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Calcitriol in Friedreich Ataxia 弗里德里希共济失调症中的骨化三醇
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-17 DOI: 10.1002/mds.29970
Shana E. McCormack MD, MTR, David R. Weber MD, MSCE, David R. Lynch MD, PhD
<p>We read with interest the recent open label trial (n = 20) of 0.25 mcg/24 h of oral calcitriol in individuals 16 to 65 years old with genetically confirmed Friedreich Ataxia (FRDA).<span><sup>1</sup></span></p><p>The authors performed this trial to follow up on previous in vitro studies in which supplementation with calcitriol (eg, 20 nmol/L) in dorsal root ganglion neurons produced biochemical changes, including restoration of mitochondrial membrane potential, decrease in markers of apoptosis and degeneration, and cell survival.<span><sup>2</sup></span> Of note, the highest upper limit of the physiologic reference range for peripheral blood 1,25-dihydroxyvitamin D (eg, Mayo Clinic, females <16 years) is 86 pg/mL or 215 pmol/L or 0.2 nmol/L, two orders of magnitude below the values achieved in vitro with calcitriol supplementation. Therefore, dose selection becomes a highly relevant consideration for this translational study. Moreover, vitamin D metabolism is cell- and tissue-specific. Thus, it challenging to extrapolate from 1,25-dihydroxyvitamin D measurements made in vitro or even in vivo in peripheral blood to predict the effects of calcitriol supplementation in cardiac, musculoskeletal, or central nervous system in humans.<span><sup>3</sup></span></p><p>The dose of 0.25 mcg of calcitriol is cited as “low” by the group, but this designation is misleading, because calcitriol is most often prescribed to address hypocalcemia or secondary hyperparathyroidism in individuals with kidney disease or hypocalcemia in individuals with hypoparathyroidism. Individuals with FRDA do not have these disorders, nor is there clear evidence of overt deficiency in 1,25-OH-vitamin D in FRDA. Therefore, whereas this calcitriol dose might be considered “low” for individuals who meet typical indications, the dose is supra-physiologic for most others, including those with FRDA.</p><p>The most concerning claim of this study is that this regimen is safe. Of the 20 participants initially studied, five were withdrawn for what were indeed conservative stopping criteria for hypercalcemia; still, one quarter represents a sizeable proportion. Moreover, the study did not include additional safety assessments to support the safety claim, for example, measurement of urinary calcium excretion (a more sensitive measurement of excess 1,25-OH-vitamin D exposure depleting calcium stores from bone) or dual energy x-ray absorptiometry (to assess areal bone mineral density), which is relevant given many individuals with FRDA already have impaired bone health.<span><sup>4, 5</sup></span> Perhaps most relevant, participants were required to stop taking any supplemental calcium and/or vitamin D3 in the 30 days before enrollment. If these individuals were not consuming the typical recommended daily intake of calcium and vitamin D3, and given the established risk of vitamin D insufficiency in this population from previous studies, then such a decision is contrary to care guidelines tha
我们饶有兴趣地阅读了最近一项开放标签试验（n = 20），该试验针对 16 至 65 岁经基因确诊的弗里德里希共济失调症（FRDA）患者口服 0.25 微克/24 小时的降钙素三醇。1 作者进行这项试验是为了跟进之前的体外研究，在这些研究中，背根神经节神经元补充降钙素三醇（如 20 毫摩尔/升）可产生生化变化，包括线粒体膜电位恢复、细胞凋亡和变性标志物减少以及细胞存活。值得注意的是，外周血 1,25-二羟维生素 D 生理参考范围的最高上限（例如，梅奥诊所，女性<16 岁）为 86 pg/mL 或 215 pmol/L 或 0.2 nmol/L，比补充钙三醇在体外达到的值低两个数量级。因此，在这项转化研究中，剂量选择是一个非常重要的考虑因素。此外，维生素 D 的代谢具有细胞和组织特异性。因此，从体外甚至体内外周血中的 1,25-二羟维生素 D 测量值推断补充钙三醇对人体心脏、肌肉骨骼或中枢神经系统的影响具有挑战性。该研究小组称 0.25 微克的降钙素三醇剂量为 "低剂量"，但这种说法具有误导性，因为降钙素三醇最常被用于治疗肾病患者的低钙血症或继发性甲状旁腺功能亢进症，或甲状旁腺功能减退症患者的低钙血症。FRDA 患者没有这些疾病，也没有明确证据表明 FRDA 患者明显缺乏 1,25-OH-维生素 D。因此，对于符合典型适应症的人来说，降钙素三醇的剂量可能被认为是 "低 "的，但对于包括 FRDA 患者在内的大多数其他人来说，该剂量是超生理剂量。在最初接受研究的 20 名参与者中，有 5 人因高钙血症而退出研究，这确实是保守的停药标准；尽管如此，四分之一的参与者仍占了相当大的比例。此外，该研究并未包括额外的安全性评估来支持安全性声明，例如，尿钙排泄测量（一种更灵敏的测量过量 1,25-OH- 维生素 D 暴露消耗骨骼中钙储存的方法）或双能 X 射线吸收测量法（用于评估骨矿物质密度），鉴于许多 FRDA 患者的骨骼健康已经受损，这一点非常重要4，5。如果这些人没有摄入典型的钙和维生素 D3 推荐日摄入量，并考虑到以前的研究已经确定了这一人群维生素 D 不足的风险，那么这样的决定就违背了护理指南，该指南提倡确保所有人群摄入充足的钙和维生素 D，尤其是那些有骨骼脆弱风险的人群。作者建议对更高剂量的钙三醇进行研究，但在考虑和解决上述问题之前，似乎没有必要这样做。特别是考虑到降钙素三醇的随时可用性，FRDA 社区需要明确补充降钙素三醇的安全性和有效性。SEM、DRW、DRL：撰写和编辑手稿的最终版本。
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引用次数: 0
What Is In A Name? 名字里有什么？
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-17 DOI: 10.1002/mds.29943
Daniel Ciampi de Andrade MD, PhD, Veit Mylius, Santiago Perez Lloret
