Movement Disorders最新文献

{"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}

{"title":"November Infographic","authors":"","doi":"10.1002/mds.29861","DOIUrl":"10.1002/mds.29861","url":null,"abstract":"<p>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 Combined Dysfunction of the Amygdala and Nucleus Basalis underlies Visual Hallucinations in Parkinson's Disease</p>","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611324","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}

{"title":"[ 11 C ]( R )‐ PK11195 Positron Emission Tomography Imaging of Skull Inflammation in Isolated Rapid‐Eye‐Movement Sleep Behavior Disorder","authors":"Andreas Myhre Baun, Michael Firbank, Rainer Hinz, Miriam Højholt Terkelsen, Alex Iranzo, Carles Gaig, Eduardo Tolosa, David J. Brooks, Nicola Pavese, Michael Keogh","doi":"10.1002/mds.70133","DOIUrl":"https://doi.org/10.1002/mds.70133","url":null,"abstract":"Background Skull bone marrow is a specialized immune compartment supplying cells to the meninges. Experimental evidence suggests skull marrow activity may contribute to neuroinflammation in early Parkinson's disease, but in vivo assessment has not yet been performed in any α‐synucleinopathy. Objective The objective is to assess skull/meningeal inflammatory activity in patients with isolated rapid‐eye‐movement sleep behavior disorder (iRBD). Methods 20 iRBD patients recieved longitudinal [ <jats:sup>11</jats:sup> C]( <jats:italic>R</jats:italic> )‐PK11195 positron emission tomography scans and were compared to 19 healthy controls. Results Global skull inflammation in the iRBD patients was 22.87% higher (95% confidence interval: 12.78–32.97) compared to controls, especially in frontal regions, differing from that previously reported in Alzheimer's disease and multiple sclerosis. This inflammation progressed during a 3‐year follow‐up period but did not correlate with phenoconversion. Conclusion This is the first in vivo evidence of skull marrow activation in an α‐synucleinopathy. Our findings support a role for the skull–meningeal immune axis in iRBD, linking peripheral and central inflammation in prodromal disease. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"116 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611086","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":"Transforming Care Across Countries: Lessons from the Integrated Care Networks for Parkinson's Disease Study (iCARE-PD).","authors":"Deepa Dash,Margherita Fabbri,Joseph Saade,Marlena van Munster,David Pedrosa,Evzen Růžička,Ota Gal,Joaquim J Ferreira,Álvaro Sánchez-Ferro,Timothy Lynch,Carsten Eggers,Aashiyan Singh,David Grimes,Monica Taljaard,Oliver Rascol,Tiago A Mestre, ","doi":"10.1002/mds.70110","DOIUrl":"https://doi.org/10.1002/mds.70110","url":null,"abstract":"BACKGROUNDThe optimal design for care delivery in Parkinson's disease (PD) that addresses changing needs of the lived experience is unclear. There is a critical need for care models to be implemented and transferable across diverse healthcare systems with agility.OBJECTIVESWe aimed to evaluate the multinational implementation and impact of a novel pragmatic integrated care delivery program for PD (iCARE-PD).METHODSWe conducted a multinational prospective observational study with a pre-post design (six national PD tertiary centers) of a 4-month integrated care program focused on individualized care plans, enhanced system navigation, and self-care support.PRIMARY OUTCOMESenrollment and program completion rates.SECONDARY OUTCOMEStransnational feasibility of program implementation, processes outcomes, acceptability, and preliminary estimates of health-related outcomes changes.RESULTSBetween May 2021 and February 2023, we enrolled 202 participants (\"Newly Diagnosed,\" n = 43; \"Intermediate,\" n = 54; \"Complex Care Needs,\" n = 105). Median site enrollment rate was 69.6% (range: 21.1-100), and the program completion rate was 96.5%. Overall, there was a positive change in Patient Assessment of Chronic Illness Care + (PACIC+ total score: 0.48; 95% confidence interval [CI]: 0.34, 0.61; P < 0.0001). We found a positive score change in the MDS-UPDRS Part II + III nontremor (4.03; 95% CI: 6.55, 1.52; P = 0.0018) in the \"Complex Care Needs\" group.CONCLUSIONSThe iCARE-PD model was successfully implemented across a social, cultural, and healthcare system diversity, with high program completion rates and improved care quality perceived by participants living at distinct stages of PD. The findings provide valuable insights about the transferability potential and impact of a pragmatic integrated care model centered in the community, with applicability to other chronic movement disorders. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 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":"204 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609914","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":"Nuclear Alpha‐Synuclein: Mechanisms and Implications for Synucleinopathies","authors":"Tiago Fleming Outeiro, David J. Koss","doi":"10.1002/mds.70138","DOIUrl":"https://doi.org/10.1002/mds.70138","url":null,"abstract":"Alpha‐synuclein (aSyn), historically studied for its synaptic functions and central role in Lewy body pathology, is emerging as a protein with significant nuclear activities relevant to Parkinson's disease (PD) and related synucleinopathies. Recent advances reveal that aSyn dynamically localizes to neuronal nuclei in both health and disease, where its interactions with chromatin and DNA may contribute to the regulation of genomic stability, DNA damage responses, and cellular aging. Studies using experimental models demonstrate that nuclear aSyn promotes neurodegeneration through transcriptional dysregulation, DNA repair deficits, and cellular senescence, especially when present in phosphorylated or oligomeric forms. The detection of nuclear aSyn in human tissues has proven challenging, but improvements in immunohistochemical and molecular techniques now allow deeper exploration of its physiological and pathological states. Mechanistic studies indicate that aSyn can modulate nuclear import pathways and directly interact with genomic repair machinery, suggesting new avenues for disease modification. As such, nuclear aSyn represents both a promising biomarker for disease stratification and a potential therapeutic target. Integrating mechanistic, biomarker, and translational research on nuclear aSyn may transform our understanding of PD progression and enable precision medicine approaches for early diagnosis and intervention in synucleinopathies. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"107 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598824","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}