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: 10379949
• 负责人: Melissa Cortez
• 金额: $ 19.94万
• 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/10379949
• 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： 这是梅丽莎·科尔特斯博士的K23奖项申请，她是一名神经科医生，也是一名年轻的研究人员，致力于患者- 创伤后头痛(PTH)感觉和自主神经功能障碍的临床研究。K23大奖 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，Cortez博士将 实现她的职业目标，成为自主神经学领域的一名独立研究员。为了追求这一点 Goal，Cortez博士已经组建了KC Brennan博士(主要导师)的指导团队，他是一名系统神经科学- Entist在头痛和创伤性脑损伤(TBI)的回路功能障碍方面拥有专业知识，以及凯瑟琳·迪克雷(联合 Mentor)，他是一位在畏光和瞳孔功能方面有专长的神经眼科医生。相辅相成的是 一个由三人组成的咨询委员会，拥有生物统计学、自主神经生理学和视觉心理健康方面的权威- 化学物理学。 甲状旁腺激素是一种臭名昭著的致残和治疗难治性慢性疼痛疾病，是最常见的并发症。 TBI的顺序。随着颅脑损伤发病率的上升，甲状旁腺激素代表着一种至关重要的、可操作的公共卫生 这一问题需要客观的诊断和疾病进展措施。根据最近的证据 和她自己的初步数据，Cortez博士的中心假设是甲状旁腺激素恐光症对应于Objec- 与持续性症状风险增加相关的瞳孔自主神经功能的动态变化。 她将通过评估PTH患者的瞳孔功能来检验这一假说。 终止这些变化是否预示着恢复不良(目标2)。她还将评估甲状旁腺激素是否与 当暴露在特定颜色的光线下时，畏光更严重(目标3)。如果成功，这项工作将带来许多 甲状旁腺激素疾病负担所需的客观测量，使及早发现并有针对性地个体化 甲状旁腺功能亢进症患者最有可能出现延长症状的药物。 这项拟议的研究意义重大，因为人们对甲状旁腺激素仍知之甚少，而且是一种疾病 目前还缺乏具体的治疗方法。这项拟议的研究具有创新性，因为它结合了感官和自动- 基因组测试，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志物，具有临床实用价值，用于识别有疾病进展风险的患者- 西翁。此外，这项工作将导致针对交感神经模式的个体化、非成瘾性治疗- 促排卵(迷走神经刺激、α和/或β-受体阻滞剂)和/或光缓解疗法治疗慢性甲状旁腺激素 相关疼痛。