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Photophobia and Pupillary Autonomic Dysfunction as Biomarkers of Post-Traumatic Headache

Dr. Melissa Cortez is a neurologist and clinical neuroscientist pursuing patient-oriented clinical research on sensory and autonomic dysfunction in post-traumatic headache (PTH). She just received a K23 award from the National Institute of Neurologic Disease and Stroke (NINDS, part of NIH). ‘K awards’ are highly competitive career development grants, awarded to our most promising clinician scientists at the beginning of their independent research careers.

Post-traumatic headache (PTH) is a notoriously disabling and difficult to treat pain condition, and it is extremely common – indeed it is the most common consequence of traumatic brain injury (TBI). Based on recent evidence and her own preliminary data, Dr. Cortez’s hypothesis is that photophobia (light aversion) and concurrent pupillary dysfunction serve as biomarkers of disease, that allow monitoring of disease course and can guide treatment decisions. She will test this hypothesis by evaluating pupillary function in

Dr. Cortez using a tilt table

PTH subjects with photophobia (Aim 1) and determine whether these changes predict poor recovery (Aim 2). She will also evaluate whether PTH-related photophobia is worse when exposed to specific colors of light (Aim 3). If successful, this work will lead to much needed objective measures of PTH disease burden, enabling early identification and individually targeted interventions for PTH patients most at risk of prolonged symptoms.

In addition to the research project itself, Dr. Cortez’s K23 award will develop critical skills in three key career development areas: clinical research methodologies, signal processing, and visual psychophysics. To pursue this goal, Dr. Cortez has assembled the mentoring team of Drs. KC Brennan (primary mentor), a systems neuroscientist with expertise in circuit dysfunction of headache and traumatic brain injury (TBI), and Kathleen Digre (co-mentor), a neuro-ophthalmologist with expertise in photophobia and pupillary function. Complementing them is an Advisory Committee with skills in human trial design, biostatistics, and visual psychophysics.

If successful, Dr. Cortez's work will provide the first, objectively measurable markers of PTH disease burden, with clinical utility for identifying patients at risk for disease progression. Additionally, this work may lead to individually tailored therapies targeting sympathetic modulation (vagal nerve stimulation, alpha and/or beta-blockade) and/or light-mitigation therapies for chronic PTH-related pain.