Unruptured Cerebral Aneurysms: Size, Shape, Location Matter

Megan Brooks

June 29, 2012

June 29, 2012 — The natural course of unruptured cerebral aneurysms is influenced not only by the size of the aneurysm but also by the specific location and shape of the aneurysm, a large prospective study confirms.

Unruptured aneurysms with the greatest risk of rupture are larger than 7 mm in diameter, are located in the posterior or anterior communicating arteries, and have a daughter sac, according to the study, which was published June 28 in the New England Journal of Medicine.

"Incidentally discovered cerebral aneurysms are common, and the best management strategy is uncertain," Akio Morita, MD, PhD, from the University of Tokyo, and investigators from the Unruptured Cerebral Aneurysm Study of Japan (UCAS Japan), note in their article.

Best Management Approach Unclear

Despite the uncertainty, more and more patients are undergoing repair of these aneurysms. "To determine the most appropriate treatment for individual patients, we need to have a better understanding of the risk of rupture of cerebral aneurysms," the authors point out.

The UCAS Japan investigators now report results of a large, prospective cohort study in the Japanese population designed to elucidate the natural course of unruptured cerebral aneurysms and to pinpoint risk factors for rupture.

From January 2001 through April 2004, they enrolled 5720 adults with 6697 unruptured saccular aneurysms at least 3 mm in diameter (mean size, 5.7 mm). Ninety-one percent of the aneurysms were discovered incidentally, and most patients were asymptomatic. The mean age of the cohort was 62.5 years, and 68% were women.

The researchers report that older patients had larger aneurysms: aneurysms measuring 7 mm or larger were found in 18% of patients younger than 59 years, in 21.4% of those aged 50 to 59 years, in 24.7% of those aged 60 to 69 years, and in 32.6% and 39.7% of those aged 70 to 79 and 70 to 89 years, respectively.

Most aneurysms were in the middle cerebral arteries (36%) and the internal carotid arteries (34%).

A total of 111 aneurysms ruptured during the 11,660 aneurysm-years of follow-up. The annual risk of rupture was 0.95% (95% confidence interval [CI], 0.79 - 1.15). Risk of rupture increased with increasing size of the aneurysm, similar to findings from other studies.

Table. Risk of Rupture by Aneurysm Size

Size Hazard Ratio (HR) 95% CI
3 - 4 mm Reference
5 - 6 mm 1.13 0.58 - 2.22
7 - 9 mm 3.35 1.87 - 6.00


10 - 24 mm 9.09 5.25 - 15.74
>25 mm 76.26 32.76 - 177.54

The location of the aneurysm also influenced the risk of rupture. As compared with aneurysms located in the middle cerebral arteries, those located in the posterior communicating arteries were more likely to rupture (HR, 1.90; 95% CI, 1.12 - 3.21), as were those located in the anterior communicating arteries (HR, 2.02; 95% CI, 1.13 - 3.58). This finding also confirms those of prior studies, the investigators say.

In addition, the shape of the aneurysm mattered. Aneurysms with an irregular protrusion of the wall of the aneurysm, or a "daughter sac," were more apt to rupture (HR, 1.63; 95% CI, 1.08 - 2.48).

A history of subarachnoid hemorrhage, former or current smoking, the presence of multiple aneurysms, and hypertension, each of which was an independent risk factor for rupture in other studies, did not significantly affect the risk of rupture in this cohort, the investigators report.

However, only 4% of patients in the study had a history of subarachnoid hemorrhage, making it difficult to assess the influence of this factor on the risk of rupture, they note.

Limitations, Caveats

The investigators say that their calculated annual risk of rupture (0.95%) may be low owing to possible case-selection bias because they censored data when patients underwent surgical intervention, and some of these patients may have been at increased risk for rupture. During follow-up, 2722 patients with 3050 aneurysms underwent surgical repair.

The fact that the study included only Japanese adults is another limitation. Researchers point out that the risk of rupture in the Japanese cohort was higher than that shown in the International ISUIA cohort, which was 90% white.

"Study of the similarities and differences in natural history between these 2 cohorts should yield valuable information about the natural course of unruptured aneurysms. The differences may be "multifactorial rather than just genetic," investigators say.

The study was supported by grants from the Ministry of Health, Labor, and Welfare in Japan; the National Cerebral and Cardiovascular Center in Japan; and the Japan Brain Foundation. Disclosures for the UCAS Japan investigators can be found on the journal's Web site.

N Engl J Med. 2012;366:2474-2482. Abstract


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