Movement Disorders最新文献

{"title":"Global Inequities in Carbidopa-Levodopa Access: A Call to Action Beyond Sub-Saharan Africa.","authors":"Sajid Hameed","doi":"10.1002/mds.70002","DOIUrl":"https://doi.org/10.1002/mds.70002","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"58 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778202","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":"Loss of ANK3 Function Causes a Recessive Neurodevelopmental Disorder with Cerebellar Ataxia","authors":"Reza Maroofian, Giulia Spoto, Dalila Moualek, Maha S. Zaki, Asthik Biswas, Felice D'Arco, Sajjad Biglari, Pooneh Nikuei, Joseph G. Gleeson, Meriem Tazir, Lamia Ali Pacha, Henry Houlden","doi":"10.1002/mds.30324","DOIUrl":"https://doi.org/10.1002/mds.30324","url":null,"abstract":"Background<jats:italic>ANK3</jats:italic> encodes ankyrin‐G, a key scaffolding protein essential for neuronal function. While both monoallelic and biallelic <jats:italic>ANK3</jats:italic> variants have been linked to neurodevelopmental disorders (NDDs), existing evidence for their pathogenicity and clinical correlation remains limited and heterogeneous.ObjectiveTo delineate the clinical features associated with biallelic <jats:italic>ANK3</jats:italic> predicted loss‐of‐function (pLOF) variants.MethodsWe employed exome sequencing, Sanger validation, detailed clinical phenotyping, and extensive international data sharing to identify patients with biallelic <jats:italic>ANK3</jats:italic> variants.ResultsWe describe five individuals from three unrelated consanguineous families with segregating homozygous <jats:italic>ANK3</jats:italic> pLOF variants. These patients presented with a relatively consistent phenotype comprising developmental delay, intellectual disability, hypotonia, variable epilepsy, and cerebellar signs including ataxia, tremor, and dysarthria. Among the three patients for whom brain magnetic resonance imaging was available, cerebellar atrophy was observed, predominantly affecting the superior vermis and cerebellar hemispheres. These clinical findings align with murine models lacking the cerebellar ankyrin‐G isoform, which similarly exhibit ataxic features and high cerebellar <jats:italic>ANK3</jats:italic> expression.ConclusionOur findings support a recognizable NDD with non‐progressive cerebellar ataxia linked to biallelic <jats:italic>ANK3</jats:italic> pLOF variants. © 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":"26 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770047","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":"Reply to: “Toward Refining and Unifying the Evaluation of Temporal Dimensions in Dystonia and Other Movement Disorders”","authors":"Alberto Albanese, Kailash P. Bhatia, Victor S.C. Fung, Mark Hallett, Joseph Jankovic, Christine Klein, Joachim K. Krauss, Anthony E. Lang, Jonathan W. Mink, Sanjay Pandey, Jan K. Teller, Marina A.J. Tijssen, Marie Vidailhet, H.A. Jinnah","doi":"10.1002/mds.30304","DOIUrl":"https://doi.org/10.1002/mds.30304","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"1 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763200","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":"Deep Brain Stimulation in Children and Adolescents with ε‐Sarcoglycan Myoclonus Dystonia Causes a Sustained Improvement in Motor Functionality and Quality of Life","authors":"Ainara Salazar‐Villacorta, Ana Cazurro‐Gutiérrez, Lucy Dougherty‐de Miguel, Julia Ferrero‐Turrión, Anna Marcé‐Grau, Marta Folch‐Benito, Álvaro Lucero‐Garófano, Alfons Macaya, Antonio Moreno‐Galdó, Maria I. Vanegas, Marta Correa‐Vela, María Victoria González, Gemma Español‐Martín, Martha Loredo, Ignacio Delgado, Esther Toro‐Tamargo, Margarita Figueroa, Dolores Vilas, Manel Tardáguila, Jorge Muñoz, Lourdes Ispierto, Ramiro Álvarez, Agustí Bescós, Belén Pérez‐Dueñas","doi":"10.1002/mds.30309","DOIUrl":"https://doi.org/10.1002/mds.30309","url":null,"abstract":"BackgroundDeep brain stimulation of the globus pallidus internus (DBS‐GPi) has shown efficacy in adult patients with <jats:italic>SGCE</jats:italic>‐related myoclonus dystonia. However, evidence regarding its impact in pediatric populations is limited.ObjectivesThe aim was to evaluate motor and non‐motor outcomes following DBS‐GPi intervention in children and adolescents with <jats:italic>SGCE</jats:italic>‐MD.MethodsTen patients (mean age 12.8 ± 3.4 years) underwent DBS‐GPi. Blinded experts rated patients with the Unified Myoclonus, Burke‐Fahn‐Marsden, Writer's cramp and Gait Dystonia rating scales. Psychiatric and quality‐of‐life outcomes were evaluated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and Quality of Life in Neurological Disorders.ResultsSignificant improvements were observed in myoclonus (68.1%), generalized dystonia (63.2%), and dystonia during writing (48.1%), walking (70.3%) and running (44.2%) after 3.8 ± 2.4 years of the surgery. Psychiatric symptoms remained stable, while quality‐of‐life assessments revealed reductions