Movement Disorders最新文献

{"title":"EFNB3 Frameshift Variant in Weimaraner Dogs with a Condition Resembling a Congenital Mirror Movement Disorder.","authors":"Cleo Schwarz,Florian Bartenschlager,Olivia Kershaw,Judith Braun,Julien Guevar,Vidhya Jagannathan,Jörg T Epplen,Wencke Reineking,Wolfgang Baumgärtner,Kailash P Bhatia,Achim D Gruber,Tosso Leeb","doi":"10.1002/mds.30243","DOIUrl":"https://doi.org/10.1002/mds.30243","url":null,"abstract":"BACKGROUNDCongenital mirror movement disorders (CMMs) are clinically and genetically heterogeneous in human patients. CMMs have not been documented to occur spontaneously in animals.OBJECTIVEThe objective of this work was to document the first case of CMMs spontaneously occurring in Weimaraner dogs and to identify the underlying genetic cause.METHODSClinical and pathological investigations were performed. Genetic investigations used linkage and autozygosity mapping followed by whole-genome sequencing of 3 affected dogs and 1489 control dogs to identify disease-associated variants.RESULTSThree of 11 puppies in a litter of Weimaraner dogs exhibited an abnormal gait characterized by synchronized saltatorial locomotion. Their phenotype was tentatively termed congenital mirror movement disorder 1 (CMM1). The underlying genetic cause was identified as a 2-bp duplication in EFNB3 encoding ephrin-B3, a transmembrane protein important for axon guidance and spinal midline barrier formation during neurodevelopment. The identified variant, XM_038536724.1:c.643_644dup, is predicted to lead to a frameshift and introduction of a premature stop codon XP_038392652.1:p.(Ala216Valfs*79). CMM1 is inherited as an autosomal recessive trait in these dogs.CONCLUSIONSSimilar to humans, CMMs may occur in dogs as an inherited disease as a result of a spontaneously arisen genetic variant. The CMM1 phenotype in dogs resembles the phenotype of experimentally induced Efnb3-/- knockout mice. So far, no human patients with EFNB3-related CMMs have been reported. Our study provides the first naturally occurring large-animal model for CMMs. EFNB3 should be considered a candidate gene in human CMM patients with unclear disease etiology. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"32 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114082","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":"Capture of Longitudinal Change in Real-Life Walking in Cerebellar Ataxia Increases Patient Relevance and Effect Size.","authors":"Jens Seemann,Theresa Beyme,Natalie John,Florian Harmuth,Martin Giese,Ludger Schöls,Dagmar Timmann,Matthis Synofzik,Winfried Ilg","doi":"10.1002/mds.30230","DOIUrl":"https://doi.org/10.1002/mds.30230","url":null,"abstract":"BACKGROUNDWith disease-modifying drugs for degenerative ataxias on the horizon, ecologically valid measures of gait performance that can detect patient-relevant changes in trial-like time frames are highly warranted.OBJECTIVESIn this 2-year longitudinal study, we aimed to unravel ataxic gait measures sensitive to longitudinal changes in patients' real lives using wearable sensors.METHODSWe assessed longitudinal gait changes of 26 participants with degenerative cerebellar disease (Scale for the Assessment and Rating of Ataxia [SARA]: 9.4 ± 4.1) at baseline, 1-year, and 2-year follow-up using three body-worn inertial sensors in two conditions: (1) laboratory-based walking (LBW); and (2) real-life walking (RLW). In RLW, a context-sensitive analysis was performed by selecting comparable walking bouts according to macroscopic gait characteristics. Gait analysis focused on measures of spatio-temporal variability, particularly stride length variability, lateral step deviation, and a compound measure of spatial variability (SPCmp).RESULTSGait variability measures showed high test-retest reliability in both walking conditions (intraclass correlation coefficient [ICC], ≥0.82). Cross-sectional analyses revealed high correlations of gait measures with ataxia severity (SARA, effect size ρ ≥ 0.75); and with patients' subjective balance confidence (Activity-specific Balance Confidence scale [ABC]: ρ ≥ 0.71). Although SARA showed longitudinal changes only after 2 years, the gait measure SPCmp revealed changes after 1 year with high effect size (rprb = 0.80). Sample size estimation for the gait measure SPCmp showed a required cohort size of n = 42 participants (n = 38; spinocerebellar ataxias [SCA]1/2/3 