Movement Disorders最新文献

{"title":"Longitudinal Blood-Biomarker-Based Assessment of Brain Injury in Patients Undergoing Deep Brain Stimulation and Magnetic Resonance-Guided Focused Ultrasound.","authors":"Justina Dargvainiene,Ann-Kristin Helmers,Juliana Naumann,Carl Alexander Gless,Bettina Möller,Julius Welzel,Frank Leypoldt,Johannes Hensler,Ina Tesseur,Klaus-Peter Wandinger,Günther Deuschl,Daniela Berg,Steffen Paschen","doi":"10.1002/mds.70071","DOIUrl":"https://doi.org/10.1002/mds.70071","url":null,"abstract":"BACKGROUNDDeep brain stimulation (DBS) and magnetic resonance-guided focused ultrasound (MRgFUS) are associated with neuroaxonal damage and astroglial activation; yet their extent and timing remain unclear despite clinical relevance for monitoring and outcome assessment.OBJECTIVEThis study assessed neuroaxonal damage and astroglial activation after DBS (n = 21) and MRgFUS (n = 19) reflected by serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP).METHODSSamples were collected at baseline, 24 h, 7 days, and 3/6/9 months posttreatment. Biomarker levels were measured using a single-molecule array (Simoa).RESULTSsNfL peaked at day 7 and sGFAP at 24 h post-intervention in both groups. sNfL normalized at 6 months in DBS and 3 months in MRgFUS. sGFAP normalized within 7 days in both groups. Biomarker elevations were higher in DBS patients.CONCLUSIONSDBS and MRgFUS cause transient neuroaxonal injury and astroglial activation, with greater extent in DBS. Biomarker monitoring suggests final clinical evaluation should be performed 6 months after treatment at the earliest. © 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":"19 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189312","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":"Early Indian Age at Onset of Parkinson's: A Case for a Gene‐Environment Lens","authors":"Halil Onder, Zeynep Pekgoz, Mehmet Fevzi Oztekin","doi":"10.1002/mds.70055","DOIUrl":"https://doi.org/10.1002/mds.70055","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"72 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188464","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":"Microglia Replacement in CSF1R-RD: Current Evidence and Future Priorities.","authors":"Tomasz Chmiela,Zbiegniew K Wszolek","doi":"10.1002/mds.70050","DOIUrl":"https://doi.org/10.1002/mds.70050","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"91 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189477","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":"Integrating Long-Read Nanopore Sequencing for Precision Resolution of Genomic Variants in Dystonia.","authors":"Ugo Sorrentino,Martin Pavlov,Nazanin Mirza-Schreiber,Melanie Brugger,Theresa Brunet,Eugenia Tsoma,Alice Saparov,Ivana Dzinovic,Philip Harrer,Antonia M Stehr,Matias Wagner,Erik Tilch,Barbara Wallacher,Shiraz Alhasan,Anne Koy,Alessio Di Fonzo,Miriam Kolnikova,Katarina Kusikova,Petra Havrankova,Raushana Tautanova,Sandy Lösecke,Sebastian Eck,Sylvia Boesch,Jan Necpal,Matej Skorvanek,Robert Jech,Holger Prokisch,Juliane Winkelmann,Konrad Oexle,Elisabeth Graf,Michael Zech","doi":"10.1002/mds.70072","DOIUrl":"https://doi.org/10.1002/mds.70072","url":null,"abstract":"BACKGROUNDAlthough many individuals with dystonia present with features indicative of single-gene etiologies, obtaining definitive genetic diagnoses can be challenging.OBJECTIVEWe assessed the value of nanopore-based long-read sequencing (LRS) in achieving molecular clarification of dystonic syndromes.METHODSFrom a large dystonia cohort with short-read sequencing (SRS) data, 14 cases with unclear, difficult-to-evaluate, or missing causative variants were recruited. Long-read whole-genome sequencing was performed according to Oxford Nanopore Technologies (ONT) protocols.RESULTSONT sequencing produced long-range haplotypes, variant calls inaccessible to short-read technology, as well as methylation data. Phase inference allowed for changes in variant classification, establishing compound heterozygosity of causative variants in four cases. We illustrate an important advantage of LRS compared with SRS in (re)defining the identity of dystonia-causing structural variants and repeat expansions for seven individuals. One patient was found to harbor a novel exonic LINE-1 insertion in SGCE, expanding the genetic mechanism in myoclonus-dystonia. ONT data also provided unexpected insights into apparent mosaic expanded