Movement Disorders最新文献

{"title":"Delayed Disease Onset Report in UK Biobank: Implications for Prodromal Studies in Parkinson's Disease","authors":"Sheida Zolfaghari, Trycia Kouchache, Aline Delva, Sarah Bouhadoun, Mirja Kuhlencord, Amélie Pelletier, Alastair J. Noyce, Sheena Waters, Daniel Belete, Tim Wilkinson, Kathryn Bush, Filip Morys, Andrew Vo, Kristiina Rannikmae, Alain Dagher, Ronald B. Postuma","doi":"10.1002/mds.70147","DOIUrl":"https://doi.org/10.1002/mds.70147","url":null,"abstract":"Background <jats:styled-content style=\"fixed-case\">UK</jats:styled-content> Biobank ( <jats:styled-content style=\"fixed-case\">UKBB</jats:styled-content> ) provides extensive genetic, imaging, and health data for ~500,000 participants, enabling studies of prodromal phases of diseases like Parkinson's disease ( <jats:styled-content style=\"fixed-case\">PD</jats:styled-content> ). However, during analysis, we became concerned about the accuracy of diagnosis timing. Objective To evaluate the accuracy of PD diagnosis timing in UKBB. Methods We examined <jats:styled-content style=\"fixed-case\">PD</jats:styled-content> diagnosis timing using hospital, primary care, death records, and self‐reported data. We assessed discrepancies between sources and identified co‐occurring diagnoses recorded on the same date as <jats:styled-content style=\"fixed-case\">PD</jats:styled-content> . Results Among 3979 <jats:styled-content style=\"fixed-case\">PD</jats:styled-content> cases, 97% of the 786 participants with both self‐reported and electronic health records ( <jats:styled-content style=\"fixed-case\">EHRs</jats:styled-content> ) reported their diagnosis earlier than recorded in the <jats:styled-content style=\"fixed-case\">EHR</jats:styled-content> , with a typical delay of 5 to 7 years. Multiple codiagnoses were often logged on the same date, suggesting retrospective or batch data entry. Conclusions Substantial delays in <jats:styled-content style=\"fixed-case\">PD</jats:styled-content> documentation may misclassify already diagnosed individuals as prodromal. This introduces significant bias into studies of early disease markers and distorts the timing between risk factors and clinical onset. © 2025 The Author(s). <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"19 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Deep Learning to Differentiate Parkinsonian Syndromes: From Proof of Concept to Clinical Trust","authors":"Giulia Maria Mattia PhD,&nbsp;Lydia Chougar MD, PhD,&nbsp;Alexandra Foubert-Samier MD, PhD,&nbsp;Wassilios G. Meissner MD, PhD,&nbsp;Margherita Fabbri MD, PhD,&nbsp;Anne Pavy-Le Traon MD, PhD,&nbsp;Olivier Rascol MD, PhD,&nbsp;David Grabli MD, PhD,&nbsp;Bertrand Degos MD, PhD,&nbsp;Nadya Pyatigorskaya MD, PhD,&nbsp;Alice Faucher MD,&nbsp;Marie Vidailhet MD,&nbsp;Jean-Christophe Corvol MD, PhD,&nbsp;Stéphane Lehéricy MD, PhD,&nbsp;Patrice Péran PhD","doi":"10.1002/mds.70136","DOIUrl":"10.1002/mds.70136","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 1","pages":"275-276"},"PeriodicalIF":7.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilateral Deep Brain Stimulation of the Subthalamic Nucleus or Globus Pallidus Internus Improves Gait Impairment in Parkinson's Disease","authors":"Jamal Al Ali, J. Lucas McKay, Joe R. Nocera, Faical Isbaine, Julie T. Tran, Paola Testini, Shirley D. Triche, Christine D. Esper, Pratibha Aia, Laura M. Scorr, Lenora Higginbotham, Richa Tripathi, Nicholas Au Yong, Svjetlana Miocinovic, Cathrin M. Buetefisch","doi":"10.1002/mds.70146","DOIUrl":"https://doi.org/10.1002/mds.70146","url":null,"abstract":"Background The effect of deep brain stimulation (DBS) on gait in patients with Parkinson's disease (PD) remains variable, and prospective, long‐term studies, especially involving globus pallidus interna (GPi) stimulation, are limited. Objectives We tested the hypothesis that subthalamic nucleus (STN) and GPi DBS exert acute and chronic effects on gait in patients with PD. Methods Gait kinematics were collected prospectively on patients with PD with bilateral or unilateral STN or GPi DBS, at baseline before initial DBS activation (n = 104), acutely after activation (n = 102), and chronically at 1 month (n = 