subgroup) to detect a 50% reduction in progression at 1 year with a hypothetical intervention, compared to n = 147 for SARA at 2 years.CONCLUSIONSBecause of their ecological validity and larger effect sizes, real-life gait characteristics represent promising performance measures as outcomes for future treatment 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":"55 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103810","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":"Intraputaminal Delivery of Adeno-Associated Virus Serotype 2-Glial Cell Line-Derived Neurotrophic Factor in Mild or Moderate Parkinson's Disease.","authors":"Amber D Van Laar,Chadwick W Christine,Nicolás Phielipp,Paul S Larson,J Bradley Elder,Aristide Merola,Waldy San Sebastian,Massimo S Fiandaca,Adrian P Kells,Michael E Wisniewski,Krystof S Bankiewicz","doi":"10.1002/mds.30193","DOIUrl":"https://doi.org/10.1002/mds.30193","url":null,"abstract":"BACKGROUNDGlial cell line-derived neurotrophic factor (GDNF) is required for development and survival of dopaminergic neurons. A previous trial evaluating lower-dose adeno-associated virus serotype 2-GDNF (AAV2-GDNF) bilateral intraputaminal infusion in participants with advanced Parkinson's disease (PD) achieved 26% mean putaminal coverage and was associated with stable motor features with no unexpected adverse events (AEs) over 60 months.OBJECTIVEWe assessed safety and preliminary clinical outcomes of optimized bilateral intraputaminal infusion of a single, higher dose of AAV2-GDNF (product code AB-1005) for PD after 18 months.METHODSThis phase 1b single-arm, open-label clinical trial enrolled participants with mild (Movement Disorder Society-revised Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III off score ≤ 32) and moderate (MDS-UPDRS Part III off score of 33-60) PD. The primary outcome was safety. Clinical outcomes were assessed using PD-specific clinical measures.RESULTSEleven participants were enrolled (n = 6 mild; n = 5 moderate). Mean (±SE) putaminal coverage of AAV2-GDNF was 63% (±2%). All participants experienced treatment-emergent AEs (63 events); most were transient and perioperative. Six serious AEs in three participants were unrelated to AAV2-GDNF. At 18 months posttreatment, the mild cohort exhibited numerically stable MDS-UPDRS, motor diary, Unified Dyskinesia Rating Scale (UDysRS) scores, and levodopa equivalent daily dose (LEDD). The moderate cohort demonstrated numerical improvements in mean (±SE) MDS-UPDRS Part III off scores (-20.4 [±4.5]), motor diary off time (-1.7 [±1.1] hours), and UDysRS scores (-2.2 [±1.9]) and reduced LEDD (-257.6 [±162.2] mg).CONCLUSIONSBilateral intraputaminal AAV2-GDNF gene therapy was well tolerated and associated with numerical stability (mild cohort) and improvement (moderate cohort) in clinical assessments at 18 months posttreatment. © 2025 AskBio Inc and 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":"131 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103851","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":"LRRK2-Associated Parkinson's Disease: Is it a Synucleinopathy After All?","authors":"Ziv Gan-Or,Roy N Alcalay","doi":"10.1002/mds.30228","DOIUrl":"https://doi.org/10.1002/mds.30228","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"1 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097739","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":"May Infographic","authors":"","doi":"10.1002/mds.29849","DOIUrl":"https://doi.org/10.1002/mds.29849","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 Beta burst characteristics and coupling within the sensorimotor cortical-STN circuit dynamically relate to bradykinesia in Parkinson's disease.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/10.1002/mds.29849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091253","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":"Movement Disorders: Volume 40, Number 5, May 2025","authors":"","doi":"10.1002/mds.30236","DOIUrl":"https://doi.org/10.1002/mds.30236","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 5","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091655","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":"Peripheral Mononuclear Cell Mitochondrial Function Associates with T-Cell Cytokines in Parkinson's Disease.","authors":"Fatima Afaar,Priscilla Youssef,Jasmin Galper,Michelle Chua,Glenda M