Understanding Rupture Risk Factors for Intracranial Aneurysms : Which Ticking Time Bomb Needs to be Defused ?

U nderstanding the natural history of a disease is paramount to defining treatment strategies and algorithms. Intracranial aneurysms are no exception to this rule. Over the past decade, an extensive body of literature has been generated with the goal of improving our understanding of intracranial aneurysms and the factors that govern their rupture risk. However, most large-scale trials have been marred with controversy, including the International Study of Unruptured Intracranial Aneurysms (ISUIA), the shortcomings of which are well documented. Although certain intrinsic and extrinsic factors have consistently been found to be associated with a higher risk of rupture in various studies, there is still a lack of a complete understanding of the natural history of intracranial aneurysms. In addition, in further analysis of the known risk factors, some discrepancies start to emerge. For example, although aneurysm size is a welldocumented risk factor, the optimal cutoff size is yet to be defined. Aneurysm location can also affect rupture risk independently of size. In addition, with the increasing number of population-based studies, certain reports of interracial differences have emerged, further adding to the complexity of the matter. In the face of all this uncertainty, Murayama et al conservatively followed up a cohort of 1960 aneurysms for up to 10 years and performed a risk analysis of rupture. From January 2003 to December 2012, the authors enrolled 1556 patients with 1960 aneurysms of 2665 patients with 3434 aneurysms screened. Patients were eligible for the study if they had an aneurysm at least 2 mm in its largest dimension. Exclusion criteria included fusiform, traumatic, or mycotic aneurysms; treatment before enrollment in the study; carotid cavernous aneurysms; and infundibular dilations. The authors recommended observation for aneurysms ,5 mm and treatment for aneurysms . 10 mm. For aneurysms between 5 and 10 mm, risks of treatment vs observation were discussed with the patients. Patients were followed up until time of subarachnoid hemorrhage (SAH), death resulting from any cause, or last possible follow-up contact. Patients were divided into 2 groups. Group 1 was composed of patients with no history of SAH, and group 2 was composed of patients with a history of SAH. Patients who presented with signs and symptoms of mass effect were treated urgently. Mean follow-up was 7388 aneurysmyears. The most common was middle cerebral artery (MCA) aneurysms (535 aneurysms, 27.3%), followed by internal carotid artery (ICA) aneurysms not connected to the origin of the posterior communicating artery (PCom; 525 aneurysms, 26.8%). Aneurysms at the origin of the PCom were the third most common (401 aneurysms, 20.5%), followed by vertebral artery–basilar artery aneurysms (169 aneurysms, 8.6%). Fifty-six aneurysms ruptured during the follow-up period, with an overall annual incidence SAH of 0.76%. Mean duration to rupture from initial presentation was 547 days. Regarding the rupture risk factors, aneurysm size, specific location, history of SAH, and the presence of a daughter sac were found to be independent risk factors in both single and multivariate Cox proportionalhazard models. On the other hand, and surprisingly, smoking, family history of SAH, age, female sex, hypertension, and diabetes mellitus were not associated with risk of rupture. Average rupture size was 7.5 6 5.74 mm. Of note, 39 ruptures (69.6%) occurred in aneurysms ,7 mm in size. The probability of rupture increased with size. The authors then performed multiple analyses with the cutoff size set at 5, 6, 7, 8, 9, and 10 mm. They noted a statistical significance in all selected cutoff sizes with and without adjustment for other risk factors. In terms of locations (Table), vertebrobasilar aneurysms were associated with the highest rupture risk, followed by PCom, MCA, anterior cerebral artery (ACA), and then finally ICA aneurysms. Vertebrobasilar and PCom aneurysms had a significantly higher hazard ratio of rupture, whereas MCA and ACA aneurysms had only a moderate increase in risk. Fifteen of the 56 aneurysm ruptures (26.8%) resulted in death, and 16 of the 56 (28.65) ended in moderate to severe disability (modified Rankin Scale score of 3-5). Fewer than half of the patients with ruptures returned to normal life. None of the patients who had large or giant aneurysms recovered without deficits. The mortality rate of these patients was 69% (9 of 13), whereas the mortality rate of aneurysms ,5 mm was 18% (4 of 22). This study confirms many concepts about intracranial aneurysms. More than half of the ruptured aneurysms ended in at least moderate disability, further revealing the devastating effect of aneurysmal SAH. Size and location have again been shown to be independent risk factors for rupture. Unlike ISUIA, however, this study