Movement Disorders最新文献

{"title":"Constipation Is Linked to Neuroinflammation in Early Parkinson's Disease","authors":"Marta Camacho, Julia C. Greenland, Alexander R.D. Peattie, Lennart R.B. Spindler, Jonathan Holbrook, Lakmini Kahanawita, Tim D. Fryer, Young T. Hong, Caroline H. Williams‐Gray","doi":"10.1002/mds.70102","DOIUrl":"https://doi.org/10.1002/mds.70102","url":null,"abstract":"Background Constipation is a risk factor for the onset and accelerated progression of Parkinson's disease (PD), but the mechanisms underlying this association are unknown. Neuroinflammation in PD has been demonstrated in postmortem and neuroimaging studies; however, its relationship with constipation has not been investigated. Methods We used <jats:sup>11</jats:sup> C‐PK11195 positron emission tomography (PET) to index neuroinflammation in a cohort of 27 people with early‐stage PD. The Gastrointestinal Dysfunction Scale for PD (GIDS‐PD) was used to assess gut symptom severity. Matched blood and cerebrospinal fluid (CSF) samples were collected. Results Higher GIDS‐PD constipation scores were associated with <jats:sup>11</jats:sup> C‐PK11195 binding in whole‐brain gray matter, frontal, parietal, temporal, and occipital lobes, and multiple subcortical and cortical regions. GIDS‐PD Constipation scores were also significantly associated with higher CSF lymphocyte count and blood T helper 1 (Th1) cell and Th17‐like Th1 cells. Conclusions Constipation in early PD is associated with widespread neuroinflammation, suggesting a possible mechanism underlying the association between constipation and faster PD progression. © 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":"51 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498748","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":"Depression in Premanifest Huntington's Disease: Aberrant Effective Connectivity of Striatum and Default Mode Network","authors":"Tamrin Barta GradDipAdvPsych,&nbsp;Leonardo Novelli PhD,&nbsp;Nellie Georgiou-Karistianis PhD,&nbsp;Julie Stout PhD,&nbsp;Samantha M. Loi PhD,&nbsp;Yifat Glikmann-Johnston PhD,&nbsp;Adeel Razi PhD","doi":"10.1002/mds.70075","DOIUrl":"10.1002/mds.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Depression frequently precedes motor symptoms in Huntington's disease gene expansion carriers (HDGECs), yet the neural mechanisms remain poorly characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We investigated effective connectivity between the default mode network (DMN) and striatal regions in HDGECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed 3-T resting-state functional magnetic resonance imaging data from 98 HDGECs (48.98% females; mean age, 42.82 years). Spectral dynamic causal modeling estimated subject-level connectivity, whereas parametric empirical Bayes determined group-level effective connectivity differences between participants with a diagnosed depression history and those without, across current, remitted, and never-depressed states. Brain-behavior associations with clinical depression measures were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Model estimation was excellent (89.82% variance-explained). HDGECs with depression history showed decreased inhibitory posterior cingulate cortex-to-hippocampal connectivity, increased hippocampus-to-posterior cingulate cortex inhibition, and increased inhibitory influence of striatum on DMN. HDGECs with a depression history showed increased inhibitory striatal influence on DMN, including left putamen, a propensity for right hippocampal involvement, and disinhibitory posterior cingulate-hippocampal connectivity. Current versus never-depressed comparisons showed more pronounced dysconnectivity, with stronger striatum-to-network connections. Current versus remitted depression exhibited distinct patterns with increased medial prefrontal cortex-to-posterior cingulate cortex connectivity, increased medial prefrontal cortex self-connectivity, and decreased posterior cingulate cortex-to-medial prefrontal cortex connectivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings establish distinct striatal-network interaction patterns in depression for HDGECs that differ from non-neurological depression. Our findings suggested the posterior DMN—posterior cingulate and hippocampus—as drivers of depression for HDGECs and potential involvement of right DMN in keeping with compensatory patterns broadly in HD. These connectivity patterns could serve as functional biomarkers for depression in HDGECs. © 2025 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 1","pages":"107-119"},"PeriodicalIF":7.