Movement Disorders最新文献

{"title":"Cortical and Corticomuscular Beta‐Gamma Phase‐Amplitude Coupling During Different Locomotion States and the Effects of Levodopa in Parkinson's Disease","authors":"Haifeng Zhao, Shenglin Hao, Peiran Zhang, Shenghong He, Laura Wehmeyer, Ziyi Feng, Lu Xu, Shikun Zhan, Wei Liu, Xiaoxiao Zhang, Marie‐Laure Welter, Dianyou Li, Bomin Sun, Yong Lu, Huiling Tan, Chunyan Cao","doi":"10.1002/mds.70031","DOIUrl":"https://doi.org/10.1002/mds.70031","url":null,"abstract":"BackgroundPhase‐amplitude coupling (PAC) in the beta‐gamma range has emerged as a promising electrophysiological biomarker of Parkinson's disease (PD).ObjectiveThis study aims to investigate how levodopa and locomotion modulate cortical (central electroencephalogram [cEEG]) and corticomuscular (cEEG‐gEMG [gastrocnemius electromyography]) beta‐gamma PAC in patients with PD.MethodsThirty patients with PD underwent simultaneous cEEG and gEMG recordings during sitting, standing, and free walking in both <jats:italic>off</jats:italic> and <jats:italic>on</jats:italic> dopaminergic states. Spectral features and PAC analyses were conducted to assess the effects of levodopa, locomotion, and their associations with motor symptoms.ResultsIn the <jats:italic>off</jats:italic> levodopa state, patients showed prolonged gait cycle intervals and shorter step lengths, correlating with higher Movement Disorder Society–revised Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) scores. The cEEG beta‐gamma PAC during sitting and standing, and cEEG‐gEMG beta‐gamma PAC during walking, positively correlated with UPDRS‐III in the <jats:italic>off</jats:italic> levodopa state. The cEEG alpha/low beta‐gamma and cEEG‐gEMG low beta‐gamma PAC increased from <jats:italic>on</jats:italic> to <jats:italic>off</jats:italic> levodopa while walking, with the latter correlating with reduced step length. Step event–related PAC analysis unveiled a dynamic enhancement of alpha/beta cEEG‐gamma gEMG PAC around heel strikes in <jats:italic>on</jats:italic> levodopa compared with <jats:italic>off</jats:italic>.ConclusionsBoth cortical and corticomuscular beta‐gamma PACs are modulated by levodopa and locomotion, with low beta‐gamma corticomuscular PAC specifically linked to gait dysfunction. Moreover, the levodopa‐related enhancement of alpha/beta–gamma PAC during heel strikes highlights the functional relevance of dopaminergic modulation during gait. These findings highlight the potential of PAC as a biomarker for PD, particularly in the development of gait phase‐locked adaptive deep brain stimulation strategies for patients with PD guided by noninvasive PAC monitoring. © 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":"24 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002773","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":"ENLITE PD: A Randomized Clinical Trial of Light Therapy for Impaired Sleep in Parkinson's Disease.","authors":"Aleksandar Videnovic,Christopher S Coffey,Elizabeth B Klerman,Merit Cudkowicz,Hyun Joo Cho,Amy Amara,Karen Marder,Phyllis Zee,Christina Desir,Holly Ernst,Erin Steinhart,Michelle Costigan,Anna Gudjonsdottir,Elizabeth Klingner,Dixie Ecklund,Marianne Chase,Amy Wang,David Charles,David Clifford,Juliana Coleman,Alberto J Espay,Albert Y Hung,Srinath Kadimi,Annie Killoran,Lan Luo,Roneil Malkani,Jason Margolesky,Jennifer Marsella,Carine Maurer,Dragos Mihaila,Paolo Moretti,Ariane Park,Nicolas Phielipp,Harini Sarva,Binit Shah,Holly A Shill,Andrew Siderowf,Valerie Suski,Jessica Tate,Winona Tse,Kara Wyant,Lin Zhang,Christine Annis,Katherine Ambrogi,Gabrielle Auerbach,Melanie Benge,Emma Blystone,Loraine Brenner,Carolina Burgos Aguilar,Grace Bwala,Juliana Dorsch,Erica Goude,Hilda Gutierrez,Kelly Harper,Samuel Hochberger,Priyanka Kalyani,Jessica Lamb,Kay Maupin,Angela Molloy,Sherri Mosovsky,Mysha Sissine,Julie Steele,Monica Szela,Mangesha Teshome,Marie Wencel,Eric A Macklin, ","doi":"10.1002/mds.70009","DOIUrl":"https://doi.org/10.1002/mds.70009","url":null,"abstract":"BACKGROUNDLight therapy (LT) in Parkinson's disease improves sleep. Specific LT parameters require further study, including optimal frequency.OBJECTIVESWe aimed to determine if once- or twice-daily bright white light therapy (BWLT) improves sleep. Secondary aims compared once-weekly BWLT to twice-daily dim red light therapy (DRLT) as controls, estimated effects on fatigue, and adherence.METHODSA 16-week, randomized, phase 2, sham-controlled, dose-selection trial to select the superior BWLT frequency based on change in Parkinson's Disease Sleep Scale-2 (PDSS-2), participant