Dystonia最新文献

{"title":"Laminar VASO fMRI in focal hand dystonia patients.","authors":"Laurentius Huber, Panagiotis Kassavetis, Omer Faruk Gulban, Mark Hallett, Silvina G Horovitz","doi":"10.3389/dyst.2023.10806","DOIUrl":"10.3389/dyst.2023.10806","url":null,"abstract":"<p><p>Focal Hand Dystonia (FHD) is a disabling movement disorder characterized by involuntary movements, cramps and spasms. It is associated with pathological neural microcircuits in the cortical somatosensory system. While invasive preclinical modalities allow researchers to probe specific neural microcircuits of cortical layers and columns, conventional functional magnetic resonance imaging (fMRI) cannot resolve such small neural computational units. In this study, we take advantage of recent developments in ultra-high-field MRI hardware and MR-sequences to capture altered digit representations and laminar processing in FHD patients. We aim to characterize the capability and challenges of layer-specific imaging and analysis tools in resolving laminar and columnar structures in clinical research setups. We scanned N = 4 affected and N = 5 unaffected hemispheres at 7T and found consistent results of altered neural microcircuitry in FHD patients: 1) In affected hemispheres of FHD patients, we found a breakdown of ordered finger representation in the primary somatosensory cortex, as suggested from previous low-resolution fMRI. 2) In affected primary motor cortices of FHD patients, we furthermore found increased fMRI activity in superficial cortico-cortical neural input layers (II/III), compared to relatively weaker activity in the cortico-spinal output layers (Vb/VI). Overall, we show that layer-fMRI acquisition and analysis tools have the potential to address clinically-driven neuroscience research questions about altered computational mechanisms at the spatial scales that were previously only accessible in animal models. We believe that this study paves the way for easier translation of preclinical work into clinical research in focal hand dystonia and beyond.</p>","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9284145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Bilateral globus pallidum internus DBS for treating tremor and dystonia in spinocerebellar ataxia 17: a thirteen-year follow-up.","authors":"Aparna Wagle Shukla, Shilpa Chitnis, Irene A Malaty, Pam Zeilman","doi":"10.3389/dyst.2023.11363","DOIUrl":"10.3389/dyst.2023.11363","url":null,"abstract":"<p><strong>Background: </strong>Spinocerebellar ataxia 17 (SCA17) is a rare autosomal dominant trinucleotide disorder. There are no effective therapies for addressing the clinical symptoms of SCA17.</p><p><strong>Case report: </strong>We describe a 46-year-old male who presented with symptoms of generalized dystonia and focal arm tremors manifesting during adolescence. He underwent bilateral globus pallidus (GPi) DBS surgery that led to notable improvements in dystonia and tremor symptoms, impacting his quality of life. At the time of surgery, he did not show cerebellar ataxia features; however, these began to manifest 2 years after DBS surgery. He subsequently underwent genetic testing that confirmed the SCA17 diagnosis. Currently, at 13 years of follow-up, although the ataxia has continued to worsen, DBS therapy has led to persistent improvements in dystonia, tremor, and many aspects of quality of life.</p><p><strong>Discussion: </strong>The current case indicates that DBS is a promising symptomatic therapy for dystonia and tremor in SCA17.</p>","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49192290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gait and balance in cervical dystonia and dystonic head tremor.","authors":"Aparna Wagle Shukla, Anjela Gurrala, Vinata Vedam-Mai","doi":"10.3389/dyst.2023.11231","DOIUrl":"10.3389/dyst.2023.11231","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have found gait and balance abnormalities in patients with cervical dystonia. However, the characteristics of gait and balance in cervical dystonia with head tremors have not been ascertained. A midline constant head tremor when walking would likely render gait and balance more difficult. The pathophysiology of dystonia has also been increasingly linked with cerebellar function abnormality, commonly implicated in gait and balance disorders.</p><p><strong>Methods: </strong>We examined the gait and balance characteristics of cervical dystonia presenting with head tremors. We used the timed up-and-go (TUG) walk test, 10 m walk test, Berg Balance Scale (BBS), and Gait and Freezing questionnaire. We then assessed the gait on an instrumented walkway system to capture spatiotemporal measures such as speed, cadence, step time, step length, stride width, swing%, stance%, single support%, double support%, and gait variability index (GVI). We also assessed whether the gait in dystonic tremor (DT) differed from essential tremor (ET) and orthostatic tremor (OT), as these tremor disorders share the cerebello-thalamo-cortical pathway as the common pathological pathway.