CARE4Kids: Autonomic Biomarker Core

项目摘要/摘要-自主生物标记核心 当发现许多自主神经系统(ANS)障碍的症状和体征时， 持续性脑震荡后症状(PPCS)，ANS功能在脑震荡中已经异常 研究不足，特别是在青少年中。尽管研究数量有限，但有明确的证据表明 脑震荡后亚急性和慢性ANS功能障碍。在最近的一项系统回顾中，33/36项研究 确定脑震荡运动员和非运动员的ANS异常。最一致的发现较低 休息时的副交感神经活动和通常增强副交感神经反应的活动，如 深呼吸，以及通常增强交感反应的活动，如立位挑战。 然而，现有的研究有很大的局限性，包括对青少年的极少数研究，从小到小 样本量适中(约20名患者)，以及在任何情况下使用的有限的ANS测量或自主挑战集 一项研究。由于这些方法学的限制，以前的研究没有提供关于 评估患有PPCS的青少年ANS功能的最佳措施和测试条件。我们将发展 对青少年ANS功能的全面、可扩展的评估。在众多创新功能中， 这个小组是：1)交感和副交感神经功能的心血管和瞳孔测量，以及 2)评估交感神经和副交感神经活动的一套标准化的简短生理挑战。 我们使用休息、恢复和深呼吸方案来最大限度地提高检测副交感神经的灵敏度。 功能障碍。我们使用立位挑战和心理压力来最大限度地提高检测的敏感度 交感神经功能障碍。心率变异性以及心率、呼吸频率和血压将 在这些活动期间同时录制。我们使用瞳孔测量法作为非心脏评估的补充。 自主神经功能障碍。我们还将根据年龄和性别为小组中的所有措施制定规范 这一点可以纳入临床决策。广泛的ANS测量和测试条件 这里使用的将确定最能预测脑震荡持续性的测量和测试条件 症状。这组测量将用于表征一个或多个ANS内表型，这些表型与 一连串PPCS症状。在这里开发的ANS测量小组将有助于阐明病理生物学 通过检查ANS和中枢神经系统标志物之间的联系和基于血液的 轴突损伤和神经炎症的标志物。

PROJECT SUMMARY/ABSTRACT – Autonomic Biomarker Core While many symptoms and signs of autonomic nervous system (ANS) disorder are found in patients with persistent post-concussive symptoms (PPCS), ANS function in concussion has been extraordinarily understudied, particularly in adolescents. Despite the limited number of studies, there is clear evidence of ANS dysfunction sub-acutely and chronically following concussion. In a recent systematic review, 33/36 studies identified ANS anomalies in concussed athletes and non-athletes. The most consistent findings are lower parasympathetic activity during rest and activities that normally enhance parasympathetic response, such as deep breathing, as well as activities that normally enhance sympathetic response, such as orthostatic challenge. There are, however, major limitations in existing studies including very few studies of adolescents, small to modest sample sizes (~20 patients), and limited sets of ANS measures or autonomic challenges used in any one study. Because of these methodological limitations, prior studies do not provide clear guidance as to the best set of measures and testing conditions to assess ANS function in adolescents with PPCS. We will develop a comprehensive, scalable assessment of ANS function in adolescents. Among the many innovative features of this panel are: 1) both cardiovascular and pupillary measures of sympathetic and parasympathetic function, and 2) a standardized set of brief physiological challenges to assess both sympathetic and parasympathetic activity. We use rest, recovery, and deep breathing protocols to maximize sensitivity for detecting parasympathetic dysfunction. We use an orthostatic challenge and a psychological stressor to maximize sensitivity for detecting sympathetic dysfunction. Heart rate variability as well as heart rate, respiratory rate, and blood pressure will be recorded concurrently during these activities. We use pupillometry as a complementary non-cardiac assessment of autonomic dysfunction. We will also 3) develop norms by age and gender for all of the measures in the panel that can be incorporated into clinical decision-making. The broad range of ANS measures and testing conditions used here will identify the measures and testing conditions that best predict the persistence of concussive symptoms. This panel of measures will be used to characterize one or more ANS endophenotypes linked to clusters of PPCS symptoms. The panel of ANS measures developed here will help elucidate the pathobiologies underlying PPCS by examining the link between ANS and central nervous system markers and blood-based markers of axonal injury and neuroinflammation.