Movement Disorders最新文献

{"title":"Reply to: \"Alcohol Intake and Parkinson's Symptoms Following Diagnosis\".","authors":"Sahar Hemeda,Mohammed Elmadani,Mohammed Merzah,Aseel Odeh,Evelyn Pintér,István Balás,József Janszky,Dávid Pintér,Norbert Kovács","doi":"10.1002/mds.70340","DOIUrl":"https://doi.org/10.1002/mds.70340","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"25 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754926","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":"Alcohol Intake and Parkinson Symptoms Following Diagnosis.","authors":"Laurie K Mischley,Joshua Farahnik","doi":"10.1002/mds.70338","DOIUrl":"https://doi.org/10.1002/mds.70338","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"47 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754928","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":"The Unusual Suspects: Macrophages in Parkinson's Disease?","authors":"Sujas Bhardwaj,Albert Stezin","doi":"10.1002/mds.70339","DOIUrl":"https://doi.org/10.1002/mds.70339","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"46 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753249","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":"Metabolic and Volumetric Alterations in the Basal Ganglia and the Cerebellum in Dopa-Responsive Dystonia in Symptomatic and Asymptomatic GCH1 Mutation Carriers.","authors":"Jannik Prasuhn,Leon van Well,Marta M Pokotylo,Feline Hamami,Joke-Lina Aßmann,Katja Lohmann,Maximilian G Ködderitzsch-Mertins,Julia Henkel,Jan Uter,Alexander Münchau,Christine Klein,Anne Weissbach,Norbert Brüggemann","doi":"10.1002/mds.70332","DOIUrl":"https://doi.org/10.1002/mds.70332","url":null,"abstract":"BACKGROUNDDopa-responsive dystonia is caused by pathogenic variants in the GCH1 gene. Although its clinical features and reduced penetrance are known, in vivo metabolic and structural alterations in symptomatic (sMC) and asymptomatic mutation carriers (aMC) remain poorly understood.OBJECTIVESThe aims were to characterize the volumetric and neurometabolic brain changes in GCH1 mutation carriers (MC) and explore their relationship with clinical severity.METHODSWe studied 20 sMCs, 5 aMCs, and 25 mutation-free healthy controls (HC) using volumetric magnetic resonance imaging (MRI) combined with 31phosphorus magnetic resonance spectroscopy imaging (31P-MRSI) of the basal ganglia and cerebellum. Analysis of covariance (ANCOVA) was used for group comparisons, and correlations were assessed using clinical symptom severity rating scales.RESULTSVolumetric analyses revealed enlarged globus pallidus (16.6%, P = 0.0010) and putamen (7.2%, P = 0.0310) volumes in sMCs and increased cerebellar gray matter in aMCs (8.0%, P = 0.0500). Nicotinamide adenine dinucleotide (NAD) levels were significantly reduced in the basal ganglia of carriers (NAD/Pi [inorganic phosphate]: -14.7%, P = 0.0460; NAD/ATP-α: -15.5%, P = 0.0180). In the cerebellum, aMCs demonstrated elevated high-energy phosphate ratios ([ATP-α + PCr]/Pi: 23.7%, P = 0.0170; ATP-α/Pi: 21.3%, P = 0.0460; PCr [phosphocreatine]/Pi: 25.2%, P = 0.0090) compared with sMCs and HCs. Smaller cerebellar volumes correlated with greater dystonia severity (Burke-Fahn-Marsden Dystonia Rating Scale, ρ = -0.557, P = 0.0133), whereas lower basal ganglia NAD ratios correlated with higher Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Part III (ρ = -0.527, P = 0.0204), and Toronto Western Spasmodic Torticollis Rating Scale scores (ρ = -0.475, P = 0.0398).CONCLUSIONSVolumetric MRI and 31P-MRSI reveal region- and subgroup-specific metabolic and structural alterations in GCH1 MCs, linking basal ganglia vulnerability and cerebellar adaptation to clinical severity. © 2026 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":"26 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751390","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":"Seeing Invisible Oligomers: Rethinking α-Synuclein Pathology Through Proximity Ligation Assay.","authors":"Hiroaki Sekiya,Nanna Møller Jensen,Dennis W Dickson,Poul Henning Jensen","doi":"10.1002/mds.70335","DOIUrl":"https://doi.org/10.1002/mds.70335","url":null,"abstract":"Parkinson's disease (PD) and multiple system atrophy are defined by α-synuclein (αSYN)-positive inclusions - Lewy bodies (LBs) and glial