Dual Lead Thalamic DBR-DBS Interface for Closed Loop Control of Severe Essential Tremor

项目摘要 原发性震颤(Essential Tremor，ET)是一种进行性疾病，可导致严重的残疾和 生活质量明显下降。腹侧中脑深部电刺激(DBS) 丘脑(Vim)一直是治疗ET控制的有效方法，但与 有问题的副作用(如构音障碍、失衡)，并可能随着时间的推移而在人体内失效 严重的ET。能够改善震颤控制和减少副作用的多焦点， 目前的转向DBS技术将是该领域的重要进步。此外， 在DBS期间同时执行深部脑记录(DBR)的能力至关重要 用于表征震颤的病理神经回路和DBS的网络机制。 我们寻求通过更换失败的ET来恢复难治性ET受试者的最佳震颤控制 单导联VIM丘脑DBS双导联(VIM+口腔肌(VOP))丘脑 DBS系统在寻求翻修手术患者中的应用。双引线系统不仅将提供 严重震颤(开环)和标准VIM失败患者的有效抢救策略 DBS，但可选的具有DBR功能的系统的使用也将为我们提供前所未有的 有机会探索闭环、按需、针对患者的震颤控制。我们建议 在10名人类受试者中进行这项临床可行性研究。我们的具体目标是： 目的1：评价双导联丘脑DBS治疗重症心绞痛的疗效和安全性。 未能通过标准VIM DBS的特发性震颤； 目的2：使用双导联DBS/DBR确定动作性震颤的神经生理学标志 系统 目标3：开发闭合环双导联的神经解码和控制策略 刺激 该提案解决了可以说是一些最重要的限制 目前可用于重症ET患者的治疗。我们集结了一支经验丰富的 调查团队并与美敦力建立了独家行业合作伙伴关系，以履行 这个项目的目标。提议的计划是由坚实的神经科学和工程学推动的。 多年来可能对DBS技术的临床应用产生重大影响的原则 来吧。

Project Abstract Essential Tremor (ET) is a progressive disease that leads to significant disability and markedly diminished quality of life. Deep brain stimulation (DBS) in the ventralis intermedius (VIM) thalamus has been an effective treatment for ET control, but is associated with problematic side effects (e.g. dysarthia, imbalance) and may lose efficacy over time in people with severe ET. The ability to improve tremor control and reduce side effects with multifocal, current steering DBS techniques will be an important advance to the field. Furthermore, the ability to concurrently perform Deep Brain Recording (DBR) during DBS is of critical importance for characterizing both the pathologic neural circuitry of tremor and network mechanisms of DBS. We seek to restore optimal tremor control to subjects with refractory ET by replacing a failing single lead VIM thalamic DBS system with a dual lead (VIM + Ventralis Oralis (VOP)) thalamic DBS system in patients seeking revision surgery. The dual lead system will not only offer an effective rescue strategy for patients with severe tremor (open loop) and failure of standard VIM DBS, but the optional use of a DBR-capable system will also afford us an unprecedented opportunity to explore closed loop, on-demand, patient-specific tremor control. We propose to conduct this clinical feasibility study in 10 human subjects. Our specific aims are: Aim 1: Evaluate the efficacy and safety of dual lead thalamic DBS for treatment of severe essential tremor that has failed standard VIM DBS; Aim 2: Identify neurophysiologic markers of action tremor using a dual lead DBS/DBR system Aim 3: Develop neural decoding and control strategies for closed loop dual lead stimulation The proposal addresses what are arguably some of the most important limitations of currently available treatment for severe ET patients. We have assembled a highly experienced team of investigators and established an exclusive industrial partnership with Medtronic to fulfill the goals of this project. The proposed plan is driven by solid neuroscience and engineering principles that may have overarching impact on clinical applications of DBS technology for years to come.