RTMS for Adults with Severe Tourette Syndrome

描述（由申请人提供）：抽动秽语综合征（TS）和相关的神经精神疾病影响多达0.3 -1%的人口。它们是慢性、复发性疾病，可能与明显的损伤和残疾有关。虽然临床护理在过去十年中有所改善，但仍有相当数量的患者对现有的治疗方法没有反应或经历无法忍受的副作用。大多数广泛使用的干预措施最多可使抽动严重程度降低30%至40%。虽然TS的病因尚不清楚，但有关潜在神经回路的新知识已被用于指导局灶性脑刺激策略的设计，以研究和治疗抽动障碍。经颅磁刺激（TMS）在过去十年中被用于研究TS，重复TMS （rTMS）至少在过去五年中被用作严重TS的研究干预措施。最初针对运动和运动前皮质部位的1 Hz或15 Hz的rTMS研究在治疗严重TS患者方面取得了有限的成功或没有成功。然而，Mantovani等人（2006）最近针对补充运动区（SMA）的研究首次证明，1 Hz rTMS对5名TS患者产生了显著的临床改善（抽动严重程度降低67%），其中2名患者的抽动症状完全缓解。这些改善持续了三个月。这是一项开放研究，患者每周接受5天治疗，持续两周，总共接受10次治疗。在治疗过程中或随后的三个月没有注意到主要的副作用。这项II期临床试验建议使用假刺激控制条件来复制Mantovani等人（2006）的研究。我们预计筛选50名患者，并选择30名患者参加随机临床试验（15名随机分配到假手术组，15名随机分配到主动rTMS组）。耶鲁大学和哥伦比亚大学将管理rTMS。我们将使用一个盲的、独立的评估者来监测这些干预措施的效果。这项试点/可行性研究将使我们能够对后续的R01进行准确的功率估计，以在更大的样本中测试rTMS对SMA的疗效和副作用，并检查副作用、继发性电生理结果（成对脉冲TMS测量运动皮层的兴奋性）、继发性临床结果（强迫症症状、抑郁症状和注意缺陷多动障碍症状）。以及同时服用药物的相对影响。

DESCRIPTION (provided by applicant): Tourette syndrome (TS) and related neuropsychiatric conditions affect as many as 0.3 -1% of the population. They are chronic, relapsing disorders that can be associated with marked impairment and disability. Although clinical care has improved over the past decade, a significant number of patients fail to respond to the available treatments or experience intolerable side effects. Most of the widely used interventions result in at best a 30 to 40% reduction in tic severity. Although the etiology of TS is unknown, emerging knowledge concerning the underlying neurocircuitry has been used to guide the design of focal brain stimulation strategies to study and treat tic disorders. Transcranial magnetic stimulation (TMS) has been used to investigate TS for the past decade and repetitive TMS (rTMS) has been used as an investigational intervention for severe TS for at least the last five years. Initial rTMS studies targeting motor and premotor cortical sites with either 1 Hz or 15 Hz have had limited or no success in treating individuals with severe TS. However, the recent study by Mantovani et al. (2006) which targeted the Supplementary Motor Area (SMA) was the first to demonstrate that 1 Hz rTMS produced clinically significant improvement (67% reduction in tic severity) in five patients with TS. Two of these patients experienced a complete remission of their tic symptoms. These improvements were maintained for three months. This was an open study in which patients were treated five days a week for two weeks, for a total of 10 treatments. No major side effects were noted during the course of treatment or the subsequent three months. This Phase II clinical trial proposes to replicate the Mantovani et al. (2006) study using a sham stimulation control condition. We anticipate screening 50 patients and selecting 30 patients to participate in a randomized clinical trial (15 randomized to sham and 15 to active rTMS). Two sites will administer rTMS, Yale and Columbia. We will monitor the effects of these interventions using a blind, independent evaluator. This pilot/feasibility study will allow us to make accurate power estimates for a subsequent R01 to test the efficacy and side effects of rTMS to the SMA in a larger sample, and to examine side effects, secondary electrophysiological outcomes (paired-pulse TMS to measure the excitability of the motor cortex), secondary clinical outcomes (obsessive-compulsive symptoms, depressive symptoms, and attention deficit hyperactivity disorder symptoms), and the relative impact of concurrently administered medications.