Karl Jessica A, Ouyang Bichun, Verhagen Metman Leo
Movement Disorder Section of Neurological Sciences, Rush University Medical Center, 1725 W. Harrison Street, Suite 755, Chicago, IL, 60612, USA.
Neurol Ther. 2019 Dec;8(2):483-489. doi: 10.1007/s40120-019-0140-5. Epub 2019 Jun 26.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) using high-frequency (130-185 Hz) stimulation (HFS) is more effective for appendicular than for axial symptoms. Low-frequency stimulation (LFS) of the STN may reduce gait/balance and speech impairment but can result in worsened appendicular symptoms, limiting its clinical usefulness. A novel dual-frequency paradigm (interleave-interlink, IL-IL) was created in order to reduce gait/balance and speech impairment while maintaining appendicular symptom control in Parkinson's disease (PD) patients chronically stimulated with DBS.
Two overlapping LFS programs are applied to each DBS lead, with the overlapping area focused around the optimal electrode contact. As a result, this area receives HFS, controlling appendicular symptoms. The non-overlapping area receives LFS, potentially reducing gait/balance and speech impairment. Patients were separated into three categories based on their chief complaint(s): gait/balance impairment, speech impairment, and/or incomplete PD symptom control. The Clinical- Global Impression of Change scale (CGI-C) was completed retrospectively based on patient/caregiver feedback in patients who remained on IL-IL (at 3 months and at the last follow-up).
Seventy-six patients were switched from optimized HFS to IL-IL. Fifty-five (72%) patients remained on IL-IL after 22 ± 8.7 months. The median (range) CGI-C for gait was 2 (1-5) at 3 months and 3 (1-4) at last follow-up, for dysarthria it was 4 (1-4) at 3 months and 4 (1-5) at last follow-up, and for PD motor it was 2 (1-3) at 3 months and 2 (1-3) at last follow-up.
A substantial number of patients remained on IL-IL because of subjective improvements in gait/balance, speech, or PD symptoms. A prospective, double-blind, crossover study with objective/quantitative outcome measures is underway.
使用高频（130 - 185赫兹）刺激（HFS）对丘脑底核（STN）进行深部脑刺激（DBS），对肢体症状的疗效比对轴性症状更显著。对STN进行低频刺激（LFS）可能会减轻步态/平衡及言语障碍，但会导致肢体症状恶化，限制了其临床应用价值。为了在帕金森病（PD）患者中，在维持对肢体症状控制的同时减轻步态/平衡及言语障碍，创建了一种新型双频模式（交错 - 互联，IL - IL），这些患者长期接受DBS刺激。
将两个重叠的LFS程序应用于每个DBS电极，重叠区域集中在最佳电极触点周围。因此，该区域接受HFS，控制肢体症状。非重叠区域接受LFS，可能减轻步态/平衡及言语障碍。根据患者的主要诉求，将患者分为三类：步态/平衡障碍、言语障碍和/或不完全的PD症状控制。根据患者/照料者对仍采用IL - IL（3个月及最后一次随访时）患者的反馈，回顾性地完成临床总体印象变化量表（CGI - C）。
76例患者从优化的HFS转换为IL - IL。55例（72%）患者在22 ± 8.7个月后仍采用IL - IL。步态的CGI - C中位数（范围）在3个月时为2（1 - 5），最后一次随访时为3（1 - 4）；构音障碍在3个月时为4（1 - 4），最后一次随访时为4（1 - 5）；PD运动症状在3个月时为2（1 - 3），最后一次随访时为2（1 - 3）。
相当数量的患者因步态/平衡、言语或PD症状的主观改善而仍采用IL - IL。一项采用客观/定量结局指标的前瞻性、双盲、交叉研究正在进行中。
