Dystonia最新文献_第2页

Cerebellar dysfunction in rodent models with dystonia, tremor, and ataxia 肌张力障碍、震颤和共济失调啮齿动物模型的小脑功能障碍

Dystonia Pub Date : 2023-12-08 DOI: 10.3389/dyst.2023.11515

Meike E. van der Heijden, R. Sillitoe

引用次数: 0

A mini-review of the pathophysiology of task-specific tremor: insights from electrophysiological and neuroimaging findings 任务特异性震颤的病理生理学综述:来自电生理和神经影像学发现的见解

Dystonia Pub Date : 2023-11-07 DOI: 10.3389/dyst.2023.11347

Yih-Chih Jacinta Kuo, Kai-Hsiang Stanley Chen

{"title":"A mini-review of the pathophysiology of task-specific tremor: insights from electrophysiological and neuroimaging findings","authors":"Yih-Chih Jacinta Kuo, Kai-Hsiang Stanley Chen","doi":"10.3389/dyst.2023.11347","DOIUrl":"https://doi.org/10.3389/dyst.2023.11347","url":null,"abstract":"Task-specific tremor (TST) is a specific type of tremor that occurs when performing or attempting to perform a specific task, such as writing or playing a musical instrument. The clinical entity of TST remains heterogeneous. Some TSTs can only be induced by conducting a specific task, while others can be elicited when adopting a particular position simulating a task. The pathophysiology of TST is controversial. Whether TST is an isolated tremor syndrome, a spectrum of dystonic tremor syndrome (DTS), or essential tremor (ET) is not yet clear. Evidence from electrophysiological studies suggests that TST patients have normal reciprocal inhibition responses but abnormal motor cortical excitability, especially relating to the maladaptive long-interval intracortical inhibitory circuitry. The blink recovery study and eyeblink classical conditioning studies demonstrated possible hyperexcitability of the brainstem circuits and cerebellar dysfunction in patients with TST. Functional MRI studies have further shown that patients with TST have reduced functional connectivity in the cerebellum, similar to patients with DTS and ET. Due to variable methodologies and the sparsity of functional MRI studies in TST, it remains uncertain if patients with TST share the connectivity abnormalities between the cortical or subcortical areas that have been demonstrated in patients with DTS. Comprehensive electrophysiological and functional neuroimaging studies may help to elucidate the pathophysiology of TST.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"37 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135476615","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

Transcriptional regulatory network for neuron-glia interactions and its implication for DYT6 dystonia 神经元-胶质细胞相互作用的转录调控网络及其对DYT6肌张力障碍的影响

Dystonia Pub Date : 2023-10-30 DOI: 10.3389/dyst.2023.11796

Dhananjay Yellajoshyula

{"title":"Transcriptional regulatory network for neuron-glia interactions and its implication for DYT6 dystonia","authors":"Dhananjay Yellajoshyula","doi":"10.3389/dyst.2023.11796","DOIUrl":"https://doi.org/10.3389/dyst.2023.11796","url":null,"abstract":"Advances in sequencing technologies have identified novel genes associated with inherited forms of dystonia, providing valuable insights into its genetic basis and revealing diverse genetic pathways and mechanisms involved in its pathophysiology. Since identifying genetic variation in the transcription factor coding THAP1 gene linked to isolated dystonia, numerous investigations have employed transcriptomic studies in DYT-THAP1 models to uncover pathogenic molecular mechanisms underlying dystonia. This review examines key findings from transcriptomic studies conducted on in vivo and in vitro DYT-THAP1 models, which demonstrate that the THAP1-regulated transcriptome is diverse and cell-specific, yet it is bound and co-regulated by a common set of proteins. Prominent among its functions, THAP1 and its co-regulatory network target molecular pathways critical for generating myelinating oligodendrocytes that ensheath axons and generate white matter in the central nervous system. Several lines of investigation have demonstrated the importance of myelination and oligodendrogenesis in motor function during development and in adults, emphasizing the non-cell autonomous contributions of glial cells to neural circuits involved in motor function. Further research on the role of myelin abnormalities in motor deficits in DYT6 models will enhance our understanding of axon-glia interactions in dystonia pathophysiology and provide potential therapeutic interventions targeting these pathways.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102305","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

Non-motor symptoms in dystonia: from diagnosis to treatment 肌张力障碍的非运动症状:从诊断到治疗

Dystonia Pub Date : 2023-10-24 DOI: 10.3389/dyst.2023.11860

Kathryn J. Peall, Brian D. Berman, Norbert Bruggemann, Giovanni Defazio, Hortensia Gimeno, H. A. Jinnah, Joel S. Perlmutter, Sarah E. Pirio Richardson, Emmanuel Roze, Anette Schrag, Michele Tinazzi, Marie Vidailhet, Aparna Wagle Shukla, Yulia Worbe, Jan K. Teller, Davide Martino