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492208","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":"Polyelectromyography Under Propofol to Differentiate Functional from Idiopathic Dystonia: A Pilot Study.","authors":"Roberto Eleopra,Fabio Paio,Sara Rinaldo,Carla Carozzi,Amanda Oriana,Grazia Devigili,Luigi Michele Romito,Roberto Cilia,Nico Golfrè Andreasi,Gianfranco Gaudiano,Marta Corradi,Antonio Emanuele Elia,Fabiana Colucci,Arianna Braccia,Roberta Telese,Michele Tinazzi,Marco Gemma,Valentina Leta","doi":"10.1002/mds.70094","DOIUrl":"https://doi.org/10.1002/mds.70094","url":null,"abstract":"BACKGROUNDFunctional dystonia (FD) is one of the most diagnostically challenging functional movement disorders. Phenomenological features often lack specificity, as many are also observed in idiopathic dystonia (ID) and validated biomarkers to distinguish FD from ID are currently unavailable OBJECTIVE: To investigate potential differences in muscle activity between ID and FD patients using polyelectromyography (PEMG) under anesthesia.METHODSWe consecutively enrolled 10 patients with FD and 17 with ID according to the current diagnostic criteria who underwent continuous PEMG before, during, and after propofol infusion. Sedation levels were monitored by electroencephalography and bispectral index and stratified via the Observer's Assessment of Alertness/Sedation Scale (OASS). PEMG recordings were performed under five definite scenarios: alert, mild and deep sedation, and partial and full recovery of consciousness status. Presence/absence of EMG activity was evaluated across these stages, and changes from baseline patterns were analyzed.RESULTSDuring mild sedation, EMG activity persisted in all ID (100%) and in 9 (90%) FD patients. During deep sedation, EMG activity persisted in 9 (53%) ID patients and was absent in all FD patients (100%) (P = 0.01). During partial recovery of consciousness, EMG activity was present in all (100%) ID and only in 1 (10%) FD patients (P < 0.001). At full recovery, a different muscular activation pattern from baseline was observed in 7 (70%) FD and only in 1 (6%) ID patients (P = 0.001) CONCLUSIONS: EMG silence during deep sedation and partial recovery may serve as a neurophysiological marker of FD. A muscular activation pattern differing from baseline may represent a neurophysiological clue for incongruence © 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":"16 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491685","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":"Brain–Computer Interface Improves Symptoms of Isolated Focal Laryngeal Dystonia: A Single‐Blind Study","authors":"Stefan K. Ehrlich, Garrett Tougas, Jacob Bernstein, Nicole Buie, Anna F. Rumbach, Kristina Simonyan","doi":"10.1002/mds.70114","DOIUrl":"https://doi.org/10.1002/mds.70114","url":null,"abstract":"Background and objective Laryngeal dystonia (LD) is a focal task‐specific dystonia, affecting speaking but not whispering or emotional vocalizations. Therapeutic options for LD are limited. We developed and tested a non‐invasive, closed‐loop, neurofeedback, brain–computer interface (BCI) intervention for LD treatment. Methods Ten patients with isolated focal LD participated in the study. The personalized BCI system included visual neurofeedback of individual real‐time electroencephalographic (EEG) activity during symptomatic speaking compared to asymptomatic whispering, presented in the virtual reality (VR) environment of real‐life scenarios. During five consecutive days of intervention, patients used the BCI to learn to modulate their abnormally increased brain activity during speaking and match it to near‐normal activity of asymptomatic whispering. Changes in voice symptoms and EEG activity were quantified for the evaluation of BCI effects. Results Compared to baseline, LD patients had a statistically significant