Movement disorders : official journal of the Movement Disorder Society最新文献

{"title":"GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations.","authors":"Yi Wen Tay, Andrew Leslie Lee, Jie Ping Schee, Chin-Hsien Lin, Eng King Tan, Jung Hwan Shin, Pin-Shiuan Chen, Sung-Pin Fan, Cheng-Hsuan Li, Ebonne Yu Lin Ng, Han Joon Kim, Beomseok Jeon, Sulev Koks, Huyen Thi Thanh Vu, Kin Ying Mok, Yi Ting Lim, Mohd Salahuddin Kamaruddin, Tzi Shin Toh, Hans Xing Ding, Anis Nadhirah Khairul Anuar, Norlisah Ramli, Ignacio J Keller Sarmiento, Maria Teresa Periñan, Zih-Hua Fang, Lara M Lange, Kishore R Kumar, Soraya Bardien, Joanne Trinh, Enza Maria Valente, Peter Heutink, Katja Lohmann, Christine Klein, Niccolò E Mencacci, Shen-Yang Lim, Azlina Ahmad-Annuar, Ai Huey Tan","doi":"10.1002/mds.70530","DOIUrl":"10.1002/mds.70530","url":null,"abstract":"<p><strong>Introduction: </strong>GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined.</p><p><strong>Objectives: </strong>Our goal was to investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant.</p><p><strong>Methods: </strong>We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n = 22,372_PD vs. n = 8,826_Controls) and meta-analysis of East Asian (EAS) cohorts (n = 4,712_PD vs. 38,733_Controls). Haplotype analyses were performed and clinico-demographic details of affected variant carriers were collated.</p><p><strong>Results: </strong>The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n = 9/2,757; 0.33%), but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio = 5.1; 95% confidence intervals [CI] = 2.3-10.7; P = 2.89 × 10^-5). A shared haplotype (~330 kbp) was identified among variant carriers. Affected carriers (mean age at onset: 56.3 ± 12.5 years) had additional occurrence of dystonia, whereas dementia was rare.</p><p><strong>Conclusions: </strong>The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofilament Light Chain and Mutant Huntingtin Across Huntington's Disease Integrated Staging System Stages in Huntington Disease: A Cross-Sectional Multimodal Analysis.","authors":"Jesús Pérez-Pérez, Gonzalo Olmedo-Saura, Arnau Puig Davi, Rocío Pérez González, Jordi Pegueroles, Andrea Horta-Barba, Anna Vázquez Oliver, Elisa Rivas Asensio, Daniel Alcolea, Juan Fortea, Marina Guasch-Jiménez, Tomas Xuclà Ferrarons, Frederic Sampedro Santaló, Lidia Bojtos, Óscar López-Lombardía, Ignacio Aracil-Bolaños, Berta Pascual-Sedano, Carla Franch Martí, Laura Pérez Carasol, Margarita Rubio Romera, Yi Ji, Alexandre Gironell, Antonia Campolongo, Raul Martínez-Fernández, Alberto Lleó, Javier Pagonabarraga, Saul Martínez-Horta, Jaime Kulisevsky","doi":"10.1002/mds.70550","DOIUrl":"https://doi.org/10.1002/mds.70550","url":null,"abstract":"<p><strong>Background: </strong>The Huntington's Disease Integrated Staging System (HD-ISS) provides a framework for staging HD but does not incorporate fluid biomarkers.</p><p><strong>Objective: </strong>The aim of this study was to examine neurofilament light chain (NfL) and mutant huntingtin (mHTT) and total tau across HD-ISS stages and their associations with genetic burden, neuroimaging, and clinical measures.</p><p><strong>Methods: </strong>We performed cross-sectional analysis of the Barcelona-Huntington's Disease (BCN-HD) cohort with external replication in the multicenter HDClarity study. HD gene expansion carriers were classified as HD-ISS stages 0 to 3. NfL (cerebrospinal fluid [CSF] and plasma), CSF mHTT, total tau, striatal volumes, and Unified Huntington's Disease Rating Scale measures were quantified. Group differences and associations were analyzed using adjusted models.