The Source for Neurovascular News and Education

August 11, 2020


But size alone is inadequate to reliably predict rupture risk, experts say.

Among patients with multiple intracranial aneurysms, the largest of the bunch is the most likely to rupture, according to a new analysis of data from the Japanese Unruptured Cerebral Aneurysm Study (UCAS). Several experts note that while these findings are clinically useful, size alone should not be used as the primary determinant of whether an aneurysm requires intervention, and the question of how to predict which will rupture is far from closed.

Juhana Frösen, MD, PhD (Kuopio University Hospital, Kuopio, Finland), commented on the study for Neurovascular Exchange. “For a long time, a widely accepted dogma has been that in a patient with acute subarachnoid hemorrhage and multiple aneurysms, the largest one is most likely the one that ruptures,” he wrote in an email. “The fact that this dogma has been pretty universally accepted for a long time demonstrates that in most cases it seems to hold true.” He pointed out, however, that experienced clinicians have all had patients with multiple aneurysms in whom the largest was not the one to rupture.

Other factors known to influence rupture risk, he said, include aneurysm shape and location, flow conditions and hemodynamics, and features of the aneurysm wall, including overall structure and the presence of inflammation. “How these factors associate with size, we do not know yet,” he noted, “but they seem to be independent markers of increased rupture risk.”

In a post hoc analysis of the UCAS, investigators led by Masaaki Shojima, MD, PhD (University of Tokyo Hospital, Japan), identified 25 patients who had multiple cerebral aneurysms and who developed subarachnoid hemorrhage out of the cohort of 5,720. Overall, 62 aneurysms were identified in the 25 patients. The investigators looked at multiple features of the aneurysms that might be predictive of rupture, including distinctiveness in size, location, and shape and compared their predictive values with UCAS and PHASES score. Their findings were published online recently ahead of print in Neurosurgery.

On multivariate analysis, distinctiveness in size (meaning the aneurysm was the single largest among the multiple aneurysms found in an individual patient)—but not in shape or location—significantly identified aneurysms prone to rupture.


Ability to Distinguish Ruptured From Unruptured Aneurysms


OR (95% CI)

P Value

Distinctiveness in Size

5.7 (1.8-17.3)


Distinctiveness in Shape

1.2 (0.1-5.1)


Distinctiveness in Location

1.6 (0.4-6.2)



Notably, the sensitivity and specificity with which distinctiveness in size identified the ruptured aneurysm compared favorably with the PHASES or UCAS scores.


Ability to Predict Rupture




Distinctiveness in Size



Highest UCAS Aneurysm Score in Each Patient



Highest PHASES Aneurysm Score in Each Patient




The authors point out that neither PHASES nor UCAS were designed to identify which aneurysm is likely to rupture in a single patient with multiple aneurysms. While the sensitivity of both these scoring systems are lower than that of distinctiveness in size, “this finding does not negate the effectiveness of these scoring systems; rather, it suggests that size is the strongest predictor (among the other aneurysm-specific factors) of the risk of aneurysm rupture in a patient with multiple aneurysms,” they write.

According to Frösen, these findings can likely be generalized to non-Japanese populations.

“Although the Japanese population has a higher incidence of aneurysmal [subarachnoid hemorrhage] than other populations, and the genetic polymorphisms associated with risk of [the event] in the Japanese are slightly different from those in other populations, I do not think that there is a reason to believe that aneurysm-related or patient-related risk factors determined in Japanese studies could not be extrapolated to other populations,” he explained. “Their significance and the added risk that this risk factor impose might, however, differ in other populations.”

Rupture Remains Unpredictable

Frösen added that these findings support the well-established impression that aneurysm size increases rupture risk and that treatment strategies in patients with multiple aneurysms should often target the largest aneurysms first. However, he noted that the largest aneurysm is not always the one to rupture, so other risk factors should be taken into consideration, including irregular shape, location in the anterior communicating artery, and growth during follow-up. In addition, he recommended that several high-risk aneurysms should be treated at once, if technically feasible.

Three commentaries were published along with the study. According to Jonathan A. Grossberg, MD (Atlanta, GA), the findings serve as a reminder that “there are no hard and fast rules regarding aneurysms.

“Although larger aneurysms are more likely to rupture, there is a lower yet very real rupture risk from small aneurysms as well,” he continued. “Particular consideration should be given to treatments such as clip ligation and flow diversion, which treat multiple aneurysms with one procedure to maximize patient benefit.”

Similarly, Fady T. Charbel, MD, and Sophia F. Shakur, MD (Chicago, IL), report that their own experience would suggest “aneurysm characteristics cannot reliably be used to determine rupture site in cases with non-definitive subarachnoid hemorrhage patterns.” With a sensitivity of only 0.76, they write, size alone should not be the primary factor used to decide whether to intervene.

Finally, Cameron M. McDougall, MD, and Babu G. Welch, MD (Dallas, TX), write that a sample size of only 25 patients is too small to provide any definitive answers on the topic.




Shojima M, Morita A, Nakatomi H, et al. Size is the most important predictor of aneurysm rupture among multiple cerebral aneurysms: post hoc subgroup analysis of Unruptured Cerebral Aneurysm Study Japan. Neurosurgery. 2017;Epub ahead of print.



Shojima, Frösen, and the commentators report no relevant conflicts of interest.