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

项目摘要 至少20%的儿童在一生中的某个时候会出现抽搐，这使得抽动障碍成为 重大的公共健康利益。然而，只有大约3%的儿童有持续一年的抽搐 或者更多。因此，包括抽动症在内的慢性抽动障碍可以概念化为两种- 分步过程：抽搐开始，然后无法汇款。从数字上看，这个过程的第二部分是 更不寻常，也许与疾病更密切相关，但令人惊讶的是，几乎没有研究 在第一次抽搐出现后，但在确定孩子是否会离开之前，检查了这段关键时期 患上了慢性抽动障碍。因此，先前的研究已经确定了大脑的异常 患有TS的儿童的结构和功能通常不能明确这些异常是否 与TiC的出现或更重要的TiC消失过程有关。此外，抽搐 可以前瞻性地观察到消失，从而允许测试强大的受试者内部分析 抽动发作后不久的脑结构或功能特征是否预示抽动症状的缓解 TS是可诊断的，并且这些特征是与状态相关的还是更持久的 易受抽搐影响。 TS领域的同事们一致认为这样的研究将是有价值的，但他们怀疑 招聘将是极其困难的。然而，我们现在已经演示了科目的注册 新抽搐(定义为在过去6个月内开始，中位数为3.6个月)比率为16% 招聘工作达到顶峰时每年的科目--尽管预算仍然很少 没有全员配备或媒体广告。我们已经落实了科目准备和质量 控制方法，使我们能够获得高质量的结构和功能磁共振数据 很多科目。 我们现在建议额外招收70名新TICS科目，并仔细描述他们的特征，网址为 基线和抽动发作一周年时(即首次诊断为抽动综合征时)。两个时间点 将包括临床数据、结构和功能核磁共振以及神经心理学测量，包括 抑制抽搐的能力。我们预计将有55-70名受试者的完整数据(包括 已经收集的)，因为MRI对运动敏感，我们正在选择抽搐的受试者 还有更多的站立困难(大约一半的抽搐儿童也有ADHD)。我们会 将此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或慢性抽动障碍的人(利用我们实验室的现有数据来提供 这些组的一些临床和MRI数据)。分析将包括特定先验的测试 假设以及对整个数据集的机器学习分析。这些比较将 让我们发现患有TS的儿童是否在TS发生之前很久就出现了影像差异 确诊后，抽搐改善后它们是否消失，以及它们是否预测儿童抽搐的结果 新的抽搐。 对这一“抽动症前期”人群的研究为病因学发现打开了一扇全新的窗口 出现抽动障碍。它还可能产生重要的临床后果，如果结果确定哪些新的- 患抽搐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.