</p><p><strong>Results: </strong>50 participants comprising DT (20 patients), ET (15 patients), and OT (15 patients) were enrolled. While the gait abnormalities were subclinical, 11/20 DT patients (55%) walked at a slower speed on the TUG, 11/20 (55%) had reduced scores on the BBS, 9/20 (45%) had increased step time, 4/20 (20%) had reduced step length, 4/20 (20%) had wider stride width, 9/20 (45%) spent greater time during double support and 8/20 (40%) patients had an abnormal GVI. Comparisons of DT with healthy control data revealed a slower gait velocity (<i>p</i> = 0.001) and a reduced step length (<i>p</i> = 0.001). Compared to DT, the ET group revealed a reduced cadence (<i>p</i> = 0.04) and the OT group revealed an increased TUG time (<i>p</i> = 0.03), reduced BBS scores (<i>p</i> = 0.02), reduced step length (<i>p</i> = 0.02), reduced cadence (<i>p</i> = 0.03), reduced GVI (<i>p</i> = 0.01), and increased double support phase (<i>p</i> = 0.045).</p><p><strong>Conclusion: </strong>DT is accompanied by multiple abnormalities affecting gait and balance, albeit subclinical and less pronounced than ET and OT, possibly related to more effective compensatory mechanisms. Nevertheless, these abnormalities indicate that rehabilitative measures warrant consideration when managing in clinical settings.</p>","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44311404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Video analysis of patients with blepharospasm and lower face dystonias.","authors":"Mahdieh Hosseini, Panagiotis Kassavetis, Mark Hallett","doi":"10.3389/dyst.2023.11385","DOIUrl":"10.3389/dyst.2023.11385","url":null,"abstract":"<p><strong>Background: </strong>Blepharospasm (BSP) is a focal dystonia. There is a lack of standardization in the length of time necessary to get a measure of BSP severity for rating scales.</p><p><strong>Objectives: </strong>1) Determine the difference between evaluating the number of eye closures in patients with blepharospasm in 1 vs. 2 min. 2) Characterize the prevalence, phenomenology and concordance of sensory trick in subjects with only blepharospasm compared to those with blepharospasm associated with other dystonias of the head.</p><p><strong>Methods: </strong>Thirty-eight, 2-min-long standardized videos of subjects with BSP without any other dystonias were reviewed (group1). Eye closure rate was measured in 0-60 s vs. 60-120 s. Wilcoxon signed-rank test and Spearman correlation coefficient were used to compare the eye closure rate between these two intervals. An additional 68 standardized videos of subjects with blepharospasm associated with dystonia of the head were reviewed (group2). Presence, phenomenology and concordance between what subjects verbally reported as their sensory trick and what they demonstrated was classified for both groups then qualitatively compared.</p><p><strong>Results/conclusion: </strong>Eye closure rates between 0-60 s and 0-120 s were not statistically different. There is no added benefit of counting the number of eye closures in 2 min, compared to 1 min, in patients with BSP. Sensory trick was reported by 57% of subjects with BSP and 80% of subjects who have blepharospasm and other dystonias of the head. With 100% and 97% concordance, patients' self-reported sensory trick accurately describes the movements that alleviate their dystonic movements.</p>","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42071483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subthalamic Nucleus Deep Brain Stimulation for Dystonia: Evidence, Pros and Cons","authors":"C. Kilbane, J. Ostrem","doi":"10.3389/dyst.2022.10609","DOIUrl":"https://doi.org/10.3389/dyst.2022.10609","url":null,"abstract":"The primary target for deep brain stimulation (DBS) for medication refractory dystonia has traditionally been the globus pallidus internus (GPi), however alternate targets have also been explored with the hope they might offer similar or superior outcomes with less side effects and reduced battery demands. Recent studies have shown comparable outcomes with both pallidal and subthalamic (STN) DBS, although the level of evidence is still superior for the GPi. There may not be an “optimal target” for all dystonia patients, with both targets offering the potential for excellent control of dystonia but more comparison studies are needed. In this review, we will discuss the history, efficacy, as well as target specific benefits and possible side effects of STN DBS for dystonia.