Nahed Brian V, Bydon Mohamad, Ozturk Ali K, Bilguvar Kaya, Bayrakli Fatih, Gunel Murat
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Neurosurgery. 2007 Feb;60(2):213-25; discussion 225-6. doi: 10.1227/01.NEU.0000249270.18698.BB.
Despite advances in the treatment of intracranial aneurysms (IA) in recent years, the overall outcome of patients with aneurysmal subarachnoid hemorrhage has shown only modest improvement. Given this poor prognosis, diagnosis of IA before rupture is of paramount importance. Currently, there are no reliable methods other than screening imaging studies of high-risk individuals to diagnose asymptomatic patients. Multiple levels of evidence suggest that environmental factors acting in concert with genetic susceptibilities lead to the formation, growth, and rupture of aneurysms in these patients. Epidemiological studies have already identified aneurysm-specific risk factors such as size and location, as well as patient-specific risk factors, such as age, sex, and presence of medical comorbidities, such as hypertension. In addition, exposure to certain environmental factors such as smoking have been shown to be important in the formation of IA. Furthermore, substantial evidence proves that certain loci contribute genetically to IA pathogenesis. Genome-wide linkage studies using relative pairs or rare families that are affected with the Mendelian forms of IA have already shown genetic heterogeneity of IA, suggesting that multiple genes, alone or in combination, are important in the disease pathophysiology. The linkage results, along with association studies, will ultimately lead to the identification of IA susceptibility genes. Identification of the genes important in IA pathogenesis will not only provide novel insights into the primary determinants of IA, but will also result in new opportunities for early diagnosis in the preclinical setting. Ultimately, novel therapeutic strategies based on biology will be developed, which will target these newly elucidated genetic susceptibilities.
尽管近年来颅内动脉瘤（IA）的治疗取得了进展，但动脉瘤性蛛网膜下腔出血患者的总体预后仅略有改善。鉴于这种不良预后，在动脉瘤破裂前进行诊断至关重要。目前，除了对高危个体进行筛查影像学检查外，没有其他可靠的方法来诊断无症状患者。多个层面的证据表明，环境因素与遗传易感性共同作用导致这些患者动脉瘤的形成、生长和破裂。流行病学研究已经确定了动脉瘤特异性危险因素，如大小和位置，以及患者特异性危险因素，如年龄、性别和是否存在高血压等内科合并症。此外，已证明接触某些环境因素，如吸烟，在IA的形成中很重要。此外，大量证据证明某些基因座在IA发病机制中具有遗传作用。使用受孟德尔形式IA影响的相对对或罕见家族进行的全基因组连锁研究已经显示出IA的遗传异质性，这表明多个基因单独或组合在疾病病理生理学中很重要。这些连锁结果以及关联研究最终将导致IA易感基因的鉴定。鉴定在IA发病机制中重要的基因不仅将为IA的主要决定因素提供新的见解，还将为临床前环境中的早期诊断带来新的机会。最终，将开发基于生物学的新型治疗策略，这些策略将针对这些新发现的遗传易感性。
