Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: CARE4Kids

项目摘要/摘要--总体 持续性脑震荡后症状(PPCS)的预测、检测、处理和预防 代表了当今创伤性脑损伤(TBI)科学中一些最重要的神经学挑战。 在本申请中，PPCS将指持续≥3个月的脑震荡后症状，一致 与国家神经疾病和中风研究所的脑震荡通用数据元素。我们 使用内表型的概念来探讨这一点，数量行为性状的特征是客观的 使用基于血液的、成像或自主测量或其他技术的测量。了解 PPCS的内表型将为早期识别和潜在的干预提供机会， 治疗和预防。这个应用程序的首要目标是开发一种预测算法 早期和中期青少年(EMA)的PPC内表型为临床筛查和管理提供信息 以及未来的研究。我们的具体目标是：具体目标1.在开发队列中，开发和表征 单项客观生物标记物结合症状群预测PPCS的研究 神经心理功能。生物标志物将在3个研究核心中进行检查：自主神经、成像和血液- 基于。具体目标2.通过将两种或两种类型的PPCS结合起来，建立和表征EMA中PPCS的内表型 更客观的生物标记物，包括症状群和神经心理测量。具体目标3.至 前瞻性验证脑震荡EMA患者AIMS 1和AIMS 2的内表型生物标记物 (验证队列)。具体目标4.使用经过验证的方法创建临床有用的风险分层算法 生物标志物，结合症状和神经行为功能，将预测 PPC。发展队列将从现有的脑震荡和运动医学诊所招募，时间为6点 四角青年联盟(4CyC)内的地点。该队列将包括0-12岁的受试者 脑震荡几个月后，可能会在PPCS患者中得到丰富，并已被证明是可行的 一项观察性的前瞻性登记。验证队列将从相同的诊所招募，但也 扩展到初级保健诊所/网络和急诊科(急性/亚急性)，并遵循 慢性时间点。有了这个更广泛和更普遍的队列，候选的基于血液的、成像和 来自开发队列的自主生物标记物将进行测试和验证。这是从这些第二个队列数据中得出的 将开发一种预测性算法(可能结合临床和生物标记物测量)。

PROJECT SUMMARY/ABSTRACT – Overall The prediction, detection, management and prevention of persistent post-concussive symptoms (PPCS) represent some of the most important neurological challenges in the science of traumatic brain injury (TBI) today. For the purposes of this application, PPCS will refer to post-concussive symptoms lasting ≥3 months, consistent with the National Institute of Neurological Disorders and Stroke Common Data Elements for concussion. We approach this using the concept of endophenotypes, quantitative behavioral traits characterized by objective measures using blood-based, imaging or autonomic measures or other techniques. Understanding the endophenotypes of PPCS will provide opportunities for early identification and potentially for intervention, treatment and prevention. The overarching goal of this application is to develop a predictive algorithm for PPCS endophenotypes in early and middle adolescents (EMA) to inform clinical screening, management and future research. Our specific aims are: Specific Aim 1. In a Development Cohort, develop and characterize individual objective biomarkers predictive of PPCS by combining biomarkers with symptom clusters and neuropsychological function. Biomarkers will be examined in 3 Research Cores: Autonomic, Imaging and Blood- based. Specific Aim 2. To develop and characterize endophenotypes of PPCS in EMA by combining two or more objective biomarkers with symptom clusters and neuropsychological measures. Specific Aim 3. To prospectively validate endophenotype biomarkers from Aims 1 and 2 in a broad group of EMA with concussion (Validation Cohort). Specific Aim 4. To create a clinically useful risk stratification algorithm using validated biomarkers, in conjunction with symptoms and neurobehavioral function, which will predict the development of PPCS. The Development Cohort will be recruited from existing concussion and sports medicine clinics at 6 sites within the Four Corners Youth Consortium (4CYC). This cohort will include subjects presenting from 0-12 months after concussion, will likely be enriched in those with PPCS, and has proven feasible for recruitment into an observational prospective registry. The Validation Cohort will be recruited from the same clinics but also expanded to primary care clinics/networks and emergency departments (acutely/subacutely) and followed to a chronic time point. With this broader and more generalizable cohort, the candidate blood-based, imaging and autonomic biomarkers from the Development Cohort will be tested and validated. It is from these 2nd cohort data that a predictive algorithm (likely combining clinical and biomarker measures) will be developed.