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

 说明(申请人提供)尽管人们的认识有所提高，但对MTBIs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)是颅脑损伤后最常见的症状之一，通常在颅脑损伤后14天至3个月内出现。甲状旁腺激素使儿童在日常活动中丧失能力(如上学、锻炼等)，更重要的是，可能会增加发展为长期疾病的风险。尽管其潜在的机制尚不清楚，但PTH可能是持续性的，也可能是由应激(身体或认知)诱发/加重的，这表明PTH涉及涉及自主神经功能的多个大脑系统和区域。此外，神经炎性过程可能在这些系统内维持/促进敏化状态。为了描述PTH患者自主神经功能障碍的特征，我们提出了一系列主要和次要结果指标：(目的1)评估PTH患者的脑网络改变。我们的假设是在自主神经系统的关键区域发现功能和结构的改变，这会加剧PTH。(目的2)评价局部脑血流量的变化。我们假设甲状旁腺高血压患者的基础rCBF和脑血管对生理和认知应激的反应发生改变，提示自主神经张力障碍。支持次要结果的措施将包括：(目标3)自主和心理标记：将大脑功能的变化与自主和心理标记联系起来。我们假设PTH+患者表现出有助于维持头痛相关变化的自主神经音调和心理特征(焦虑)的变化，以及疼痛相关恐惧的测量与头痛慢性化的缓解或抵抗相关。(目的4)炎症标志物：将脑功能和结构的改变(脑和三叉神经系统中的白质束)与PTH的炎症标志物联系起来：我们假设MTBIs诱导外周(颅脑损伤部位)和中枢神经系统的炎症分子(细胞因子)的变化，促炎症细胞因子(如IL-6)的升高可能推动或维持PTH。我们的团队在偏头痛成像领域拥有丰富的经验，拥有必要的临床和研究人员、接触患者的途径和成像设施，以完成拟议的研究。

 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.