in anxiety, fatigue, and stigma (<jats:italic>P</jats:italic> &lt; 0.05).ConclusionsDBS‐GPi in children with <jats:italic>SGCE</jats:italic>‐myoclonus dystonia mitigates long‐term disability, potentially enhancing academic, social, and professional prospects. © 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":"98 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763268","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 Homozygous c.74A>G Variant in PRKRA Causes DYT‐PRKRA: Extensive Familial Segregation and a Variant of Uncertain Significance (VUS) Reclassification","authors":"Fatemeh Soleymani, Fahimeh Piryaei, Arezoo Farhadi, Elham Pourbakhtyaran, Javad Behroozi","doi":"10.1002/mds.30323","DOIUrl":"https://doi.org/10.1002/mds.30323","url":null,"abstract":"BackgroundDYT‐PRKRA is a rare, autosomal recessive movement disorder caused by mutations in the <jats:italic>PRKRA</jats:italic> gene. While <jats:italic>PRKRA</jats:italic> mutations are recognized in DYT‐PRKRA, a significant number of identified variants are still classified as “variant of uncertain significance” (VUS).ObjectiveIn this study we identified a causative variant previously reported as a VUS.MethodsA 4.5‐year‐old female born to consanguineous, healthy parents presented with progressive neurodevelopmental regression, similar to two affected relatives. Whole‐exome sequencing was performed, and segregation analysis was conducted across two generations.ResultsA homozygous <jats:italic>PRKRA</jats:italic> c.74A&gt;G (p.Lys25Arg) variant co‐segregated with the DYT‐PRKRA phenotype. Unaffected family members were identified as heterozygous carriers.ConclusionsThis is the first report of DYT‐PRKRA in the Iranian population. Strong evidence from familial segregation and in silico analyses support the reclassification of this variant to likely pathogenic. This reclassification has significant implications for the diagnosis and genetic counseling of families affected by DYT‐PRKRA. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"15 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763266","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":"Toward Refining and Unifying the Evaluation of Temporal Dimensions in Dystonia and Other Movement Disorders","authors":"Ali Shalash","doi":"10.1002/mds.30303","DOIUrl":"https://doi.org/10.1002/mds.30303","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"27 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763267","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 CGG Repeat Expansion in CSNK1E Associated with Progressive Myoclonic Epilepsy with Incomplete Penetrance","authors":"Fulya Akçimen, Pilar Alvarez Jerez, Ulviyya Guliyeva, Jasmine Lee, Laksh Malik, Breeana Baker, Kamran Salayev, Sughra Guliyeva, Kimberley J. Billingsley, Henry Houlden, Andrew B. Singleton, Cornelis Blauwendraat, Sara Bandres‐Ciga, Rauan Kaiyrzhanov","doi":"10.1002/mds.30326","DOIUrl":"https://doi.org/10.1002/mds.30326","url":null,"abstract":"BackgroundProgressive myoclonic epilepsy is a heterogeneous neurodegenerative disorder characterized by early‐onset myoclonus, epilepsy, generalized tonic–clonic seizures, and progressive neurological deterioration. Recently, a CGG repeat expansion and increased <jats:italic>CSNK1E</jats:italic> DNA methylation have been shown to be associated with developmental and epileptic encephalopathies.ObjectiveTo identify structural variants or repeat expansions associated with progressive myoclonic epilepsy in an Azerbaijani family using long‐read sequencing.MethodsKnown genetic causes of progressive myoclonic epilepsy were ruled out through quadro‐exome sequencing in an individual exhibiting tonic–clonic seizures, dementia, and cerebellar ataxia with an age at onset of 10 years. After ruling out the presence of any other pathogenic mutation, long‐read whole genome sequencing was performed to investigate structural variants or repeat expansions potentially associated with the disease.ResultsWe identified a heterozygous expanded (CGG)<jats:sub>n</jats:sub> repeat in exon 1 of <jats:italic>CSNK1E</jats:italic> in the proband (longest repeat length, n = 745) and her unaffected sister (longest repeat length, n = 980). The unaffected father was wild‐type, while the unaffected mother had an intermediate‐sized repeat expansion (n = 131), which might have expanded to a pathogenic length in the siblings upon transmission. The expanded allele exhibited higher methylation levels than the wild‐type, with globally elevated methylation in both siblings compared with parental samples.ConclusionsWe suggest the association of the <jats:italic>CSNK1E</jats:italic>‐CGG expansion with incomplete penetrance in an Azerbaijani case with progressive myoclonic epilepsy, broadening its phenotypic spectrum. Our findings support the utility of long‐read sequencing and methylation analysis as powerful approaches to identifying and characterizing disease‐associated expanded repeats. © 