Movement Disorders最新文献

{"title":"Global Inequities in Carbidopa-Levodopa Access: A Call to Action Beyond Sub-Saharan Africa","authors":"Sajid Hameed MBBS, FCPS","doi":"10.1002/mds.70002","DOIUrl":"10.1002/mds.70002","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 9","pages":""},"PeriodicalIF":7.6,"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":"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":"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":"Reply to: “Toward Refining and Unifying the Evaluation of Temporal Dimensions in Dystonia and Other Movement Disorders”","authors":"Alberto Albanese MD,&nbsp;Kailash P. Bhatia MD, DM, FRCP,&nbsp;Victor S.C. Fung PhD, FRACP,&nbsp;Mark Hallett MD,&nbsp;Joseph Jankovic MD,&nbsp;Christine Klein MD,&nbsp;Joachim K. Krauss MD,&nbsp;Anthony E. Lang MD, FRCPC,&nbsp;Jonathan W. Mink MD, PhD,&nbsp;Sanjay Pandey DM,&nbsp;Jan K. Teller MA, PhD,&nbsp;Marina A.J. Tijssen MD,&nbsp;Marie Vidailhet MD,&nbsp;H.A. Jinnah MD, PhD","doi":"10.1002/mds.30304","DOIUrl":"10.1002/mds.30304","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 9","pages":"2021-2022"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","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":"Toward Refining and Unifying the Evaluation of Temporal Dimensions in Dystonia and Other Movement Disorders","authors":"Ali Shalash MD, PhD","doi":"10.1002/mds.30303","DOIUrl":"10.1002/mds.30303","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 9","pages":"2019-2020"},"PeriodicalIF":7.6,"publicationDate":"2025-08-01","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":"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":"Reply to: “Juvenile Dystonia Associated with Heterozygous Missense Variant in KCNJ10”","authors":"Xiaojun Huang MD,&nbsp;Li Cao MD, PhD","doi":"10.1002/mds.30301","DOIUrl":"10.1002/mds.30301","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 8","pages":"1750-1751"},"PeriodicalIF":7.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755604","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 MD, PhD,&nbsp;Sara C.B. Casagrande MD, PhD,&nbsp;Matheus A. Castro MD,&nbsp;André Pessoa MD, PhD,&nbsp;Cleonisio Leite Rodrigues MD,&nbsp;Laura Silveira Moriyama MD, PhD,&nbsp;Fernando Kok MD, PhD,&nbsp;Paulo Ribeiro Nóbrega MD, PhD","doi":"10.1002/mds.30298","DOIUrl":"10.1002/mds.30298","url":null,"abstract":"&lt;p&gt;We have read with interest the report by Huang et al describing pathogenic monoallelic variants in the &lt;i&gt;KCNJ10&lt;/i&gt; gene associated with paroxysmal kinesigenic dyskinesia (PKD).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Here, we report on an individual with segmental dystonia and a pathogenic variant in &lt;i&gt;KCNJ10&lt;/i&gt;, potentially expanding the phenotypic spectrum.&lt;/p&gt;&lt;p&gt;The proband is a 16-year-old boy without a significant past medical history. Around age 14, he developed involuntary right-hand movements. On examination, there is dystonic posturing of the right hand with wrist flexion, intermittent closure of the fingers, and thumb extension. There are mild dystonic features elsewhere, including mild dystonic posturing of the shoulders and mouth. There was no reported paroxysmal worsening; repeated kinesigenic provocative maneuvers performed in the office were negative (knee-high stress test) (Video 1). The remainder of the neurological examination was normal, including cognition, hearing, and cerebellar function. MR and magnetic resonance angiography (MRA) imaging of the brain were unremarkable. Electromyography (EMG) demonstrated dystonic muscular activity, with co-contraction of wrist flexors and extensors and intrinsic hand muscles, worsening during a writing task. Family history was notable for generalized anxiety and borderline personality in his father; mother is healthy. He has a younger sister with attention-deficit disorder. Laboratory work-up did not demonstrate electrolyte abnormalities. A treatment trial with levodopa was unsuccessful. Exome sequencing performed in a clinical diagnostic laboratory identified a heterozygous pathogenic variant in &lt;i&gt;KCNJ10&lt;/i&gt;: NM_002241:c.596G&gt;A, p.Arg199Gln. This variant has been previously reported in the context of paroxysmal dyskinesia and has a functional study determining deleterious impact in protein function.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; After diagnosis, carbamazepine was trialed but unsuccessful. We were not able to genotype his parents to determine whether it was inherited or occurred “de novo”.&lt;/p&gt;&lt;p&gt;The &lt;i&gt;KCNJ10&lt;/i&gt; gene encodes the Kir4.1 inwardly rectifying potassium channel, which is important for glial function, control of neuronal excitability, and systemic potassium homeostasis.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In the cases described thus far with &lt;i&gt;KCNJ10&lt;/i&gt; monoallelic pathogenic variants, the clinical presentation consisted of brief attacks (&lt;10 seconds in most) with predominant dystonic posturing, often affecting the face and/or limbs.&lt;span&gt;&lt;sup&gt;1, 2, 4, 5&lt;/sup&gt;&lt;/span&gt; The condition has variable penetrance and good response to carbamazepine.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Previously, biallelic loss-of-function variants in &lt;i&gt;KCNJ10&lt;/i&gt; had been associated with SESAME syndrome (OMIM # 612780), which combines seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance due to renal tubulopathy.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Notably, in some reported individuals with SESAME sy","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 8","pages":"1748-1749"},"PeriodicalIF":7.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30298","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}