repeats in FMR1 in a subject with isolated focal dystonia. We further showed that LRS outperformed SRS in avoiding erroneous calls resulting from confounding pseudogene sequences and in discovering pathogenic alterations missed by conventional pipeline utilization (three cases). Moreover, simultaneous methylome analysis aided in directing the interpretation of three variants, including a KMT2B variant of uncertain significance that was reclassified as causal by LRS-based episignature profiling.CONCLUSIONSONT-based LRS uniquely improves analysis of dystonia-associated variations that had not previously been resolved by SRS, implying broad utility for future exploration of the molecular origins of the condition. © 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":"7 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194582","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":"Temporal Dynamics of Beta Power Related to the Stun Effect in Parkinson's Disease Patients after Deep Brain Stimulation Surgery.","authors":"Martijn G J de Neeling,Stijn Geraats,Bart E K S Swinnen,Mariëlle J Stam,Rob M A de Bie,Bernadette C M van Wijk,P Rick Schuurman,Arthur W G Buijink,Martijn Beudel","doi":"10.1002/mds.70042","DOIUrl":"https://doi.org/10.1002/mds.70042","url":null,"abstract":"BACKGROUNDDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for patients with advanced Parkinson's disease (PD). Early programming of DBS may be complicated by the postoperative \"stun effect,\" which also may impact local field potentials (LFPs).METHODSPercept PC neurostimulators (Medtronic) were used to continuously record LFPs from the STN in 32 PD patients at home during the first 2 months after DBS surgery. Average beta peak power (\"beta power\") per day was analyzed using change-point analysis.RESULTSMedian beta power across patients showed an upward trend with a changepoint 24 to 40 days after surgery. Median beta power directly following DBS activation did not significantly drop but continued to increase beyond the DBS activation visit.CONCLUSIONThe neurophysiological stun effect persists for at least 3 weeks and should be taken into consideration when timing and applying sensing-informed or adaptive DBS based on beta power. © 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":"116 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189313","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":"Public Healthcare for People with Parkinson's Disease in Portugal: Rising to the Challenge.","authors":"Sara Varanda,Gisela Carneiro,João Pinho","doi":"10.1002/mds.70078","DOIUrl":"https://doi.org/10.1002/mds.70078","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"145 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182592","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":"AZP2006 in Progressive Supranuclear Palsy: Outcomes from a Phase 2a Multicenter, Randomized Trial, and Open-Label Extension on Safety, Biomarkers, and Disease Progression.","authors":"Jean-Christophe Corvol,Mickael Alexandre Obadia,Caroline Moreau,Louise-Laure Mariani,Jean-Philippe Brandel,David Devos,Sara Sambin,Nicolas Carrière,Günter Höglinger,Marie Lebouteux,Graziella Mangone,Noelle Callizot,Aurélien Blondel,Olivier Defert,Cecilia Estrella,Artin Karapet,Philippe Verwaerde,Luc Defebvre","doi":"10.1002/mds.70049","DOIUrl":"https://doi.org/10.1002/mds.70049","url":null,"abstract":"OBJECTIVESThe aim was to evaluate the safety, tolerability, pharmacokinetics, and potential clinical efficacy of AZP2006, an oral pleiotropic drug modulating progranulin levels, in patients with progressive supranuclear palsy (PSP), a rare tauopathy.METHODSA randomized, double-blind, placebo-controlled, parallel-group trial was conducted at three sites in France. Eligible participants (age 40-80 years, diagnosed with probable or possible PSP) were randomized to receive AZP2006 (60 mg once per day [QD] or 80/50 mg QD [80 mg for 10 days followed by 50 mg]) or placebo for 12 weeks. Assessments included safety, pharmacokinetics (plasma and whole blood), pharmacodynamics (cerebrospinal fluid and plasma biomarkers), and exploratory clinical efficacy (PSP rating scale, clinical global impression, and activities of daily living). Approximately 2 years post-trial, an open-label extension (OLE) enrolled 15 patients who received active treatment (AZP2006) for 6 months.RESULTSForty-one patients were screened, 36 randomized, and 34 