cytoplasmic inclusions - yet mounting evidence indicates that these inclusions represent only a fraction of disease-relevant pathology. αSYN exists in dynamic conformational states, and soluble oligomeric assemblies, often undetectable by conventional immunohistochemistry, are increasingly implicated as key neurotoxic species. The αSYN proximity ligation assay (αSYN-PLA) enables in situ detection of widespread non-inclusion oligomeric pathology across synucleinopathies. Notably, PLA studies in LRRK2-associated PD demonstrate abundant oligomeric αSYN even in cases lacking LBs, challenging the centrality of inclusions in defining disease. In this Perspective, we outline the principles of αSYN-PLA, discuss antibody strategies and structural implications of detected species, review current evidence - including LB-negative LRRK2-PD - and consider temporal dynamics and clinical applications of PLA-positive aggregates as biomarkers and therapeutic targets. © 2026 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":"8 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751388","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":"Target-Dependent Postoperative Weight Gain after Pallidothalamic Tractotomy versus Pallidotomy for Dystonia.","authors":"Ryosuke Jozuka,Masahiko Nishitani,Eriko Kamijo,Kilsoo Kim,Satoru Miyao,Mika Fujiwara,Taku Nonaka,Bohui Qian,Takakazu Kawamata,Takaomi Taira,Shiro Horisawa","doi":"10.1002/mds.70323","DOIUrl":"https://doi.org/10.1002/mds.70323","url":null,"abstract":"BACKGROUNDPostoperative weight gain is a recognized complication of deep brain stimulation, but whether ablative surgery produces target-dependent weight effects remains unknown. We investigated whether pallidothalamic tractotomy (PTT) causes greater weight gain than pallidotomy and explored spatial associations.METHODSWe retrospectively analyzed 79 patients with focal, segmental, or generalized dystonia who underwent unilateral PTT (n = 41) or globus pallidus internus (GPi) lesioning (n = 38). Multivariable linear regression quantified the effect of target on weight and body mass index (BMI) changes, adjusting for age, sex, side, preoperative BMI, follow-up duration, and Burke-Fahn-Marsden dystonia rating scale (BFMDRS) improvement. In a subset with postoperative magnetic resonance imaging (MRI), lesion overlap (N) maps and voxel-wise mean BMI-change maps were generated to explore anatomical associations.RESULTSPTT resulted in greater postoperative weight gain than GPi lesioning (+6.7 ± 7.5 kg vs. +1.1 ± 4.7 kg), with ≥10 kg gain in 29.3% versus 5.3% of patients. After covariate adjustment, PTT remained independently associated with greater weight gain (adjusted difference + 5.18 kg; 95% confidence interval [CI] +13 to +8.23) and BMI increase (+1.92 kg/m2; 95% CI +0.85 to +2.99). Lesion mapping localized PTT lesions to Forel's field H1. Weight-gain hotspots mapped medial to the inferior border of the subthalamic nucleus, whereas GPi maps showed no consistent intranuclear hotspot.CONCLUSIONSPTT was associated with greater postoperative weight gain than pallidotomy, independent of covariates. These findings suggest that lesion target influences postoperative body-weight regulation, highlighting the potential risk of lesions extending into the caudal subthalamic region. © 2026 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"21 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735551","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":"Indirect Striatal Projection Neurons Drive a D2 Receptor-Dependent Pathway to Dyskinesia and Dystonia.","authors":"Laura Andreoli,Teodor Nyman,Elena Espa,Johan Jakobsson,Osama F Elabi,Maria Angela Cenci","doi":"10.1002/mds.70299","DOIUrl":"https://doi.org/10.1002/mds.70299","url":null,"abstract":"BACKGROUNDL-DOPA-induced dyskinesia is attributed to opposite activity changes mediated by D1 and D2 dopamine receptors in the two striatal output pathways. Whereas the causal role of direct-pathway D1 receptors is well established, the specific involvement of indirect-pathway D2 receptors in dopaminergic dyskinesias has remained elusive.OBJECTIVESWe used conditional knockout approaches in mice to determine whether indirect-pathway D2 receptors causally contribute to dyskinetic and dystonic