Progression and differential control of postural and kinetic tremor with deep brain stimulation

摘要 原发性震颤(ET)，尽管是最常见的运动障碍，影响着4%的40岁以上的成年人， 在发病机制、神经生理学、临床分型和 根据患者的具体情况优化治疗。对于25%-55%的药物耐药患者来说， 症状已变得功能受限，建议进行手术治疗，最常见的是深度 脑刺激(DBS)。然而，尽管星展银行的引线技术最近取得了进展，但关于 最佳目标，副作用频繁发生，随着时间的推移，高达73%的患者会失去益处。AS 因此，显然有必要改进和深化对ET优化治疗的理解。这 该项目将利用一项正在进行的前瞻性临床研究，对被诊断为ET和 植入定向DBS导联，集成高场磁共振成像，患者- DBS、定量传感器和综合体的特异性通路激活模型 肌电测量以进一步了解背后的神经和肌肉机制 震颤控制和进展。具体地说，目标1将确定小脑-丘脑-皮质通路 通过定向DBS导联参与运动性和体位性震颤控制，优化通路激活 算法和定量传感器。目标2将确定震颤控制的基本机制 从周围肌肉端用全身肌电图仪。最后，目标3将决定如何 对刺激、疾病进展或导线放置的耐受性导致震颤中DBS的长期失败 控制力。虽然DBS可以改善临床震颤评分，但医生仍难以捕捉到 短期动感震颤，长期维持治疗效益。了解这些途径 通过基于模型的、特定于患者的编程方法增加震颤和副作用将允许 通过DBS治疗改善和更一致地控制患者的症状。

Abstract Essential Tremor (ET), despite being the most common movement disorder affecting 4% of adults over age 40, remains relatively understudied in terms of its pathogenesis, neurophysiology, clinical classification, and optimization of treatments on a patient-specific basis. For the 25-55% of medication-refractory patients whose symptoms have become functionally limiting, surgical management is recommended, most commonly with deep brain stimulation (DBS). However, despite recent advances in DBS lead technology, controversy exists over the optimal target, side effects occur frequently, and up to 73% of patients experience loss of benefit over time. As a result, there is a clear need for refinement and deepened understanding of optimizing treatments for ET. This project will leverage an ongoing prospective clinical study in human patients diagnosed with ET and implanted with directional DBS leads, integrating high-field magnetic resonance imaging, patient- specific pathway activation modeling of DBS, quantitative sensors, and comprehensive electromyography measurements to further understand the neural and muscular mechanisms behind tremor control and progression. Specifically, Aim 1 will identify the cerebello-thalamo-cortical pathways involved in kinetic and postural tremor control with directional DBS leads, pathway activation optimization algorithms, and quantitative sensors. Aim 2 will approach identifying the underlying mechanisms of tremor control from the peripheral muscular end using whole-body electromyography. Finally, Aim 3 will determine how tolerance to stimulation, disease progression, or lead placement contribute to long-term DBS failure in tremor control. While DBS can result in improvement of clinical tremor scores, physicians still have trouble capturing action tremor in the short-term and maintaining therapeutic benefit in the long-term. Understanding the pathways contributing to tremor and to side effects via a model-based, patient-specific programming approach would allow for improved and more consistent control of patients’ symptoms with DBS therapy.