Trigeminovascular sensitization in post-traumatic headache: electrophysiologic and blood biomarkers in youth

PROJECT SUMMARY/ABSTRACT Candidate: I am a headache specialist at the Children’s Hospital of Philadelphia (CHOP). I have a PhD in visual systems neuroscience that focused on studying properties of neuronal adaptation in the visual cortex. More recently, I have begun clinical research related to pediatric headache disorders and the study of photophobia in migraine. My long-term goal is to elucidate the pathophysiology of concussion and headache, identify relevant biomarkers, and improve the treatment of these conditions in young people. This grant will enable me to build skills in concussion biomarker development to become an independent, translational neuroscientist dedicated to improving the care of concussion and headache in children. Research: Concussion is a major health concern, affecting 20% of youth in the United States. Headache is the most common symptom following concussion and is associated with longer recovery times and greater disability. However, there are no accepted guidelines on how or when to treat post-traumatic headache (PTH), and there are no early biomarkers to identify youth at risk for prolonged PTH. PTH and migraine share many clinical features and may have overlapping pathophysiology. The goal of this proposal is to determine if pathophysiologic substrates of migraine are present early in PTH. I will examine electrophysiologic and blood candidate biomarkers associated with trigeminovascular pathway sensitization (central to migraine pathogenesis) at multiple time points in youth with PTH lasting longer than 1 month. These measures will be compared to youth with symptom resolution. Environment and Career Development: CHOP and University of Pennsylvania (Penn) offer a rich environment for me to develop as an independent investigator. My mentorship team has diverse expertise and will provide me with a unique set of skills to support biomarker development in pediatric concussion. My primary mentor, Dr. Geoffrey K Aguirre, is an accomplished vision neuroscientist with expertise in the visual system in migraine. He will provide the mentorship needed to develop advanced techniques in signal processing for electrophysiologic biomarkers. My co-mentor, Dr. Ramon Diaz-Arrastia, is a leader in traumatic brain injury biomarker research. He will provide guidance and support on study design for blood biomarker development including the use of biomarkers in clinical trials. My second co-mentor, Dr. Christina Master, is an expert in pediatric concussion who has built the Frontier Minds Matter concussion program at CHOP. This program provides an extensive and well-integrated clinical and research infrastructure for longitudinal concussion studies in youth, which will provide crucial support to the proposed studies.