Movement Disorders最新文献

{"title":"Combined Dietary Restriction and Chelation Therapy Reduces Manganese Burden in SLC39A14-Associated Manganism.","authors":"Michael C Kruer,Peter T Skidmore,Brielle Edwards,Jennifer Heim,James Kelbert,Nathan Evans,Alex King,Patricia Cornejo,Francisco Ponce,Lisa Vanatta,Alex M Pagnozzi,Ningning Zhao","doi":"10.1002/mds.70085","DOIUrl":"https://doi.org/10.1002/mds.70085","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"73 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351495","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":"Transcranial Ultrasound Stimulation of Internal Globus Pallidus Region and Motor Cortex in Parkinson's Disease.","authors":"Yi-Ying Lin,Nasem Raies,Talyta Grippe,Carolyn A Gunraj,Can Sarica,Utpal Kumar Saha,Amitabh Bhattacharya,Ghazaleh Darmani,Robert Chen","doi":"10.1002/mds.70095","DOIUrl":"https://doi.org/10.1002/mds.70095","url":null,"abstract":"BACKGROUNDMany patients with Parkinson's disease (PD) have motor impairments despite dopaminergic therapy. Low-intensity transcranial ultrasound stimulation (TUS) is a non-invasive neuromodulation method with high spatial precision. The effects of motor cortex (M1) and internal globus pallidus (GPi) TUS on PD motor signs and cortical excitability are still uncertain.OBJECTIVESTo compare the effects of M1 theta burst TUS (tbTUS), GPi region tbTUS, and dual-site (M1 + GPi region) tbTUS on neurophysiology and motor signs in PD patients.METHODSSequential bilateral real M1/sham GPi, real GPi/sham M1, and simultaneous dual-site tbTUS were administered in three separate study visits in random order to 13 PD patients. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) scores and transcranial magnetic stimulation measures of cortical excitability were recorded at baseline and at several time points up to 60 min after sonication.RESULTSMDS-UPDRS-III scores and bradykinesia subscores decreased compared with baseline after GPi tbTUS at 30 min after sonication. Motor evoked potential (MEP) ratio to baseline increased after M1 tbTUS compared with GPi tbTUS at 10 min after sonication (T10). The stimulation intensity to elicit 1 mV MEP ratio to baseline in the GPi tbTUS condition was higher compared with baseline and with M1 tbTUS and dual-site tbTUS at T10. MEP amplitudes and MDS-UPDRS-III scores did not significantly change after the M1 and dual-site tbTUS conditions.CONCLUSIONSBilateral GPi region tbTUS is a potential non-invasive approach for improving motor signs in PD patients, particularly bradykinesia. © 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":"20 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338963","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":"Effects of a Four-Strain Probiotic on Gut Microbiota, Inflammation, and Symptoms in Parkinson's Disease: A Randomized Clinical Trial.","authors":"Valentina Leta,Pavlos Zinzalias,Lucia Batzu,Gargi Mandal,Juliet Staunton,Frida Jernstedt,Kristina Rosqvist,Jonathan Timpka,Trinette van Vliet,Dhaval Trivedi,Aleksandra Podlewska,Miriam Parry,Daniel J van Wamelen,Alexandra Rizos,Carolina Sportelli,Ana Laura Bonder,Guy Chung-Faye,Cristian Falup-Pecurariu,Simon Gaisford,Edoardo Moretto,Gwenaelle Le Gall,David Vauzour,Ana Rodriguez-Mateos,Anna Sauerbier,Carmen Rodriguez Blazquez,Jonas Ghyselinck,Benoît Marsaux,Carmine Maria Pariante,Alessandra Borsini,Per Odin,Kallol Ray Chaudhuri","doi":"10.1002/mds.70047","DOIUrl":"https://doi.org/10.1002/mds.70047","url":null,"abstract":"BACKGROUNDGut dysbiosis and gut-brain-axis involvement in people with Parkinson's disease (PwP) support the use of gut-microbiota-modulating interventions. Probiotics may help manage constipation in PwP; however, mechanisms underpinning additional beneficial properties are unknown.OBJECTIVEThe aim was evaluating the effects of a probiotic (Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Enterococcus faecium) on gut microbiota, inflammation, motor and non-motor symptoms (NMS) in PwP and constipation.METHODSIn this multicenter, randomized, double-blind, placebo-controlled trial (NCT05146921), PwP and constipation were randomized (1:1) to receive either the probiotic (4.08 × 108 CFU/mL) or placebo orally (70 mL/day) for 12 weeks. The primary endpoint was the differential abundance of gut microbiota taxa between baseline and end-of-treatment in the active versus placebo group. Secondary/exploratory endpoints included changes in inflammatory cytokines plasma levels, short-chain fatty acids (SCFAs) plasma and fecal levels, motor