Dystonia最新文献_第3页

Editorial: Models, mechanisms, and maturation in developmental dystonia 社论：发育性肌张力障碍的模型、机制和成熟

Dystonia Pub Date : 2023-09-11 DOI: 10.3389/dyst.2023.11922

Jason S. Gill, Meike E. van der Heijden, A. Shaikh, R. Sillitoe

引用次数: 0

Disrupted sleep in dystonia depends on cerebellar function but not motor symptoms in mice 在小鼠中，肌张力障碍的睡眠中断取决于小脑功能，而不是运动症状

Dystonia Pub Date : 2023-08-24 DOI: 10.3389/dyst.2023.11487

Luis E. Salazar Leon, Roy V. Sillitoe

{"title":"Disrupted sleep in dystonia depends on cerebellar function but not motor symptoms in mice","authors":"Luis E. Salazar Leon, Roy V. Sillitoe","doi":"10.3389/dyst.2023.11487","DOIUrl":"https://doi.org/10.3389/dyst.2023.11487","url":null,"abstract":"Although dystonia is the third most common movement disorder, patients often also experience debilitating nonmotor defects including impaired sleep. The cerebellum is a central component of a “dystonia network” that plays various roles in sleep regulation. Importantly, the primary driver of sleep impairments in dystonia remains poorly understood. The cerebellum, along with other nodes in the motor circuit, could disrupt sleep. However, it is unclear how the cerebellum might alter sleep and mobility. To disentangle the impact of cerebellar dysfunction on motion and sleep, we generated two mouse genetic models of dystonia that have overlapping cerebellar circuit miswiring but show differing motor phenotype severity: Ptf1a Cre ; Vglut2 fx/fx and Pdx1 Cre ; Vglut2 fx/fx mice. In both models, excitatory climbing fiber to Purkinje cell neurotransmission is blocked, but only the Ptf1a Cre ; Vglut2 fx/fx mice have severe twisting. Using in vivo ECoG and EMG recordings we found that both mutants spend greater time awake and in NREM sleep at the expense of REM sleep. The increase in awake time is driven by longer awake bouts rather than an increase in bout number. We also found a longer latency to reach REM in both mutants, which is similar to what is reported in human dystonia. We uncovered independent but parallel roles for cerebellar circuit dysfunction and motor defects in promoting sleep quality versus posture impairments in dystonia.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135420542","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}

引用次数: 0

Transcranial magnetic stimulation: the road to clinical therapy for dystonia 经颅磁刺激:肌张力障碍的临床治疗之路

Dystonia Pub Date : 2023-08-16 DOI: 10.3389/dyst.2023.11660

Patrick J. Mulcahey, Angel V. Peterchev, Nicole Calakos, Noreen Bukhari-Parlakturk

引用次数: 0

Spinal dystonia and other spinal movement disorders 脊柱肌张力障碍和其他脊柱运动障碍

Dystonia Pub Date : 2023-08-16 DOI: 10.3389/dyst.2023.11303

Shlok Sarin, Temitope Lawal, H. Abboud

引用次数: 0

Bradykinesia and dystonia 运动迟缓和肌张力障碍

Dystonia Pub Date : 2023-08-08 DOI: 10.3389/dyst.2023.11448

G. Paparella, A. Guerra, S. Galosi, A. Cannavacciuolo, Luca Angelini, Traian Popa, A. Berardelli, M. Bologna

{"title":"Bradykinesia and dystonia","authors":"G. Paparella, A. Guerra, S. Galosi, A. Cannavacciuolo, Luca Angelini, Traian Popa, A. Berardelli, M. Bologna","doi":"10.3389/dyst.2023.11448","DOIUrl":"https://doi.org/10.3389/dyst.2023.11448","url":null,"abstract":"Background: Bradykinesia has been reported in patients with dystonia. Despite this, the pathophysiological mechanisms of bradykinesia in dystonia remain largely unknown.Methods: We here performed a comprehensive literature search and reviewed clinical and experimental studies on bradykinesia in patients with dystonia.Results: Many studies have documented the presence of bradykinesia in patients with idiopathic and inherited isolated dystonia, regardless of the presence of parkinsonism. In addition, bradykinesia has been observed as a side effect in dystonic patients who have undergone deep brain stimulation, in those with functional dystonia as well as in those with combined dystonia, e.g., dystonia-parkinsonism. These clinical and experimental findings support the hypothesis that dysfunction in a brain network involving the basal ganglia, primary sensorimotor cortex, and cerebellum may play a key role in the pathophysiology of both bradykinesia and dystonia.Conclusion: Bradykinesia is frequently observed in dystonia. We may gain insights into the pathophysiological underpinnings of two distinct movement disorders by investigating this issue. Furthermore, a deeper understanding of bradykinesia in dystonia may have terminological implications in this field.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48434823","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}

引用次数: 2

Deconstructing motor and non-motor aspects of dystonia with neuroimaging 用神经影像学分析肌张力障碍的运动和非运动方面