</p><p><strong>Results: </strong>The BCN-HD cohort included 78 participants (50 HD gene expansion carriers [HDGECs], 28 controls) and HDClarity included 218 participants (166 HDGECs, 52 controls). CSF NfL increased across HD-ISS stages and discriminated premanifest from manifest individuals, as well as HD-ISS stage 0 from stage 1. Plasma NfL showed parallel increases and strongly correlated with CSF NfL (ρ = 0.88, P < 0.001). More than half of HD-ISS 0 individuals had NfL levels above the age-adjusted 95th percentile (P95) and shorter predicted time to onset (13 years for CSF and 10 years for plasma). From HD-ISS 1 onward, NfL levels exceeded P95 in most individuals. Higher NfL concentrations were associated with genetic burden, striatal atrophy, and clinical measures (all P < 0.001). CSF mHTT was detectable from HD-ISS 0 but showed weaker associations, whereas CSF total tau increased only from HD-ISS 3.</p><p><strong>Conclusions: </strong>NfL identifies biological activity across the HD-ISS continuum and shows neuroaxonal injury in a subset of individuals classified as stage 0. These findings suggest that fluid biomarkers may complement current HD-ISS criteria and support biological stratification in observational studies and clinical trials. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consistency of Serial Cerebrospinal Fluid α-Synuclein Seed Amplification Assay Results in the Parkinson's Precision Medicine Initiative.","authors":"David G Coughlin, Caroline Gochanour, Jie Yin, Luis Concha-Marambio, Carly Farris, Yihua Ma, David-Erick Lafontant, Edwin Jabbari, Tanya Simuni, Ken Marek, Thomas F Tropea","doi":"10.1002/mds.70509","DOIUrl":"https://doi.org/10.1002/mds.70509","url":null,"abstract":"<p><strong>Background: </strong>Studies reporting α-synuclein seed amplification assay (aSyn-SAA) results are often cross-sectional.</p><p><strong>Objectives: </strong>In this study, we investigated the intraindividual consistency of aSyn-SAA results (Amprion) over time from participants in the Parkinson's Precision Medicine Initiative (PPMI).</p><p><strong>Methods: </strong>A total of 1238 participants had >1 cerebrospinal fluid (CSF) aSyn-SAA result for analysis (Parkinson's disease [PD] = 633, prodromal = 563, healthy control [HC] = 42), collected over a median (minimum, maximum) of 2.0 (0.4, 11.4) years. Emphasis was placed on evaluating consistency in aSyn-SAA-PD participants, aSyn-SAA + HC participants, and conversion rates from aSyn-SAA negative to positive results prodromal participants.</p><p><strong>Results: </strong>Of aSyn-SAA + PD participants, 96% (474/493, 95% confidence interval [CI]: 94%-98%) remained positive in subsequent samples, and 92% (116/126, 95% CI: 86%-96%) of aSyn-SAA-PD participants remained negative. Ninety-nine percent (303/307, 95% CI: 97%-99%) of aSyn-SAA + prodromal participants remained positive, and 95% (234/247, 95% CI: 91%-97%) of aSyn-SAA-prodromal participants remained negative. Eighty-nine percent (16/18, 95% CI: 67%-97%) of aSyn-SAA + HC participants remained positive, and 87% (20/23, 95% CI: 68%-95%) of aSyn-SAA-HC participants remained negative.</p><p><strong>Conclusions: </strong>aSyn-SAA testing is highly consistent over time, even in less expected scenarios. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Lipid Remodeling across Preclinical Burden, Disease Onset, and Early Motor Severity in Huntington's Disease.","authors":"Mohamed Bendimerad, Dominique Bonneau, Clarisse Scherer-Gagou, Adriana Prundean, Karim Chikh, Oriane Vitalis, Audrey Olivier, Odile Blanchet, Judith Nzoughet-Kouassi, Christophe Verny, Pascal Reynier, Juan Manuel Chao de la Barca","doi":"10.1002/mds.70531","DOIUrl":"https://doi.org/10.1002/mds.70531","url":null,"abstract":"<p><strong>Background and objectives: </strong>Huntington's disease (HD) evolves silently for years before motor onset, yet the systemic metabolic alterations accompanying cumulative exposure to mutant huntingtin and disease progression remain poorly understood. We aimed to identify plasma metabolic signatures associated with disease burden, disease onset and motor severity in HD.