Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: CARE4Kids

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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.