Dystonia最新文献

{"title":"Effort to differentiate essential tremor plus and dystonic tremor using whole exome sequencing: an exploratory study","authors":"Sanjay Pandey, Navneesh Yadav, Shreya Dinesh, Chandra Shekhar Rawat, B. K. Thelma","doi":"10.3389/dyst.2024.13181","DOIUrl":"https://doi.org/10.3389/dyst.2024.13181","url":null,"abstract":"The clinical differentiation between essential tremor plus (ETP) and dystonic tremor (DT) is challenging. This study aimed at the genetic diagnosis of ETP and DT.Whole exome sequencing was performed on 50 probands (ETP = 25; DT = 25) and analysed to identify variants in known genes linked with dystonia and essential tremor plus phenotypes.We identified pathogenic/likely pathogenic variants [THAP1 (n = 1) and ANO3 (n = 1)] in two patients with DT. In addition, one DT patient had a variant of uncertain significance in FUS and four patients had benign variants [CIZ1 (n = 1), COL6A3 (n = 1), GCH1 (n = 1), TENM4 (n = 1)]. One patient with ETP was detected to have a variant of uncertain significance in TENM4 and five patients with ETP had benign variants [COL6A3 (n = 2), VPS16 (n = 1), TAF1 (n = 1), KMT2B (n = 1)].Genetic studies may be in an important biomarker in differentiating patients with ET plus from DT which is challenging in a clinical setting.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141802838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of GNAL linked dystonia","authors":"M. Moehle","doi":"10.3389/dyst.2024.12079","DOIUrl":"https://doi.org/10.3389/dyst.2024.12079","url":null,"abstract":"Mutations in the GNAL gene, encoding Gαolf, are causative for an adult-onset, isolated dystonia that may provide unique insights into the etiology of adult-onset idiopathic dystonia. Gαolf is an alpha subunit of heterotrimeric G protein that replaces Gαs in the striatum and has unique expression patterns outside of the striatum. Gαolf additionally has defined molecular functions in GPCR signaling. These defined molecular pathways and expression pathways point to defined circuit deficits underlying the causes of this adult-onset dystonia that may provide additional insights into broader idiopathic dystonia. Here, we will review the available evidence for normal Gαolf function, and how this is corrupted by GNAL mutations to cause dystonia. Thes include the molecular signaling and expression profiles of Gαolf and the other G proteins, β2γ7, complexedwith it., Additionally, we will discuss the circuits that Gαolf influences, and how GNAL mutations may reorganize these circuits to cause dystonia.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":" 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140995127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Striatal cholinergic interneuron development in models of DYT1 dystonia","authors":"Lauren N. Miterko-Myers","doi":"10.3389/dyst.2024.12413","DOIUrl":"https://doi.org/10.3389/dyst.2024.12413","url":null,"abstract":"Dystonia is a neurodevelopmental disorder characterized by severe involuntary twisting movements, hypothesized to arise from a dysfunctional motor network involving the cortex, basal ganglia, and cerebellum. Within this network, striatal cholinergic interneurons have been identified as possible contributors to dystonia pathophysiology. However, little is known about striatal cholinergic interneuron development in the mammalian brain, limiting our understanding of its role in dystonia and therapeutic potential. Here, I review striatal cholinergic interneuron development in the context of early-onset DYT1 (or “DYT-TOR1A”) dystonia. I discuss clinical and laboratory research findings that support cholinergic dysfunction in DYT1 dystonia and the implications of abnormal cholinergic cell development on disease penetrance and striatal connectivity.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":"107 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141017424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tremor in cervical dystonia","authors":"S. Beylergil, Krishna Nikhil Mukunda, Mohamed Elkasaby, J. Perlmutter, Stewart Factor, Tobias Bäumer, Jeanne Feurestein, E. Shelton, Steven Bellows, Joseph Jankovic, Abhimanyu Mahajan, Tila Wamer-Rosen, Stephen G. Reich, A. Wagle Shukla, Irene Malaty, Alberto Espay, Kevin Duque, M. LeDoux, Rachel Saunders-Pullman, Katherine Leaver, Samuel Frank, Alexander Pantelyat, Victor Fung, S. Pirio Richardson, Brian Berman, Natividad Stover, Andres Deik, William Ondo, Christopher Groth, H. A. Jinnah, A. Shaikh","doi":"10.3389/dyst.2024.11309","DOIUrl":"https://doi.org/10.3389/dyst.2024.11309","url":null,"abstract":"Background: Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources.Methods: We analyzed the largest cohort of CD patients (n = 3117) available to