burden, and safety. Participants were randomized to 8 weeks of twice-daily BWLT, once-daily BWLT, once-weekly BWLT, or twice-daily DRLT. An improvement of ≥1.7 points in 8-week change of PDSS-2 by daily BWLT relative to either control warranted advancing to a phase 3 trial.RESULTSA total of 150 participants were randomized (mean [SD], 67 [8.6] years; 57 [38%] female; PDSS-2 17.1 [6.7]). Mean 8-week change from baseline in PDSS-2 score improved (twice-daily BWLT -2.6 [95% CI: -4.4, -0.7]; once-daily BWLT -1.5 [-3.3, 0.3]; once-weekly BWLT -0.4 [-2.2, 1.4]; twice-daily DRLT -1.8 [-3.6, 0.1]) but did not meet criteria for advancing. Mean 8-week change from baseline in Parkinson's Disease Fatigue Scale (PFS-16) score improved (twice-daily BWLT -6.4 [-9.8, -3.0]; once-daily BWLT -2.2 [-5.5, 1.1]; once-weekly BWLT -0.5 [-3.9, 2.8]; and twice-daily DRLT -3.8 [-7.3, -0.4]). Mean adherence to LT was 63%-86%.CONCLUSIONSENLITE-PD did not meet the criteria for advancing daily LT to a phase 3 trial. LT was safe and well-tolerated with good adherence. Once-weekly BWLT was a non-inferior control compared with twice-daily DRLT. © 2025 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"42 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003285","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":"Abnormal Connectivity of the Head Neural Integrator in Cervical Dystonia.","authors":"Giuseppe A Zito,Emmanuel Roze,Clément Tarrano,Salim Ouarab,Prasanthi Jegatheesan,Asya Ekmen,Benoît Béranger,Romain Valabregue,Cécile Hubsch,Sophie Sangla,Cécilia Bonnet,Cécile Delorme,Aurélie Méneret,Bertrand Degos,Floriane Bouquet,Marion Apoil Brissard,Marie Vidailhet,Dominique Hasboun,Pierre Pouget,Yulia Worbe,Cécile Gallea","doi":"10.1002/mds.70014","DOIUrl":"https://doi.org/10.1002/mds.70014","url":null,"abstract":"BACKGROUNDCervical dystonia is characterized by abnormal neck and head movements, possibly related to a dysfunction of the interstitial nucleus of Cajal (INC) and the head neural integrator, a system responsible for the control of head and eye movements. However, neuroanatomical evidence of alterations in the head neural integrator in cervical dystonia is sparse.OBJECTIVESWe investigated structural and functional integrity of the INC and its connections in cervical dystonia.METHODSThis cross-sectional, observational study compared 19 cervical dystonia patients and 21 healthy controls, using anatomical, diffusion-weighted, and resting-state functional images. We reconstructed tracts converging on the INC, and involved in the control of head movements. We evaluated group differences in microstructural integrity using fixel-based analysis, and effective connectivity using dynamic causal modeling.RESULTSCompared with controls, patients showed microstructural abnormalities within the INC and cerebral peduncle. Effective connectivity showed abnormal self-inhibition in the INC, substantia nigra, and vermis in patients, with decreased excitation from the substantia nigra to the INC, increased inhibition from the deep cerebellar nuclei and primary sensorimotor cortex, and decreased excitation from the INC to the cerebellar vermis.CONCLUSIONSA dysfunction of the INC might contribute to altered sensorimotor integration in cervical dystonia, and abnormal feedback from its afferent connections could alter its integrative function, resulting in a disturbed head and neck posture. © 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":"24 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995664","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":"Transcutaneous Spinal Magnetic Stimulation Affects Subthalamic Activity in Parkinson's Disease.","authors":"Anna Letícia de Moraes Alves,Juliana da Silva Simões,Luiz Ricardo Trajano da Silva,Arnaldo Fim Neto,Fábio Godinho,Rafael Bernhart Carra,Janaína Reis Menezes,Glaucia Aline Nunes,Daniele Salgado Barros,Thiago Trajano da Silva,Maria Sheila Guimarães Rocha,Manoel Jacobsen Teixeira,Egberto Reis Barbosa,Diogo Coutinho Soriano,Rubens Gisbert Cury","doi":"10.1002/mds.70035","DOIUrl":"https://doi.org/10.1002/mds.70035","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"59 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960088","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":"Functional Magnetic Resonance Imaging (fMRI) Signatures of Progression and Phenoconversion in Prodromal Synucleinopathies","authors":"Lachlan Churchill, Anna Ignatavicius, Ajay Konuri, Jack Anderson, Natasha Taylor, Simon J.G. Lewis, Elie