevalence (95% prediction interval: 1.64-19.18 cases per 100,000), indicate the scale of heterogeneity between studies and settings. While such heterogeneity currently limits the validity and utility of quantitative synthesis, developing an accepted consensus on the minimum standards and reporting requirements for HD prevalence studies could reduce the methodological heterogeneity between future studies, enabling more valid and meaningful quantitative synthesis in future.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"534"},"PeriodicalIF":4.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707817","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":"Serum GFAP predicts survival in advanced ALS: a prospective multicenter study.","authors":"Hee-Jae Jung, Woo-Seung Jeong, Heung-Won Kang, Minsung Kang, Eun-Jae Lee, Young-Min Lim, Jin-Sung Park, Hyunjin Kim","doi":"10.1007/s00415-025-13272-0","DOIUrl":"10.1007/s00415-025-13272-0","url":null,"abstract":"<p><strong>Background: </strong>Neurofilament light chain (NfL) is a well-established biomarker of axonal damage in amyotrophic lateral sclerosis (ALS), but its limited disease specificity warrants the identification of complementary markers. This study aimed to evaluate the prognostic value of serum glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) as adjunctive biomarkers to NfL in ALS.</p><p><strong>Methods: </strong>Serum NfL, GFAP, and BDNF levels were measured using ultrasensitive single-molecule array (SIMOA) assays in two independent ALS cohorts from Asan Medical Center (n = 65) and Kyungpook National University Chilgok Hospital (n = 53), along with 15 healthy controls. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Associations with clinical severity, disease progression rate, and survival were evaluated using correlation analyses, Kaplan-Meier survival estimates, and Cox proportional hazards models.</p><p><strong>Results: </strong>Serum NfL, GFAP, and BDNF levels were significantly elevated in ALS versus controls, with area under the curve (AUC) values of 0.969, 0.613, and 0.875, for NfL, GFAP, and BDNF, respectively. NfL and GFAP levels increased with advancing King's stage (NfL: τ = 0.226, p = 0.011; GFAP: τ = 0.160, p = 0.023), though only NfL correlated with disease progression rate (r = 0.309, p = 0.001). Notably, elevated GFAP was independently associated with poorer survival in advanced ALS (King's stage 3-4), with a hazard ratio of 6.907 (95% CI: 1.978-24.119, p = 0.002).</p><p><strong>Conclusions: </strong>While NfL remains a robust marker of ALS progression, GFAP may serve as an independent prognostic marker in late-stage disease. Combining these markers may enhance prognostic accuracy and support personalized ALS care.</p><p><strong>What is already known on this topic: </strong>Neurofilament light chain (NfL) is a widely accepted biomarker for axonal damage in ALS and correlates with disease progression. However, its lack of disease specificity limits its standalone prognostic value, necessitating the discovery of complementary biomarkers to improve prognostic accuracy.</p><p><strong>What this study adds: </strong>This study demonstrates that while NfL remains a strong indicator of ALS progression, glial fibrillary acidic protein (GFAP) serves as an independent prognostic marker, particularly in advanced stages of the disease. Furthermore, it shows that serum BDNF levels are also elevated in ALS patients.</p><p><strong>How this study might affect research, practice or policy: </strong>Combining NfL and GFAP as a biomarker panel could significantly enhance prognostic accuracy and facilitate more personalized treatment strategies for ALS patients, especially in later disease stages. This could guide clinical trial design and improve patient stratification for therapeutic interventions.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"532"},"PeriodicalIF":4.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698814","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":"Interaction of metabolic and inflammatory dysregulation on central degeneration and cognitive function in behavioral variant Frontotemporal dementia.","authors":"Jia-Hui Hou, Min Chu, Zhong-Yun Chen, De-Ming Jiang, Yu-Fei Chen, Ai-Ling Yue, Qian-Qian He, Hua Lu, Yu-Xuan Xu, Miao Qu, Li-Yong Wu","doi":"10.1007/s00415-025-13268-w","DOIUrl":"10.1007/s00415-025-13268-w","url":null,"abstract":"<p><strong>Background: </strong>Metabolic and inflammation dysregulation are important mechanisms in neurodegenerative diseases, but their study in behavioral variant frontotemporal dementia (bvFTD) is very scarce; we aimed to investigate the separate and interactive effects of metabolic and inflammatory dysregulation on central degeneration and cognitive function in patients with bvFTD.</p><p><strong>Methods: </strong>This study recruited participants with bvFTD and healthy controls (HC) from December 15, 2017, to September 5, 2024, in the Department of Neurology of Xuanwu Hospital, underwent assessment of plasma targeted metabolite, plasma inflammatory factors, 18F-fludeoxyglucose-positron emission tomography/magnetic resonance imaging, and neuropsychological assessments. Linear regression models and interaction models were implemented using age, sex and education level as covariates to explore the association between differential metabolites and peripheral inflammatory markers with neuroimaging, and clinical measures.</p><p><strong>Results: </strong>Forty bvFTD patients and 40 HC (56.25% female, mean age of 63.55 years) were involved. A total of 36 plasma differential metabolites were screened out with variable importance in projection (VIP) > 1 and p < 0.05. Differential metabolites distributed in metabolic pathways that regulate inflammation, such as Aminoacyl-tRNA biosynthesis, mTOR signaling and amino acid metabolism. Furthermore, differential metabolites and plasma inflammatory factors are correlated with atrophy and glucose metabolism in certain frontal-temporal brain regions, as well as cognitive function (p < 0.05). Additionally, the interaction between differential metabolites and inflammatory factors is associated with atrophy and glucose metabolism in the entire frontal-temporal brain region, as well as cognitive function (p < 0.05). Under conditions of dysregulation of inflammatory factors such as Interleukin, Interferons, and Tumour necrosis factor, metabolites in Aminoacyl-tRNA biosynthesis, mTOR signaling, and amino acid metabolism have a more pronounced impact on frontotemporal lobar degeneration and cognitive symptoms (p < 0.05).</p><p><strong>Conclusions: </strong>This study shows that bvFTD exhibits peripheral metabolic and inflammatory dysregulation, which are associated with frontotemporal lobar degeneration and clinical symptoms, and the interaction effects of metabolic and inflammatory dysregulation have a greater impact on bvFTD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"533"},"PeriodicalIF":4.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707814","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}