reduction of their voice symptoms on Days 1–5 of BCI intervention. Thi was paralleled by improved controllability of the visual neurofeedback and a significant reduction of left frontal delta power, including superior and middle frontal gyri, on Day 1 and left central gamma power, including premotor, primary sensorimotor, and inferior parietal areas, on Days 3 and 5. The majority of patients (70%) reported sustained positive effects of the BCI intervention on their voice quality 1 week after the study participation. Conclusion The closed‐loop BCI neurofeedback intervention specifically targeting disorder pathophysiology shows significant potential as a novel treatment option for patients with LD and likely other forms of task‐specific focal dystonia. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"24 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461269","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":"Dentate Nucleus Deep Brain Stimulation for Spinocerebellar Ataxia: Results of a 6‐Month Follow‐Up","authors":"Liang Zhao, Chang Qiu, Wenwen Dong, Bei Luo, Jian Sun, Jiuqi Yan, Xiang Wei, Guanghan Lu, Jingxuan Liu, Wenbin Zhang","doi":"10.1002/mds.70116","DOIUrl":"https://doi.org/10.1002/mds.70116","url":null,"abstract":"Background Spinocerebellar ataxia (SCA) is a genetically heterogeneous neurodegenerative disorder with no effective treatments. Although noninvasive cerebellar neuromodulation has shown positive outcomes, invasive approaches such as deep brain stimulation (DBS) remain inadequately evaluated in SCA. Objectives This study assessed the treatment outcomes of DBS targeting the cerebellar dentate nucleus (DN) in SCA patients over a 6‐month follow‐up. Methods Six patients with heterogeneous SCA underwent bilateral DN‐DBS. The stimulation parameters were programmed iteratively, and ataxia symptoms were evaluated at predefined intervals using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Results Individualized appropriate stimulation parameters (current, frequency, and pulse width) were established. At the 6‐month follow‐up, the SARA scores decreased by 43% ( <jats:italic>P</jats:italic> = 0.014) and the ICARS scores by 51% ( <jats:italic>P</jats:italic> = 0.013) compared with baseline. Conclusions These findings provide evidence for the potential therapeutic efficacy of DN‐DBS in SCA and offer preliminary insights for stimulation parameter programming. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"108 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461268","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":"Expanding the Genetic and Phenotypic Spectrum of DYT-VPS16: The Importance of Splice-Site Variants","authors":"Ana Westenberger,&nbsp;Edgard Verdura,&nbsp;Mandy Radefeldt,&nbsp;Leslie E. Sanderson,&nbsp;Kornelia Tripolszki,&nbsp;Anna Marcé-Grau,&nbsp;Ana Cazurro-Gutiérrez,&nbsp;Anita Nikoncuk,&nbsp;Rebecca Herzog,&nbsp;Ruslan Al-Ali,&nbsp;Mariana Ferreira,&nbsp;Ligia S. Almeida,&nbsp;Tainá Regina Damaceno Silveira,&nbsp;Suliman Khan,&nbsp;Raphael Doyle Maia,&nbsp;Péter Klivényi,&nbsp;András Salamon,&nbsp;Volkan Baltaci,&nbsp;Asli Subasioglu,&nbsp;Jeanette Prada-Arismendy,&nbsp;Goran Čuturilo,&nbsp;Sebastian Loens,&nbsp;Vera Tadic,&nbsp;Isabelle Maystadt,&nbsp;Deniz Karadurmus,&nbsp;Barbara Leube,&nbsp;Jonathan De Winter,&nbsp;Alice Monticelli,&nbsp;Liesbeth De Waele,&nbsp;Jonathan Baets,&nbsp;Mateja Vinkšel,&nbsp;Aleš Maver,&nbsp;Lorena Tschopp,&nbsp;Gabriela Ziegler,&nbsp;Ana Sanguinetti,&nbsp;Katja Lohmann,&nbsp;Tahsin Stefan Barakat,&nbsp;Peter Bauer,&nbsp;Belén Perez-Dueñas,&nbsp;Aida M. Bertoli-Avella","doi":"10.1002/mds.70089","DOIUrl":"10.1002/mds.