RTMS for Adults with Severe Tourette Syndrome

描述（由申请人提供）：妥瑞氏综合征（TS）和相关神经精神疾病影响多达0.3 - 1%的人群。它们是慢性、复发性疾病，可能与明显的损伤和残疾有关。尽管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治疗无效或出现无法忍受的副作用。大多数广泛使用的干预措施最多可使抽搐严重程度降低30%至40%。虽然TS的病因是未知的，新兴的知识有关的神经回路已被用来指导设计局灶性脑刺激策略，研究和治疗抽动障碍。在过去的十年中，经颅磁刺激（TMS）已被用于研究TS，重复TMS（rTMS）已被用作至少在过去五年中严重TS的研究干预。针对运动和运动前皮质部位的1 Hz或15 Hz的初始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在5例TS患者中产生了临床显著改善（抽搐严重程度降低67%）。其中两名患者的抽搐症状完全缓解。这些改进保持了三个月。这是一项开放性研究，患者每周接受5天治疗，持续2周，共接受10次治疗。在治疗过程中或随后的三个月内没有发现重大副作用。本II期临床试验拟使用假刺激对照条件复制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名随机分配至假手术组，15名随机分配至活性rTMS组）。耶鲁和哥伦比亚两个研究中心将管理rTMS。我们将使用盲法、独立评估者监测这些干预措施的效果。该初步/可行性研究将使我们能够对后续R 01进行准确的把握度估计，以在更大样本中测试rTMS对SMA的疗效和副作用，并检查副作用、继发性电生理结局（成对脉冲TMS测量运动皮层的兴奋性），次要临床结局（强迫症状、抑郁症状和注意缺陷多动障碍症状），以及同时给予药物的相对影响。

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.