Time Course of Parkinson's Symptoms in Response to Deep Brain Stimulation

描述(申请人提供)：脑深部刺激(DBS)治疗帕金森病(PD)的主要症状，包括运动迟缓、僵硬和震颤，DBS的疗效强烈依赖于找到刺激参数(频率、脉冲宽度、电压)，以最大限度地减少症状而不引起副作用。然而，目前几乎没有指导原则来告知程序员有关刺激参数的选择。因此，设备编程是一个特别的过程，存在时间、费用和患者不适的困难，患者经常被剥夺刺激的最佳好处。为帕金森病制定合理的脑深部刺激参数的方法的一个主要障碍是缺乏对运动症状对刺激条件变化的反应的时间演变的了解。虽然震颤会立即做出反应，但运动迟缓和僵硬会延迟对刺激变化的反应。延迟响应导致编程过程中的遗留效应，并使有效刺激参数的选择复杂化。这项研究的长期目标是开发用于编程最佳刺激参数的自动化方法。这项建议的直接目标是量化DBS打开或关闭时症状的时间变化，并制定适当的方案来测量刺激参数变化对运动症状的影响。在目标1中，在人类受试者的DBS打开和关闭后，运动症状将以固定的间隔被量化。在目标2中，将运动症状反应数据与数学模型进行拟合，以量化症状变化的时间常数，并确定时间变化是否依赖于刺激持续时间和/或参数。目标1和目标2的结果将用于目标3，以设计一种方案，在刺激开启后的短时间内测量对刺激的稳态反应。其结果将是了解在开启和关闭刺激后症状如何随时间变化。这将使编程方法的设计能够最大限度地减少遗留影响，并选择最佳的DBS参数。最佳的刺激参数将最大限度地缓解症状，允许患者减少他们的多巴胺能药物，最大限度地延长电池寿命，并将电气和药物相关的副作用降至最低。 公共卫生相关性：成功地用脑深部刺激治疗帕金森氏病致残运动症状取决于刺激参数的正确选择。这项研究的结果将是了解帕金森氏症的运动症状如何随着时间的推移对大脑深部刺激做出反应。需要了解症状如何随着时间的推移而变化，才能开发出选择最佳脑深部刺激参数的方法。

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) treats the cardinal symptoms of Parkinson's disease (PD) including bradykinesia, rigidity, and tremor, and the efficacy of DBS is strongly dependent on finding stimulation parameters (frequency, pulse width, voltage) that maximize symptom reduction without causing side effects. However, there are presently few guidelines to inform programmers regarding selection of stimulation parameters. Thus, device programming is an ad-hoc process, with difficulties of time, expense, and patient discomfort, and patients are often deprived of the optimal benefits of stimulation. A major obstacle to developing rational methods of programming deep brain stimulation parameters for PD is the lack of understanding of the temporal evolution of the motor symptom response to changes in stimulation condition. While tremor responds immediately, bradykinesia and rigidity have delayed responses to changes in stimulation. The delayed responses result in carry-over effects during programming and complicate selection of effective stimulation parameters. The long-term goal of this research is to develop automated methods for programming optimal stimulation parameters. The immediate goals of this proposal are to quantify the temporal changes in symptoms when DBS is turned ON or OFF, and develop an appropriate protocol to measure the effects of stimulation parameter variations on motor symptoms. In aim 1, motor symptoms will be quantified at regular intervals after DBS is turned ON and OFF in human subject volunteers. In aim 2, the motor symptom response data will be fit with mathematical models to quantify the time constants of symptom change and to determine whether the temporal changes depend on the stimulation duration and/or parameters. The results of aims 1 and 2 will be used in aim 3 to design a protocol to measure the steady-state response to stimulation at short times after stimulation is turned ON. The outcome will be an understanding of how the symptoms change over time after stimulation is turned ON and OFF. This will enable the design of programming methods which minimize carry-over effects and the selection of optimal DBS parameters. Optimal stimulation parameters will maximize symptom relief, allow patients to reduce their dopaminergic medications, maximize battery life, and minimize both electrical and drug- related side effects. PUBLIC HEALTH RELEVANCE: Successful treatment of the disabling motor symptoms of Parkinson's disease with deep brain stimulation depends on the proper selection of stimulation parameters. The outcome of this research will be an understanding of how the motor symptoms of Parkinson's disease respond over time to deep brain stimulation. Understanding how the symptoms change over time is required to develop methods to select optimal deep brain stimulation parameters.