and NMS outcomes after 12 weeks. A per-protocol analysis was performed.RESULTSBetween July 17, 2019 and February 6, 2022, 74 participants were randomized. Data from 35 (probiotic) and 33 (placebo) participants were analyzed. Enrichments of bacteria with beneficial health-related properties (Odoribacteraceae, Enterococcaceae, and Blautia faecicola) were observed in the active group compared to placebo (P ≤ 0.05). Proinflammatory cytokine TNF-α plasma levels decreased with probiotic treatment and increased with placebo (P < 0.05). No changes in SCFAs levels were observed. Reductions in time-to-on and NMS scale scores (P < 0.05) were observed only in the active group.CONCLUSIONSThis probiotic was effective in beneficially enriching the gut microbiota with potential to reduce systemic inflammation, shortening time-to-on following levodopa administration, and alleviating NMS burden in PwP experiencing constipation. © 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":"108 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338964","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":"A Network Centered on the Visual-Motor Cortex Is Critically Involved in Postural Abnormality in Parkinson's Disease.","authors":"Zhuang Wu,Sha Zhu,Ronghua Hong,Zhuoyu Zhang,Yanzi Peng,Jingxing Zhang,Lizhen Pan,Qiang Guan,Yuhui Chen,Lingjing Jin","doi":"10.1002/mds.70088","DOIUrl":"https://doi.org/10.1002/mds.70088","url":null,"abstract":"BACKGROUNDPostural abnormality (PA) is a key motor symptom in Parkinson's disease (PD) that leads to disability and death. However, the pathophysiology underlying PA is still unknown.OBJECTIVEThe objective of this study was to explore the neural patterns behind PAs and measures toward functional restoration using repetitive transcranial magnetic stimulation (TMS) in PD.METHODSWe included cross-sectional (n = 181) and TMS-based therapy-response (n = 45) analyses of PD. Posture features, structural magnetic resonance imaging (MRI), and functional MRI data were collected. After regressing out covariates, brain maps of morphometry image and functional MRI data were compared to determine stimulation targets for the subsequent TMS sessions. Spearman's correlation analysis was conducted to explore relationships between posture features and MRI data.RESULTSPD patients with PA (PD_PA) showed a greater extent of brain atrophy and functional alterations in bilateral lingual gyri and precentral gyri than patients without PA (PD_NPA). Furthermore, the PD_PA group had decreased functional connectivity between the left lingual gyrus and the left precentral gyrus compared with the PD_NPA group. The degree of such alteration inversely correlated with posture features. After 10 sessions of excitatory neuromodulation over the bilateral lingual gyri and precentral gyri, the Verum TMS group showed significant improvement in PA. We also observed increased degree centrality of the left lingual gyrus and enhanced functional connectivity between the left lingual gyrus and left inferior parietal lobule. Those changes were correlated with the improvement of PAs.CONCLUSIONSOur study identifies a specific visual-motor integration circuitry involved in PAs of PD, where precentral gyrus and lingual gyrus are core nodes. © 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":"39 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351530","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":"Feasibility of Simon Two-Stage Futility Trials in People with Early, Symptomatically Treated Parkinson's Disease.","authors":"Marcus W Koch,Lorraine V Kalia,Justyna Sarna,Camila Aquino,Daryl Wile,Tiago A Mestre,Michael G Schlossmacher,Miguel D'Haeseleer,Jop Mostert,Eva M M Strijbis,Bernard Uitdehaag,Tarrant McPherson,Gary Cutter","doi":"10.1002/mds.70090","DOIUrl":"https://doi.org/10.1002/mds.70090","url":null,"abstract":"BACKGROUNDDisease-modifying treatments are a critical unmet need in Parkinson's disease (PD). Phase 2 futility trials using the Simon two-stage design offer an efficient strategy to evaluate candidate treatments in an early PD population.OBJECTIVEThe aim was to assess the feasibility of Simon two-stage futility trials in early, levodopa-treated PD subjects using historical patient-level clinical trial datasets.METHODSWe analyzed patient-level data from two completed trials, that is, STEADY-PD 3 (n = 336, untreated at baseline) and NET-PD LS1 (n = 1741, treated at baseline). We defined disability progression as a ≥5-point worsening on the motor (Part III) subscore of the Unified