丘脑底核变频刺激对帕金森步态的调节作用研究

Freezing of gait is a common axial symptom that occurs in late stages of Parkinson’s disease, which is clinically characterized by movement hesitation and walking difficulty, correlating with high disability. Freezing of gait responds poorly to both pharmacological and surgical therapies, such as levodopa medication and deep brain stimulation, respectively. Prior studies have shown that motor symptoms improve well with high frequency stimulation of the subthalamic nucleus, while freezing of gait is only alleviated with relatively low frequency stimulation. Based on these findings, we for the first time proposed the hypothesis of variable frequency stimulation, which has been tested in a small-scale clinical trial. It has been proven that subthalamic nucleus stimulation with alternating high and low frequency electrical pulses can comprehensively improve the motor and axial symptoms of Parkinson's disease. However, it is hard to determine the number of frequencies as well as the duration for each frequency in one cycle, which makes this new stimulation paradigm more complicated and difficult to promote in clinical practice. This project aims to explore the effects of stimulation duration of different stimulus frequencies and the mechanism of the electrophysiological regulation of the subthalamic nucleus on gait regulation. This study will not only provide a clinically feasible solution for the treatment of freezing gait, but also further elucidates the mechanism of the subthalamic nucleus on gait regulation in Parkinson's disease.

冻结步态（FOG）是常见于中晚期帕金森病（PD）患者的一种中线症状，临床表现为起始犹豫，行走困难，致残性极高。研究表明，尽管丘脑底核高频刺激（STN-HFS）能有效改善PD患者的运动症状，对FOG改善相对有限。而相对的低频刺激（LFS）则仅对FOG等中线症状有效果，患者常常面临两难的选择。针对以上问题，本课题组首次提出变频刺激（VFS）假说，而且前期小规模的临床试验证明HFS和LFS交替刺激能够综合改善PD的症状。然而，如何确定频率的种类以及每个频率持续的时间等参数，以及选择的依据，成为制约STN-VFS后续临床推广的关键因素。本项目拟依托两个VFS相关的临床试验，重点研究刺激持续时间对STN不同刺激频率发挥作用的影响规律，初步探索STN核团电生理特性及其调节在步态调控中的作用机制。本研究旨在为STN-VFS治疗FOG提供可行的程控操作解决方案，并进一步阐明STN在PD步态中的作用机制。

冻结步态（FOG）作为中晚期帕金森病（PD）患者常见的一种中线症状，严重影响患者生活质量。临床上迫切需要探索新的治疗方法。脑深部电刺激（deep brain stimulation, DBS） 是一种新兴的神经调控技术，已经用于多种神经精神类疾病的治疗。在前期临床实践及国内外研究结果的基础上，我们提出了变频刺激理论(variable frequency stimulation, VFS)。本项目旨在对STN进行交替的 HFS和LFS刺激，即VFS刺激，预期能够结合两种模式的优势，对 PD 患者的运动症状和中线症状实现综合改善。本项目总计纳入54例受试者，随机对照结果显示，与CFS相比，VFS可显著改善受试者冻结步态症状。此外，通过对患者刺激参数的分析，表明不同刺激触点、电压、频率、刺激时间等参数设置对于患者中线症状的改善具有重要意义，对临床程控操作具有指导意义。机制研究进一步阐明了STN在PD治疗中的作用机制。本项目的研究结果对帕金森病的治疗，综合改善患者的临床症状具有重要的临床意义。此外，本项目对于新治疗模式的探索亦具有指导意义。项目资助发表核心论文1篇，待发表1篇，申请专利1项。