<p>We read with interest the OXYDOPA study by Brefel-Courbon et al,<span><sup>1</sup></span> where central pain in people with Parkinson's disease (PwP) was treated by prolonged-release oxycodone, increase in levodopa, or placebo. The authors should be complimented for conducting such a complex multicenter trial on a topic that needs urgent new data and that extended itself through times of coronavirus disease pandemics. Bravo.</p><p>Pain is among the most burdensome non-motor symptoms of Parkinson's disease (PD) and to date no effective evidence-based treatment exists for its control. Different pain types have different mechanisms of disease, which respond differently to therapeutic interventions. This means that clinicians should first assess the pain type PwP have and then proceed to a specific therapy.</p><p>To do that, three steps need to be completed. First, clinicians need to ascertain that pain is chronic (ie, being present most of the days for more than 3 months). Interestingly, several classification systems for pain in PD do not ascertain that pain is chronic. Second, since pain affects at least 20% of the general population, one needs to ascertain that chronic pain in PwP is related to PD. By ignoring this point, one risks misclassifying, for example, migraine, or previously existing fibromyalgia as PD-related pain. More than 20% of PwP have pains not related to the disease. Third, the classification should acknowledge general classification frameworks and previous knowledge generated by the field of PD and pain.<span><sup>2</sup></span></p><p>The present study aimed at chronic pain in PwP, therefore, fulfilling the first step. However, it classified PD-related pain using a classification system that has not yet been validated. There was no reference to the relationship between patient's pain and PD. Therefore, the study sample may have included PwP with different pain mechanisms.</p><p>What is more problematic is the use of “central neuropathic pain.” Central neuropathic pain because of PD does not stand with any current classification of central neuropathic pain (see Table 1).<span><sup>3</sup></span> There is no doubt that the clinical phenotype described as being of central neuropathic pain exists in PwP, but it is rare.<span><sup>4</sup></span></p><p>The authors also mixed the concept of “central neuropathic pain” with “central parkinsonian pain.” The problematic definition of the pain type under study makes the results of this study difficult to apply to the clinical practice.</p><p>“Central parkinsonian pain” fits the definition of nociplastic pain (as suggested in the very same paper used for pain classification in the present study)<span><sup>5</sup></span> (Table 1). The classification of PD-related pains according to its mechanistic descriptors (nociceptive, neuropathic, and nociplastic) has been validated clinically, has shown to provide different profiles of somatosensory and cortical excitability changes in PwP,<span><su
我们饶有兴趣地阅读了 Brefel-Courbon 等人进行的 OXYDOPA 研究1，在该研究中，帕金森病（PwP）患者的中枢性疼痛通过缓释羟考酮、增加左旋多巴或安慰剂进行治疗。作者应该受到表扬，因为他们针对一个急需新数据的课题进行了如此复杂的多中心试验，并且在冠状病毒疾病大流行期间仍在进行试验。疼痛是帕金森病（PD）最繁重的非运动症状之一，迄今为止还没有有效的循证治疗方法来控制疼痛。不同的疼痛类型有不同的发病机制，对治疗干预的反应也不同。这意味着临床医生应首先评估患者的疼痛类型，然后再进行特定治疗。首先，临床医生需要确定疼痛是慢性的（即大部分时间疼痛超过 3 个月）。有趣的是，一些帕金森病疼痛分类系统并不确定疼痛是慢性的。其次，由于至少有 20% 的普通人群会受到疼痛的影响，因此需要确定老年患者的慢性疼痛与帕金森病有关。如果忽视这一点，就有可能将偏头痛或先前存在的纤维肌痛等错误归类为与帕金森病有关的疼痛。超过 20% 的 PwP 患者的疼痛与疾病无关。第三，分类应承认一般的分类框架和先前在帕金森病和疼痛领域产生的知识。2 因此，本研究以帕金森病患者的慢性疼痛为目标，完成了第一步。2 因此，本研究针对的是残疾人的慢性疼痛，满足了第一步的要求。然而，本研究使用了一个尚未得到验证的分类系统对与帕金森病相关的疼痛进行了分类。没有提及患者疼痛与帕金森病之间的关系。因此，研究样本中可能包括了不同疼痛机制的患者。更有问题的是 "中枢神经病理疼痛 "的使用。由帕金森病引起的中枢神经病理痛并不符合目前中枢神经病理痛的任何分类（见表 1）。3 毫无疑问，帕金森病患者中存在被描述为中枢神经病理痛的临床表型，但这种情况很少见。中枢性帕金森病痛 "符合神经痉挛性疼痛的定义（与本研究中用于疼痛分类的论文相同）5 （表 1）。根据帕金森病相关疼痛的机理描述（痛觉性疼痛、神经病理性疼痛和非运动性疼痛）对帕金森病相关疼痛进行分类已在临床上得到验证，并显示出帕金森病患者躯体感觉和皮质兴奋性变化的不同特征6 ，最近还显示出神经调控策略对帕金森病患者缓解疼痛非常有用7。疼痛研究是各领域之间丰富交叉的领域，为了患者的利益，使用适当的术语和有效的分类框架只会使PD疼痛领域更快地发展：A.构思，B.组织，C.执行；2.手稿准备：D.C.A.: 1B, 2A, 2BV.M.: 1B, 2A, 2BS.P.L.: 1B, 2A, 2B
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引用次数: 0
CAG Repeat Expansion in THAP11 Is Not Detected in a Cohort with Spinocerebellar Ataxia from Hokkaido, the Northernmost Island of Japan 在日本最北端岛屿北海道的脊髓小脑共济失调队列中未检测到 THAP11 的 CAG 重复扩增
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-17 DOI: 10.1002/mds.29975
Shinichi Shirai MD, PhD, Keiichi Mizushima MD, Yuka Shibata MPH, PhD, Masaaki Matsushima MD, PhD, Ikuko Iwata MD, PhD, Hiroaki Yaguchi MD, PhD, Ichiro Yabe MD, PhD
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引用次数: 0
September Infographic 九月份信息图表
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-17 DOI: 10.1002/mds.29486