{"title":"Non-motor symptoms in dystonia: from diagnosis to treatment","authors":"Kathryn J. Peall, Brian D. Berman, Norbert Bruggemann, Giovanni Defazio, Hortensia Gimeno, H. A. Jinnah, Joel S. Perlmutter, Sarah E. Pirio Richardson, Emmanuel Roze, Anette Schrag, Michele Tinazzi, Marie Vidailhet, Aparna Wagle Shukla, Yulia Worbe, Jan K. Teller, Davide Martino","doi":"10.3389/dyst.2023.11860","DOIUrl":"https://doi.org/10.3389/dyst.2023.11860","url":null,"abstract":"The Dystonia Medical Research Foundation organized an expert virtual workshop in March 2023 to review the evidence on non-motor symptoms across the spectrum of dystonia, discuss existing assessment methods, need for their harmonisation and roadmap to achieve this, and evaluate potential treatment approaches. Albeit the most investigated non-motor domains, experts highlighted the need to identify the most accurate screening procedure for depression and anxiety, clarify their mechanistic origin and quantify their response to already available therapies. Future exploration of sleep disruption in dystonia should include determining the accuracy and feasibility of wearable devices, understanding the contribution of psychotropic medication to its occurrence, and defining the interaction between maladaptive plasticity and abnormal sleep patterns. Despite recent advances in the assessment of pain in dystonia, more research is needed to elucidate the relative importance of different mechanisms called into play to explain this impactful sensory feature and the most appropriate treatments. Amongst the different non-motor features investigated in dystonia, cognitive dysfunction and fatigue require an in-depth observation to evaluate their functional impact, their clinical profile and assessment methods and, in the case of cognition, whether impairment represents a prodrome of dementia. Finally, experts identified the development and field validation of a self-rated screening tool encompassing the full spectrum of non-motor symptoms as the most urgent step towards incorporating the management of these features into routine clinical practice.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"7 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135266082","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

Functional imaging of deep brain stimulation in dystonia: a review 深部脑刺激治疗肌张力障碍的功能影像学研究进展

Dystonia Pub Date : 2023-10-06 DOI: 10.3389/dyst.2023.11440

Ian O. Bledsoe, Melanie A. Morrison

{"title":"Functional imaging of deep brain stimulation in dystonia: a review","authors":"Ian O. Bledsoe, Melanie A. Morrison","doi":"10.3389/dyst.2023.11440","DOIUrl":"https://doi.org/10.3389/dyst.2023.11440","url":null,"abstract":"Much remains to be learned about the mechanism of benefit of deep brain stimulation in movement disorders in general and dystonia specifically. A full accounting of the pathophysiology of dystonia additionally remains unclear. Given its ability to evaluate whole-brain network changes, functional neuroimaging is an important tool to advance understanding of the effects of deep brain stimulation, which in turn could offer insight into the pathophysiology of dystonia and suggest novel deep brain stimulation targets for the disorder. This review surveys the published literature of functional neuroimaging studies evaluating deep brain stimulation effects in dystonia, including PET, SPECT, and functional MRI studies. To date, study cohorts have been relatively small, though several general patterns emerge when studies are viewed collectively, including reduced functional activation patterns with stimulation turned on during motor tasks, particularly in frontal cortical regions. During rest with stimulation on, several studies showed areas of relatively decreased perfusion only in those participants who experienced clinical benefit from deep brain stimulation. Future research may benefit from larger cohorts with more homogeneous forms of dystonia, potentially enabled by multi-center initiatives. Additional benefits may result from more detailed longitudinal assessments and greater use of functional MRI, with study designs that take into account the technical limitations of this modality in the context of movement disorders and deep brain stimulation.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135345562","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

The role of protein kinase R in dystonia 蛋白激酶R在肌张力障碍中的作用

Dystonia Pub Date : 2023-09-22 DOI: 10.3389/dyst.2023.11718

Benjamin Dodd, Stephanie L. Moon

{"title":"The role of protein kinase R in dystonia","authors":"Benjamin Dodd, Stephanie L. Moon","doi":"10.3389/dyst.2023.11718","DOIUrl":"https://doi.org/10.3389/dyst.2023.11718","url":null,"abstract":"Dystonia is a progressive neurological motor disease with few treatment options and no cure. This review synthesizes the results of recent studies that implicate protein kinase R in mediating the molecular mechanisms of dystonia pathogenesis. Mutations in the PKR gene EIF2AK2 and the PKR activator protein PACT are associated with early-onset generalized dystonia. Protein kinase R (PKR) is important for neuronal function. Genetic depletion or inhibition of PKR is associated with increased long-term potentiation and memory, while also causing neuronal hyper-excitability and seizures in mouse models. PKR also senses double stranded RNA within cells and activates the integrated stress response (ISR). The ISR is a conserved signaling pathway that hinges on controlled translational suppression to remodel gene expression during stress. When PKR is activated through binding double stranded RNA or the PKR activator protein PACT, PKR dimerizes, autophosphorylates, and phosphorylates the translation initiation factor eIF2. Translation suppression by p-eIF2 causes stress granule formation and the upregulation of stress-induced genes. The ISR is thought to drive cellular resilience during acute stress. However, chronic ISR activation is associated with neurological diseases, traumatic brain injury, and aging. Neurodevelopmental and neurodegenerative diseases are associated with mutations in other integrated stress response genes, suggesting a critical role for ISR regulation in neuronal health. A growing body of work suggests the ISR is also dysfunctional in dystonia. Future research investigating the molecular mechanisms of the ISR in dystonia will likely reveal therapeutic targets and treatment strategies for this currently incurable disease.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136061112","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

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