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":"73 12 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763283","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":"Demographic and Clinical Profiles of Parkinson's Disease in India: Observations from a Nation‐Wide Multicenter Study","authors":"Asha Kishore, Rupam Borgohain, Divya Kalikavil Puthenveedu, Roopa Rajan, Pramod Kumar Pal, Rukmini‐Mridula Kandadai, Ravi Yadav, Sahil Mehta, Hrishikesh Kumar, Niraj Kumar, Prashanth Lingappa Kukkle, Soaham Desai, Kuldeep Shetty, Pettarusp Wadia, Annu Aggarwal, Pankaj Ashok Agarwal, Mirza Masoom Abbas, Syam Krishnan, Divya Madathiparambil Radhakrishnan, Gurusidheswar Mahadevappa Wali, Achal Srivastava, Nitish Kamble, Teresa Maria D′ Costa Ferreira, Vivek Lal, Ashwin Ashok Kumar Sreelatha, Luis‐Giraldo Gonzalez‐Ricardo, Manas Chacko, Manu Sharma","doi":"10.1002/mds.30310","DOIUrl":"https://doi.org/10.1002/mds.30310","url":null,"abstract":"BackgroundParkinson's disease (PD) phenotype may vary with genetic, ethno‐geographic, cultural, and environmental factors.ObjectivesThe aim was to develop a clinical database of PD in India and assess the influence of age‐at‐onset (AAO), gender, and motor subtype on the clinical profile of PD.MethodsA cross‐sectional study of PD was conducted across 18 Indian hospitals. Standardized assessments were performed by movement disorder specialists. Data were collected using uniform questionnaires during the recruitment visit. A total of 3300 age‐ and gender‐matched case–control pairs were analyzed for environmental exposures, habits, and co‐morbidities.ResultsWe recruited 7918 PD cases with a mean AAO of 54.2 ± 11.8 years and a median disease duration of 5 years (interquartile range: 2–9). Subgroup analyses based on AAO, gender, and motor phenotype revealed significant differences in motor and non‐motor symptoms, exposures, habits, and co‐morbidities. Except coffee consumption, previously known associations were observed for exposure to insecticides/pesticides/fungicides (odds ratio [OR]: 1.67), head injury (OR: 3.11), coffee consumption (OR: 1.73), diabetes (OR: 1.48), hypertension (OR: 1.73), and smoking (OR: 0.74) in the Indian population.ConclusionsThis large pan‐Indian study highlights the clinical characteristics, environmental exposures, habits, and comorbid diseases associated with PD, which were broadly similar to those observed in European populations. The earlier AAO in Indian PD patients suggests a potentially higher genetic risk, warranting further investigation. A nationwide, community‐based, epidemiological study is needed to achieve a comprehensive understanding of all risk factors for PD in India and to validate the risk factors identified in this hospital‐based study. © 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":"7 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747229","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":"Juvenile Dystonia Associated with Heterozygous Missense Variant in KCNJ10","authors":"Claudio M. de de Gusmao, Sara C.B. Casagrande, Matheus A. Castro, André Pessoa, Cleonisio Leite Rodrigues, Laura Silveira Moriyama, Fernando Kok, Paulo Ribeiro Nóbrega","doi":"10.1002/mds.30298","DOIUrl":"https://doi.org/10.1002/mds.30298","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"15 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747228","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 and Structural Characterization of LRRK2 p.V1447L in Parkinson's Disease","authors":"Neringa Pratuseviciute, Pawel Lis, Sacha Weber, Nicolas Gruchy, Lionel Arnaud, Dario R. Alessi, Esther Sammler","doi":"10.1002/mds.30284","DOIUrl":"https://doi.org/10.1002/mds.30284","url":null,"abstract":"BackgroundGain‐of‐kinase‐function variants in LRRK2 are a leading cause of monogenic Parkinson's disease (PD).ObjectivesWe tested the functional impact of a novel LRRK2 variant p.V1447L identified in a young‐onset PD patient in vivo in peripheral blood, as well as in a robust cellular assay, alongside other variants in close proximity to V1447.MethodsWe measured LRRK2‐dependent Rab10 phosphorylation in neutrophils and monocytes of a LRRK2 p.V1447L carrier with PD. We performed structural mapping and evaluated the potential impact of other LRRK2 variants at and around LRRK2 V1447.ResultsLRRK2 p.V1447L strongly increases LRRK2 kinase activity. We identified additional variants in the LRRK2 ROC:COR<jats:sub>B</jats:sub> interface with critical impact on kinase activity and demonstrated that different substitutions at the same residue can have opposing effects.ConclusionsWe recommend reclassifying LRRK2 p.V1447L from variant of uncertain significance to likely pathogenic. Our study expands the range of putative loss‐of‐kinase function variants to LRRK2 missense variants. © 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":"27 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747269","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}