date, collected from 37 movement disorder centers in North America, Europe, and Asia. We used machine learning to determine what clinical features from clinician reports predicted the presence of tremor as well as its regular or irregular appearance.Results: Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was interpreted as irregular in 1,022, regular in 345, and mixed (both irregular and regular) in 442. A feature importance analysis determined that greater severity of CD, longer disease duration, and older age, in descending order, predicted the presence of neck tremor. The probability of neck tremor was reduced if the dystonia affected other body parts in addition to the neck. We also found a significantly heightened risk for developing neck tremor in women. An additional feature importance analysis indicated that increased severity of dystonia affecting other body parts, severity of CD, and prolonged disease duration was associated with a lower likelihood of regular neck tremor while increased age predicted a higher likelihood.Conclusion: Machine learning recognized the most relevant clinical features that can predict concurrent neck tremor and its irregularity in a large multi-center dystonia cohort. These results may facilitate a more accurate description of neck tremor and improved care path in CD.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":" 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140218810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical developmental periods of vulnerability in dystonia","authors":"Simon A. Lowe","doi":"10.3389/dyst.2024.12125","DOIUrl":"https://doi.org/10.3389/dyst.2024.12125","url":null,"abstract":"Dystonia is a heterogenous movement disorder characterised by involuntary muscle contractions, leading to abnormal postures and movements. Despite being the third most common movement disorder, the pathophysiological mechanisms causing dystonia are incompletely understood. Isolated dystonia is often caused by pathogenic mutations in single genes. An emerging body of evidence suggests that at least some forms of isolated dystonia have a strong developmental component, with pathogenic effects acting within discrete periods of increased vulnerability during neurodevelopment. The extent to which this is a common feature of genetically distinct forms of dystonia, and which developmental mechanisms might be disrupted during these periods, remains unclear. During critical periods of development, neuronal activity is instructive in the maturation of neuronal circuits, and inappropriate levels of activity during this period can lead to permanent defects. This review, with an intentional focus on our work, outlines evidence implicating disruptions to neuronal activity during critical developmental periods as a potential mechanism underlying inherited motor disorders in general, and dystonia in particular.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":"25 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140247418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-motor symptoms in patients with isolated dystonia: comparison between the age of onset","authors":"Yifan Zhou, Lingbing Wang, Hongxia Li, Yiwen Wu","doi":"10.3389/dyst.2024.11468","DOIUrl":"https://doi.org/10.3389/dyst.2024.11468","url":null,"abstract":"Background: The etiology and motor presentation differs between pediatric- and adult-onset dystonia. Emerging evidence has demonstrated that non-motor symptoms are frequent in adult dystonia, which affect the quality of life. By contrast, little is known about the frequency and severity of such presentations in pediatric-onset individuals. Here, we investigated the motor and non-motor symptoms in a large cohort of Chinese patients with isolated dystonia and compared between pediatric-onset and adult-onset groups.Methods: In this retrospective study, 34 pediatric-onset patients and 197 adult-onset patients with isolated dystonia were recruited. Motor impairment was assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Non-motor symptoms were evaluated through several validated scales, including fatigue (by Fatigue Severity Scale, FSS), excessive daytime sleepiness (by Epworth Sleepiness Scale, ESS), sleep disturbance (by Pittsburgh Sleep Quality Index, PSQI), anxiety (by Beck Anxiety Inventory, BAI) and depression (by Beck Depression Inventory 21, BDI-21).Results: Generalized dystonia was more common in pediatric-onset patients and focal dystonia was more common in adult-onset patients (p < 0.001). Generally, the BFMDRS score in total pediatric-onset group was higher than adult-onset group (p = 0.002). No differences was found in BFMDRS score between pediatric-onset and adult-onset patients with cervical and multifocal subtype