Post-Traumatic Headache (PTH) in Children: Alterations of Brain Function, Blood Flow and Inflammatory Processes

儿童创伤后头痛 (PTH)：脑功能、血流和炎症过程的改变

• 批准号: 9315956
• 负责人: DAVID BORSOOK
• 金额: $ 53.47万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315956
• 关键词: Accident and Emergency department; Activities of Daily Living; Acute; Age; Anterior; Anxiety; Autonomic Dysfunction; Autonomic nervous system; Awareness; Back; Blood flow; Brain; Brain Concussion; Brain region; Breathing; Cerebrovascular Circulation; Child; Childhood; Chronic; Chronic Brain Damage; Clinic; Clinical Research; Cognition; Cognitive; Craniocerebral Trauma; Data; Diffusion Magnetic Resonance Imaging; Disease; Disease remission; Event; Exercise; Exhibits; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Gene Chips; Headache; Hypothalamic structure; Image; Incidence; Inflammation; Inflammatory; Injury; Insula of Reil; Interleukin-6; Lead; Magnetic Resonance Imaging; Maintenance; Measures; Memory; Migraine; Mild Concussions; Neuraxis; Neuronal Plasticity; Nociception; Outcome Measure; Pain; Patients; Peripheral; Post-Traumatic Headaches; Process; Public Health; Recovery; Reporting; Research; Research Infrastructure; Research Personnel; Resistance; Rest; Risk; Saliva; Sampling; Schools; Series; Severities; Short-Term Memory; Site; Stress; Structure; Suggestion; System; Time; Trigeminal System; aged; brain pathway; cerebrovascular; common symptom; cytokine; experience; experimental study; gray matter; inflammatory marker; insight; mild traumatic brain injury; neuroinflammation; primary outcome; psychologic; public health relevance; response; secondary outcome; sex; trait; white matter

 DESCRIPTION (provided by applicant) Despite increased awareness, a comprehensive understanding of the acute and chronic effects of mTBIs on central nervous system structure and function remains incomplete. Post Traumatic Headache (PTH) is one of the most common symptoms following mTBI and typically develops within 14 days to 3 months after the head injury. PTH incapacitates children in their daily activities (i.e., school, exercise, etc.), and mot importantly, may increase the risk for developing long-term disorders. Although the underlying mechanism remains unknown, PTH may be continuous or evoked/exacerbated by stress (physical or cognitive) indicating that PTH involves multiple brain systems and regions involved in autonomic function. In addition, neuroinflammatory processes may be maintaining/facilitating-sensitized states within these systems. To characterize the autonomic dysfunction in patients with PTH we propose a series of primary and secondary outcomes measures; (Aim 1) To Evaluate brain network alterations in PTH. We hypothesize to find functional and structural alterations in key regions of the autonomic nervous system, which exacerbate PTH. (Aim 2) To Evaluate Alterations in Regional Cerebral Blood Flow (rCBF). We hypothesize that patients with PTH exhibit alterations in basal rCBF and cerebrovascular responses to physical and cognitive stress, suggestive of a dysfunction in autonomic tone. Supporting secondary outcome measures will include; (Aim 3) Autonomic and psychological Markers: To Correlate Alterations in brain function with autonomic and Psychological Markers. We hypothesize that patients with PTH+ exhibit alterations in autonomic tone and psychological trait (anxiety) that contributes to the maintenance of headache related changes and that measures of pain related fear correlate with remission or resistance to headache chronification. (Aim 4) Inflammatory Markers: To Correlate Alterations in brain function and structure (white matter tracts in the brain and trigeminal system with Inflammatory Markers in PTH: We hypothesize that mTBIs induce changes in inflammatory molecules (cytokines) in the periphery (site of head injury) and in the central nervous system and that elevation of pro-inflammatory cytokines (e.g., IL-6) may drive or maintain PTH. Our group has extensive experience in the field of migraine imaging and has the necessary clinical and research personnel, access to patients, and imaging facilities to complete the proposed study.

 描述（由申请人提供）尽管人们的认识有所提高，但对 mTBI 对中枢神经系统结构和功能的急性和慢性影响的全面了解仍然不完整，创伤后头痛 (PTH) 是 mTBI 后最常见的症状之一，通常在以下时间发生。头部受伤后 14 天到 3 个月内，PTH 会使儿童无法进行日常活动（即上学、锻炼等），更重要的是，可能会增加患病的风险。尽管潜在的机制仍不清楚，但 PTH 可能会因压力（身体或认知）而持续或诱发/加剧，这表明 PTH 涉及涉及自主功能的多个大脑系统和区域。此外，神经炎症过程可能正在维持/加剧。为了表征 PTH 患者的自主神经功能障碍，我们提出了一系列主要和次要结果测量（目标 1）：评估 PTH 中的大脑网络变化，以发现功能和结构。自主神经系统关键区域的改变，加剧了 PTH（目标 2）评估局部脑血流 (rCBF) 的变化，我们发现 PTH 患者表现出基础 rCBF 和脑血管对身体和认知压力的反应的改变。支持次要结果指标包括：（目标 3）自主神经和心理标记：将大脑功能的变化与自主神经和心理联系起来。心理标志物。我们发现 PTH+ 患者表现出自主神经张力和心理特征（焦虑）的改变，这有助于维持头痛相关的变化，并且疼痛相关恐惧的测量与头痛慢性化的缓解或抵抗相关（目标 4）。标记物：将大脑功能和结构（大脑和三叉神经系统中的白质束）的变化与 PTH 中的炎症标记物相关联：我们发现 mTBIs 会引起以下变化：外周（头部受伤部位）和中枢神经系统的炎症分子（细胞因子），促炎细胞因子（例如 IL-6）的升高可能驱动或维持 PTH。偏头痛成像并拥有必要的临床和研究人员、接触患者和成像设施来完成拟议的研究。