Department of Critical Care Medicine, Room 646A, Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA.
Safar Center for Resuscitation Research John G. Rangos Research Center, 6th Floor; 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.
Curr Neurol Neurosci Rep. 2018 Nov 7;18(12):105. doi: 10.1007/s11910-018-0912-9.
Standard clinical protocols for treating cerebral edema and intracranial hypertension after severe TBI have remained remarkably similar over decades. Cerebral edema and intracranial hypertension are treated interchangeably when in fact intracranial pressure (ICP) is a proxy for cerebral edema but also other processes such as extent of mass lesions, hydrocephalus, or cerebral blood volume. A complex interplay of multiple molecular mechanisms results in cerebral edema after severe TBI, and these are not measured or targeted by current clinically available tools. Addressing these underpinnings may be key to preventing or treating cerebral edema and improving outcome after severe TBI.
This review begins by outlining basic principles underlying the relationship between edema and ICP including the Monro-Kellie doctrine and concepts of intracranial compliance/elastance. There is a subsequent brief discussion of current guidelines for ICP monitoring/management. We then focus most of the review on an evolving precision medicine approach towards cerebral edema and intracranial hypertension after TBI. Personalization of invasive neuromonitoring parameters including ICP waveform analysis, pulse amplitude, pressure reactivity, and longitudinal trajectories are presented. This is followed by a discussion of cerebral edema subtypes (continuum of ionic/cytotoxic/vasogenic edema and progressive secondary hemorrhage). Mechanisms of potential molecular contributors to cerebral edema after TBI are reviewed. For each target, we present findings from preclinical models, and evaluate their clinical utility as biomarkers and therapeutic targets for cerebral edema reduction. This selection represents promising candidates with evidence from different research groups, overlap/inter-relatedness with other pathways, and clinical/translational potential. We outline an evolving precision medicine and translational approach towards cerebral edema and intracranial hypertension after severe TBI.
综述目的： 数十年来，治疗严重颅脑创伤后脑水肿和颅内高压的标准临床方案仍惊人地相似。脑水肿和颅内高压在治疗上可以互换使用，而事实上颅内压（ICP）是脑水肿的替代指标，但也代表着其他过程，如质量病变的范围、脑积水或脑血容量。多种分子机制的复杂相互作用导致严重颅脑创伤后发生脑水肿，而目前临床可用的工具并未测量或针对这些机制。解决这些潜在问题可能是预防或治疗严重颅脑创伤后脑水肿和改善预后的关键。
最新发现： 本综述首先概述了脑水肿与 ICP 之间关系的基本原理，包括 Monro-Kellie 学说和颅内顺应性/弹性的概念。随后简要讨论了目前 ICP 监测/管理的指南。然后，我们将重点大部分综述放在针对 TBI 后脑水肿和颅内高压的不断发展的精准医学方法上。介绍了包括 ICP 波形分析、脉搏幅度、压力反应性和纵向轨迹在内的侵入性神经监测参数的个性化。接下来讨论了脑水肿亚型（离子/细胞毒性/血管源性水肿的连续体和进行性继发性出血）。回顾了 TBI 后潜在分子因素导致脑水肿的机制。对于每个靶点，我们展示了来自临床前模型的研究结果，并评估了它们作为脑水肿减少的生物标志物和治疗靶点的临床应用价值。这一选择代表了具有不同研究小组证据、与其他途径重叠/相关以及临床/转化潜力的有前途的候选者。我们概述了针对严重颅脑创伤后脑水肿和颅内高压的不断发展的精准医学和转化方法。