75) and 12 months (n = 82) OFF‐medications. Gait speed was the main outcome. Kinematic measures of pace, rhythm, and variability and clinical scales were secondary outcomes. Results Average gait speed at baseline was abnormally slow (80.6 cm/s). DBS activation acutely increased gait speed (97.4 cm/s, <jats:italic>P</jats:italic> &lt; 0.001) which was maintained at 1‐month (93.0 cm/s, <jats:italic>P</jats:italic> &lt; 0.001) and 12‐month follow‐up (91.2 cm/s, <jats:italic>P</jats:italic> &lt; 0.001). Acute changes predicted chronic changes. When DBS targets were analyzed separately, only bilateral STN or GPi DBS improved gait speed along with pace, rhythm, and variability. Presurgical levodopa response on the MDS‐UPDRS axial subscore correlated with the response to DBS while the total score did not. Discussion Bilateral STN or GPi DBS should be considered for treatment of gait as both targets improved gait kinematics acutely and chronically. Acute effects of STN or GPi DBS on gait speed should be considered when programming patients as they predict chronic effects. When determining DBS candidacy, the levodopa response on the MDS‐UPDRS axial subscore should be considered. © 2025 The Author(s). <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"32 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning to Differentiate Parkinsonian Syndromes: From Proof of Concept to Clinical Trust","authors":"Qihao Zhang MD,&nbsp;Yuan Li MD, PhD,&nbsp;Wei Mao MD, PhD,&nbsp;Hui Zhang MD, PhD","doi":"10.1002/mds.70139","DOIUrl":"10.1002/mds.70139","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 1","pages":"273-274"},"PeriodicalIF":7.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bipolar Disorder as a Long-Term Risk Factor for Parkinson's Disease: A Nationwide Case-Control Study.","authors":"Elina Jaakkola,Marjaana Koponen,Valtteri Kaasinen,Jarmo Hietala,Sirpa Hartikainen,Anna-Maija Tolppanen","doi":"10.1002/mds.70135","DOIUrl":"https://doi.org/10.1002/mds.70135","url":null,"abstract":"BACKGROUNDPrevious studies suggest an association between bipolar disorder (BD) and an increased risk of Parkinson's disease (PD), but the long-term temporal relationship remains unclear. Particularly, it is unclear whether the risk of PD is influenced by the duration since BD diagnosis.OBJECTIVEThe aim was to examine the association between BD and PD across time windows extending up to 35 years before PD diagnosis.METHODSThis nationwide, register-based, nested case-control study from Finland included 22,189 incident PD patients diagnosed between 1996 and 2015 and 148,009 age-, sex-, and region-matched controls. BD diagnoses from 1972 up to the PD diagnosis date (index date) were identified from health-care registers. Conditional logistic regression was used to estimate the association between BD and PD in various exposure windows with a 0- to 35-year lag. Main analyses considered BD diagnosed at least 8 years before the index date (8-year lag).RESULTSBD was diagnosed before the index date in 172 (0.87%) PD patients and 509 (0.34%) controls. Elevated PD risk was evident already with a 20-year lag between BD and PD diagnoses, with a trend toward increased risk even at 30 years. In the main analysis using the 8-year lag, BD diagnosis was associated with over a twofold higher relative risk of PD (adjusted odds ratio, 95% confidence interval: 2.32, 1.85-2.91).CONCLUSIONSBD is associated with a significantly elevated risk of PD, observable decades before PD onset. These findings suggest that BD may reflect a long-term vulnerability to PD rather than a short-term prodromal state, emphasizing the need to explore shared pathophysiological mechanisms. