Department of Neurology, Centre for Movement Disorders and Neurorestoration, University of Florida College of Medicine, 100 S Newell Drive, Gainesville, FL 32610, USA.
Brain. 2012 May;135(Pt 5):1455-62. doi: 10.1093/brain/aws026. Epub 2012 Feb 17.
A major concern regarding ventralis intermedius nucleus deep brain stimulation for essential tremor has been the loss of surgical efficacy over time in a minority of patients. Some experts have ascribed the worsening tremor to tolerance, while other evidence has suggested that disease progression may play a role. Suboptimal lead placement has also been reported to be a factor in worsening tremor following deep-brain stimulation; however, most authors consider this phenomenon to manifest within a few months of the actual surgery. We aimed to dissect the tolerance versus disease progression issue by analysing preoperative versus long-term post-surgical Fahn-Tolosa-Marin Tremor Rating Scale scores both on and off stimulation among 28 patients who underwent ventralis intermedius nucleus deep brain stimulation and 21 age-matched controls. Of the 28 patients in the treatment arm of the cohort, seven (25%) demonstrated evidence of tremor progression, and had a 34% increase in the tremor score off stimulation at the 36 month follow-up compared with a 32% increase among controls (P = 0.67). In one of the seven patients there was evidence of suboptimal lead placement given the lateral position of the lead, and the motor side effects during threshold testing. This patient demonstrated a loss of stimulation benefit between 24 and 36 months, which may have been more indicative of tolerance. The other six subjects (86%) maintained stimulation benefit throughout the follow-up period, despite worsening tremor off stimulation (at a comparable rate to that of controls), making disease progression the most likely explanation. The data suggest that deep brain stimulation tolerance may be over-reported in the literature, and that a tolerance versus disease progression work-up should include: examining the trend in off stimulation scores, accounting for image based lead locations, and during programming sessions checking for thresholds which may elicit clinical benefits and side effects.
对于特发性震颤的腹侧中间核深部脑刺激，一个主要的关注点是少数患者随时间推移手术疗效的丧失。一些专家将震颤恶化归因于耐受性，而其他证据表明疾病进展可能起作用。也有报道称，在深部脑刺激后震颤恶化与导联位置不佳有关；然而，大多数作者认为这种现象在手术实际发生后的几个月内表现出来。我们旨在通过分析 28 例接受腹侧中间核深部脑刺激和 21 例年龄匹配的对照组患者术前与长期术后 Fahn-Tolosa-Marin 震颤评定量表评分，来剖析耐受性与疾病进展问题，这些患者的评分在刺激和不刺激时都进行了评估。在研究组的 28 例治疗组患者中，有 7 例（25%）出现震颤进展的证据，并且在 36 个月随访时，与对照组相比，不刺激时的震颤评分增加了 34%（P=0.67）。在这 7 例患者中有 1 例证据表明导联位置偏侧导致导联位置不佳，并且在阈值测试期间出现运动副作用。该患者在 24 至 36 个月之间失去了刺激获益，这可能更表明是耐受性的原因。其他 6 名患者（86%）在整个随访期间保持了刺激获益，尽管不刺激时的震颤恶化（与对照组相比速度相当），使疾病进展成为最有可能的解释。这些数据表明，深部脑刺激的耐受性在文献中可能被过度报告，并且对耐受性与疾病进展的检查应包括：检查不刺激评分的趋势，考虑基于图像的导联位置，以及在编程期间检查可能产生临床获益和副作用的阈值。
