Personalized Medicine in Cerebrovascular Neurosurgery: Precision Neurosurgical Management of Cerebral Aneurysms and Subarachnoid Hemorrhage.
Personalized Medicine in Cerebrovascular Neurosurgery: Precision Neurosurgical Management of Cerebral Aneurysms and Subarachnoid Hemorrhage.
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DOI：
10.3389/fsurg.2016.00034
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发表时间：
2016
影响因子：
1.8
通讯作者：
Steinberg GK
中科院分区：
文献类型：
--
作者：
Achrol AS;Steinberg GK
脑动脉瘤是常见的血管病变。关于这些病变的发病机制以及它们不稳定和进展到破裂的过程知之甚少。治疗决策的动机是希望防止破裂和毁灭性的发病率和死亡率与导致蛛网膜下腔出血（SAH）。对于出现SAH的患者，需要紧急干预以稳定病变并防止再次破裂。那些幸运地在SAH和随后的动脉瘤固定中存活下来的患者仍然必须面对一系列继发性后遗症，这些后遗症可能包括脑血管痉挛、迟发性缺血、癫痫发作、脑水肿、脑积水以及心、肺和肾系统中内分泌和儿茶酚胺诱导的全身功能障碍。更多地关注了解这些次级过程的病理生理学和分子特征，将有助于开发靶向治疗和新型诊断方法，以改善SAH个性化药物试验中的患者选择。在未破裂的脑动脉瘤中，治疗决策不太明确，目前仅基于治疗较大的病变，使用从最近的研究中概括的刚性动脉瘤尺寸截止值，这些研究是持续争议的主题。进一步加剧这一争议的是，在出血表现时引起临床注意的绝大多数动脉瘤尺寸较小，这表明小动脉瘤确实不是良性病变。因此，更好地预测哪些动脉瘤代表需要临床干预的高风险病变的患者特异性生物标志物至关重要。基因组学和蛋白质组学技术的最新进展使得能够鉴定分子特征，这些分子特征可能被证明在跟踪动脉瘤生长和进展以及鉴定预防性治疗干预的靶点方面是有用的。新的定量神经成像技术最近也出现了，能够非侵入性表征血流动力学因素，炎症和血管壁的结构变化。这些定量神经成像和基于分子的方法的结合使用，称为放射基因组学，是一种在更好地表征个体动脉瘤方面具有巨大前景的技术。在不久的将来，这些放射基因组学技术可能有助于改善生活质量和患者的结局，通过患者特定的方法来治疗未破裂的脑动脉瘤和个性化的医疗管理继发性过程后的蛛网膜下腔出血。
Cerebral aneurysms are common vascular lesions. Little is known about the pathogenesis of these lesions and the process by which they destabilize and progress to rupture. Treatment decisions are motivated by a desire to prevent rupture and the devastating morbidity and mortality associated with resulting subarachnoid hemorrhage (SAH). For patients presenting with SAH, urgent intervention is required to stabilize the lesion and prevent re-rupture. Those patients fortunate enough to survive a presenting SAH and subsequent securing of their aneurysm must still face a spectrum of secondary sequelae, which can include cerebral vasospasm, delayed ischemia, seizures, cerebral edema, hydrocephalus, and endocrinologic and catecholamine-induced systemic dysfunction in cardiac, pulmonary, and renal systems. Increased focus on understanding the pathophysiology and molecular characteristics of these secondary processes will enable the development of targeted therapeutics and novel diagnostics for improved patient selection in personalized medicine trials for SAH. In unruptured cerebral aneurysms, treatment decisions are less clear and currently based solely on treating larger lesions, using rigid aneurysm size cutoffs generalized from recent studies that are the subject of ongoing controversy. Further compounding this controversy is the fact that the vast majority of aneurysms that come to clinical attention at the time of a hemorrhagic presentation are of smaller size, suggesting that small aneurysms are indeed not benign lesions. As such, patient-specific biomarkers that better predict which aneurysms represent high-risk lesions that warrant clinical intervention are of vital importance. Recent advancements in genomic and proteomic technologies have enabled the identification of molecular characteristics that may prove useful in tracking aneurysm growth and progression and identifying targets for prophylactic therapeutic interventions. Novel quantitative neuroimaging technologies have also recently emerged, capable of non-invasive characterization of hemodynamic factors, inflammation, and structural changes in aneurysmal walls. The combined use of these quantitative neuroimaging and molecular-based approaches, called Radiogenomics, is a technique that holds great promise in better characterizing individual aneurysms. In the near future, these radiogenomic techniques may help improve quality of life and patient outcomes via patient-specific approaches to the treatment of unruptured cerebral aneurysms and personalized medical management of secondary processes following aneurysmal SAH.