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91283872","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":"Potential interactions between cerebellar dysfunction and sleep disturbances in dystonia.","authors":"Luis E Salazar Leon, Roy V Sillitoe","doi":"10.3389/dyst.2022.10691","DOIUrl":"10.3389/dyst.2022.10691","url":null,"abstract":"<p><p>Dystonia is the third most common movement disorder. It causes debilitating twisting postures that are accompanied by repetitive and sometimes intermittent co- or over-contractions of agonist and antagonist muscles. Historically diagnosed as a basal ganglia disorder, dystonia is increasingly considered a network disorder involving various brain regions including the cerebellum. In certain etiologies of dystonia, aberrant motor activity is generated in the cerebellum and the abnormal signals then propagate through a \"dystonia circuit\" that includes the thalamus, basal ganglia, and cerebral cortex. Importantly, it has been reported that non-motor defects can accompany the motor symptoms; while their severity is not always correlated, it is hypothesized that common pathways may nevertheless be disrupted. In particular, circadian dysfunction and disordered sleep are common non-motor patient complaints in dystonia. Given recent evidence suggesting that the cerebellum contains a circadian oscillator, displays sleep-stage-specific neuronal activity, and sends robust long-range projections to several subcortical regions involved in circadian rhythm regulation, disordered sleep in dystonia may result from cerebellum-mediated dysfunction of the dystonia circuit. Here, we review the evidence linking dystonia, cerebellar network dysfunction, and cerebellar involvement in sleep. Together, these ideas may form the basis for the development of improved pharmacological and surgical interventions that could take advantage of cerebellar circuitry to restore normal motor function as well as non-motor (sleep) behaviors in dystonia.</p>","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099477/pdf/nihms-1856489.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9324011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Botulinum Toxin in the Treatment of Cervical Dystonia: Evidence-Based Review","authors":"N. Hammoud, J. Jankovic","doi":"10.3389/dyst.2022.10655","DOIUrl":"https://doi.org/10.3389/dyst.2022.10655","url":null,"abstract":"Cervical dystonia is the most common form of dystonia encountered in a movement disorders clinic. Botulinum toxin has been a long-established first line therapy. Several studies, including nearly two dozen randomized clinical trials, have shown that botulinum toxin is safe and effective in reducing the clinical severity of cervical dystonia. Longitudinal data have demonstrated decades of sustained benefit and safety. Although there is a potential for the development of botulinum toxin immunoresistance, this is quite rare, and partly determined by frequency of administration, cumulative dosage, and properties of the injected product. When immunoresistance does occur, switching to an alternative type of botulinum toxin (e.g., from type A to type B) usually restores the efficacy. In this evidence-based review we highlight the results of published double blind, placebo-controlled studies. We also briefly discuss injection techniques and some unmet needs, such as the development of practical assays to detect immunoresistance and longer-acting formulations of botulinum toxin.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46495673","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":"Approach to the Treatment of Pediatric Dystonia","authors":"C. Gorodetsky, A. Fasano","doi":"10.3389/dyst.2022.10287","DOIUrl":"https://doi.org/10.3389/dyst.2022.10287","url":null,"abstract":"Dystonia is the most common movement disorder in the pediatric population. It can affect normal motor development and cause significant motor disability. The treatment of pediatric dystonia can be very challenging as many children tend to be refractory to standard pharmacological interventions. Pharmacological treatment remains the first-line approach in pediatric dystonia. However, despite the widespread use of different ani-dystonia medications, the literature is limited to small clinical studies, case reports, and experts’ opinions. Botulinum neurotoxin (BoNT) is a well-established treatment in adults with focal and segmental dystonia. Despite the widespread use of BoNT in adult dystonia the data to support its use in children is limited with the majority extrapolated from the spasticity literature. For the last 2 decades, deep brain stimulation (DBS) has been used for a wide variety of dystonic conditions in adults and children. DBS gained increased popularity in the pediatric population because of the dramatic positive outcomes reported in some forms of genetic dystonia and the subsequent consensus that DBS is generally safe and effective. This review summarizes the available evidence supporting the efficacy and safety of pharmacological treatment, BoNT, and DBS in pediatric dystonia and provides practical frameworks for the adoption of these modalities.