Matar","doi":"10.1002/mds.70025","DOIUrl":"https://doi.org/10.1002/mds.70025","url":null,"abstract":"BackgroundIsolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal manifestation of synucleinopathies and provides a critical window to identify early markers of progression to Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Time‐averaged (static) and time‐varying (dynamic) functional connectivity between large‐scale brain networks may sensitively capture early pathophysiological changes and offer prognostic value beyond structural imaging.ObjectivesTo use functional magnetic resonance imaging (fMRI) on a longitudinal iRBD cohort to assess alterations in static and dynamic functional connectivity and explore their relationship with disease conversion and regional neurotransmitter density.MethodsStatic and dynamic resting state fMRI and clinical testing were acquired from 41 iRBD participants and 38 healthy controls, with 21 iRBD participants undergoing repeated scanning.ResultsCross‐sectional analysis revealed reduced static connectivity within the visual network and a shift toward a more segregated functional architecture in iRBD. Longitudinally, a further increase in segregation was observed, characterized by heightened modularity and reduced intermodular connectivity. These changes were accompanied by static connectivity disruptions in somatomotor and attentional networks, particularly pronounced in patients who converted to DLB. Regions showing the greatest connectivity decline overlapped with areas rich in cholinergic and noradrenergic transporters, suggesting early neuromodulatory dysfunction as a potential driver.ConclusionsOur findings reveal progressive functional segregation and widespread disrupted static connectivity of resting‐state networks in iRBD. These results identify imaging biomarkers of disease progression, describe likely neurotransmitter associations, and support the implementation of fMRI as a sensitive tool for detecting early neurobiological signatures of synucleinopathies. © 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":"38 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927998","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":"Allogeneic Bone Marrow‐Derived Mesenchymal Stem Cells for Parkinson's Disease: A Randomized Trial","authors":"Mya C. Schiess, Jessika Suescun, Juan D. Martinez‐Lemus, Charles Green, Tia S. Thomas, Mohammad Shahnawaz, Emily Tharp, Nikunj B. Satani, Jerome G. Saltarrelli, Christopher Adams, Marie‐Francoise Doursout, Vanessa Thyne, Rula Abuamouneh, Elsa M. Rodarte, Sean I. Savitz, Timothy M. Ellmore","doi":"10.1002/mds.70028","DOIUrl":"https://doi.org/10.1002/mds.70028","url":null,"abstract":"BackgroundNeuroinflammation contributes to Parkinson's disease (PD) progression and motor dysfunction. Allogeneic human mesenchymal stem cells (allo‐hMSCs) may reduce neuroinflammation and improve motor symptoms.ObjectivesTo evaluate the efficacy of repeated intravenous doses of 10 × 10<jats:sup>6</jats:sup>/kg allo‐hMSCs in improving motor symptoms in patients with PD (PwP).MethodsIn this phase 2, randomized, placebo‐controlled trial (November 2020–July 2023), mild‐to‐moderate PwP received either three allo‐hMSC infusions, one placebo followed by two allo‐hMSC infusions, or three placebo infusions at 18‐week intervals. Follow‐up lasted 88 weeks. The primary outcome was a &gt;70% posterior probability (PP) of a difference in the proportion of participants with ≥5‐point improvement in OFF‐medication Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale‐Part III (MDS‐UPDRS‐III) at week 62. Bayesian analysis was conducted using R v4.2.0.ResultsForty‐five PwP were enrolled. A larger proportion of subjects achieved a ≥5‐point improvement in MDS‐UPDRS‐III in the three‐infusion arm compared with placebo at week 62 (mean difference [MD]: 5.0%, PP = 93.7%), translating to a 16.9‐point improvement in MDS‐UPDRS‐III in the three‐infusion arm compared with a 14.6‐point improvement in the placebo arm. Conversely, fewer subjects in the two‐infusion arm compared with placebo showed ≥5‐point improvement at week 62 (MD: –62.4%, PP ≥ 99.9%), translating to only a 3.9‐point improvement in MDS‐UPDRS‐III in the two‐infusion arm. However, improvement in MDS‐UPDRS‐III was seen across all treatment arms. Adverse events were mild and transient.ConclusionsThree infusions of 10 × 10<jats:sup>6</jats:sup> allo‐hMSCs/kg improved motor function in mild‐to‐moderate PwP, while two infusions showed less improvement than placebo. To address this discrepancy, future studies should conduct functional potency assays to understand batch‐to‐batch