</p><p><strong>Methods: </strong>Mutation carriers with 36 or more cytosine-adenine-guanine (CAG) repeats in the HTT gene were prospectively recruited and classified as premanifest or early manifest. Fasting plasma samples were analyzed using targeted metabolomics and lipidomics. Linear models adjusted for covariates were used to investigate associations with CAG-Age Product (CAP) score, disease stage, and motor severity (Unified Huntington's Disease Rating Scale total motor score). Lipid-class enrichment, acyl-chain enrichment and composite lipid score analyses were performed to characterize coordinated metabolic remodeling.</p><p><strong>Results: </strong>Ninety-three mutation carriers (54 premanifest and 39 early manifest individuals) were included. Increasing CAP scores were associated with coordinated enrichment of eicosapentaenoic (20:5) and docosahexaenoic (22:6) acid-containing phospholipids together with depletion of triglycerides. In contrast, disease onset was characterized by enrichment of triglycerides and of lipids containing palmitate, palmitoleate, and arachidonate, accompanied by an increased palmitoleate-to-palmitate ratio of cholesteryl esters. In early manifest individuals, increasing motor severity was associated with depletion of docosahexaenoic acid-containing phospholipids, an increased phosphatidylserine-to-phosphatidylcholine ratio and reduced circulating acylcarnitines. These findings were supported by composite lipid scores and leave-one-subject-out sensitivity analyses.</p><p><strong>Conclusions: </strong>HD is associated with coordinated plasma lipid remodeling across disease stages. Distinct lipid signatures characterize cumulative mutant huntingtin exposure, disease onset and motor progression, providing insights into the metabolic consequences of HD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative Functional Imaging Predicts Deep Brain Stimulation Outcome in Craniocervical Dystonia.","authors":"Houyou Fan, Alexandre Boutet, Gavin J B Elias, Tiantian Hua, Rujin Wang, Zixiao Yin, Yichen Xu, Zehua Zhao, Yan-Hua Su, Aaron Loh, Julianna Pijar, Iva Bogojevic, Hezekiah C T Au, Yanwen Wang, Tianxue Hu, Jason Yuen, Sarah Iskin, Gerardo Chavira-Hernandez, Anchao Yang, Andres M Lozano, Yutong Bai, Jürgen Germann, Jianguo Zhang","doi":"10.1002/mds.70552","DOIUrl":"https://doi.org/10.1002/mds.70552","url":null,"abstract":"<p><strong>Background: </strong>Deep brain stimulation (DBS) is an established treatment for craniocervical dystonia (CCD), yet postoperative benefit varies widely and cannot be estimated before surgery. Resting-state functional MRI (rs-fMRI) has shown prognostic value across DBS indications. The objective of this study was to develop and externally validate preoperative rs-fMRI models estimating DBS response in CCD.</p><p><strong>Methods: </strong>Forty-two patients from two independent centers underwent preoperative 3 T rs-fMRI (discovery, n = 26; validation, n = 16). Using 12 literature-informed, symptom-relevant regions of interest, we quantified the amplitude of low-frequency fluctuation as a measure of intrinsic regional neural activity. We applied regularized modeling to classify super-responders, distinguish responders from non-responders, and estimate improvement in Burke-Fahn-Marsden Dystonia Rating Scale motor subscore.</p><p><strong>Results: </strong>When applied to the validation cohort, the imaging models achieved a three-category classification accuracy of 75.0% (50.5%-89.8%) using a sequential two-step procedure (P_perm = 0.002). Predicted continuous improvement was also correlated with empirical improvement (R_ext = 0.65, Q² = 0.34, P_perm = 0.004). Within the discovery cohort, nested leave-one-out-cross-validation, in which feature selection and decision-threshold derivation were repeated independently within each training fold, yielded areas under the curve (AUCs) of 0.73 (0.50-0.96) and 0.77 (0.51-1.00). Across models, baseline primary motor cortex activity was consistently associated with diminished postoperative benefit.