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>DYT-<i>VPS16</i>, an early-onset isolated dystonia caused by variants in the <i>VPS16</i> gene, has been reported in fewer than 70 patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We explored the clinical and genotypic spectrum of DYT-<i>VPS16</i> by investigating early-onset dystonia patients with <i>VPS16</i> variants discovered in our large Biodatabank and through gene-matching initiatives. Patient samples were analyzed by exome/Sanger and RNA/cDNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 16 previously unreported DYT-<i>VPS16</i> patients (7 male, median age at onset [AAO]: 12 years). Patients with initial leg involvement had an AAO more than 10 years earlier than those with involvement of the arms/craniocervical region. Dystonia progressed in 95%, generalized in 50%, and was accompanied by pyramidal, cerebellar, or psychiatric features in 25% of patients. Two young individuals benefited greatly from timely deep brain stimulation (DBS) surgery. Of the 11 identified <i>VPS16</i> variants, 10 were novel. Utilizing RNA-Seq or cDNA sequencing, we discovered alternatively spliced transcripts, thereby elucidating the effects of splice-site, near-splice-site, and exonic variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We expand the phenotypic and mutational spectrum of DYT-<i>VPS16</i>, emphasize the utility of RNA-Seq in clarifying <i>VPS16</i> variant pathogenicity, and advocate for timely DBS as a promising therapeutic option for DYT-<i>VPS16</i> patients. © 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":"41 1","pages":"84-94"},"PeriodicalIF":7.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455458","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":"Glucocerebrosidase Target Engagement and Therapeutic Plasma and Cerebrospinal Fluid Levels After GT ‐02287 Administration in Healthy Volunteers","authors":"Raffaella Pozzi, Michele De Sciscio, Manuela Bosetti, Sara Cano‐Crespo, Joanne Taylor, Terenzio Ignoni, Jonas Hannestad","doi":"10.1002/mds.70111","DOIUrl":"https://doi.org/10.1002/mds.70111","url":null,"abstract":"Background Variants in the <jats:italic>GBA1</jats:italic> gene can increase the risk of Parkinson's disease (PD) by reducing glucocerebrosidase (GCase) activity, disrupting lysosomal and mitochondrial function, and increasing alpha‐synuclein aggregation. The molecule GT‐02287 prevents misfolding of GCase and ameliorates downstream pathway abnormalities. Objectives To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GT‐02287. Methods The safety, tolerability, and plasma pharmacokinetics of single and multiple oral doses were evaluated in 73 healthy volunteers, and GT‐02287 levels in cerebrospinal fluid (CSF) and GCase activity in blood were measured. Results All dose levels tested were safe and generally well‐tolerated. No serious or severe adverse events occurred. The most common events were nausea and headache. Plasma and CSF exposures were within the projected therapeutic range, and GCase activity increased after GT‐02287 administration. Conclusions GT‐02287 was safe and well‐tolerated in healthy volunteers. Plasma and CSF levels were consistent with levels in rodents that modulate PD biology. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"95 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447386","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":"Integrative Multi-Omics Analysis Prioritizes Candidate Genes for Essential Tremor and Reveals a Gap Between Computational Prediction and Experimental Validation.","authors":"Aishanjiang Yusufujiang,Shan Zeng,Likun Xu,Gong Li,Zebin Wang,Hongyan Li","doi":"10.1002/mds.70101","DOIUrl":"https://doi.org/10.1002/mds.70101","url":null,"abstract":"BACKGROUNDThe genetic architecture of essential tremor (ET) remains incompletely understood. A key challenge is translating genome-wide association study (GWAS) loci into specific effector genes to elucidate disease mechanisms and develop targeted therapies.OBJECTIVETo implement a multistage computational framework to prioritize high-confidence candidate genes for ET and to assess these predictions against publicly available, patient-derived transcriptomic data.METHODSWe employed a convergent evidence strategy to prioritize genes, integrating cross-tissue (UTMOST) and tissue-specific (FUSION) transcriptome-wide association studies (TWAS) with gene-based association tests (MAGMA). Prioritized genes were subjected to causal inference analyses (summary-data-based Mendelian randomization [SMR] and colocalization), co-expression network analysis (GeneMANIA), and pharmacogenomic analysis (DGIdb). We leveraged spatial transcriptomics to characterize gene expression patterns across cortical layers and cell types. Finally, we validated computational predictions using two