variability affecting clinical efficacy. © 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":"13 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928258","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":"Digital Outcomes of Upper Limb Ataxia Capture Meaningful Longitudinal Change and Treatment Response","authors":"Dominik Hermle, Robin Schubert, Pascal Barallon, Winfried Ilg, Rebecca Schüle, Ralf Reilmann, Matthis Synofzik, Andreas Traschütz","doi":"10.1002/mds.70012","DOIUrl":"https://doi.org/10.1002/mds.70012","url":null,"abstract":"BackgroundDigital‐motor outcomes promise better responsiveness than clinician‐reported outcomes in ataxia trials. However, their patient meaningfulness and sensitivity to change remain to be demonstrated, particularly in the upper limb domain.ObjectivesValidation of quantitative motor (Q‐Motor) assessment for upper limb ataxia against patient‐reported outcomes and regarding sensitivity to both longitudinal and treatment‐induced change, the latter in n‐of‐1 treatment settings.MethodsSingle‐center longitudinal assessment of finger tapping, diadochokinesia, grip‐lift, spiral drawing, and target reaching in (1) 36 cross‐genotype ataxia patients and 20 controls, validating digital measures for correlations with patient‐reported outcome measure (PROM)‐ataxia, 2‐weeks test–retest reliability, and sensitivity to change within a trial‐relevant 1‐year follow‐up, anchored in Patient Global Impression of Change (PGI‐C); and (2) two patients with spinocerebellar ataxia type 27B (SCA27B) on versus off treatment with 4‐aminopyridine.ResultsTwenty‐four digital measures correlated with the PROM‐ataxia upper‐limb composite (|ρ| = 0.4–0.7) and had excellent test–retest reliability (ICC = 0.91–0.99). Correlations to individual PROM‐ataxia items were specific for functional impairment the respective measure was hypothesized to capture. Speed of finger tapping and diadochokinesia, and smoothness of target reaching (spectral arc length of movement in three dimensions [SPARC<jats:sub>3D</jats:sub>]) captured 1‐year progression in ataxia patients (|<jats:italic>r</jats:italic><jats:sub>prb</jats:sub>| = 0.38–0.51), and specifically in patients with worsening PGI‐C. Estimated sample sizes to detect longitudinal change were lower for digital than clinical outcomes (SPARC<jats:sub>3D</jats:sub>: n = 33, Scale for the Assessment and Rating of Ataxia (SARA): n = 79, nine‐hole peg‐test: n = 214). Speed of diadochokinesia, stability of grip‐lift, and variability of target reaching captured treatment responses to 4‐aminopyridine in SCA27B, exceeding minimal detectable and minimal important change.ConclusionDigital upper limb measures capture patient‐meaningful 1‐year longitudinal and treatment‐induced change, and are therefore promising outcomes for upcoming ataxia trials. © 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":"84 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923860","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":"Structural Alterations in the Gray Matter Volume in Rapid‐Onset Dystonia‐Parkinsonism","authors":"Ihtsham U. Haq, Kristina Simonyan, Eleonora Napoli, Laurie J. Ozelius, Beverly M. Snively, Christopher T. Whitlow, Kathleen J. Sweadner, Allison Brashear","doi":"10.1002/mds.30320","DOIUrl":"https://doi.org/10.1002/mds.30320","url":null,"abstract":"BackgroundPreviously, we identified decreased thalamic blood flow in patients with ATP1A3 variants.ObjectiveThis study evaluated structural gray matter organization in rapid‐onset dystonia‐parkinsonism (RDP) patients compared with controls and two phenotypically overlapping movement disorders.MethodsStructural magnetic resonance imaging data were examined for whole‐brain gray matter volume (GMV) abnormalities in 17 RDP patients, 20 isolated dystonia patients, 20 Parkinson's disease (PD) patients, and 20 controls.ResultsLeft prefrontal cortical volume was increased in the RDP group in all comparisons. RDP patients showed additional bilateral volumetric increases in the right inferior temporal cortex and fusiform gyrus compared with controls, GMV changes in the inferior parietal cortex and thalamus compared with dystonia, and in the cerebellum compared with PD. Negative correlations between RDP duration and GMV were found in the right prefrontal cortex and bilateral caudate nucleus.ConclusionOur data suggest that structural alterations in RDP involve sensorimotor and executive brain regions. © 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":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924076","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":"Compound