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

深部脑刺激对姿势性和运动性震颤的进展和差异控制

• 批准号: 10536431
• 负责人: Rebecca Doran Butler
• 金额: $ 4.04万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10536431
• 关键词: Adult; Affect; Age; Algorithms; Analysis of Variance; Area; Brain; Cell Nucleus; Classification; Client satisfaction; Clinical; Clinical Research; Clinical Trials; Computer Models; Deep Brain Stimulation; Diagnosis; Disease Progression; Distal; Effectiveness; Electromyography; Essential Tremor; Failure; Frequencies; Grant; Head and neck structure; Human; Image; Implant; Intention Tremor; Kinetics; Lead; Linear Models; Location; Lower Extremity; Magnetic Resonance Imaging; Measurement; Measures; Methods; Minnesota; Modeling; Motion; Motor; Movement; Movement Disorders; Muscle; Musculoskeletal Equilibrium; Operative Surgical Procedures; Outcome; Output; Pathogenesis; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Peripheral; Pharmaceutical Preparations; Physicians; Posture; Refractory; Reporting; Structure; Surface; Surgical Management; Symptoms; Technology; Thalamic structure; Therapeutic; Time; Tremor; Universities; Upper Extremity; Visit; base; cohort; combat; design; experience; follow-up; implantation; improved; machine learning algorithm; magnetic field; neuromechanism; neurophysiology; novel; particle; prospective; reduce symptoms; relating to nervous system; sensor; side effect; treatment optimization; wearable sensor technology; zona incerta

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.

抽象的 基本震颤（ET），尽管是影响40岁以上成年人的最常见运动障碍，但 从其发病机理，神经生理学，临床分类和 特定于患者的治疗优化。对于25-55％的药物 - 征服患者 症状在功能上已限制，建议手术管理，最常见的是 脑刺激（DBS）。但是，DBS领导技术的最新进步，争议 最佳目标，副作用频繁发生，多达73％的患者会随着时间的推移而经历损失。作为 结果，显然需要细化并加深对ET优化处理的理解。 项目将利用正在进行的前瞻性临床研究中诊断为ET和ET的患者 用定向DBS导线植入，整合了高场磁共振成像，患者 - DB，定量传感器和全面的特定途径激活模型 肌电图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。具体而言，AIM 1将识别小脑 - thalamo-cortical途径 参与方向性DBS导线的动力学和姿势树控制，途径激活优化 算法和定量传感器。 AIM 2将接近识别树控制的潜在机制 使用全身肌电图的外周肌肉端。最后，AIM 3将决定如何 对刺激，疾病进展或铅置放置的耐受性导致震颤中的长期DBS失败 控制。虽然DBS可以改善临床树的分数，但医生仍然很难捕获 从短期内进行动作树，并长期保持治疗益处。了解路径 通过基于模型的，特定于患者的编程方法为震颤和副作用做出贡献将允许 为了改善DBS治疗对患者症状的改善和更一致的控制。