Halliday,Simon J G Lewis,Nicolas Dzamko","doi":"10.1002/mds.30233","DOIUrl":"https://doi.org/10.1002/mds.30233","url":null,"abstract":"BACKGROUNDParkinson's disease (PD) is the most common neurodegenerative movement disorder and one of the world's fastest-growing neurological diseases. Although the exact causes of PD are unknown, mitochondrial dysfunction and inflammation may have significant roles in disease progression. As well as being prevalent in the brain, there is also evidence that peripheral mitochondrial dysfunction and inflammation occur in PD. However, if/how peripheral mitochondrial dysfunction and inflammation are linked is still unclear.OBJECTIVESThis study aimed to determine the extent that mitochondrial dysfunction in peripheral immune cells is associated with inflammation in PD.METHODSThe study comprised of 35 controls and 35 PD patients that were age and sex matched. Flow cytometry was used to assess mitochondrial content and superoxide production in mononuclear cells, in the presence and absence of the mitochondrial stressor antimycin A. Serum inflammatory cytokines were measured by ELISA.RESULTSSuperoxide levels were significantly increased in PD patient mononuclear cells at baseline, and PD mononuclear cells had an impaired response to antimycin A. Immune cell superoxide levels correlated with serum cytokines associated with T-cell responses, namely interleukin (IL) IL-12, interferon-γ, and IL-17A.CONCLUSIONSResults show that mitochondrial dysfunction is prevalent in PD immune cells and may contribute to an inflammatory phenotype. © 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":"5 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065873","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":"Rapid Eye Movements (REMs) during Non-REM Sleep as a Marker of Alpha-Synucleinopathies.","authors":"Estefania Vargas Gonzalez,Zhongmei Yang,Pauline Dodet,Smaranda Leu-Semenescu,Andreas Brink-Kjaer,Paul Roujansky,Poul Joergen Jennum,François-Xavier Lejeune,Marie Vidailhet,Isabelle Arnulf","doi":"10.1002/mds.30211","DOIUrl":"https://doi.org/10.1002/mds.30211","url":null,"abstract":"BACKGROUNDAlpha-synuclein-related neurodegeneration affects sleep figures, whether in the prodromal (rapid eye movement [REM] sleep behavior disorder, iRBD) or established (Parkinson's disease [PD] and multiple system atrophy [MSA]) stages.OBJECTIVETo look for abnormal intrusions of REMs in non-REM sleep in alpha-synucleinopathies.METHODSClinical measures and polysomnography were collected from 554 participants with PD (N = 257), iRBD (N = 110), and MSA (N = 71) and 115 controls. Initially, the polysomnography was visually examined for REMs in N2 (presence and index). Subsequently, REMs were automatically detected in all wake and sleep stages, and thresholds discriminating between the disorders were sought.RESULTSThe REMs index in N2 (visually measured) was lower in controls than all patients groups. The REMs index in N2 (automatically measured) was lower in controls than in patients with PD and MSA, but not different from iRBD participants. The optimal cutoff of 4.6 REMs/h of N2 yielded a 77% specificity to discriminate controls from all neurodegenerative groups but sensitivity was 60%. The cutoff to discriminate MSA from PD participants had a low specificity (58%). The optimal cutoff of 2.1/h in iRBD patients had an 80% specificity for distinguishing them from controls.CONCLUSIONSAbnormal intrusion of REMs into non-REM sleep distinguishes participants with alpha-synucleinopathies from controls. This automated technique could be used to identify patients with neurodegenerative disorders in the large number of polysomnograms obtained for other purposes in the elderly. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"78 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982436","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 Brain Iron Metabolism is Linked to Altered Neural Function in Isolated Laryngeal Dystonia.","authors":"Giovanni Battistella,Laura de Lima Xavier,Alexander O Vortmeyer,Kristina Simonyan","doi":"10.1002/mds.30217","DOIUrl":"https://doi.org/10.1002/mds.30217","url":null,"abstract":"BACKGROUNDLaryngeal dystonia (LD) is an isolated focal dystonia causing involuntary spasms in the laryngeal muscles that selectively impair speech production. LD is characterized as a functional and structural neural network