Movement Disorders最新文献

{"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":"RAB32-Linked Parkinson's Disease: Deep Phenotyping, MDSGene Literature Review, and Application of SynNeurGe Criteria","authors":"Teresa Kleinz MD,&nbsp;Francesco Cavallieri MD, PhD,&nbsp;Max Borsche MD,&nbsp;Giulia Toschi PhD,&nbsp;Franco Valzania MD,&nbsp;Valentina Fioravanti MD, PhD,&nbsp;Enza Maria Valente MD,&nbsp;Pierfrancesco Mitrotti MD,&nbsp;Micol Avenali MD,&nbsp;Simone Zittel MD,&nbsp;Rommi Born MD,&nbsp;Michele Matarazzo MD,&nbsp;Alessio Di Fonzo MD, PhD,&nbsp;Edoardo Monfrini MD,&nbsp;Mandy Radefeldt MSc,&nbsp;Letizia Santinelli MSc,&nbsp;Norman Griebner MD,&nbsp;Cholpon Shambetova MD,&nbsp;Max Brand MSc,&nbsp;Carolin Gabbert PhD,&nbsp;Cornelis Blauwendraat PhD,&nbsp;Joanne Trinh PhD,&nbsp;Katja Lohmann PhD,&nbsp;Christian Beetz PhD,&nbsp;Peter Bauer MD,&nbsp;Norbert Brüggemann MD,&nbsp;Global Parkinson's Genetics Program (GP2),&nbsp;Christine Klein MD","doi":"10.1002/mds.70037","DOIUrl":"10.1002/mds.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The <i>RAB32</i> p.Ser71Arg variant is a novel cause of monogenic Parkinson's disease (PD), for which detailed phenotypic information is currently scarce.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Our aim was to clinically and biologically characterize individuals with PARK-<i>RAB32</i> to gain insights into genotype–phenotype relationships, disease severity, and underlying pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a literature review following the MDSGene protocol, alongside detailed phenotyping of 11 PARK-<i>RAB32</i> patients and one prodromal individual from the Rostock International PD (ROPAD) study. In addition to comprehensive scale-based assessments, including olfactory testing, we obtained neuroimaging data and various biomaterials, and performed α-synuclein seeding assays (SAA) in cerebrospinal fluid in a subset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>83 patients (72 from the literature) were included in the analysis. The median age at onset was 54 (IQR: 46–61) years. Typical parkinsonism with a favorable dopaminergic response was observed in all patients.</p>\u0000 \u0000 <p>In our cohort, after a median disease duration of 11 years (IQR: 7–19.5), the mean Movement Disorders Society Modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III score was 38.5 ± 21.8 points. Targeted testing revealed autonomic symptoms were present in all individuals, and 10 of 11 patients had hyposmia. Misfolded α-synuclein was identified in 2 of 2 patients, but not in the prodromal individual. 123I-FP-CIT imaging was available for eight patients, revealing neurodegeneration in all of them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While PARK-<i>RAB32</i> is clinically and likely pathologically similar to idiopathic PD, our study underscores the importance of carefully assessing non-motor symptoms in this newly described form of PD. According to SynNeurGe criteria, PARK-<i>RAB32</i> is classified as <b>S</b>⁺ (evidence of synucleinopathy), <b>N</b>⁺ (neurodegeneration supported by imaging data), and <b>G</b>_P⁺ (presence of a genetic variant). © 2025 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 12","pages":"2746-2769"},"PeriodicalIF":7.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310529","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":"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 MD,&nbsp;Roberto Erro MD, PhD,&nbsp;Mohammad Abdullah MBChB,&nbsp;Tanya S. Hauck MD, PhD,&nbsp;Daniel Ciccarone MD,&nbsp;Christy Sutherland MD,&nbsp;Parisa Saiyarsarai PhD,&nbsp;Connie Marras MD, PhD,&nbsp;Susan H. Fox MRCP, PhD,&nbsp;Alfonso Fasano MD, PhD,&nbsp;Anthony E. Lang MD,&nbsp;Jonathan Squires MD,&nbsp;Kailash P. Bhatia FRCP, MD","doi":"10.1002/mds.70048","DOIUrl":"10.1002/mds.70048","url":null,"abstract":"&lt;p&gt;Movement disorders resulting from illicit drug use can present with both hypokinetic and hyperkinetic features often leading to severe functional impairment. The seminal publication by Langston and colleagues,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; for example, described four adults who became parkinsonian within a week of being exposed to heroin contaminated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These first cases marked the beginning of sporadic outbreaks of parkinsonism linked to synthetic opioid use.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The cause was attributed to MPP+, a MAO-B metabolite of MPTP, which results in mitochondrial dysfunction and neuronal death.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Importantly, although these cases affected relatively few individuals worldwide, they were pivotal in highlighting the vulnerability of dopamine-producing neurons to a variety of neurotoxins and established groundbreaking models for studying Parkinson's disease (PD).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Other examples of drug-induced movement disorders include dystonia-parkinsonism resulting from manganese toxicity due to ephedrine (methcathinone) use&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and chorea and dystonia—also referred to as “crack-dancing”—or tics caused by cocaine use.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Over the past few years, a new and much larger-scale trend of people with movement disorders caused by illicit drug use has emerged. This phenomenon appears to be driven by synthetic opioids such as fentanyl and its analogues, often combined with the veterinary sedative xylazine, the combination colloquially known as “tranq,” as well as methamphetamines.&lt;span&gt;&lt;sup&gt;5-7&lt;/sup&gt;&lt;/span&gt; Although the epicenter is the United States and Canada, cases have been reported by prominent media outlets in various parts of the world.