Stepwise Functional Brain Architecture Correlates with Atrophy in Progressive Supranuclear Palsy

渐进性核上性麻痹患者大脑功能结构与萎缩的关系
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引用次数: 0
Reply to: “Calcitriol in Friedreich Ataxia” 答复"弗里德里希共济失调的骨化三醇"
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-17 DOI: 10.1002/mds.29971
Berta Alemany-Perna MD, Jordi Tamarit PhD, Elisa Cabiscol PhD, Joaquim Ros PhD
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引用次数: 0
Reply to: “CAG Repeat Expansion in THAP11 is Not Detected in a Cohort with Spinocerebellar Ataxia from Hokkaido, the Northernmost Island of Japan” 答复"日本最北端岛屿北海道脊髓小脑共济失调队列中未检测到 THAP11 的 CAG 重复扩增 "的答复
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-17 DOI: 10.1002/mds.29978
Cheng-Tsung Hsiao MD, PhD, Yi-Chu Liao MD, PhD, Yi-Chung Lee MD, PhD
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引用次数: 0
Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy. 进行性核上性麻痹血细胞中的免疫代谢特征和 Tauopathy 标记物
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-16 DOI: 10.1002/mds.30009
Marco Rosina, Federica Veltri, Valentina Nesci, Jacopo Bissacco, Roberta Bovenzi, Davide Mascioli, Clara Simonetta, Henri Zenuni, Daniela Maftei, Massimo Marano, Mariangela Pierantozzi, Alessandro Stefani, Valerio Chiurchiù, Patrizia Longone, Cristiana Valle, Nicola Biagio Mercuri, Alberto Ferri, Tommaso Schirinzi

