Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
JAMA Neurol. 2013 Jan;70(1):85-94. doi: 10.1001/jamaneurol.2013.580.
To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome.
We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS.
A university movement disorders center.
Five patients with implanted DBS.
A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness.
This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches.
clinicaltrials.gov Identifier: NCT01329198.
收集必要的信息，设计一项针对妥瑞氏综合征的计划深部脑刺激（DBS）的更大试验的方法和结果变量。
我们进行了一项由美国国立卫生研究院（NIH）资助的小型临床试验规划研究，以评估双侧中央丘脑核植入 DBS 的安全性和初步疗效。该研究使用了一种颅内置恒流装置，并采用了计划刺激（而非经典的连续刺激）模式。收集并分析了基线和 6 个月时的结果。此外，我们还比较了急性计划刺激与急性连续刺激和关闭刺激的效果。
一所大学运动障碍中心。
5 名接受 DBS 植入的患者。
耶鲁整体抽动严重程度量表（YGTSS）总分改善 50%。
参与研究的受试者平均年龄为 34.4 岁（范围，28-39 岁），平均患病时间为 28.8 年。未发生明显的不良事件或与硬件相关的问题。基线与 6 个月时的数据显示，YGTSS 总分的降低并未达到研究前设定的标准，即在计划刺激设置下 YGTSS 总分改善 50%。然而，YGTSS 总分（平均[标准差]变化，-17.8[9.4]；P=.01）、损伤评分（-11.3[5.0]；P=.007）和运动评分（-2.8[2.2]；P=.045）均有显著改善；改良 Rush 抽动严重程度量表评分总分（-5.8[2.9]；P=.01）和发声性抽动严重程度评分（-2.2[2.6]；P=.04）也有显著改善。在植入后 6 个月进行的急性实验中，对连续、关闭和计划刺激条件进行了盲法评估。所有 3 种条件下的评分均显示出改善的趋势。连续和计划刺激条件的改善趋势优于关闭刺激条件。在腹侧（深部）接触时通常会出现抽动抑制，而导致抽动抑制的编程设置通常与一种平静的主观感觉相关。
本研究提供了安全性和概念验证，表明计划 DBS 方法可改善妥瑞氏综合征的运动和发声性抽动。改进神经刺激器电池寿命、选择结果测量和编程设置的灵活性，可用于提高未来更大规模研究的结果。计划刺激有希望成为将运动和神经精神障碍转向更具反应性神经调节方法的潜在第一步。
clinicaltrials.gov 标识符：NCT01329198。