Parkinson's Disease Rating Scale at 12 and 24 months. We tested multiple scenarios, including the reanalysis of STEADY-PD 3 participant data after starting dopaminergic treatment. We assessed predictors of progression using logistic regression analysis and calculated sample size estimates.RESULTSBoth trials showed similar progression rates at 12 months (~26%) and 24 months (~35%). In NET-PD LS1, older age and lower baseline motor scores were associated with worsening; no predictors were significant in STEADY-PD 3. We estimate that in futility trials that use OFF-state scores to assess motor performance, 39 early PD participants are required to detect significant disability worsening over an observation period of 12 months.CONCLUSIONSPhase 2 futility trials using the Simon two-stage methodology are feasible in early PD, including in treated and untreated patients. OFF-state scores are preferable to ON-state scores as the primary outcome measure. Futility trials offer a smaller-scale, faster, and cost-effective approach to assessing new candidate treatments in 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":"78 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331709","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":"Perampanel as an Effective Treatment for Cortical Reflex Myoclonus in Juvenile Huntington's Disease.","authors":"Ken Yamada,Maya Tojima,Etsuro Nakanishi,Takashi Ayaki,Ryosuke Takahashi,Akio Ikeda,Riki Matsumoto","doi":"10.1002/mds.70091","DOIUrl":"https://doi.org/10.1002/mds.70091","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"53 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331916","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":"Analyzing the 'Bradykinesia Complex' in Parkinson's Disease.","authors":"Giulia Paparella,Martina De Riggi,Antonio Cannavacciuolo,Daniele Birreci,Davide Costa,Luca Angelini,Danilo Alunni Fegatelli,Alfonso Fasano,Alberto J Espay,Matteo Bologna","doi":"10.1002/mds.70082","DOIUrl":"https://doi.org/10.1002/mds.70082","url":null,"abstract":"BACKGROUNDBradykinesia is the hallmark sign of parkinsonism. We recently proposed redefining bradykinesia as a complex of motor abnormalities, each reflecting separate pathophysiological elements.OBJECTIVETo analyze the 'bradykinesia complex' in Parkinson's disease (PD) and healthy elderly individuals.METHODSWe conducted a finger-tapping kinematic analysis in 350 individuals (192 PD patients OFF medication and 158 healthy controls). A subsample of 129 patients was also tested ON medication. Group comparisons were followed by unsupervised clustering. Receiver operating characteristic (ROC) analyses defined optimal kinematic cut-offs to detect individual motor abnormalities. We then quantified the prevalence and combinations of these features per subject. Using Bayes' theorem, we estimated the probability of PD based on the observed combination of bradykinesia features. Regression analyses served to identify predictors of kinematic alterations.RESULTSPatients exhibited reduced velocity and amplitude as well as altered rhythm and sequence effect compared with controls (all P-values < 0.001). Cluster analysis revealed substantial group overlap. ROC analyses showed that bradykinesia (movement slowness) was the most common and accurate feature for distinguishing PD, with its diagnostic power improving when combined with other motor abnormalities (hypokinesia, dysrhythmia, sequence effect). The likelihood of correctly identifying PD increased with the number of observed abnormalities, reaching up to 95% when all features were present. Levodopa improved motor performance, but the motor abnormality patterns remained unchanged.CONCLUSIONSThe detailed bradykinesia features assessment was crucial for differentiating PD individuals from controls. Diagnostic accuracy requires considering multiple motor abnormalities together, irrespective of the specific combination. Advancing our understanding of the 'bradykinesia complex' has clinical and pathophysiological implications. © 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":"26 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305761","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":"Frozen in Addiction: A New Wave of Drug-Induced Movement Disorders?","authors":"Christos Ganos,Roberto Erro,Mohammad Abdullah,Tanya S Hauck,Daniel Ciccarone,Christy Sutherland,Parisa Saiyarsarai,Connie Marras,Susan H Fox,Alfonso Fasano,Anthony E Lang,Jonathan Squires,Kailash P