ELECTRO-BOOST: Electroencephalography for cerebral trauma recovery and oxygenation

项目总结 脑电惊厥(ESZ)和高频周期性放电(HF-PD)出现在 大约 30% 的 严重 创伤性的 大脑 伤害 (STBI) 病人 和 是 相联 使用 贫穷 结果 横穿 一个 射程 的 急性 大脑 受伤。 ESZ和HF-PD与高代谢有关，需要 能量供不应求，特别是在易受急性脑损伤的患者。知识上的差距 关于ESZ和HF-PD是否会导致sTBI的继发性脑损伤以及是否对治疗有反应存在。 到目前为止，还没有现有的治疗指南可用于哪些癫痫样异常导致 颅脑损伤后继发性脑损伤或对治疗有反应。因此，我们的中心假设是ESZ和HF- 帕金森病是高危组织代谢危机和继发性脑损伤的一个可治疗的生物标志物。长的- 我们研究计划的范围目标是通过开发治疗方法来改善sTBI患者的预后。 减少急性继发性脑损伤的策略。拟议的项目意义重大，因为它将 确定ESz和HF-PD暴露是否与代谢危机有关，2)量化ESz和HF-PD的影响 3)临床治疗对ESZ和HF-Pd暴露的影响， 颅脑损伤患者的可推广人群。BOOST-3(重型颅脑损伤3期试验中的脑氧优化， U01 NS099946)是一项多中心临床试验，旨在评估一种治疗策略的临床疗效 侵入性监测以优化PbtO2和ICP，与单独使用ICP值相比。它提供独特的基础设施， 量化脑电异常、PbtO2、颅内压、临床结果、 和治疗。我们将在250名Boost-3患者中评估我们的中心假设，这些患者来自选定的Boost-3站点 连续脑电(CEEG)作为颅脑损伤患者多模式介入治疗的标准 监控。我们将解决以下具体目标：具体目标1：展示ESZ的影响 HF-PD对颅脑损伤后脑组织氧合的影响。我们将建立ESZ、HF-PD、 脑缺氧和升高的颅内压以确定ESZ和HF-PD是否是继发性脑的动态生物标志物 颅脑损伤后代谢危象相关的损伤。具体目标2：量化ESZ和HF-Pd暴露的影响 对颅脑损伤后功能转归的影响。我们将确定海拔高度对ESZ和 颅脑损伤后6个月用格拉斯哥预后评定量表(GOSE)评定HF-PD对功能预后的影响。 具体目标3：量化ESZ和HF-PD暴露对sTBI后功能结局的影响。我们 将评估抗癫痫药物干预后ESz和HF-PD暴露的变化。此外，我们还将 测量脑电频率和网络以及格拉斯哥昏迷定量测量的变化 抗癫痫药物治疗前后的GCS评分变化趋势。由此得出的结论是 这项研究将导致未来针对与以下疾病相关的代谢紊乱的干预措施的临床试验 ESZ和HF-PD，以改善sTBI后患者的预后。

PROJECT SUMMARY Electrographic seizures (ESz) and high-frequency periodic discharges (HF-PD) are present in approximately 30% of severe traumatic brain injury (sTBI) patients and are associated with poor outcomes across a range of acute brain injuries. ESz and HF-PD are associated with hypermetabolism that demands more energy than supplied, particularly in patients vulnerable from acute brain injury. A gap in knowledge exists regarding whether ESz and HF-PD result in secondary brain injury in sTBI and are treatment-responsive. To date, no existing treatment guidelines are available regarding which epileptiform abnormalities result in secondary brain injury or respond to treatment after sTBI. Thus, our central hypothesis is that ESz and HF- PD represent a treatable biomarker of metabolic crisis and secondary brain injury in at-risk tissue. The long- range goal of our research program is to improve the outcomes of sTBI patients by developing treatment strategies that reduce acute secondary brain injury. The proposed project is significant because it will 1) establish if ESz and HF-PD exposure is linked with metabolic crisis, 2) quantify the impact of ESz and HF-PD on clinical outcome, and 3) investigate the effect of clinical treatment on ESz and HF-PD exposure in a large, generalizable population of sTBI patients. BOOST-3 (Brain Oxygen Optimization in Severe TBI Phase 3 trial, U01 NS099946) is a multicenter clinical trial to evaluate the clinical efficacy of a treatment strategy using invasively monitoring to optimize PbtO2 and ICP compared to ICP alone. It offers a unique infrastructure in a codified cohort to quantify the complex relationship between EEG abnormalities, PbtO2, ICP, clinical outcomes, and treatment. We will evaluate our central hypothesis in 250 BOOST-3 patients from selected BOOST-3 sites performing continuous EEG (cEEG) as standard of care in sTBI patients undergoing invasive multimodality monitoring. We will address the following specific aims: Specific Aim 1: Demonstrate the influence of ESz and HF-PD on brain tissue oxygenation after sTBI. We will establish the relationship between ESz, HF-PD, brain hypoxia, and elevated ICP to determine if ESz and HF-PD are a dynamic biomarker of secondary brain injury related to metabolic crisis after sTBI. Specific Aim 2: Quantify the effect of ESz and HF-PD exposure on functional outcome after sTBI. We will determine the effect of elevations in the peak exposure to ESz and HF-PD on functional outcome measured by Glasgow Outcome Scale – Extended (GOSE) 6 months after sTBI. Specific Aim 3: Quantify the effect of ESz and HF-PD exposure on functional outcome after sTBI. We will evaluate the change in ESz and HF-PD exposure after anti-seizure drug intervention. Further, we will measure the change in quantitative measures of EEG frequency and networks as well as Glasgow Coma Scale (GCS) score trends before and after the administration of anti-seizure drugs. The findings from this study will lead to future clinical trials of interventions targeting disrupted metabolism associated with ESz and HF-PD, in order to improve patient outcomes after sTBI.