Movement Disorder Section of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Medtronic Brain Modulation, Minneapolis, Minnesota, USA.
Mov Disord. 2020 Aug;35(8):1369-1378. doi: 10.1002/mds.28048. Epub 2020 Apr 4.
High-frequency (130-185 Hz) deep brain stimulation (DBS) of the subthalamic nucleus is more effective for appendicular than axial symptoms in Parkinson's disease (PD). Low-frequency (60-80 Hz) stimulation (LFS) may reduce gait/balance impairment but typically results in worsening appendicular symptoms. We created a "dual-frequency" programming paradigm (interleave-interlink, IL-IL) to address both axial and appendicular symptoms. In IL-IL, 2 overlapping LFS programs are applied to the DBS lead, with the overlapping area focused on the optimal cathode. The nonoverlapping area (LFS) is thought to reduce gait/balance impairment, whereas the overlapping area (high-frequency stimulation, HFS) aims to control appendicular symptoms.
We performed a randomized, double-blind crossover trial comparing patients' previously optimized IL-IL and conventional HFS paradigms. Each arm was 2 weeks in duration. The primary outcome measure was the patient/caregiver Modified Clinical Global Impression Severity (CGI-S). Secondary outcome measures included blinded motor evaluations, timed tests, patient/caregiver questionnaires, and Personal KinetiGraphs (PKG).
Twenty-five patients were enrolled, and 20 completed. The patient/caregiver CGI-S for gait/balance (P = 0.01) and appendicular symptom control (P = 0.001), and the blinded rater MDS-UPDRS-III (-5.22, P = 0.02), CGI-S gait/balance (P = 0.01), and CGI-S speech (P = 0.02) were better while on IL-IL. Scores on Parkinson's Disease Quality of Life (P = 0.002) and Freezing-of-Gait Questionnaires (P = 0.04) were better on IL-IL. The Timed-Up-and-Go was 9.8% faster (P = 0.01), with 11.8% reduction in steps (P = 0.001) on IL-IL. There was no difference in PKG bradykinesia (P = 0.18) or tremor (P = 0.23) between paradigms.
Our results prompt consideration of this novel programming paradigm (IL-IL) for PD patients with axial symptom impairment as a new treatment option for both axial and appendicular symptoms. © 2020 International Parkinson and Movement Disorder Society.
高频（130-185Hz）深脑刺激（DBS）对帕金森病（PD）的附属症状比轴向症状更有效。低频（60-80Hz）刺激（LFS）可能会减少步态/平衡障碍，但通常会导致附属症状恶化。我们创建了一种“双频”编程模式（交错链接，IL-IL），以解决轴向和附属症状。在 IL-IL 中，将 2 个重叠的 LFS 程序应用于 DBS 导联，重叠区域集中在最佳阴极上。非重叠区域（LFS）被认为可以减少步态/平衡障碍，而重叠区域（高频刺激，HFS）旨在控制附属症状。
我们进行了一项随机、双盲交叉试验，比较了患者之前优化的 IL-IL 和常规 HFS 方案。每个手臂持续 2 周。主要观察指标是患者/护理人员的改良临床总体印象严重程度（CGI-S）。次要观察指标包括盲法运动评估、计时测试、患者/护理人员问卷调查和个人动态图（PKG）。
共纳入 25 例患者，20 例完成。患者/护理人员的 CGI-S 步态/平衡（P=0.01）和附属症状控制（P=0.001），盲法评定者 MDS-UPDRS-III（-5.22，P=0.02），CGI-S 步态/平衡（P=0.01）和 CGI-S 言语（P=0.02）在 IL-IL 时更好。帕金森病生活质量（P=0.002）和冻结步态问卷（P=0.04）评分在 IL-IL 时更好。计时起立行走测试快 9.8%（P=0.01），步伐减少 11.8%（P=0.001）。在 PKG 运动迟缓（P=0.18）或震颤（P=0.23）方面，两种方案之间没有差异。
我们的结果促使考虑这种新型编程模式（IL-IL）作为轴向症状受损的 PD 患者的新治疗选择，以治疗轴向和附属症状。
