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脑血管神经外科中的个性化医疗:脑动脉瘤和蛛网膜下腔出血的精准神经外科管理

Personalized Medicine in Cerebrovascular Neurosurgery: Precision Neurosurgical Management of Cerebral Aneurysms and Subarachnoid Hemorrhage.

作者信息

Achrol Achal Singh, Steinberg Gary K

机构信息

Department of Neurosurgery, Stanford University School of Medicine , Stanford, CA , USA.

出版信息

Front Surg. 2016 Jun 22;3:34. doi: 10.3389/fsurg.2016.00034. eCollection 2016.

Abstract

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.

摘要

脑动脉瘤是常见的血管病变。人们对这些病变的发病机制以及它们失稳并发展至破裂的过程知之甚少。治疗决策的动机是预防破裂以及与蛛网膜下腔出血(SAH)相关的毁灭性发病率和死亡率。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。那些有幸在首次SAH及随后动脉瘤夹闭术后存活下来的患者仍必须面对一系列继发性后遗症,其中可能包括脑血管痉挛、延迟性缺血、癫痫发作、脑水肿、脑积水以及心脏、肺和肾脏系统中内分泌和儿茶酚胺诱导的全身功能障碍。越来越关注对这些继发性过程的病理生理学和分子特征的理解,将有助于开发针对性的治疗方法和新型诊断手段,以便在SAH的个性化医学试验中更好地选择患者。对于未破裂的脑动脉瘤,治疗决策尚不明确,目前仅基于治疗较大的病变,采用从近期研究中归纳出的严格动脉瘤大小阈值,而这些研究正存在争议。使这一争议更加复杂的是,在出血性发作时引起临床关注的绝大多数动脉瘤尺寸较小,这表明小动脉瘤确实并非良性病变。因此,能够更好地预测哪些动脉瘤代表需要临床干预的高危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识别可能有助于追踪动脉瘤生长和进展以及确定预防性治疗干预靶点的分子特征。新型定量神经成像技术最近也已出现,能够对动脉瘤壁的血流动力学因素进行非侵入性表征、炎症和结构变化。这些定量神经成像和基于分子的方法的联合使用,即放射基因组学,是一种在更好地表征个体动脉瘤方面具有巨大潜力的技术。在不久的将来,这些放射基因组技术可能通过针对未破裂脑动脉瘤的患者特异性治疗方法以及动脉瘤性SAH后继发性过程的个性化医疗管理,帮助改善生活质量和患者预后。

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