dystonia. Compared with adult-onset group, pediatric-onset group had a lower rate of sleep disturbance (p < 0.0001) and similar rates of fatigue, excessive daytime sleepiness, depression and anxiety. Logistic regression analysis on patients with cervical dystonia indicated that the adult-onset and motor severity were independently associated with increased odds of sleep disturbance (p = 0.03) and depression (p = 0.01), respectively.Conclusion: Pediatric-onset dystonia patients were less likely to display focal dystonia. Most non-motor symptoms in pediatric-onset patients were comparable to their adult-onset counterparts. Non-motor presentations may to some extent correlate with motor symptoms, but their underlying pathophysiology need to be investigated further.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":" 95","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139787959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REEP4 variant analysis in blepharospasm and other neurological disorders","authors":"Samira Saeirad, Mark S LeDoux","doi":"10.3389/dyst.2024.12016","DOIUrl":"https://doi.org/10.3389/dyst.2024.12016","url":null,"abstract":"Introduction: In preceding work, a deleterious REEP4 variant [GRCh38/hg38, NC_000008.11:g.22140245G>A, NM_025232.4:c.109C>T, p.Arg37Trp] was found to co-segregate with blepharospasm (BSP) in a large African-American pedigree. Other REEP4 variants have been reported in genetic screening studies of dystonia. The REEP4 paralogs, REEP1 and REEP2, are associated with spastic paraplegia. The causal contributions of REEP4 variants to dystonia and other neurological disorders remains indecisive.Methods: Sanger sequencing was used to screen subjects (N = 307) with BSP and BSP-plus dystonia affecting additional anatomical segments (BSP+) phenotypes for variants in REEP4. In silico tools were used to examine the deleteriousness of reported (ClinVar) and previously published REEP4 variants.Results: No highly deleterious variant was identified in coding or contiguous splice site regions of REEP4 in our cohort of 307 subjects. In silico analysis identified numerous deleterious REEP4 variants in published screening studies of dystonia and several highly deleterious single nucleotide REEP4 variants in ClinVar.Conclusion: Highly deleterious REEP4 variants are rare in BSP and BSP+ phenotypes.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":" 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139793342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REEP4 variant analysis in blepharospasm and other neurological disorders","authors":"Samira Saeirad, Mark S LeDoux","doi":"10.3389/dyst.2024.12016","DOIUrl":"https://doi.org/10.3389/dyst.2024.12016","url":null,"abstract":"Introduction: In preceding work, a deleterious REEP4 variant [GRCh38/hg38, NC_000008.11:g.22140245G>A, NM_025232.4:c.109C>T, p.Arg37Trp] was found to co-segregate with blepharospasm (BSP) in a large African-American pedigree. Other REEP4 variants have been reported in genetic screening studies of dystonia. The REEP4 paralogs, REEP1 and REEP2, are associated with spastic paraplegia. The causal contributions of REEP4 variants to dystonia and other neurological disorders remains indecisive.Methods: Sanger sequencing was used to screen subjects (N = 307) with BSP and BSP-plus dystonia affecting additional anatomical segments (BSP+) phenotypes for variants in REEP4. In silico tools were used to examine the deleteriousness of reported (ClinVar) and previously published REEP4 variants.Results: No highly deleterious variant was identified in coding or contiguous splice site regions of REEP4 in our cohort of 307 subjects. In silico analysis identified numerous deleterious REEP4 variants in published screening studies of dystonia and several highly deleterious single nucleotide REEP4 variants in ClinVar.Conclusion: Highly deleterious REEP4 variants are rare in BSP and BSP+ phenotypes.","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139853406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Exploring dystonia symptoms through animal models and patient studies","authors":"Cécile Gallea, Daniela Popa","doi":"10.3389/dyst.2023.12554","DOIUrl":"https://doi.org/10.3389/dyst.2023.12554","url":null,"abstract":"","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139827994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Exploring dystonia symptoms through animal models and patient studies","authors":"Cécile Gallea, Daniela Popa","doi":"10.3389/dyst.2023.12554","DOIUrl":"https://doi.org/10.3389/dyst.2023.12554","url":null,"abstract":"","PeriodicalId":505768,"journal":{"name":"Dystonia","volume":"70 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139888209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}