responses to dopaminergic agents.METHODSStudies were conducted in mice with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway receiving subchronic treatments with L-DOPA or D2/D1-selective agonists. A conditional knockout of indirect-pathway D2 receptors was produced either through the entire striatum (double-transgenic Adora2a-Cre/Drd2loxP/loxP mice) or selectively in the dopamine-denervated dorsal striatum (proenkephalin promoter-driven Cre vector delivery to Drd2loxP/loxP mice).RESULTSThe severity of L-DOPA-induced abnormal involuntary movements and dystonia was halved in both knockout models compared with control mice, whereas the treatment effect on normal motor behaviors was either not reduced or improved. All dyskinetic and dystonic features induced by the D2-selective receptor agonist sumanirole were completely abolished, whereas those induced by the D1-class agonist SKF38393 were largely unaffected. Using phosphorylated ribosomal protein S6 as an activity marker, we detected a treatment-induced recruitment of prototypical parvalbumin-positive neurons in the external globus pallidus (a target of indirect-pathway projections). This effect was inhibited in both knockout models.CONCLUSIONSWe provide experimental evidence that indirect-pathway D2 receptors significantly contribute to the expression of dyskinesia during L-DOPA treatment and mediate D2 agonist-dependent dystonic features. © 2026 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":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719510","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":"Ex Vivo LRRK2 Activation in Asian G2385R and R1628P Variant Carriers and Idiopathic Parkinson's Disease.","authors":"Tzi Shin Toh,Lei Cheng Lit,Shen-Yang Lim,Jia Wei Hor,Choey Yee Lew,Anis Nadhirah Khairul Anuar,Yi Wen Tay,Kirsten Black,Jia Lun Lim,Jannah Zulkefli,Kai Shi Lim,Hans Xing Ding,Shalini Padmanabhan,Azlina Ahmad-Annuar,Eng King Tan,Dario R Alessi,Esther Sammler,Ai Huey Tan","doi":"10.1002/mds.70314","DOIUrl":"https://doi.org/10.1002/mds.70314","url":null,"abstract":"BACKGROUNDLeucine-rich repeat kinase 2 (LRRK2) kinase inhibition is a promising therapeutic strategy for Parkinson's disease (PD), but the functional impact of Asian-prevalent LRRK2 p.G2385R and p.R1628P variants remains unclear. Robust patient stratification and target engagement markers are needed for global LRRK2-targeted trials.OBJECTIVEThe aim of this study was to characterize ex vivo LRRK2 activation status and its clinical correlates in patients with PD carrying LRRK2 p.G2385R and/or p.R1628P variants and in patients with idiopathic PD (iPD).METHODSWe recruited 242 participants: patients with PD carrying LRRK2 p.G2385R (PD-G2385R; n = 57), p.R1628P (PD-R1628P; n = 61), or both (n = 5); patients with iPD (n = 61); and healthy control subjects (HCs; n = 58). Monocyte LRRK2 activity markers (pRab10Thr73 and pLRRK2Ser935) were analyzed using multiplexed quantitative immunoblotting. Clinical severity was assessed using the International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Clinical Impression of Severity Index for PD, and Montreal Cognitive Assessment.RESULTSCompared with HCs, pRab10Thr73 was elevated (indicative of LRRK2 kinase hyperactivation) in PD-G2385R (~1.2-fold, P = 0.011) and in double-variant carriers (~2.8-fold, P = 0.008), but not in PD-R1628P or iPD. Inversely correlated with pRab10Thr73 (rs = -0.611, P < 0.001), pLRRK2Ser935 was reduced (indicative of a more active LRRK2 conformation) in all PD subgroups (lowest in double-variant carriers). All double-variant carriers, the majority of single-variant carriers, and one-third of participants with iPD had pRab10Thr73 greater than the control median. Higher pRab10Thr73 correlated with better cognition.CONCLUSIONSLRRK2 kinase activity is enhanced in patients with PD carrying LRRK2 p.G2385R, with further elevation observed in a small group of double-variant carriers. Elevated kinase activity in a subset of iPD underscores the relevance of LRRK2 signaling and therapeutics beyond coding variants. The observed interindividual variability indicates additional genetic or environmental modifiers and highlights the need for biochemical stratification beyond genotyping in future LRRK2 trials. © 2026 