&lt;span&gt;&lt;sup&gt;7-11&lt;/sup&gt;&lt;/span&gt; Affected individuals commonly exhibit characteristic postural and other motor abnormalities, which from a phenomenological standpoint have important similarities with movement disorders such as camptocormia in parkinsonism or generalized dystonia. This hypothesis-driven connection has not been sufficiently considered, despite its potential to deepen our knowledge about the mechanisms modulating postural motor control. Given the alarming prevalence of this phenomenon, it further holds significant implications for public health.&lt;/p&gt;&lt;p&gt;Here, we draw from our own experience and use knowledge from neuroscience of motor control and movement disorders to speculate about the relationship between abnormal postural control and regular exposure to illicit fentanyl, xylazine, and methamphetamines, including combination use. We also highlight open questions that will need to be addressed in future research.&lt;/p&gt;&lt;p&gt;A characteristic phenotype linked to the current drug-use epidemic reported in the media is people with markedly bent spines, often flexed forward and while standing.&lt;span&gt;&lt;sup&gt;7-11&lt;/sup&gt;&lt;/span&gt; This distinctive posture that is primarily attributed to","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 12","pages":"2596-2603"},"PeriodicalIF":7.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70048","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":"OA","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 PhD,&nbsp;Natalie A. Bovin BS,&nbsp;Jordan D. Clemsen BA,&nbsp;Alexander Weiss PhD,&nbsp;Abigail M. Key BS,&nbsp;Monica L. Janz MD,&nbsp;Alex Pinto MS,&nbsp;Deven K. Burks PhD,&nbsp;Henrik Zetterberg MD, PhD,&nbsp;Kathleen M. Shannon MD","doi":"10.1002/mds.70067","DOIUrl":"10.1002/mds.70067","url":null,"abstract":"<p>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). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 12","pages":"2578-2595"},"PeriodicalIF":7.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70067","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysphagia in Multiple System Atrophy Does Not Correlate with Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein.","authors":"Martin Klietz,Katharina Pannewitz-Makaj,Franziska Baacke,Florian Wegner,Matthias Höllerhage,Lea Krey,Lan Ye,Christoph Schrader,Günter U Höglinger,Tobias Warnecke","doi":"10.1002/mds.70092","DOIUrl":"https://doi.org/10.1002/mds.70092","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"75 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261213","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 Role of Basal Ganglia Theta Oscillations in Predicting the Onset of Levodopa‐Induced Dyskinesias","authors":"Miguel Wilken, Luna Granda, Ivonne Cruz, Malco Rossi, Daniel Cerquetti, Marcelo Merello","doi":"10.1002/mds.70065","DOIUrl":"https://doi.org/10.1002/mds.70065","url":null,"abstract":"BackgroundLevodopa‐induced dyskinesias (LIDs) are an important burden for patients with Parkinson's disease (PD), yet their mechanisms remain incompletely understood.ObjectiveThe objective of this study was to investigate the temporal and spatial relationship between local field potential (LFP) changes and dyskinesia development in PD.MethodsWe recorded bilateral subthalamic LFPs, electromyography, and accelerometry in patients with PD with peak‐dose LIDs undergoing deep brain stimulation (DBS) surgery. Apomorphine was administered to induce dyskinesias, and recordings continued for 200 seconds postonset. Spectral power changes were analyzed over time and mapped to the DBS “sweet spot.” A machine‐learning algorithm detected dyskinetic movements.ResultsIn 9 of 36 patients, dyskinesias were preceded by a bilateral beta power decrease (<jats:italic>P</jats:italic> &lt; 0.001) and contralateral theta increase (<jats:italic>P</jats:italic> = 0.02), followed by gamma elevation (<jats:italic>P</jats:italic> = 0.03). These changes peaked in the DBS sweet spot.ConclusionsOur results provide insights into the sequential nature of beta, theta, and gamma oscillatory changes. Theta activity may serve as a key biomarker for adaptive DBS. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"23 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260618","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":"Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.","authors":"Zhen Hu,Qin-Qin Yan,Jing-Jin Wan,Yu Fan,Jun Liu","doi":"10.1002/mds.70081","DOIUrl":"https://doi.org/10.1002/mds.70081","url":null,"abstract":"BACKGROUNDNucleotide repeat expansions are a potential factor in Parkinson's disease (PD) risk, but previous studies were inconsistent. We investigated 14 non-coding repeat expansion genes (C9ORF72, FMR1, AFF2, ATXN8OS, ATXN10, CNBP, CSTB, DMPK, FXN, NOP56, NOTCH2NLC, PPP2R2B, RFC1, and TCF4) in a large cohort.METHODSWe used whole-genome sequencing (WGS) data from the United Kingdom (UK) Biobank, including 3588 PD cases and 388,532 controls. Repeat sizes were determined using ExpansionHunter. We also conducted a sensitivity analysis.RESULTSAfter Bonferroni correction, no genes showed a statistically significant association with PD risk. However, nominal associations were found for pathogenic repeats in C9ORF72 (odds ratio [OR] = 1.780, P = 0.037) and for gray zone repeats in FMR1 (OR = 0.695, P = 0.016), which suggests a potential protective effect.CONCLUSIONOur large-scale study provides hypothesis-generating evidence. We report a nominal association linking pathogenic C9ORF72 repeats to increased PD risk and, importantly, a novel observation that FMR1 repeats may be protective. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"51 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261214","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}