completed the study. AZP2006 demonstrated acceptable tolerability and safety with no treatment-related serious adverse events. Pharmacokinetic analysis confirmed rapid absorption, a long half-life (60 mg: 764.3 hours; 80/50 mg: 684.7 hours), and steady-state by day 45 (60 mg) and day 28 (80/50 mg). Biomarker analyses indicated blood-brain barrier crossing, target engagement, and stabilized progranulin levels. Trends in efficacy favored slower disease progression in AZP2006 groups. The OLE demonstrated a slowed progression of the disease and revealed no notable safety concerns.CONCLUSIONSAZP2006 was well-tolerated and demonstrated favorable trends in biomarker and clinical outcomes. These preliminary signals support further investigation to determine whether a meaningful clinical benefit can be achieved in PSP with AZP2006. © 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":"73 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153385","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 Novel PRNP Gene Mutation Associated with Gerstmann-Sträussler-Scheinker Syndrome.","authors":"Alexandra Bakolas,Mario Manto,Isabelle Maystadt,Mathieu Surin","doi":"10.1002/mds.70074","DOIUrl":"https://doi.org/10.1002/mds.70074","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"193 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal Fluid Proenkephalin Predicts Striatal Atrophy Decades before Clinical Motor Diagnosis in Huntington's Disease.","authors":"Mena Farag,Michael J Murphy,Nicola Z Hobbs,Michela Leocadi,Kate Fayer,Olivia Thackeray,Johan Gobom,Marc Ciosi,Amanda Heslegrave,Henrik Zetterberg,Douglas R Langbehn,Darren G Monckton,Edward J Wild,Sarah J Tabrizi,Rachael I Scahill","doi":"10.1002/mds.70062","DOIUrl":"https://doi.org/10.1002/mds.70062","url":null,"abstract":"BACKGROUNDHuntington's disease (HD) is characterized by early, selective, progressive vulnerability of striatal medium spiny neurons (MSNs). Proenkephalin (PENK), a precursor of opioid peptides abundantly expressed in MSNs, is a promising biomarker of striatal integrity, but region-specific associations and its potential for early-stage discrimination have not been characterized.OBJECTIVESWe investigated cross-sectional and longitudinal associations between baseline cerebrospinal fluid (CSF) PENK concentration and regional brain atrophy, compared identified patterns with CSF neurofilament light (NfL), and evaluated PENK and NfL for discriminating between HD Integrated Staging System (HD-ISS) stage 0 versus 1 in a far-from-onset HD gene-expanded (HDGE) cohort.METHODSWhole-brain voxel-based morphometry was performed in 149 participants (72 HDGE, 77 controls) cross-sectionally and 88 participants (54 HDGE, 34 controls) longitudinally over a mean interval of 4.8 years. Voxel-wise linear regression tested associations between baseline biofluid biomarkers and gray/white matter volume, adjusting for age, sex and CAG-Age Product score, with false discovery rate correction. Logistic regression and receiver operating characteristic analyses assessed stage discrimination.RESULTSLower baseline CSF PENK predicted longitudinal gray and white matter loss, predominantly in the striatum bilaterally. Higher baseline CSF NfL predicted widespread longitudinal white matter loss. For stage discrimination, PENK (area under curve [AUC], 0.706; P = 0.0002) outperformed NfL (AUC, 0.661; P = 0.1596) with minimal gain from combining both (AUC, 0.714; joint P = 0.0007).CONCLUSIONSLower baseline CSF PENK concentration predicted longitudinal striatal atrophy and CSF PENK outperformed CSF NfL in distinguishing HD-ISS stages 0 and 1, supporting its role as a striatum-specific biomarker with potential to enrich early-stage HD trial cohorts. © 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":"153 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140416","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 STOP-Gain RNF213 Variant Causes Chorea, Stroke-Like Episodes, and Leigh Syndrome-Like Encephalopathy.","authors":"Roberta Bovenzi,Mariasavina Severino,Jennifer Nichols,Fred Shen,Ignacio J Keller Sarmiento,Bernabe I Bustos,Lisa Kinsley,Dimitri Krainc,Niccolò E Mencacci","doi":"10.1002/mds.70077","DOIUrl":"https://doi.org/10.1002/mds.70077","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"154 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140374","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}