Reconciling the devastating and common occurrence of subarachnoid hemorrhage from small anterior circulation aneurysms with seemingly benign natural history reports of similar sized asymptomatic aneurysms remains a major puzzle in modern neuroscience care. The International Study of Unruptured Intracranial Aneurysms (ISUIA) suggested that intracranial aneurysms <7 mm in the anterior circulation have very low rupture risk in patients with no history of subarachnoid hemorrhage (SAH).1 Subsequent studies from Japan,2,3 however, have suggested higher rupture rates than those seen in this subgroup in ISUIA. To study this important issue, Guresir et al4 analyzed their prospective aneurysm database, which was initiated in 1999. The timespan of the study was June 1999 through June 2012. Data on 1114 unruptured intracranial aneurysms were recorded during this time period. Of these aneurysms, 967 were located in the anterior circulation and 688 were <7 mm, highlighting how predominant this subgroup is. Of this subgroup, the authors treated 301 aneurysms, and 387 were observed with annual magnetic resonance angiography (MRA) (Figure). It is on these 387 patients that the authors focus their report, which was published in the September 2013 issue of Stroke.4 Their database included information on aneurysm size, multiplicity, and location as well as the patient's age, sex, history of SAH, smoking status, and the presence of arterial hypertension. Each of these aneurysms was treated conservatively and followed-up yearly by an MRA as long as there was no change in size or morphology of the aneurysm.
The mean follow-up duration was 48.5 ± 37 months, during which three of the 387 aneurysms underwent enlargement and were subsequently treated by surgical clipping. Another three aneurysms, which were stable in size, ruptured. Two of the 3 ruptured aneurysms were located in the middle cerebral artery (MCA) and one of them was located in the distal anterior cerebral artery (ACA). The median time interval from diagnosis to rupture was 4 years and the median size of the ruptured aneurysms was 3 mm. The annual incidence of SAH was 0.2% during the follow-up of 1537.5 aneurysms-years. The cumulative rupture rate increased from 0.05% in 4 years to 1.3% in 5 years and 2.9% in 7 years. The univariate analysis showed that the patient's sex and age did not differ between the group of patients with aneurysm rupture compared to that without aneurysm rupture. The multivariate analysis of the study showed that hypertension (P < .001; HR, 2.6; 95% CI, 2.1-3.3) and < 50 years of age (P = .04; HR, 1.3; 95% CI, 1.01-1.7) are significant predictors of aneurysmal rupture. In the multivariate analysis, no effect on the rupture rate of anterior circulation aneurysms <7 mm was observed by smoking status, size of the aneurysm, and multiplicity of the aneurysm.
While this study suggests low annual rupture rates for anterior circulation aneurysms <7 mm, the rupture rate the authors found was higher than that published in ISUIA. This study does have several limitations. First, patients with high risk factors (previous SAH, symptomatic UIAs, family history of SAH) were treated during the study phase. Second, while the follow-up interval is commendable, it is still relatively short considering that an aneurysm's natural history can play out over decades. Third, the authors did not account for all confounding factors that can influence treatment decisions such as aneurysm morphology (example, the presence of daughter sacs). Furthermore, it is possible that the rupture rates might be diluted by including small paraclinoid aneurysms in the conservative group.
The authors are to be commended for establishing a prospective database and thoughtfully analyzing their data. This paper confirms that even when low risk aneurysms are selected by clinicians for a conservative approach, growth and rupture can still occur. Further refinements in the selection of patients are needed to realize the goal of “precision medicine” in aneurysm management. It is our hope that the authors will continue to follow this cohort and report longer-term follow-up.
1. Wiebers DO, Whisnant JP, Huston J III, et al.. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103–110.
2. Investigators UJ, Morita A, Kirino T, et al.. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med. 2012;366(26):2474–2482.
3. Sonobe M, Yamazaki T, Yonekura M, Kikuchi H. Small unruptured intracranial aneurysm verification study: SUAVe study, Japan. Stroke. 2010;41(9):1969–1977.
4. Guresir E, Vatter H, Schuss P, et al.. Natural history of small unruptured anterior circulation aneurysms: a prospective cohort study. Stroke. 2013. [Epub ahead of print].