Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: CARE4Kids

青少年持续性脑震荡后症状的内表型：CARE4Kids

• 批准号: 10203597
• 负责人: GERARD A. GIOIA
• 金额: $ 334.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203597
• 关键词: Accident and Emergency department; Acute; Adolescent; Affect; Algorithms; American; Anxiety; Axon; Behavioral; Biochemical; Biological; Biological Markers; Blood; Brain; Brain Concussion; Cardiovascular system; Categories; Childhood; Chronic; Clinic; Clinical; Clinical Trials; Cognitive; Collaborations; Common Data Element; Data; Detection; Development; Diffusion Magnetic Resonance Imaging; Early Intervention; Early identification; Early treatment; Enrollment; Foundations; Future; Goals; Headache; Image; Impairment; Individual; Injury; Intervention; Lesion; Longitudinal cohort study; Magnetic Resonance Imaging; Measurement; Measures; Membrane; Migraine; Molecular; Moods; Movement; National Institute of Neurological Disorders and Stroke; Neurobehavioral Manifestations; Neurocognitive; Neurologic; Neuropsychology; Phenotype; Phospholipids; Physiological; Population; Post-Concussion Syndrome; Postural adjustments; Prevention; Primary Health Care; Psychophysiology; Radiology Specialty; Registries; Research; Resolution; Risk; Science; Site; Sports Medicine; Symptoms; Techniques; Testing; Time; Traumatic Brain Injury; Validation; Work; Youth; base; biological adaptation to stress; biomarker development; biomarker panel; candidate marker; clinical biomarkers; cohort; cytokine; endophenotype; functional disability; imaging biomarker; imaging modality; innovation; medical specialties; mild traumatic brain injury; molecular marker; neurobehavioral; neuroimaging; neuroinflammation; novel; patient subsets; prediction algorithm; predictive marker; prospective; recruit; respiratory; risk stratification; screening; symptom cluster; symptom treatment; symptomatology; trait

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.

项目总结/摘要-总体 持续性脑震荡后症状（PPCS）的预测、检测、管理和预防 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。 出于本申请的目的，PPCS将指持续≥3个月的脑震荡后症状， 与国家神经疾病和中风研究所共同数据元素的脑震荡。我们 使用内表型的概念来处理这一点，定量行为特征的特点是客观的 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的内在表型将为早期识别和潜在干预提供机会， 治疗和预防。该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PPCS内在表型，以告知临床筛查，管理 和未来的研究。我们的具体目标是：具体目标1。在开发队列中，开发和表征 通过将生物标志物与症状群组合来预测PPCS的个体客观生物标志物， 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。通过结合两种或两种以上的方法，开发和表征EMA中PPCS的内表型。 更客观的生物标志物与症状集群和神经心理学措施。具体目标3。到 前瞻性验证目标1和2中的脑震荡EMA广泛组的内表型生物标志物 （验证队列）。具体目标4。使用经验证的风险分层算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，这将预测发展， PPCS。发展队列将于6岁时从现有的脑震荡和运动医学诊所招募 四角青年联盟（Four Corners Youth Consortium，4CYC）该队列将包括0-12岁的受试者 脑震荡后几个月，可能会在那些与PPCS丰富，并已被证明是可行的招募到 观察性前瞻性登记研究。验证队列将从相同的诊所招募，但也 扩大到初级保健诊所/网络和急诊科（急性/亚急性），并随访至 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 将测试和验证来自发育组群的自主生物标志物。从第二组的数据来看， 将开发一种预测算法（可能结合临床和生物标志物测量）。