Background: Peripheral immune cells critically contribute to the clinical-pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard.

Objective: Our goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort.

Methods: Seventy-one PSP patients scored on the PSP Rating Scale (PSPRS), and 59 controls were enrolled. The blood cell count was collected, together with the neutrophil-to-lymphocyte ratio (NLR) calculation. In a subgroup of patients and controls, the peripheral blood mononuclear cells (PBMCs) were analyzed by the mitochondrial bioenergetic performance and the western blot assay of the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase 1 (HO-1) pathway and the total tau (t-tau) and phosphorylated tau (p-tau) proteins. Case-control comparison and correlation analyses were performed.

Results: PSP patients had a NLR higher than controls, with increased circulating neutrophils. The leukocyte metabolism was also globally increased and the NRF2/HO-1 pathway activated in patients. P-tau, but not t-tau, significantly accumulated in PSP PBMCs and inversely correlated with the PSPRS.

Conclusions: PSP displays a systemic inflammatory shift of the peripheral immunity, which may justify a metabolic reprogramming of the blood leukocytes. Consistently, the NRF2/HO-1 pathway, a master regulator of inflammatory and metabolic response, was activated. PBMCs also engulf tau proteins, especially p-tau, in a way inverse to the disease severity, allowing for a peripheral tracking of tauopathy in patients. Immunometabolic targets may, therefore, gain relevance to PSP in biomarker or therapeutic purposes. © 2024 International Parkinson and Movement Disorder Society.

背景：外周免疫细胞对神经退行性疾病的临床病理进展起着至关重要的作用，同时也是转化应用的可靠框架。然而，有关进行性核上性麻痹（PSP）的这方面数据几乎是稀缺的：我们的目标是对选定的 PSP 患者群的外周免疫细胞进行广泛的生物学特征描述：方法：我们招募了 71 名根据 PSP 评定量表（PSPRS）评分的 PSP 患者和 59 名对照组患者。收集血细胞计数并计算中性粒细胞与淋巴细胞比率（NLR）。在一组患者和对照组中，对外周血单核细胞（PBMCs）进行了线粒体生物能分析，并对核因子红细胞2相关因子（NRF2）/血红素加氧酶1（HO-1）通路以及总tau（t-tau）和磷酸化tau（p-tau）蛋白进行了Western印迹检测。进行了病例对照比较和相关性分析：结果：PSP 患者的 NLR 高于对照组，循环中性粒细胞增加。患者的白细胞新陈代谢也全面增加，NRF2/HO-1通路被激活。P-tau 而非 t-tau 在 PSP PBMCs 中明显累积，并与 PSPRS 成反比：结论：PSP 表现出外周免疫系统的系统性炎症转变，这可能是血液白细胞代谢重编程的原因。NRF2/HO-1 通路是炎症和新陈代谢反应的主要调节因子，它也被激活了。白细胞介导细胞还能吞噬 tau 蛋白，尤其是 p-tau，其吞噬方式与疾病的严重程度成反比，从而能对患者的 tau 病变进行外周追踪。因此，免疫代谢目标可能与帕金森病的生物标记或治疗目的相关。© 2024 国际帕金森病和运动障碍协会。
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引用次数: 0
NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations. NeuroBooster 阵列：研究不同人群神经系统疾病的全基因组基因分型平台。
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-16 DOI: 10.1002/mds.29902
Sara Bandres-Ciga, Faraz Faghri, Elisa Majounie, Mathew J Koretsky, Jeffrey Kim, Kristin S Levine, Hampton Leonard, Mary B Makarious, Hirotaka Iwaki, Peter Wild Crea, Dena G Hernandez, Sampath Arepalli, Kimberley Billingsley, Katja Lohmann, Christine Klein, Steven J Lubbe, Edwin Jabbari, Paula Saffie-Awad, Derek Narendra, Armando Reyes-Palomares, John P Quinn, Claudia Schulte, Huw R Morris, Bryan J Traynor, Sonja W Scholz, Henry Houlden, John Hardy, Sonya Dumanis, Ekemini Riley, Cornelis Blauwendraat, Andrew Singleton, Mike Nalls, Janina Jeff, Dan Vitale

