Wearable-Sensor Driven Responsive Deep Brain Stimulation for the Improved Treatment of Essential Tremor

可穿戴传感器驱动的响应性深部脑刺激可改善特发性震颤的治疗

• 批准号: 10160652
• 负责人: Stephanie Lynn Cernera
• 金额: $ 1万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2021-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10160652
• 关键词: Adult; Adverse effects; Cell Nucleus; Chronic; Clinical; Clinical Data; Deep Brain Stimulation; Detection; Development; Devices; Diagnosis; Disease; Electromyography; Essential Tremor; Family; Frequencies; Gap Junctions; Goals; Heterogeneity; Human; Implant; Investigation; Lead; Life; Limb structure; Measurement; Measures; Mechanics; Methodology; Motor; Movement; Movement Disorders; Muscle; Operative Surgical Procedures; Outcome; Parkinson Disease; Pathologic; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Physiological; Postoperative Period; Quality of life; Research; Research Project Grants; Severities; Signal Transduction; Site; Symptoms; System; Techniques; Thalamic structure; Therapeutic; Time; Tremor; Uncertainty; Upper Extremity; Visit; base; clinically significant; cohort; design; follow-up; improved; individualized medicine; innovation; neuromuscular; novel; patient response; response; sensor; side effect; standard of care; wearable sensor technology

Project Summary/Abstract Clinically associated with chronic, disabling tremors within the 4-12 Hz range, essential tremor (ET) is the most prevalent adult-onset tremor disorder. There is marked heterogeneity in the site of tremor, in the occurrence of non-tremulous symptoms, and in the response to different drugs, alluding to the fact that ET may have several undefined subtypes or is a family of disorders rather than one sole distinguishable disease. Current diagnosis solely depends on subjective clinical measurements, such as the Fahn-Tolosa-Marin Tremor Rating Scale. Once diagnosed, ET can be treated pharmacologically, but for patients unresponsive to medication or with severe tremor, surgical options become viable. Deep brain stimulation (DBS) of the motor nucleus in the thalamus is proven to ameliorate tremor; however, DBS operates in a continuous fashion, leading to adverse effects from unspecific stimulation, rapid battery depletion of the implantable neurostimulator (INS), and impersonalized stimulation paradigms, thus, causing suboptimal clinical outcomes. The current methodology is an inefficient solution especially for patients with tremor, which can dynamically change throughout the day. The objective of this application is to establish physiologic correlates of movement and to characterize the neuromuscular mechanics of tremor throughout the upper extremities using electromyography (EMG) signals in a cohort of humans with ET. This research will lead to a deeper understanding of both the pathological basis of tremor within the extremities, and DBS as well as its mechanisms of action. Our central hypothesis is that wearable sensors, specifically those that measure EMG, can detect correlates of movement that will provide the control signal for responsive DBS in a targeted and personalized manner. Since tremor is paroxysmal and only occurs during movement in ET, responsive DBS only initiates once a movement is detected and then ceases stimulation once movement ends. In Aim 1, we will identify and characterize physiological correlates of tremor throughout the upper limb using EMG signals. In Aim 2, we will establish and clinically validate a responsive DBS system that utilizes physiological correlates of movement to initiate and terminate stimulation in humans with ET. We will initiate responsive DBS based on both the presence of movement and phase of tremor. This research is significant and innovative because it will provide improved tremor suppression through personalized DBS paradigms, reduce adverse effects associated with continuous stimulation, and prolong battery life of the INS, subsequently decreasing the frequency of surgical procedures needed to replace these devices. Additionally, this research has the potential to uncover other uncertainties about ET, including its neuromuscular origin, propagation, and distribution, and to develop an objective measurement of tremor severity, which is an unmet clinical need. Lastly, a sensor-based responsive DBS system can be translatable to other movement disorders, such as Parkinson’s disease.

项目摘要/摘要 临床上与4-12赫兹范围内的慢性致残性震颤有关，原发性震颤(ET)是最常见的 流行的成人发作性震颤障碍。震颤发生的部位有明显的不均一性。 无颤抖症状，在对不同药物的反应中，暗示ET可能有几个 未定义的亚型或是一系列疾病，而不是一种唯一可区分的疾病。当前诊断 仅取决于主观的临床测量，如Fahn-Tolosa-Marin Tremor评定量表。一次 确诊后，ET可以药物治疗，但对于药物无效或严重的患者 震颤，手术选择变得可行。丘脑运动核深部脑刺激(DBS)是 已证实可改善震颤；然而，星展银行持续运作，导致以下不良影响 非特异性刺激，植入式神经刺激器(INS)电池迅速耗尽，且非个性化 因此，刺激模式导致了不太理想的临床结果。目前的方法是一种低效的 解决方案特别适用于震颤患者，震颤可以全天动态变化。的目标是 这一应用是为了建立运动的生理关联，并表征神经肌肉 使用肌电(EMG)信号在一组受试者中研究上肢震颤机制 人类与外星人。这项研究将使我们对震颤的病理基础有更深入的了解 四肢、DBS及其作用机制。我们的中心假设是可穿戴传感器， 具体地说，那些测量肌电的人可以检测运动的相关性，这将为 以针对性和个性化的方式响应DBS。因为震颤是阵发性的，只有在 在ET中，响应性DBS仅在检测到运动后才开始运动，然后停止刺激一次 运动结束了。在目标1中，我们将识别和表征整个脑震颤的生理相关性 上肢使用肌电信号。在目标2中，我们将建立并临床验证一个响应性的DBS系统 利用运动的生理关联来启动和终止ET患者的刺激。我们会 启动基于运动和震颤相位的响应DBS。这项研究是 重大和创新，因为它将通过个性化的DBS提供更好的震颤抑制 范例，减少与持续刺激相关的不良影响，并延长INS的电池寿命， 随后减少了更换这些装置所需的外科手术的频率。另外， 这项研究有可能揭示关于ET的其他不确定性，包括它的神经肌肉来源， 传播和分布，并制定震颤严重程度的客观测量，这是一种未满足的 临床需要。最后，基于传感器的响应性DBS系统可以翻译为其他运动障碍， 比如帕金森氏症。