Unruptured intracranial aneurysm (UIA)
aneurysm) is an abnormal bulge that forms on the wall of an intracranial artery, mostly located at the bifurcation site. Ruptured intracranial aneurysm is the main cause of spontaneous subarachnoid hemorrhage, with a high mortality and disability rate. According to the results of the latest Japanese cohort study, the lethality rate can reach 35%, and the incidence of moderate to severe (Hunt & Hess classification grade 3-5) disability can reach 29%. Therefore, research on the rupture factors of unruptured aneurysms has gradually increased in recent years, and has gradually advanced to the molecular biology level. Hu Peng, Department of Neurosurgery, Xuanwu Hospital, Capital Medical University I. Epidemiological characteristics of unruptured aneurysms: The most representative epidemiological study on intracranial unruptured aneurysms is the systematic evaluation of the epidemiology of intracranial unruptured aneurysms by Monique H M Vlak published in Lancet Neurol in 2011. Sixty-eight studies were included in their study, including four case-control studies and 63 cross-sectional studies, as well as one combined cross-sectional and autopsy study. These 68 studies included 83 study populations, 94,912 patients and 1,450 unruptured aneurysms. The overall aneurysm population incidence for all studies was 2.8% with a 95% confidence interval of 2.0-3.9. The incidence of aneurysms fluctuated from 0-41.8%. The population aneurysm rate was estimated to be 3.2% (1.9-5.2) if the mean age of a population was 50 years and 50% of the population was male. The study also analyzed risk factors for a high incidence of intracranial unruptured aneurysms, including polycystic kidney, a family history of at least two first-generation immediate family members with intracranial unruptured aneurysms or subarachnoid hemorrhage. However, atherosclerosis and pituitary aneurysm are not factors for the high incidence of unruptured intracranial aneurysms. Compared to the male population, the female population had a high incidence of aneurysms, with an age-corrected risk of 1.61 (1.02-2.54). When age is taken into account, the aneurysm incidence rate is 1.1 (0.6-1.8) for women compared to men for those younger than or equal to 50 years of age, but becomes 2.2 (1.3-3.6) for those older than 50 years of age. In terms of regional differences in the incidence of aneurysms, there are no differences in Japan, China, Finland, the United Kingdom, Italy, Germany, and New Zealand compared to the United States. II. Natural history of intracranial unruptured aneurysms There are three landmark studies on the natural history of intracranial unruptured aneurysms. The first study was a worldwide multicenter study published by ISUIA in NEJM in 1998, encompassing 53 centers in Europe and North America. Its study analyzed the regression of included patients using a retrospective cohort study approach. It concluded that the risk of hemorrhage for intracranial unruptured aneurysms less than 10 mm in diameter without a previous history of subarachnoid hemorrhage is extremely low, less than 0.05 per year. However, for unruptured intracranial aneurysms less than 10 mm in diameter with a history of previous subarachnoid hemorrhage, the risk of rupture is increased 11-fold. The article was criticized after publication. The main issues focused on the study design methodology, the criteria for inclusion of patients, and the high selectivity bias in the study. In response, the group published data from its prospective cohort study in the Lancet in 2003. The problems with this study were: 1. All included patients with unruptured aneurysms were divided into two major groups: the surgical group (open clamping) and the inoperative group. The criteria for surgery in this group were not uniform and were based on the independent judgment of each center. This resulted in a selective natural history study group. This is also evident in the comparison of the analysis of the two groups of patients, in which the unoperated group had the majority of 2-7 mm aneurysms. The number of operated patients was nearly 40% more than the number of unoperated patients, which confirms the high selectivity of the unoperated group.2 The unoperated group used for natural history analysis was divided into group 1 (no history of bleeding) and group 2 (history of bleeding) based on whether there was a previous history of subarachnoid hemorrhage. Group 2 included patients who may have undergone previous clamping or embolization of the responsible lesion for the subarachnoid hemorrhage. There is also the possibility of treating the responsible lesion along with other unruptured aneurysms. Therefore, there was also a selective bias in the group 2 patients. It was concluded that anterior circulation unruptured aneurysms smaller than 7 mm without a history of subarachnoid hemorrhage had a very low hemorrhage rate (0 in this group). Because of the selective bias of this study, its external validity is compromised. The Japanese observers of the 2012 Unruptured Aneurysm Study published their results in the NEJM. The study was a prospective multicenter cohort study. Patients with unruptured aneurysms aged greater than or equal to 20 years were included. Initially, 6697 unruptured aneurysms were included, and as the study progressed, 3050 of these aneurysms were successively treated surgically before rupture. The overall annual risk of rupture for aneurysms was 0.95%; the annual risk of rupture for unruptured aneurysms of 3-4 mm diameter was 0.36%, and the risk of rupture increased with increasing diameter, with the risk ratios for each group being: 5-6 mm: 1.13; 7-9 mm: 3.35; 10-24 mm: 9.09; and ≥25 mm: 76.26. ≥The independent risk factors for rupture of unruptured aneurysms were: aneurysm diameter greater than or equal to 7 mm, anterior and posterior communicating aneurysms, and the presence of small caruncles in the aneurysm wall. Women and hypertension increased the risk of aneurysm rupture, and hyperlipidemia decreased the risk of aneurysm rupture, but did not meet the criteria for statistical significance. History of previous subarachnoid hemorrhage, previous and current smoking history, family history of subarachnoid hemorrhage, and multiple aneurysms did not significantly increase the risk of aneurysm rupture. The study excluded unruptured aneurysms of the cavernous sinus segment of the internal carotid artery, as well as clotted and spindle-type aneurysms. Therefore, it is more accurate than previous studies. However, this study was also subject to selective bias. The main reasons for this are: (1) some patients were not included in the study for unknown reasons; (2) nearly half of the patients underwent surgery during the study, and these patients may be at higher risk of rupture; (3) 40% of the patients in the study population were older than 70 years, so the external validity of the results was affected; and (4) there were deficiencies in the collection of information on hypertension and smoking history, so the study of these factors was flawed. The study was flawed by these factors. In summary, a true and accurate natural history study cannot be completed due to ethical issues. From the above data, only a trend and hint can be obtained to provide inspiration for future basic research. Currently, unruptured aneurysms larger than 7 mm in diameter, aneurysms with sites in anterior and posterior traffic, the presence of a small caruncle in the aneurysm, a history of previous subarachnoid hemorrhage, and a history of uncontrolled or poorly controlled hypertension are considered risk factors for rupture of unruptured aneurysms.