IntroductionCoordinated Reset Deep Brain Stimulation (CR DBS) is a novel DBS approach for treating Parkinson's disease (PD) that uses lower levels of burst stimulation through multiple contacts of the DBS lead. Though CR DBS has been demonstrated to have sustained therapeutic effects on rigidity, tremor, bradykinesia, and akinesia following cessation of stimulation, i.e., carryover effect, its effect on Parkinsonian gait has not been well studied. Impaired gait is a disabling symptom of PD, often associated with a higher risk of falling and a reduced quality of life. The goal of this study was to explore the carryover effect of subthalamic CR DBS on Parkinsonian gait.MethodsThree non-human primates (NHPs) were rendered Parkinsonian and implanted with a DBS lead in the subthalamic nucleus (STN). For each animal, STN CR DBS was delivered for several hours per day across five consecutive days. A clinical rating scale modified for NHP use (mUPDRS) was administered every morning to monitor the carryover effect of CR DBS on rigidity, tremor, akinesia, and bradykinesia. Gait was assessed quantitatively before and after STN CR DBS. The stride length and swing speed were calculated and compared to the baseline, pre-stimulation condition.ResultsIn all three animals, carryover improvements in rigidity, bradykinesia, and akinesia were observed after CR DBS. Increased swing speed was observed in all the animals; however, improvement in stride length was only observed in NHP B2. In addition, STN CR DBS using two different burst frequencies was evaluated in NHP B2, and differential effects on the mUPDRS score and gait were observed.DiscussionAlthough preliminary, our results indicate that STN CR DBS can improve Parkinsonian gait together with other motor signs when stimulation parameters are properly selected. This study further supports the continued development of CR DBS as a novel therapy for PD and highlights the importance of parameter selection in its clinical application.

中文翻译：

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丘脑底协调复位深部脑刺激对帕金森步态的影响

简介协调复位深部脑刺激 (CR DBS) 是一种治疗帕金森病 (PD) 的新型 DBS 方法，通过 DBS 导线的多次接触使用较低水平的突发刺激。尽管CR DBS已被证明对刺激停止后的强直、震颤、运动迟缓和运动不能具有持续的治疗效果，即残留效应，但其对帕金森步态的影响尚未得到充分研究。步态受损是帕金森病的一种致残症状，通常与跌倒风险较高和生活质量下降有关。本研究的目的是探讨丘脑 CR DBS 对帕金森步态的后继效应。方法将三只非人类灵长类动物 (NHP) 制成帕金森病，并在丘脑底核 (STN) 中植入 DBS 导线。对于每只动物，连续五天每天进行几个小时的 STN CR DBS。每天早上使用针对 NHP 使用而修改的临床评定量表 (mUPDRS)，以监测 CR DBS 对强直、震颤、运动不能和运动迟缓的残留效应。在 STN CR DBS 之前和之后对步态进行定量评估。计算步长和摆动速度，并与基线、刺激前条件进行比较。结果在所有三只动物中，CR DBS 后观察到僵硬、运动迟缓和运动不能的持续改善。所有动物都观察到摆动速度增加；然而，仅在 NHP B2 中观察到步幅长度的改善。此外，在 NHP B2 中评估了使用两种不同突发频率的 STN CR DBS，并观察到对 mUPDRS 评分和步态的不同影响。讨论虽然是初步的，但我们的结果表明 STN CR DBS 在刺激时可以与其他运动体征一起改善帕金森步态参数选择正确。这项研究进一步支持 CR DBS 作为 PD 新型疗法的持续发展，并强调了参数选择在其临床应用中的重要性。