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":"91 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719509","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":"Glymphatic Dysfunction, Brain Damage, and Clinical Disability in Spinocerebellar Ataxia Type 3.","authors":"Jing Guo,Jun Xie,Yunshuang Fan,Bharat B Biswal,Xinyuan Liu,Xingang Wang,Wei Sheng,Wei Chen,Huafu Chen,Jian Wang,Wei Huang,Chen Liu","doi":"10.1002/mds.70311","DOIUrl":"https://doi.org/10.1002/mds.70311","url":null,"abstract":"BACKGROUNDThe glymphatic system, a key fluid clearance pathway in the central nervous system, is emerging as a potential therapeutic target for synucleinopathies. Dysregulation of this system may contribute to spinocerebellar ataxia type 3 (SCA3) pathogenesis, in which the accumulation of misfolded proteins acts as a central driver.OBJECTIVESThe goal was to investigate glymphatic system function in SCA3 patients and evaluate its relationship with brain damage and clinical disability.METHODSNinety-two SCA3 patients (14 with premanifest SCA3 and 78 with manifest SCA3) and 98 healthy controls underwent clinical evaluation and magnetic resonance imaging (MRI) scans. MRI parameters, including the diffusion along the perivascular space (DTI-ALPS) index (a proxy for glymphatic function); cerebral, cerebellar, and subcortical gray matter volumes; and whole-brain microstructural properties of white matter, were calculated.RESULTSPatients with premanifest and manifest SCA3 had lower ALPS indices compared with healthy controls, and patients with manifest SCA3 had a lower ALPS index compared with premanifest SCA3. In SCA3 patients, lower ALPS index was associated with more severe disability and longer disease duration. A negative correlation between ALPS and disease duration emerged after 3 years, with no significant association observed before the 3-year cutoff. Moreover, lower ALPS index was correlated with more pronounced cortical and subcortical gray matter atrophy, decreased fractional anisotropy, and elevated mean diffusivity in white matter.CONCLUSIONSOur findings demonstrate that glymphatic function is impaired, particularly in the presymptomatic stage of SCA3, and this impairment is associated with disability, neurodegeneration, and demyelination. Therefore, glymphatic dysfunction may contribute to the pathogenesis of SCA3. © 2026 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"15 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719511","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":"The Global Parkinson's Disease Genetics (GP2) Genome Browser.","authors":"Zih-Hua Fang,Riley H Grant,Dan Vitale,Carlos F Hernandez,Samantha Hong,Hampton L Leonard,Mary B Makarious,Lara M Lange,Matthew Solomonson,Peter Heutink,Allison A Dilliott,Kamalini Ghosh Galvelis,Mike A Nalls,Andrew B Singleton,Cornelis Blauwendraat, ","doi":"10.1002/mds.70309","DOIUrl":"https://doi.org/10.1002/mds.70309","url":null,"abstract":"BACKGROUNDLarge-scale sequencing initiatives have generated extensive genomic resources essential for variant interpretation, yet their effective use often requires bioinformatics expertise. To support identification of Parkinson's disease (PD) risk and disease-causing variants, we developed an open-access, summary-level genomic data browser.METHODSWe performed uniform joint variant calling to harmonize whole-genome sequencing (WGS) data from AMP-PD Release 4, GP2 Data Releases, and additional controls from the Alzheimer's Disease Sequencing Project. Clinical-exome sequencing (CES) data from GP2 Release 8 were also included.RESULTSThe integrated dataset included 31,665 WGS and 9,559 CES samples, spanning 11 ancestries and over 300 million variants.CONCLUSIONSThe GP2 Genome Browser is a lightweight, flexible platform providing intuitive gene- and variant-level summaries with ancestry-stratified allele frequencies and functional annotations. It is open source and freely accessible at https://gp2.broadinstitute.org, enabling broad access to PD genomic data and supporting global research efforts. © 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.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"246 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719525","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}