</p><p><strong>Conclusions: </strong>Preoperative rs-fMRI captures clinically relevant variation in baseline brain state in CCD, with predictive performance supported in an external validation. These findings provide preliminary support for rs-fMRI as a potential source of information to aid patient counseling and clinical decision-making, pending prospective validation. © 2026 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building Scalable Recruitment Models for Precision Medicine in Parkinson's Disease: Insights from GBA1 Trials.","authors":"Jean-Christophe Corvol, Christelle Tesson, Sophie Liot, Stéphanie Carvalho, Giovanni Castelnovo, Philippe Damier, Luc Defebvre, Caroline Giordana, Jean-Luc Houeto, Ana Marques, Wassilios G Meissner, Philippe Remy, Stéphane Thobois, Margherita Fabbri, Olivier Rascol","doi":"10.1002/mds.70537","DOIUrl":"https://doi.org/10.1002/mds.70537","url":null,"abstract":"","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alkaline Phosphatases: A Potential Cause of Variability in Therapeutic Response to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion?","authors":"Manon Auffret, Marc Vérin","doi":"10.1002/mds.70414","DOIUrl":"10.1002/mds.70414","url":null,"abstract":"","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":"2787-2788"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Intronic Variable Number Tandem Repeat (VNTR) Expansions of the HSF1 Gene in Essential Tremor Patients from Eastern China.","authors":"Lanxiao Cao, Jiaxin Li, Qianhui Zhao, Yuhang Zhao, Huiqian Wang, Zhilin Zheng, Qing'er Mo, Xiaohan Chen, Yesong Liu, Tian Xu, Guohua Zhao","doi":"10.1002/mds.70282","DOIUrl":"10.1002/mds.70282","url":null,"abstract":"<p><strong>Background: </strong>The association between intronic variable number tandem repeat (VNTR) expansions in intron 10 of the HSF1 gene and essential tremor (ET) has not yet been validated in larger, more diverse populations.</p><p><strong>Objectives: </strong>This study aimed to investigate the association between HSF1 gene VNTR expansions and ET in the population of Eastern China.</p><p><strong>Methods: </strong>We screened 324 patients and 197 healthy controls (HCs) using fluorescence amplicon length analysis polymerase chain reaction (PCR) then precisely identified and analyzed repeat expansions at this locus by combining repeat-primed PCR with long-read whole-genome sequencing.</p><p><strong>Results: </strong>Despite identifying 18 patients (5.6%) carrying large HSF1 intronic VNTR expansions (>700 bp), our study found no significant difference in the overall distribution of repeat expansion lengths between the entire cohort of 324 ET patients and HCs, nor between familial and sporadic ET subgroups.</p><p><strong>Conclusion: </strong>The amplification of this repetitive sequence in intron 10 of the HSF1 gene does not constitute a universal, major, or reliable genetic risk factor for ET. © 2026 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":"2773-2776"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homocysteine as a Key Biomarker of Metabolic Stress During Foslevodopa/Foscarbidopa Infusion Therapy.","authors":"Fabienne Ory-Magne, Solene Frismand, Sophie Drapier, Guillaume Baille","doi":"10.1002/mds.70539","DOIUrl":"10.1002/mds.70539","url":null,"abstract":"","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":"2803-2804"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PET-DWI Colocalization Core: Defining Active Disease in CSF1R-Leukoencephalopathy.","authors":"Xinting Zhuang, Zhibao Zhu, Ying Wang, Bin Cai","doi":"10.1002/mds.70371","DOIUrl":"10.1002/mds.70371","url":null,"abstract":"","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":"2783-2784"},"PeriodicalIF":7.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148039232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}