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48615395","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":"Electrophysiological characterization of the striatal cholinergic interneurons in <i>Dyt1 ΔGAG</i> knock-in mice.","authors":"Hong Xing,&nbsp;Fumiaki Yokoi,&nbsp;Ariel Luz Walker,&nbsp;Rosemarie Torres-Medina,&nbsp;Yuning Liu,&nbsp;Yuqing Li","doi":"10.3389/dyst.2022.10557","DOIUrl":"https://doi.org/10.3389/dyst.2022.10557","url":null,"abstract":"<p><p>DYT1 dystonia is an inherited early-onset movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, and abnormal postures. Most DYT1 patients have a heterozygous trinucleotide GAG deletion mutation (<i>ΔGAG</i>) in <i>DYT1/TOR1A,</i> coding for torsinA. <i>Dyt1</i> heterozygous ΔGAG knock-in (KI) mice show motor deficits and reduced striatal dopamine receptor 2 (D2R). Striatal cholinergic interneurons (ChIs) are essential in regulating striatal motor circuits. Multiple dystonia rodent models, including KI mice, show altered ChI firing and modulation. However, due to the errors in assigning KI mice, it is essential to replicate these findings in genetically confirmed KI mice. Here, we found irregular and decreased spontaneous firing frequency in the acute brain slices from <i>Dyt1</i> KI mice. Quinpirole, a D2R agonist, showed less inhibitory effect on the spontaneous ChI firing in <i>Dyt1</i> KI mice, suggesting decreased D2R function on the striatal ChIs. On the other hand, a muscarinic receptor agonist, muscarine, inhibited the ChI firing in both wild-type (WT) and <i>Dyt1</i> KI mice. Trihexyphenidyl, a muscarinic acetylcholine receptor M1 antagonist, had no significant effect on the firing. Moreover, the resting membrane property and functions of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, μ-opioid receptors, and large-conductance calcium-activated potassium (BK) channels were unaffected in <i>Dyt1</i> KI mice. The results suggest that the irregular and low-frequency firing and decreased D2R function are the main alterations of striatal ChIs in <i>Dyt1</i> KI mice. These results appear consistent with the reduced dopamine release and high striatal acetylcholine tone in the previous reports.</p>","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629210/pdf/nihms-1842383.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40465525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Observing the Diversity of Alleviating Manoeuvres in Cervical Dystonia","authors":"L. Avanzino, F. Di Biasio, G. Bonassi, E. Pelosin, N. Cothros, R. Marchese, D. Martino","doi":"10.3389/dyst.2022.10283","DOIUrl":"https://doi.org/10.3389/dyst.2022.10283","url":null,"abstract":"The alleviating manoeuvres (AMs), classically referred to as “sensory tricks” are voluntary manoeuvres that temporarily improve dystonic postures. Although self-induced application of sensory stimuli is the most common AM, clinical experience suggests that the phenomenon is more diverse, possibly reflecting the complexity of the pathophysiological mechanisms provoking dystonia. We specifically explored five different categories of AMs in patients with cervical dystonia (CD): 1) pure sensory; sensorimotor manoeuvres in which sensory input is associated with a motor output component incorporating 2) active non-oppositional, 3) active oppositional or 4) passive motion; and 5) complex motor manoeuvres. Using an ad hoc structured clinical interview, we collected data on the frequency and efficacy of each subgroup and the possible correlation with some clinical features of CD. One-hundred patients were included in this study. Seventy-five percent of patients reported at least one AM. Half of those reporting AMs acknowledged the use of different phenomenological categories of AMs. Different categories of AMs showed noteworthy differences in prevalence of use amongst CD patients, and in the relationship of frequency of use and efficacy to patient demographic and clinical characteristics. Our observational study supports the existence of different AMs that are phenomenologically different and could be related to different degrees of sensorimotor integration dysfunction. Given that AMs are probably the most efficacious, non-invasive strategy to ameliorate CD and other dystonias, accurate phenotyping and physiological exploration of their diversity may produce relevant insight for new therapeutic strategies or appraisal of existing ones.","PeriodicalId":72853,"journal":{"name":"Dystonia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43131881","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}