Dystonia Pub Date : 2023-07-13 DOI: 10.3389/dyst.2023.11526

A. Mahajan

引用次数: 0

Dystonia Pub Date : 2023-02-23 DOI: 10.3389/dyst.2023.11117

M. Kasiri, Sina Javadzadeh, Jaya Nataraj, Seyyed Alireza Seyyed Mousavi, T. Sanger

{"title":"Correlated activity in globus pallidus and thalamus during voluntary reaching movement in three children with primary dystonia","authors":"M. Kasiri, Sina Javadzadeh, Jaya Nataraj, Seyyed Alireza Seyyed Mousavi, T. Sanger","doi":"10.3389/dyst.2023.11117","DOIUrl":"https://doi.org/10.3389/dyst.2023.11117","url":null,"abstract":"Classical models of the physiology of dystonia suggest that involuntary muscle contractions are caused by inappropriately low activity in Globus Pallidus internus (GPi) that fails to adequately inhibit thalamic inputs to cortex. We test this prediction in three children with primary dystonia undergoing depth electrode recording in basal ganglia and thalamus during selection of targets for deep brain stimulation (DBS) implantation. We compare muscle activity to the power in the spectrogram of the local field potential, as well as to counts of identified spikes in GPi, subthalamic nucleus (STN), and the Ventral oralis (VoaVop) and Ventral Anterior (VA) subnuclei of the thalamus, while subjects are at rest or attempting to make active voluntary arm or leg reaching movements. In all three subjects, both spectrogram power and spike activity in GPi, STN, VoaVop, and VA are significantly positively correlated with movement. In particular, GPi and STN both increase activity during attempted movement. These results contradict the classical rate model of the physiology of dystonia, and support more recent models that propose abnormalities in the detailed pattern of activity rather than the overall lumped activity of pallidum and thalamus.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47899247","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}

引用次数: 3

DYT-TOR1A genotype alters extracellular vesicle composition in murine cell model and shows potential for biomarker discovery DYT-TOR1A基因型改变小鼠细胞模型的细胞外囊泡组成，显示出发现生物标志物的潜力

Dystonia Pub Date : 2023-02-16 DOI: 10.3389/dyst.2023.11053

Connor S. King, Z. Caffall, E. Soderblom, N. Calakos

{"title":"DYT-TOR1A genotype alters extracellular vesicle composition in murine cell model and shows potential for biomarker discovery","authors":"Connor S. King, Z. Caffall, E. Soderblom, N. Calakos","doi":"10.3389/dyst.2023.11053","DOIUrl":"https://doi.org/10.3389/dyst.2023.11053","url":null,"abstract":"Introduction: Biomarkers that can be used to identify patient subgroups with shared pathophysiology and/or that can be used as pharmacodynamic readouts of disease state are valuable assets for successful clinical trial design. In translational research for brain diseases, extracellular vesicles (EVs) have become a high-priority target for biomarker discovery because of their ubiquity in peripheral biofluids and potential to indicate brain state. Materials and methods: Here, we applied unbiased quantitative proteomics of EVs isolated from DYT-TOR1A knockin mouse embryonic fibroblasts and littermate controls to discover candidates for protein biomarkers. We further examined the response of genotype perturbations to drug treatment conditions to determine their pharmacodynamic properties. Results: We found that many DYT-TOR1A MEF EV differences were significantly corrected by ritonavir, a drug recently shown to correct DYT-TOR1A phenotypes in cell and mouse disease models. We also used tool compounds to explore the effect of the integrated stress response (ISR), which regulates protein synthesis and is implicated in dystonia pathogenesis. Integrated stress response inhibition in WT cells partially phenocopied the effects of DYT-TOR1A on EV proteome composition, and ISR potentiation in DYT-TOR1A caused changes that paralleled ritonavir treatment. Conclusion: These results collectively show that DYT-TOR1A genotype alters EV protein composition, and these changes can be dynamically modulated by a candidate therapeutic drug and ISR activity state. These mouse model findings provide proof-of-concept that EVs may be a useful source of biomarkers in human populations and further suggest specific homologs to evaluate in cross-species validation.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43789194","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}

引用次数: 0

Treatment of writer’s cramp based on current pathophysiological concepts 基于当前病理生理学概念的作家痉挛的治疗

Dystonia Pub Date : 2023-02-09 DOI: 10.3389/dyst.2023.11067

K. Zeuner, A. Baumann, K. Witt

{"title":"Treatment of writer’s cramp based on current pathophysiological concepts","authors":"K. Zeuner, A. Baumann, K. Witt","doi":"10.3389/dyst.2023.11067","DOIUrl":"https://doi.org/10.3389/dyst.2023.11067","url":null,"abstract":"Task specific dystonia belongs to the group of focal dystonias. They are debilitating movement disorders that present with co-contraction of antagonist muscles during a specific task. The most common one is writer’s cramp. Botulinum toxin is the symptomatic standard treatment. Its response rate is 50% after 1 year, and the overall efficacy limited due to unwanted weakness in not injected muscles. The pathophysiology of writer’s cramp remains unclear, but genetic and additional environmental causes have been proposed. A possible underlying mechanism may be maladaptive reorganization in the sensorimotor cortex. Based on this background alternative treatment strategies were developed such as several different sensory and motor training programs that have been applied to reverse these brain abnormalities. In some studies, sensory and motor training were combined and adjunct with fitness exercises. They were conducted either as an outpatient setting or were established home based. Clinical outcome was measured with different clinical scales such as the writer’s cramp rating scale, the arm dystonia rating scale or the Burke, Fahn Marsden Scale. For objective assessment, kinematic handwriting parameters were analyzed. Functional or structural changes of the sensorimotor cortex were estimated using functional magnetic tomography, magnetencephalography and voxel-based morphometry. The results of these training programs were promising; however, one drawback is that the number of patients studied were small and the programs were not controlled since it is difficult to establish a control training to conduct a randomized controlled study.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43389272","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}

引用次数: 0

Treatment of tardive dystonia: A review 迟发性肌张力障碍的治疗：综述

Dystonia Pub Date : 2023-02-06 DOI: 10.3389/dyst.2023.10957

Paola Testini, S. Factor

引用次数: 1