Background: Commercial genome-wide genotyping arrays have historically neglected coverage of genetic variation across populations.

Objective: We aimed to create a multi-ancestry genome-wide array that would include a wide range of neuro-specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies.

Methods: We developed the Illumina NeuroBooster Array (NBA), a custom high-throughput and cost-effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples. This novel platform includes approximately 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease-related genome-wide association study loci across diverse populations.

Results: In this article, we describe NBA's potential as an efficient means for researchers to assess known and novel disease genetic associations in a multi-ancestry framework. The NBA can identify rare genetic variants and accurately impute more than 15 million common variants across populations. Apart from enabling sample prioritization for further whole-genome sequencing studies, we envisage that NBA will play a pivotal role in recruitment for interventional studies in the precision medicine space.

Conclusions: From a broader perspective, the NBA serves as a promising means to foster collaborative research endeavors in the field of neurological disorders worldwide. Ultimately, this carefully designed tool is poised to make a substantial contribution to uncovering the genetic etiology underlying these debilitating conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

背景：商业全基因组基因分型阵列历来忽视对不同人群遗传变异的覆盖：商业全基因组基因分型阵列历来忽视对不同人群遗传变异的覆盖：我们的目标是创建一个多祖先全基因组阵列，该阵列将包含广泛的神经特异性遗传内容，以促进跨多个祖先群体的神经系统疾病遗传研究，促进研究的多样性和包容性：我们开发了Illumina NeuroBooster Array（NBA），这是一个定制的高通量、高性价比平台，以Infinium Global Diversity Array的1,914,934个变异为基础，添加了与70多种神经疾病或性状相关的95,273个变异的定制内容，并在2000多个患者样本上对其性能进行了进一步测试。这个新颖的平台包括约 10,000 个标记变异，便于对不同人群中与神经退行性疾病相关的全基因组关联研究位点进行估算和分析：在这篇文章中，我们描述了 NBA 作为研究人员在多种群框架内评估已知和新型疾病遗传关联的有效手段的潜力。NBA 可以识别罕见的遗传变异，并在不同人群中准确估算出 1,500 多万个常见变异。除了能为进一步的全基因组测序研究确定样本的优先顺序外，我们预计NBA还将在精准医疗领域的干预研究招募中发挥关键作用：从更广阔的视角来看，NBA 是促进全球神经系统疾病领域合作研究的有效手段。最终，这一精心设计的工具将为揭示这些使人衰弱的疾病的遗传病因做出重大贡献。©2024年作者。运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。本文由美国政府雇员撰写，其作品在美国属于公共领域。
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引用次数: 0
Consensus Guidance for Genetic Counseling in GBA1 Variants: A Focus on Parkinson's Disease GBA1 基因变异遗传咨询共识指南：聚焦帕金森病
IF 8.6 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-11 DOI: 10.1002/mds.30006
Sophia R.L. Vieira, Roxana Mezabrovschi, Marco Toffoli, Sara Lucas Del Pozo, Elisa Menozzi, Stephen Mullin, Selen Yalkic, Naomi Limbachiya, Sofia Koletsi, Nadine Loefflad, Grisel J. Lopez, Ziv Gan‐Or, Roy N. Alcalay, Ellen Sidransky, Anthony H.V. Schapira
Glucocerebrosidase (GBA1) variants constitute numerically the most common known genetic risk factor for Parkinson's disease (PD) and are distributed worldwide. Access to GBA1 genotyping varies across the world and even regionally within countries. Guidelines for GBA1 variant counseling are evolving. We review the current knowledge of the link between GBA1 and PD, and discuss the practicalities of GBA1 testing. Lastly, we provide a consensus for an approach to counseling people with GBA1 variants, notably the communication of PD risk. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