independent post-mortem brain datasets from ET patients and controls.RESULTSOur prioritization pipeline identified 12 high-confidence candidate genes. Co-expression network analysis revealed 83.3% of candidates exhibit functional relationships, forming three modules centered on RNA processing (NRBP1), metabolic regulation (SLC5A6), and nucleotide synthesis (CAD). Pharmacogenomic analysis demonstrated 66.7% of candidates possess therapeutic target potential. Spatial transcriptomics revealed preferential expression in cortical Layer 5 pyramidal neurons. However, validation in post-mortem cerebellar tissue showed no significant differential expression.CONCLUSIONSOur study provides a robust pipeline for ET gene prioritization and puts forward a novel cortical hypothesis for the disease. The discordance between strong computational predictions and their lack of validation in available patient tissue highlights a critical gap in the field. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"54 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427862","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":"Genetic Variation Analysis of Essential Tremor: Insights from the China Essential Tremor Alliance Cohort.","authors":"Mingqiang Li,Yuwen Zhao,Yuzheng Wang,Runcheng He,Guohua Zhao,Xuejing Wang,Yanming Xu,Hongmei Cao,Hong Liu,Chengjie Mao,Heng Wu,Wei Di,Yuhu Zhang,Puqing Wang,Wei Huang,Yan Xu,Oumei Cheng,Guiyun Cui,Zhentao Zhang,Kezhong Zhang,Yiwen Wu,Tao Chen,Nian Xiong,Lifang Lei,Xun Zhou,Hongxu Pan,Xiaomei Duan,Sheng Zeng,Dong Chang,Liang Jin,Jinchen Li,Qian Xu,Zhenhua Liu,Jifeng Guo,Chunyu Wang,Tao Wang,Chunfeng Liu,Jun Liu,Qiying Sun,Beisha Tang, ","doi":"10.1002/mds.70106","DOIUrl":"https://doi.org/10.1002/mds.70106","url":null,"abstract":"BACKGROUND AND OBJECTIVEEssential tremor (ET) is a common movement disorder (MD) with significant genetic contributions, yet its genetic basis remains poorly understood. To clarify ET's genetic architecture and improve clinical diagnostics, we investigated pathogenic variants and their clinical implications in a large Chinese cohort.METHODSWhole-genome sequencing was conducted on 3097 Chinese patients with ET and 2050 healthy control subjects. We analyzed variants within 26 known ET-associated genes and 437 broader MD-associated genes. Variants were classified as pathogenic or likely pathogenic (P/LP) following American College of Medical Genetics and Genomics guidelines.RESULTSTwenty-six patients with ET (0.84%) harbored P/LP variants in ET-associated genes, involving eight genes and 24 distinct variants, with CACNA1G (n = 9) and GPR151 (n = 4) most frequently implicated. Only two patients carried previously reported ET-associated variants. Genetic segregation analysis in five families did not confirm clear cosegregation. In addition, 83 patients (2.68%) carried P/LP variants in broader MD-associated genes, notably, GSN (n = 7), FAT2 (n = 6), and FIG4 (n = 6). Clinical follow-up rediagnosed six individuals carrying GCH1, SGCE, GRN, and NOTCH3 variants with alternative MDs, and two individuals with PRKN and PSEN1 variants developed additional MDs. The remaining patients maintained ET diagnosis without MD progression. Six individuals (0.24%) were identified with Klinefelter's syndrome (47, XXY).CONCLUSIONSOur findings underscore ET's genetic heterogeneity. Integrating genetic screening and longitudinal clinical evaluation is critical for precise diagnosis and identifying patients at risk for alternative or concurrent MDs. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"152 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427884","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 rs6971 TSPO Polymorphism Does Not Influence Disease Presentation or Progression in Parkinson's Disease rs6971 TSPO Polymorphism in PD","authors":"Bina Patel, Marta Camacho, Jonathan R. Evans, David P. Breen, Thomas Foltynie, Sarah L. Mason, Gemma Cummins, Ruwani Wijeyekoon, Roger A. Barker, Caroline Helen Williams‐Gray","doi":"10.1002/mds.70105","DOIUrl":"https://doi.org/10.1002/mds.70105","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"167 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427428","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}