The Natural Course of Unruptured Cerebral Aneurysms in a Japanese Cohort

The natural history of unruptured cerebral aneurysms has not been clearly defined.


From January 2001 through April 2004, we enrolled patients with newly identified, unruptured cerebral aneurysms in Japan. Information on the rupture of aneurysms, deaths, and the results of periodic follow-up examinations were recorded. We included 5720 patients 20 years of age or older (mean age, 62.5 years; 68% women) who had saccular aneurysms that were 3 mm or more in the largest dimension and who initially presented with no more than a slight disability.


Of the 6697 aneurysms studied, 91% were discovered incidentally. Most aneurysms were in the middle cerebral arteries (36%) and the internal carotid arteries (34%). The mean (±SD) size of the aneurysms was 5.7±3.6 mm. During a follow-up period that included 11,660 aneurysm-years, ruptures were documented in 111 patients, with an annual rate of rupture of 0.95% (95% confidence interval [CI], 0.79 to 1.15). The risk of rupture increased with increasing size of the aneurysm. With aneurysms that were 3 to 4 mm in size as the reference, the hazard ratios for size categories were as follows: 5 to 6 mm, 1.13 (95% CI, 0.58 to 2.22); 7 to 9 mm, 3.35 (95% CI, 1.87 to 6.00); 10 to 24 mm, 9.09 (95% CI, 5.25 to 15.74); and 25 mm or larger, 76.26 (95% CI, 32.76 to 177.54). As compared with aneurysms in the middle cerebral arteries, those in the posterior and anterior communicating arteries were more likely to rupture (hazard ratio, 1.90 [95% CI, 1.12 to 3.21] and 2.02 [95% CI, 1.13 to 3.58], respectively). Aneurysms with a daughter sac (an irregular protrusion of the wall of the aneurysm) were also more likely to rupture (hazard ratio, 1.63; 95% CI, 1.08 to 2.48).


This study showed that the natural course of unruptured cerebral aneurysms varies according to the size, location, and shape of the aneurysm. (Funded by the Ministry of Health, Labor, and Welfare in Japan and others; UCAS Japan UMIN-CTR number, C000000418.)

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.

Disclosure forms provided by the authors are available with the full text of this article at

The members of the UCAS Japan writing committee — Akio Morita, M.D., Ph.D., UCAS Japan Coordinating Office University of Tokyo, and Department of Neurosurgery, NTT Medical Center Tokyo, Tokyo; Takaaki Kirino, M.D., Ph.D., National Center for Global Health and Medicine, Tokyo; Kazuo Hashi, M.D., Ph.D., Pacific Neurosurgical Consulting, Sapporo, Japan; Noriaki Aoki, M.D., Ph.D., University of Texas Health Science Center at Houston, Houston, and Center for Health Service, Outcomes Research and Development–Japan (CHORD-J), Tokyo; Shunichi Fukuhara, M.D., Department of Healthcare Epidemiology, Kyoto University School of Medicine and Public Health, Kyoto, Japan; Nobuo Hashimoto, M.D., Ph.D., National Cerebral and Cardiovascular Center, Osaka, Japan; Takeo Nakayama, M.D., Ph.D., Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan; Michi Sakai, Ph.D., CHORD-J, Tokyo; Akira Teramoto, M.D., Ph.D., Department of Neurosurgery, Nippon Medical School, and the Japan Neurosurgical Society, Tokyo; Shinjiro Tominari, M.D., Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan; and Takashi Yoshimoto, M.D., Ph.D., National Center for University Entrance Examination, Tokyo — assume responsibility for the overall content and integrity of the article.

We thank Robert L. Martuza, David G. Piepgras, and Laligam N. Sekhar for their review and comments and Julie Yamamoto for editorial assistance.

Source Information

The Unruptured Cerebral Aneurysm Study of Japan (UCAS Japan) investigators are listed in the Supplementary Appendix, available at