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

畏光和瞳孔自主神经功能障碍作为创伤后头痛的生物标志物

• 批准号: 10623166
• 负责人: Melissa Cortez
• 金额: $ 20.08万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10623166
• 关键词: Acute; Advisory Committees; Age; Applications Grants; Area; Authorization documentation; Autonomic Dysfunction; Award; Biological; Biological Markers; Biometry; Brain Concussion; Chronic; Chronic Headaches; Clinical; Clinical Research; Color; Colorimetry; Complement; Complex; Data; Development; Diagnosis; Diagnostic; Disease; Disease Marker; Disease Progression; Early Intervention; Early identification; Early treatment; Environment; Exhibits; Exposure to; Functional disorder; Goals; Headache; Headache Disorders; Health; Incidence; Individual; Injury; Institution; Learning; Light; Lighting; Manuscripts; Measurable; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Migraine; Monitor; Nature; Nerve; Neurologist; Neurology; Ophthalmologist; Pain; Pain management; Patients; Pattern; Persons; Phenotype; Photophobia; Photosensitivity; Physiological; Positioning Attribute; Post-Traumatic Headaches; Psychophysics; Public Health; Pupil light reflex; Recovery; Refractory; Reporting; Research; Research Personnel; Risk; Screening procedure; Sensory; Severity of illness; Stimulus; Symptoms; System; Testing; Therapeutic; Traction; Training; Traumatic Brain Injury; Vision; Visual; Visual Psychophysics; Work; authority; burden of illness; career; career development; chronic painful condition; disability; disorder risk; experience; improved; innovation; insight; lens; mild traumatic brain injury; multimodality; neurophysiology; novel; patient oriented; persistent symptom; personalized approach; post intervention; preference; primary outcome; progression risk; response; secondary outcome; sensory mechanism; sex; signal processing; skill acquisition; skills; success; targeted treatment; treatment trial

PROJECT SUMMARY/ABSTRACT: This is a K23 award application for Dr. Melissa Cortez, a neurologist and young investigator pursuing patient- oriented clinical research on sensory and autonomic dysfunction in post-traumatic headache (PTH). A K23 award will provide her with the means to acquire critical skills in three key career development areas: biostatistics, signal processing, and visual function testing (visual psychophysics). By acquiring these skills, Dr. Cortez will fulfill her career goal of becoming an independent investigator in the field of autonomic neurology. To pursue this goal, Dr. Cortez has assembled the mentoring team of Drs. KC Brennan (primary mentor), a systems neurosci- entist 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 a three-person Advisory Committee with authorities in biostatistics, autonomic neurophysiology, and visual psy- chophysics. PTH is a notoriously disabling and treatment refractory chronic pain condition, and is the most common conse- quence of TBI. With the rising incidence of TBI, PTH represents a critically important, actionable public health issue, in which objective diagnostic and disease progression measures are needed. Based on recent evidence and her own preliminary data, Dr. Cortez's central hypothesis is that photophobia in PTH corresponds to objec- tive changes in pupillary autonomic function that are associated with an increased risk of persistent symptoms. She will test this hypothesis by evaluating pupillary function in PTH subjects with photophobia (Aim 1) and de- termining 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 inter- ventions for PTH patients most at risk of prolonged symptoms. The proposed research is significant because PTH remains poorly understood and is a disorder where disease specific treatments are lacking. The proposed research is innovative because it combines sensory and auto- nomic testing to better understand and conceptualize the underlying disease mechanisms, as well as provide objectively measurable markers of disease with clinical utility for identifying patients at risk for disease progres- sion. Additionally, this work will lead to individually targeted, non-addictive therapies targeting sympathetic mod- ulation (vagal nerve stimulation, alpha and/or beta-blockade) and/or light-mitigation therapies for chronic PTH- related pain.

项目总结/摘要： 这是一个K23奖申请梅丽莎·科尔特斯博士，神经学家和年轻的研究人员追求病人- 创伤后头痛（PTH）感觉和自主神经功能障碍的临床研究。K23奖 将为她提供在三个关键职业发展领域获得关键技能的手段：生物统计学， 信号处理和视觉功能测试（视觉心理物理学）。通过掌握这些技能，科尔特斯博士将 实现她的职业目标，成为自主神经学领域的独立研究者。追求这个 Cortez博士已经组建了KC Brennan博士（主要导师）的指导团队，他是一位系统神经科学家， 在头痛和创伤性脑损伤（TBI）的电路功能障碍方面具有专业知识的医生，和Kathleen Digre（合作， 导师），神经眼科专家与专业知识的恐惧症和瞳孔功能。与之相辅相成的是 一个由生物统计学、自主神经生理学和视觉心理学权威人士组成的三人咨询委员会， 生物物理学 PTH是一种众所周知的致残和治疗难治性慢性疼痛状况，并且是最常见的后果。 TBI的顺序。随着TBI发病率的上升，PTH代表了一个至关重要的，可操作的公共卫生 这些问题需要客观的诊断和疾病进展措施。根据最近的证据 根据她自己的初步数据，Cortez博士的中心假设是，PTH中的畏光对应于客观- 瞳孔自主神经功能的积极变化与持续症状的风险增加有关。 她将通过评估患有恐惧症的PTH受试者的瞳孔功能（目标1）和去甲肾上腺素（去甲肾上腺素）来验证这一假设。 确定这些变化是否预示着不良恢复（目标2）。她还将评估是否与PTH相关 当暴露在特定颜色的光下时，恐惧症会更严重（目标3）。如果成功的话，这项工作将带来许多 PTH疾病负担需要客观的措施，使早期识别和个别针对性的间， PTH患者最有可能出现长期症状。 这项拟议中的研究意义重大，因为对PTH的了解仍然很少， 缺乏具体的治疗方法。这项研究是创新的，因为它结合了感官和自动 基因组学测试，以更好地理解和概念化潜在的疾病机制，以及提供 客观可测量的疾病标记物，其具有临床效用，用于鉴定处于疾病进展风险中的患者， 锡永。此外，这项工作将导致针对交感神经调制的个体靶向，非成瘾性疗法， 刺激（迷走神经刺激，α和/或β-阻滞）和/或光缓解治疗慢性PTH- 相关疼痛