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"200 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect on Dyskinesia of the Early Combination of Amantadine to Levodopa-Therapy in Parkinson's Disease: A Randomized, Placebo-Controlled Study (PREMANDYSK).","authors":"Olivier Rascol,Fabienne Ory-Magne,Wassilios G Meissner,David Maltête,Luc Defebvre,Jean-Philippe Azulay,Stéphane Thobois,Jean-Luc Houeto,Claire Thalamas,Agnès Sommet,Christian Geny,Philippe Damier,Mathieu Anheim,Ana Marquès,François Viallet,Maurice Giroud,Romain Lefaucheur,Guillaume Costentin,Umberto Spampinato,Alexandra Samier-Foubert,Nicolas Carrière,Eugénie Mutez,Louise-Laure Mariani,Alexandre Eusebio,Stéphane Prange,Isabelle Benatru,Mahmoud Charif,Christine Brefel-Courbon,Margherita Fabbri,Monique Galitzky,Vanessa Rousseau,Amandine Saubion,Hélène Catala,Joaquim J Ferreira,David J Burn,Jean-Christophe Corvol, ","doi":"10.1002/mds.70120","DOIUrl":"https://doi.org/10.1002/mds.70120","url":null,"abstract":"OBJECTIVEInvestigate the efficacy of immediate-release (IR) amantadine in reducing the risk of peak-dose dyskinesia in early Parkinson's disease (PD) as add-on to levodopa.BACKGROUNDWhile the use of amantadine to manage dyskinesia in PD is well supported by controlled clinical trials, data on its efficacy in patients without motor complications remain limited.METHODSThis 22-month, multicenter, randomized, placebo-controlled trial (NCT01538329) enrolled early PD patients on stable levodopa (≥150 mg/day for ≤1 year) without motor complications. The study included three double-blind phases: an 18-month treatment phase with adjunct amantadine-IR (200 mg/day) or placebo (Period 1), a 3-month delayed-start phase where all participants received amantadine-IR (Period 2), and a 1-month washout with placebo (Period 3). The primary outcome was dyskinesia incidence at month 18; secondary outcomes included dyskinesia rates at the end of Periods 2 and 3 to assess potential long-lasting mechanisms of the drug. Exploratory outcomes investigated the potential effects of amantadine-IR on motor and non-motor symptoms and quality of life.RESULTSA total of 207 patients were randomized to amantadine-IR (N = 99) or placebo (N = 108). Significantly fewer patients in the amantadine-IR group developed dyskinesia versus placebo during Period 1 (11% vs. 22%, P = 0.025), while the mean daily dose of levodopa (95% CI) increased by 70 (21-119) mg less (P = 0.005). The proportion of patients with dyskinesia was less in the amantadine-IR group versus placebo at the end of Periods 2 and 3, but the difference was not statistically significant (12% vs. 20%, P = 0.13 and 16% vs. 22%, P = 0.23, respectively). Mild but significant positive effects on freezing of gait, fatigue, and quality of life were observed during Period 1. The safety profile of amantadine-IR was in line with previous reports.CONCLUSIONSAdjunctive amantadine-IR in early PD halved dyskinesia incidence over 18 months. Long-lasting mechanisms could not be demonstrated and merit further investigation. Exploratory positive findings on the potential benefit of amantadine-IR on symptoms like freezing of gait and fatigue also call for further investigation. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"55 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal Fluid Biomarkers of NLRP3 Pathway, Immune Dysregulation, and Neurodegeneration in Parkinson's Disease: A Meta-Analysis.","authors":"Alina-Măriuca Marinescu,Venissa Machado,Gennaro Pagano,Nicoletta Milani Muelhardt,Thomas Kustermann,Eva Zsuzsanna Mracsko,Kathrin Brockmann,Nima Shariati,Judith Anzures-Cabrera,Bastian Zinnhardt","doi":"10.1002/mds.70103","DOIUrl":"https://doi.org/10.1002/mds.70103","url":null,"abstract":"BACKGROUNDThe activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and associated immune dysregulation is one of the key pathological processes preceding and accompanying α-synuclein pathology, neuronal damage, and cell death in Parkinson's disease (PD). Biomarkers indicative of ongoing immune dysregulation could potentially serve as early indicators of disease activity and may support the development of novel immunomodulatory therapies.METHODSWe performed a meta-analysis on 17 biomarkers related to specific components of the neuroinflammatory response in the cerebrospinal fluid of people with PD (PwP) and controls. We included studies that measured biomarkers related to NLRP3 inflammasome priming and activation (interleukin [IL]-1β, IL-18, IL-6, C-reactive protein, tumor necrosis factor [TNF]-α); reactive glial cells (soluble triggering receptor expressed on myeloid cells 2, chitinase 3-like-protein 1, glial fibrillary acidic protein, and s100); neurodegeneration (neurofilament light chain [NfL]); and