Stanford University School of Medicine, Department of Neurology and Neurological Sciences, Stanford, CA, USA.
Stanford University School of Engineering, Department of Bioengineering, Stanford, CA, USA.
J Parkinsons Dis. 2023;13(4):537-548. doi: 10.3233/JPD-223368.
The sequence effect is the progressive deterioration in speech, limb movement, and gait that leads to an inability to communicate, manipulate objects, or walk without freezing of gait. Many studies have demonstrated a lack of improvement of the sequence effect from dopaminergic medication, however few studies have studied the metric over time or investigated the effect of open-loop deep brain stimulation in people with Parkinson's disease (PD).
To investigate whether the sequence effect worsens over time and/or is improved on clinical (open-loop) deep brain stimulation (DBS).
Twenty-one people with PD with bilateral subthalamic nucleus (STN) DBS performed thirty seconds of instrumented repetitive wrist flexion extension and the MDS-UPDRS III off therapy, prior to activation of DBS and every six months for up to three years. A sub-cohort of ten people performed the task during randomized presentations of different intensities of STN DBS.
The sequence effect was highly correlated with the overall MDS-UPDRS III score and the bradykinesia sub-score and worsened over three years. Increasing intensities of STN open-loop DBS improved the sequence effect and one subject demonstrated improvement on both open-loop and closed-loop DBS.
Sequence effect in limb bradykinesia worsened over time off therapy due to disease progression but improved on open-loop DBS. These results demonstrate that DBS is a useful treatment of the debilitating effects of the sequence effect in limb bradykinesia and upon further investigation closed-loop DBS may offer added improvement.
序列效应是导致言语、肢体运动和步态无法进行，无法交流、无法操作物体或无法行走的一种渐进性恶化，其特征为步态冻结。许多研究表明，多巴胺能药物并不能改善序列效应，但很少有研究对该效应进行时间上的度量，也没有研究过在帕金森病（PD）患者中应用开环式深部脑刺激（DBS）的效果。
研究序列效应是否随时间恶化，以及是否可以通过临床（开环式）DBS 改善。
21 名双侧丘脑底核（STN）DBS 的 PD 患者在 DBS 开启前和开启后每 6 个月进行 3 年的治疗，进行 30 秒的仪器化重复腕关节屈伸运动，并完成 MDS-UPDRS III 测试（治疗期间停药）。10 名患者的子组在 STN DBS 不同刺激强度的随机呈现期间完成该任务。
序列效应与总体 MDS-UPDRS III 评分和运动迟缓子评分高度相关，且在 3 年内逐渐恶化。增加 STN 开环式 DBS 的刺激强度可改善序列效应，1 名患者在开环和闭环 DBS 两种模式下均有改善。
由于疾病进展，治疗期外的肢体运动迟缓序列效应会随时间恶化，但开环式 DBS 可改善这一效应。这些结果表明，DBS 是一种治疗肢体运动迟缓的有效方法，可改善序列效应带来的不良影响，进一步的研究表明，闭环式 DBS 可能会带来进一步的改善。
