The New Tics Study: A Novel Approach to Pathophysiology and Cause of Tic Disorders

项目摘要 至少有20%的儿童在一生中的某个时候有过抽搐，这使得抽搐障碍成为一个研究的主题。 重大公共卫生利益。然而，只有大约3%的儿童抽搐持续一年 个或多个.因此，慢性抽动障碍，包括图雷特综合征，可以被概念化为两个- 步进过程：抽搐开始，然后他们无法缓解。根据数字，这个过程的第二部分是 越不寻常，也许与疾病的关系越密切，但令人惊讶的是，几乎没有研究 研究了在第一次抽搐出现之后，但在清楚孩子是否会抽搐之前， 得了慢性抽动症因此，先前的研究已经确定了大脑的异常， TS儿童的结构和功能通常无法澄清这些异常是否 与抽搐的出现或更重要的抽搐消失过程有关。此外，Tic 可以前瞻性地观察到消失，允许强大的受试者内分析来测试 抽搐发作后不久的脑结构或功能特征是否能预测抽搐发作前的缓解， TS是可诊断的，以及这些特征是否是状态相关的或更持久的标记， 容易抽搐 TS领域的同事们一致认为，此类研究是有价值的，但他们怀疑， 招募工作将极为困难。然而，我们现在已经证明了受试者的入组 新发抽搐（定义为在过去6个月内开始，中位数为3.6个月）的发生率为16 当招聘工作处于高峰期时，尽管预算仍然很少， 没有充分的人员配备或媒体广告。我们已经实施了主题准备和质量 控制方法，使我们能够获得高质量的结构和功能MRI数据， 许多科目。 我们现在建议再招募70例新抽搐受试者，并在 基线和抽动发作1周年时（首次诊断为TS时）。两个时间点 将包括临床数据，结构和功能MRI，以及神经心理学测量，包括 抑制抽搐的能力我们预计将获得55-70名受试者的完整数据（包括 已经收集的数据），因为MRI对运动敏感，我们正在选择患有抽搐的受试者 以及保持静止的额外困难（大约一半的抽搐儿童也患有多动症）。我们将 将该样本的基线数据与匹配的无抽搐对照受试者和匹配的受试者进行比较 已经患有TS或慢性抽动障碍的患者（利用我们实验室的现有数据， 这些组的一些临床和MRI数据）。分析将包括特定先验的测试 假设以及完整数据集的机器学习分析。这些比较将 使我们能够发现TS儿童的影像学差异是否在TS可以被诊断之前就存在。 诊断，当抽搐改善时它们是否消退，以及它们是否预测患有 新的抽搐 对这一“抽动秽语症前”人群的调查为病因学发现打开了一扇全新的窗口 抽动障碍的症状它也可能有重要的临床后果，如果结果确定哪些新的- 抽动的儿童患慢性抽动障碍的风险最高。

Project Abstract At least 20% of all children have tics at some time in their life, making tic disorders a subject of substantial public health interest. However, only about 3% of all children have tics that last for a year or more. Thus chronic tic disorders, including Tourette syndrome, can be conceptualized as a two- step process: tics start, and then they fail to remit. By the numbers, the second part of this process is the more unusual and perhaps more closely related to disease, yet surprisingly, almost no research has examined this critical period after a first tic appears but before it is clear whether the child will go on to have a chronic tic disorder. Therefore prior research that has identified abnormalities of brain structure and function in children with TS generally does not clarify whether these abnormalities are related to tic appearance or to the more important process of tic disappearance. Furthermore, tic disappearance can be observed prospectively, allowing powerful within-subject analyses to test whether features of brain structure or function shortly after tic onset predict remission of tics before TS is diagnosable, and whether such features are state-related or more durable markers of vulnerability to tics. Colleagues in the TS field have agreed that such studies would be valuable, but have suspected that recruitment would be extremely difficult. However, we have now demonstrated enrollment of subjects with New Tics (defined as beginning within the previous 6 months, median 3.6 months) at a rate of 16 subjects per year when recruitment efforts were at their peak—though still on a shoestring budget without full staffing or media advertisements. We have implemented subject preparation and quality control methods that have allowed us to acquire structural and functional MRI data of high quality in many subjects. We now propose to enroll an additional 70 subjects with New Tics and characterize them carefully at baseline and at the 1-year anniversary of tic onset (when TS can first be diagnosed). Both time points will include clinical data, structural and functional MRI, and neuropsychological measures including ability to suppress tics. We expect that complete data will be available for 55-70 subjects (including those already collected), since MRI is sensitive to movement and we are selecting for subjects with tics and additional difficulty holding still (about half of children with tics also have ADHD). We will compare baseline data from this sample to matched tic-free control subjects, and to matched subjects who already have TS or a chronic tic disorder (leveraging existing data in our laboratories to provide some of the clinical and MRI data for these groups). Analyses will include tests of specific a priori hypotheses as well as machine learning analyses of the complete dataset. These comparisons will allow us to discover whether imaging differences in children with TS are present long before TS can be diagnosed, whether they fade when tics improve, and whether they predict outcome in children with new tics. Investigation of this “pre-Tourette” population opens an entirely new window for etiologic discovery in tic disorders. It may also have important clinical consequences, if the results identify which newly- ticcing children are at highest risk for development of a chronic tic disorder.