在数量上，葡糖脑苷脂（GBA1）变体是帕金森病（PD）最常见的已知遗传风险因素，而且分布在世界各地。在世界各地，甚至在各国的不同地区，获得 GBA1 基因分型的途径也不尽相同。GBA1变异咨询指南也在不断发展。我们回顾了目前关于 GBA1 与帕金森病之间联系的知识，并讨论了 GBA1 检测的实用性。最后，我们就为GBA1变异体患者提供咨询的方法达成了共识，特别是关于帕金森病风险的交流。© 2024 作者姓名运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。
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引用次数: 0
Amelioration of Focal Hand Dystonia via Low-Frequency Repetitive Somatosensory Stimulation. 通过低频重复性躯体感觉刺激改善局灶性手部肌张力障碍症
IF 8.6 1区 医学 Q1 CLINICAL NEUROLOGY
Movement Disorders
Pub Date : 2024-09-10 DOI: 10.1002/mds.30011
Lorenzo Rocchi,Anna Latorre,Elisa Menozzi,Vittorio Rispoli,John C Rothwell,Alfredo Berardelli,Kailash P Bhatia
BACKGROUNDDystonia presents a growing concern based on evolving prevalence insights. Previous research found that, in cervical dystonia, high-frequency repetitive somatosensory stimulation (RSS; HF-RSS) applied on digital nerves paradoxically diminishes sensorimotor inhibitory mechanisms, whereas low-frequency RSS (LF-RSS) increases them. However, direct testing on affected body parts was not conducted.OBJECTIVEThis study aims to investigate whether RSS applied directly to forearm muscles involved in focal hand dystonia can modulate cortical inhibitory mechanisms and clinical symptoms.METHODSWe applied HF-RSS and LF-RSS, the latter either synchronously or asynchronously, on forearm muscles involved in dystonia. Outcome measures included paired-pulse somatosensory evoked potentials, spatial lateral inhibition measured by double-pulse somatosensory evoked potentials, short intracortical inhibition tested with transcranial magnetic stimulation, electromyographic activity from dystonic muscles, and behavioral measures of hand function.RESULTSBoth synchronous and asynchronous low-frequency somatosensory stimulation improved cortical inhibitory interactions, indicated by increased short intracortical inhibition and lateral spatial inhibition, as well as decreased amplitude of paired-pulse somatosensory evoked potentials. Opposite effects were observed with high-frequency stimulation. Changes in electrophysiological markers were paralleled by behavioral outcomes: although low-frequency stimulations improved hand function tests and reduced activation of dystonic muscles, high-frequency stimulation operated in an opposite direction.CONCLUSIONSOur findings confirm the presence of abnormal homeostatic plasticity in response to RSS in the sensorimotor system of patients with dystonia, specifically in inhibitory circuits. Importantly, this aberrant response can be harnessed for therapeutic purposes through the application of low-frequency electrical stimulation directly over dystonic muscles. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
背景肌张力障碍是一个日益受到关注的问题，其发病率也在不断提高。以前的研究发现，在颈性肌张力障碍患者中，对数字神经进行高频重复体感刺激（RSS；HF-RSS）会自相矛盾地削弱感觉运动抑制机制，而低频重复体感刺激（LF-RSS）则会增强这种机制。本研究旨在探讨直接在局灶性手部肌张力障碍患者的前臂肌肉上施加 RSS 是否会调节大脑皮层的抑制机制和临床症状。方法我们在肌张力障碍患者的前臂肌肉上施加高频 RSS 和低频 RSS，后者可同步或非同步施加。结果测量包括成对脉冲体感诱发电位、双脉冲体感诱发电位测量的空间侧向抑制、经颅磁刺激测试的皮层内短抑制、肌张力障碍肌肉的肌电活动以及手部功能的行为测量。结果同步和异步低频躯体感觉刺激都能改善大脑皮层的抑制性相互作用，表现为皮层内短抑制和侧向空间抑制的增强，以及成对脉冲躯体感觉诱发电位振幅的降低。高频刺激则产生了相反的效果。我们的研究结果证实，肌张力障碍患者的感觉运动系统（尤其是抑制回路）在对 RSS 的反应中存在异常的静态可塑性。重要的是，这种异常反应可以通过直接对肌张力障碍肌肉进行低频电刺激达到治疗目的。©2024年作者。运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。
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引用次数: 0
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