Heterozygous Structural Variants in Cases with Unsolved PRKN‐Associated Parkinson's Disease","authors":"Agata Fant, Sara Trova, Edoardo Monfrini, Gaia Treves, Francesco Musacchia, Fabio Landuzzi, Paola Mandich, Antonio Amoroso, Remo Sanges, Luca Pandolfini, Francesco Cavallieri, Franco Valzania, Valentina Fioravanti, Giulia Di Rauso, Gloria Brescia, Enza Maria Valente, Valeria Tiranti, Luigi Michele Romito, Chiara Reale, Barbara Garavaglia, Antonio Emanuele Elia, Andrea Cavalli, Alessio Di Fonzo, Manuela Vecchi, Stefano Gustincich","doi":"10.1002/mds.70027","DOIUrl":"https://doi.org/10.1002/mds.70027","url":null,"abstract":"BackgroundBiallelic mutations in the <jats:italic>PRKN</jats:italic> gene are a common cause of early‐onset Parkinson's disease (EOPD). In addition to single nucleotide variants, structural variants contribute substantially to the mutational profile of <jats:italic>PRKN</jats:italic>. A significant portion of patients with EOPD remains genetically unsolved.ObjectivesBy using short‐read whole genome sequencing (sr‐WGS), we aimed to uncover complex genetic alterations at the <jats:italic>PRKN</jats:italic> locus in EOPD cases which tested negative for mutations in Mendelian PD genes with clinical exome sequencing (CES) and multiplex ligation‐dependent probe amplification (MLPA).MethodsWe evaluated 498 unrelated EOPD patients, who tested negative using gold‐standard diagnostic methods, using sr‐WGS. In selected cases, long‐read whole genome sequencing (lr‐WGS) with Oxford Nanopore technology was employed for an in‐depth analysis and validation. The Parkinson's Progression Markers Initiative (PPMI) dataset was interrogated to assess the prevalence of any newly identified elusive pathogenic genetic configurations.Resultssr‐WGS revealed elusive compound heterozygous structural variations, consisting of partially overlapping deletions and duplications within the <jats:italic>PRKN</jats:italic> gene in three unrelated EOPD cases (two familial, one sporadic). In familial cases, biallelic <jats:italic>PRKN</jats:italic> structural variants co‐segregated with the disease. The exact structure of each variant was resolved using lr‐WGS. Similar variants were absent in the large PPMI database, suggesting that they are a rare occurrence.ConclusionsIn this article we describe a rare configuration of compound heterozygous structural variations involving partially overlapping chromosomal regions at the <jats:italic>PRKN</jats:italic> locus, which are difficult to detect through standard diagnostic genetic technologies. This study highlights the importance of integrating WGS into clinical practice. © 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":"37 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919055","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 Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy.","authors":"Andrea Quattrone,Nicolai Franzmeier,Hans-Jürgen Huppertz,Nicholas Seneca,Gabor C Petzold,Annika Spottke,Johannes Levin,Johannes Prudlo,Emrah Düzel, ,Günter U Höglinger","doi":"10.1002/mds.70026","DOIUrl":"https://doi.org/10.1002/mds.70026","url":null,"abstract":"BACKGROUNDClinical progression rate is the typical primary endpoint measure in progressive supranuclear palsy (PSP) clinical trials.OBJECTIVESThis longitudinal multicohort study investigated whether baseline clinical severity and regional brain atrophy could predict clinical progression in PSP-Richardson's syndrome (PSP-RS).METHODSPSP-RS patients (n = 309) from the placebo arms of clinical trials (NCT03068468, NCT01110720, NCT02985879, NCT01049399) and DescribePSP cohort were included. We investigated associations of baseline clinical and volumetric magnetic resonance imaging (MRI) data with 1-year longitudinal PSP rating scale (PSPRS) change. Machine learning (ML) models were tested to predict individual clinical trajectories.RESULTSPSP-RS patients showed a mean PSPRS score increase of 10.3 points/yr. The frontal lobe volume showed the strongest association with subsequent clinical progression (β: -0.34, P < 0.001). However, ML models did not accurately predict individual progression rates (R2 <0.15).CONCLUSIONSBaseline clinical severity and brain atrophy could not predict individual clinical progression, suggesting no need for MRI-based stratification of patients in future PSP trials. © 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":"32 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959997","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}