Bhatia","doi":"10.1002/mds.70048","DOIUrl":"https://doi.org/10.1002/mds.70048","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"19 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305622","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 Second Hit Hypothesis in Animal and Human Dystonia: The Role of Peripheral Nerve Trauma and Spinal Cord Injury","authors":"Lisa Harder‐Rauschenberger, Chi Wang Ip","doi":"10.1002/mds.70087","DOIUrl":"https://doi.org/10.1002/mds.70087","url":null,"abstract":"Dystonia is a complex movement disorder characterized by involuntary muscle contractions and abnormal postures. Although genetic factors have been implicated in dystonia pathogenesis, recent evidence suggests that additional environmental triggers, referred to as the second hit, may play a significant role in the development and progression of the disease. A remarkably low penetrance in some of the monogenic forms of dystonia supports the need for additional triggers to unmask the phenotype. Given that dystonia has been reported to develop after traumatic events, this review explores the second hit hypothesis in animal models of dystonia and its potential relevance to human dystonia, with particular emphasis on the role of nerve and spinal cord injuries. These injuries trigger significant peripheral changes and profound brain and spinal cord circuit alterations, which require a healthy immune system and functional and structural plasticity responses. We discuss how nerve and spinal cord injuries initiate these key pathomechanistic processes, including neuroinflammation and the reorganization of the central sensorimotor network, which entails adaptive modifications in neural pathways to compensate for the injury. We further highlight future challenges and potential therapeutic implications of nerve and spinal cord injury–induced dystonia. Understanding the interplay between nerve injury, spinal cord injury, neuroinflammation, and dystonia may pave the way for novel therapeutic strategies targeting these factors. © 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":"11 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282741","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":"Systematic Review with Meta-Analysis of Biofluid Markers for Huntington's Disease.","authors":"Jane S Paulsen,Natalie A Bovin,Jordan D Clemsen,Alexander Weiss,Abigail M Key,Monica L Janz,Alex Pinto,Deven K Burks,Henrik Zetterberg,Kathleen M Shannon","doi":"10.1002/mds.70067","DOIUrl":"https://doi.org/10.1002/mds.70067","url":null,"abstract":"Primary therapeutic objectives for Huntington's disease (HD) necessitate continued therapy for a long period before clinical motor diagnosis and its concurrent functional incapacities. Therefore, the need is paramount for alternative biomarkers that are not only highly sensitive but also clearly reflect the disease progression. Current trials increasingly rely upon biological definitions of disease to initiate intervention before significant decline. The primary biological measure of early-stage HD is volumetric evidence of structural decline on magnetic resonance imaging. This comprehensive review of biofluid markers is a systematic review documenting 804 records identified in a literature search. Updating a previous comprehensive review from 2018, we summarize effect sizes and conduct meta-analyses for 55 studies with reproducible findings. Evidence for neurofilament light (NfL) is sufficient to meet evidentiary guidelines as a prognostic biomarker in preHD (ie, before clinical motor diagnosis). Significant meta-analyses are found for 24-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), NfL, and T-tau (total tau) in early-stage HD and for cortisol, high-density lipoprotein (HDL), mutant huntingtin (mHTT), and HTT in mid-stage HD after clinical motor diagnosis. Despite over 800 published studies of biomarkers in HD and over 200 reviews of those efforts, the current state of the literature is limited by inconsistent reporting of necessary detail in existing reports. This is compounded by an inability to effectively compare outcomes and by continued publication when rigor is compromised, revealing a significant knowledge gap for HD clinical trial methodology improvements. Findings support validation for eight biofluid markers in HD: one in preHD, four in early-stage HD, and four in mid-stage HD after clinical motor diagnosis. © 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":"53 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277160","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}