disorder; however, the mechanistic aspects of network dysfunction in dystonia remain unknown.OBJECTIVEWe hypothesized that iron-induced abnormal metabolic processes may underlie microstructural neuronal damage, contributing to altered neural activity within the dystonic network and, subsequently, the development of the dystonic state.METHODSWe used 7 Tesla magnetic resonance imaging (MRI) at ultra-high field resolution for quantitative susceptibility mapping (QSM) of iron content, multi-echo multi-band resting-state functional MRI (fMRI) of brain activity and functional connectivity, positron emission tomography with [11C]flumazenil radioligand of GABAA neuroreceptor availability, and immunohistochemistry of postmortem brain tissue to investigate iron metabolism in LD patients and healthy controls.RESULTSThe QSM analysis found increased iron content in primary sensorimotor and premotor cortices, inferior frontal, middle frontal, and middle temporal gyri, middle cingulate cortex, superior and inferior parietal lobules, insula, putamen, and cerebellum. Histopathology substantiated the neuroimaging findings by showing focal clusters of iron precipitates in these regions. Increased iron content in the supplementary motor area and middle cingulate cortex was associated with altered neural activity, while increased iron in the middle cingulate cortex, premotor cortex, and putamen had associations with GABAA receptor availability in LD patients.CONCLUSIONAbnormal iron accumulations are likely to contribute to the imbalance of excitatory and inhibitory signaling within the dystonic neural network, leading to altered network dynamics that ultimately contribute to LD development. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"53 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982453","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":"Development and Preliminary Validation of a Parkinsonism-Dystonia Scale for Infants and Young Children.","authors":"Roser Pons,Toni S Pearson,Belen Perez-Dueñas,Angels Garcia-Cazorla,Manju A Kurian,Zoi Dalivigka,Vasiliki Zouvelou,Chrysa Outsika,Eleftheria Kokkinou,Maria Sigatullina-Bondarenko,Alejandra Darling,Maria Del Mar O'Callaghan,Robert Spaull,Dora B D Steel,Evdokia Salamou,Maria João Forjaz,Carmen Rodriguez-Blazquez","doi":"10.1002/mds.30219","DOIUrl":"https://doi.org/10.1002/mds.30219","url":null,"abstract":"BACKGROUNDParkinsonism in infancy is rare and is highly correlated with the presence of dystonia. Advances in treating and characterizing developmental and infantile degenerative parkinsonism have highlighted the need for a specialized assessment scale.OBJECTIVEThe aim of this study was to design and validate a scale that effectively assesses parkinsonism-dystonia in early life.METHODSThe Infantile Parkinsonism-Dystonia Rating Scale (IPDRS) was designed to capture the key clinical features of parkinsonism-dystonia in early life. It consists of 28 items across three subscales: Non-motor symptoms, Motor symptoms, and Dyskinesias. Thirty-two patients with hypokinetic movement disorder were scored following a standardized protocol. Filmed motor examinations were analyzed independently by three pediatric movement disorders specialists to evaluate interrater reliability. Twenty additional patients with primary neurotransmitter disorders were scored, and nine of them were evaluated at baseline and after treatment. Psychometric validation was conducted.RESULTSA total of 52 patients were scored using the IPDRS. Mean age was 3.1 years (standard deviation [SD]: 2.0), and the mean IPDRS score was 40.8 (SD: 13.17). Internal consistency analysis demonstrated a Cronbach's α of 0.21 for Non-motor symptoms subscale, 0.84 for Motor symptoms subscale, and 0.95 for Dyskinesia subscale. Kappa indexes exceeded 0.70 in seven items. Correlation coefficients for dystonia items with the Barry-Albright-Dystonia Scale ranged from 0.46 to 0.64. After treatment, all IPDRS scores changed significantly, with an effect size of 2.42.CONCLUSIONSThe IPDRS appears to be a reliable and valid tool for assessing parkinsonism in early life. Further validation studies with a larger sample size are needed to confirm these findings and complete the validation process. © 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":"2 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945247","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}