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: 9977619
• 负责人: Melissa Cortez
• 金额: $ 20.07万
• 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/9977619
• 关键词: Acute; Advisory Committees; Applications Grants; Area; 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; Learning; Light; Lighting; Manuscripts; Measurable; Measures; Mediating; Melissa; 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; base; 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; response; secondary outcome; sensory mechanism; sex; signal processing; 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.

项目摘要/摘要： 这是梅利莎·科尔特斯（Melissa Cortez）博士的K23奖项，他是一名神经病学家和年轻研究者，追求患者 - 有关创伤后头痛（PTH）的感觉和自主功能障碍的定向临床研究。 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）。通过获得这些技能，Cortez博士将 实现她成为自主神经病领域的独立研究者的职业目标。追求这一点 目标是科尔特斯博士组建了DRS的指导团队。 KC Brennan（主要导师），系统神经科学 在头痛和创伤性脑损伤（TBI）的电路功能障碍和凯瑟琳·迪格（Kathleen digre）方面具有专业知识（共同） Mentor），一位具有辉煌恐惧症和瞳孔功能专业知识的神经浏览器学家。补充它们是 由生物统计学，自主神经生理学和视觉PSY的当局的三人咨询委员会 chophysics。 PTH是一种臭名昭著的残疾和治疗难治性的慢性疼痛状况，是最常见的疾病 tbi的问题。随着TBI发病率的上升，PTH代表了一个至关重要的，可行的公共卫生 问题，其中需要进行客观的诊断和疾病进展措施。基于最近的证据 以及她自己的初步数据，科尔特斯博士的中心假设是，PTH中的恐惧症对应于Objec- 与持续症状的风险增加有关的瞳孔自主功能的变化。 她将通过评估pth受试者（AIM 1）和DE-的PTH受试者中的瞳孔功能来检验这一假设。 终止这些变化是否预示着恢复不良（AIM 2）。她还将评估是否与PTH相关 暴露于光的特定颜色时，恐惧症会更糟（AIM 3）。如果成功，这项工作将导致很多 需要对PTH疾病负担的客观度量，实现早期识别和单独针对的相互作用 PTH患者的班级最有长期症状的风险。 拟议的研究很重要，因为PTH仍然很熟悉，并且是一种疾病的疾病 缺乏具体的治疗方法。拟议的研究具有创新性，因为它结合了感官和自动 提名测试以更好地理解和概念化潜在的疾病机制，并提供 客观测量的疾病标志物具有临床实用性，用于识别有疾病疾病风险的患者 锡。此外，这项工作将导致针对性化的单独针对性的，非添加性的疗法 ULATION（迷走神经刺激，α和/或β-阻滞）和/或慢性PTH-的轻度缓解疗法 相关疼痛。