Bilateral Closed Loop Deep Brain Stimulation for Freezing of Gait using Neural and Kinematic Feedback

利用神经和运动学反馈进行双边闭环深部脑刺激以冻结步态

• 批准号: 10218278
• 负责人: Helen Bronte-Stewart
• 金额: $ 120.42万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218278
• 关键词: Adverse effects; Affect; Age; Algorithms; Behavior Control; Behavioral; Bilateral; Bluetooth; Bradykinesia; Brain; Cessation of life; Clinical Research; Complication; Data; Deep Brain Stimulation; Development; Device or Instrument Development; Devices; Disease; Dose; Emerging Technologies; Environment; Family; Feedback; Freezing; Frequencies; Future; Gait; Gap Junctions; Glues; Home; Home environment; Impairment; Implant; Incidence; Independent Living; Industry Collaboration; Injury; Lead; Leg; Lewy Body Dementia; Locomotion; Measurement; Measures; Motor; Movement Disorder Society Unified Parkinson' s Disease Rating Scale; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Outcome; Outcome Measure; Parkinson Disease; Patients; Periodicity; Pharmaceutical Preparations; Policies; Population; Progressive Supranuclear Palsy; Research; Research Priority; Safety; Signal Transduction; Structure of subthalamic nucleus; System; Technology; Testing; Time; Translating; Tremor; Walking; arm; base; bench to bedside; cohort; design; disability; effective therapy; experience; experimental study; fall injury; falls; feasibility testing; foot; home test; improved; kinematics; motor disorder; motor symptom; nervous system disorder; neuroregulation; next generation; novel; partial response; participant safety; patient safety; prevent; primary outcome; relating to nervous system; response; safety and feasibility; safety testing; secondary outcome; sensor; side effect; symposium; wearable sensor technology

Gait impairment and Freezing of gait (FOG), lead to falls, injury (even death), loss of independent living, and are common in neurodegenerative diseases such as Parkinson’s Disease (PD), affecting over 7 million people worldwide. The incidence of neurodegenerative diseases increases with age and as the population lives longer, the societal consequences of FOG, will be very significant. Gait impairment and FOG have a partial response to medication and subthalamic nucleus (STN) open loop deep brain stimulation (olDBS), which cannot adjust therapy in response to underlying brain signals or motor symptoms such as FOG. One reason is that FOG may respond to different parameters of DBS, such as lower frequency, than that needed for tremor and most patients do not tolerate 60 Hz DBS for long periods of time. Emerging technology using sensing neurostimulators and Bluetooth enabled wearable sensors has allowed research into closed loop or adaptive (a)DBS using neural or behavioral control variables. FOG is episodic and usually occurs in predictable environments, so it is well suited for ‘on demand’ aDBS. ADBS, responding to markers of gait impairment and intermittent FOG, with changes in DBS intensity or frequency, could then prevent FOG, falls and injury, while still treating other motor signs of PD. From over four years of research and regulatory experience in an academic-industry collaboration with Medtronic, we have provided design inputs for the next generation aDBS devices, and have determined that aDBS for tremor and bradykinesia is safe and tolerable in the largest freely-moving PD cohort implanted with a Medtronic investigative neurostimulation/sensing system (Activa® PC+S-Nexus D/D3/E). We have discovered neural and behavioral markers of gait impairment and FOG using synchronized neural and kinematic recordings during gait tasks that elicit FOG. Our research findings and the technological advances embedded in the Medtronic Summit® RC+S-system now enable the next step: the first clinical studies of lateralized, independent, bilateral STN aDBS control algorithms for FOG in PD, driven by subject-specific neural (Aim 1) or behavioral (Aim 2) control variables, and in response to medication (Aim 3). The project will translate stepwise in a ‘bench to bedside’ manner, testing aDBS during the stepping in place (SIP) task, where the subject is in a harness and steps in place on dual force-plates. Then aDBS will be tested during the forward walking Turning and Barrier Course, which mimics environments known to trigger FOG in the real world, and then how aDBS responds to subject-specific doses of medication, while freely moving. The outcome of these experiments will provide critical next-steps for safety and feasibility of testing aDBS for gait impairment and FOG in the subject’s home environment, and on their normal medication. Patient safety, tolerability, adverse effects, gait parameters, and the number and duration of freezing episodes (FEs), during no DBS, olDBS, aDBS and a control, intermittent (i)olDBS will provide inputs for future devices and novel algorithms applicable to NaDBS or KaDBS for gait impairment and FOG in other neurological diseases.

步态障碍和冻结步态 (FOG) 可导致跌倒、受伤（甚至死亡）、丧失独立生活，并且 常见于帕金森病 (PD) 等神经退行性疾病，影响超过 700 万人 全世界。神经退行性疾病的发病率随着年龄的增长和人口寿命的延长而增加， FOG 的社会后果将非常重大。步态障碍和 FOG 有部分反应 药物治疗和丘脑底核 (STN) 开环深部脑刺激 (olDBS)，无法调节 针对潜在的大脑信号或运动症状（例如 FOG）的治疗。原因之一是 FOG 可能 对 DBS 的不同参数有反应，例如比震颤和大多数患者所需的频率更低 请勿长时间忍受 60 Hz DBS。使用传感神经刺激器和 支持蓝牙的可穿戴传感器允许使用神经或自适应 (a)DBS 来研究闭环或自适应 (a)DBS 行为控制变量。 FOG 是偶发性的，通常发生在可预测的环境中，因此非常适合 对于“按需”aDBS。 ADBS，对步态障碍和间歇性 FOG 标记做出反应，并发生变化 DBS 强度或频率可以预防 FOG、跌倒和受伤，同时仍然可以治疗 PD 的其他运动症状。 凭借四年多的学术与行业合作研究和监管经验 美敦力（Medtronic），我们为下一代 aDBS 设备提供了设计输入，并确定 在植入 aDBS 的最大的自由活动 PD 队列中，aDBS 治疗震颤和运动迟缓是安全且可耐受的。 美敦力研究性神经刺激/传感系统 (Activa® PC+S-Nexus D/D3/E)。我们发现 使用同步神经和运动记录的步态障碍和 FOG 的神经和行为标记 在引发 FOG 的步态任务中。我们的研究成果和技术进步体现在 美敦力 Summit® RC+S 系统现在可以迈出下一步：第一个侧化、独立、 用于 PD 中 FOG 的双边 STN aDBS 控制算法，由受试者特定神经（目标 1）或行为驱动 （目标 2）控制变量，以及对药物的反应（目标 3）。该项目将在“长凳”中逐步转化 以“床边”的方式，在就地踏步 (SIP) 任务期间测试 aDBS，其中受试者佩戴安全带， 双测力台上的步骤到位。然后，aDBS 将在向前行走、转弯和障碍时进行测试 课程，模拟现实世界中已知触发 FOG 的环境，以及 aDBS 如何响应 受试者特定剂量的药物，同时自由移动。这些实验的结果将提供关键的 在受试者家中测试 aDBS 步态障碍和 FOG 的安全性和可行性的后续步骤 环境和正常用药。患者安全、耐受性、不良反应、步态参数和 无 DBS、olDBS、aDBS 和对照期间间歇性冻结发作 (FE) 的次数和持续时间 (i)olDBS将为未来的设备提供输入，并提供适用于NaDBS或KaDBS步态的新颖算法 其他神经系统疾病中的损伤和 FOG。