Weiss Daniel, Cebi Idil, Dorrmann Lisanne, Löffler Moritz, Klocke Philipp, Schneider Marlieke, Gharabaghi Alireza
Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research (HIH), Centre for Neurology, University of Tübingen, Tübingen, Germany.
Institute for Neuromodulation and Neurotechnology, University Hospital and University of Tübingen, 72076, Tübingen, Germany.
J Neuroeng Rehabil. 2025 Sep 9;22(1):191. doi: 10.1186/s12984-025-01712-x.
Innovative technology allows for personalization of stimulation frequency in dual-site deep brain stimulation (DBS), offering promise for challenging symptoms in advanced Parkinson's disease (PD), particularly freezing of gait (FoG). Early results suggest that combining standard subthalamic nucleus (STN) stimulation with substantia nigra pars reticulata (SNr) stimulation may improve FoG outcomes. However, patient response and the optimal SNr stimulation frequency vary. Our randomized controlled trial studied patients with advanced PD and persistent FoG, while recording gait kinematics through wearable inertial sensors, along with clinical assessments and patient-reported outcomes. In a with-subjects design, we compared a no-stimulation control with four stimulation conditions: Mono-site STN stimulation at 119 Hz and three dual-site protocols (STN + SNr) with SNr stimulation at 119 Hz, 71 Hz, or 30 Hz, keeping total electrical energy delivered (TEED) constant between SNr conditions. Significant interindividual variability was observed for the optimal stimulation protocol, with comparable proportions favoring STN, STN + SNr119, and STN + SNr71. Changes in spatial and temporal gait parameters, such as stride length and swing time, correlated significantly with FoG clinical improvements, with high correlation coefficients (> 0.8). Optimized stimulation parameters also led to improvements in patient-reported outcomes, highlighting the potential of digital biomarkers in tailoring DBS protocols for individualized outcomes.
创新技术允许在双位点深部脑刺激（DBS）中对刺激频率进行个性化设置，为晚期帕金森病（PD）的挑战性症状，尤其是步态冻结（FoG）带来了希望。早期结果表明，将标准的丘脑底核（STN）刺激与黑质网状部（SNr）刺激相结合可能会改善FoG的治疗效果。然而，患者的反应以及最佳的SNr刺激频率各不相同。我们的随机对照试验研究了晚期PD且存在持续性FoG的患者，同时通过可穿戴惯性传感器记录步态运动学，以及进行临床评估和患者报告的结果。在一项受试者内设计中，我们将无刺激对照组与四种刺激条件进行了比较：119赫兹的单位点STN刺激以及三种双位点方案（STN + SNr），其中SNr刺激频率分别为119赫兹、71赫兹或30赫兹，在不同的SNr条件下保持总传递电能（TEED）恒定。对于最佳刺激方案，观察到了显著的个体间差异，支持STN、STN + SNr119和STN + SNr71的比例相当。空间和时间步态参数的变化，如步长和摆动时间，与FoG的临床改善显著相关，相关系数较高（> 0.8）。优化的刺激参数还导致患者报告的结果得到改善，突出了数字生物标志物在为个体化结果定制DBS方案方面的潜力。