other inflammatory mediators (interferon-ɣ, IL-2, IL-4, IL-8, IL-10, monocyte chemoattractant protein-1, chemokine C-X3-C motif chemokine ligand 1).RESULTSRandom-effects meta-analyses show markers downstream of the NLRP3 inflammasome priming and activation (IL-1β, IL-6, TNF-α), the astrocytic marker s100 calcium-binding protein B and neuroaxonal damage marker NfL are significantly increased in the cerebrospinal fluid (CSF) of PwP.CONCLUSIONSThe elevation in key downstream and general inflammatory mediators results is consistent with the hypothesized involvement of the NLRP3 inflammasome pathway and neurodegeneration in PD pathogenesis. These results highlight the potential use of CSF inflammatory markers and support further investigation into immunomodulatory strategies for PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"27 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'What's in a Name?' Naming Genetically Determined Movement Disorders: Gap and Controversy.","authors":"Connie Marras,Alberto Albanese,Mark Hallett,Christine Klein,Katja Lohmann, ,H A Jinnah","doi":"10.1002/mds.70143","DOIUrl":"https://doi.org/10.1002/mds.70143","url":null,"abstract":"In 2016, the International Parkinson and Movement Disorder Society (MDS) Task Force for Genetic Nomenclature in Movement Disorders laid out a new proposal for naming genetically determined movement disorders. This proposal sought to address the difficulties arising from the practical usage of numbered loci (eg, DYT1, DYT2, DYT3, etc.) as names for disorders. The proposal incited commentary highlighting concerns of subjectivity, neglecting relevant non-movement features, and predicting the need for constant change as knowledge. An evaluation of the use of the nomenclature in the recent peer-reviewed literature revealed variable implementation across movement phenotypes. The nomenclature has strengths and weaknesses, which are discussed in this article. A consideration of opportunities for improvement is warranted, and weighing the options will be the task of the MDS Nomenclature in Genetic Movement Disorders Study Group. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"9 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss‐of‐Function Variants in CPT1C : No Support for a Causal Role in Hereditary Spastic Paraplegia","authors":"Rui Zhu, Lang Liu, Mehrdad A. Estiar, Farnaz Asayesh, Jamil Ahmad, Meron Teferra, Grace Yoon, Mark Tarnopolsky, Kym M. Boycott, Nicolas Dupre, Patrick A. Dion, Oksana Suchowersky, Albena Jordanova, Yi‐Chung Lee, Giovanni Stevanin, Stephan Zuchner, Guy A. Rouleau, Ziv Gan‐Or","doi":"10.1002/mds.70144","DOIUrl":"https://doi.org/10.1002/mds.70144","url":null,"abstract":"Background Hereditary spastic paraplegias (HSPs) are neurodegenerative disorders characterized by lower‐limb spasticity. Pathogenic variants in <jats:italic>CPT1C</jats:italic> have been implicated in HSP. Objective The objective of this study was to assess whether <jats:italic>CPT1C</jats:italic> loss‐of‐function (LOF) variants are causally associated with HSP. Methods We analyzed whole‐genome sequencing data from UK Biobank (UKBB), whole‐exome sequencing data from a Canadian HSP cohort (Can‐HSP), and genetic data from the GENESIS cohort—a large international cohort of patients with rare hereditary diseases, including HSP. Results Among &gt;170 <jats:italic>CPT1C</jats:italic> LOF carriers in the UKBB (n = 150,119), none exhibited HSP phenotypes. Among 585 HSP patients from Can‐HSP, we did not find patients with <jats:italic>CPT1C</jats:italic> LOF variants. In the GENESIS cohort (n = 21,217), three individuals carrying <jats:italic>CPT1C</jats:italic> LOF variants were also diagnosed with HSP; however, all three also carry pathogenic variants in established HSP‐associated genes. Conclusions Our study does not support a causal role for <jats:italic>CPT1C</jats:italic> LOF variants in HSP. © 2025 The Author(s). <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"114 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Movement Disorders: Volume 40, Number 11, November 2025","authors":"","doi":"10.1002/mds.70121","DOIUrl":"10.1002/mds.70121","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}