Management of Unruptured Intracranial Aneurysms

Natural History ( Table 42.1 )

Intracranial aneurysms are common and may generally be classified as saccular (hemodynamic or “berry”) and fusiform (dissecting, infectious, arteriosclerotic, or traumatic) types. The saccular type is by far the most common and is the focus of this chapter. Autopsy studies have shown that the overall prevalence of intracranial aneurysms in the general population ranges from 0.2% to 9.9%. The population-based incidence of aneurysmal subarachnoid hemorrhage varies from 6 to 21.6 cases per 100,000 persons per year.

The decision of whether to treat an unruptured aneurysm is based on the likelihood of its rupture during the patient’s lifetime. The natural history study with the longest follow-up comes from Helsinki, Finland, where Juvela and colleagues reviewed a series of 142 patients with unruptured aneurysms followed without treatment from 1956 to 198 (median follow-up of 19.7 years). An advantage of the study is that it avoids treatment selection bias, because no unruptured aneurysms were treated in Helsinki before 1979. During 2575 person-years, 33 of the 142 patients (23%) had subarachnoid hemorrhage, resulting in an annual rupture rate of 1.3%. The cumulative rates of rupture were 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years. Twenty-nine of 33 aneurysms that eventually ruptured were smaller than 10 mm in diameter at the time of the original diagnosis (18 were ≤6 mm). ^{, ,} Those aneurysms that ruptured were more likely to have increased in size (≥1 mm) compared to those that did not rupture. Notably, the majority of the patients (131 of 142) had previous subarachnoid hemorrhage from another aneurysm, thus comprising a group of patients which may have had a higher rupture rate compared to those with no prior history of subarachnoid hemorrhage. Nevertheless, the study by Juvela and colleagues provided substantial long-term data on the natural history of unruptured aneurysms, and the annual rupture rate of 1.3% was similar to previously published reports (1% to 2.3%).

Between 1976 and 1997, Tsutsumi and colleagues observed 62 patients who had noncalcified unruptured intradural aneurysms and no prior history of subarachnoid hemorrhage. For small aneurysms (<10 mm), the 5- and 10-year rupture risks were 4.5% and 13.9%, respectively, an annual rupture rate similar to that reported by Juvela and colleagues. ^{, ,} For large aneurysms (>10 mm), the 5- and 10-year rupture risks were several-fold higher, 33.5% and 55.9%, respectively.

From 2003 to 2006, Ishibashi and colleagues elected to observe unruptured intracranial aneurysms at their institution. Of a total of 419 patients with 529 aneurysms, 19 aneurysms ruptured during the observation period, resulting in a 1.4% annual rupture rate. Eight of the 19 aneurysms that ruptured were under 5 mm in size.

In 1998, a large retrospective international study, Phase I of the International Study of Unruptured Intracranial Aneurysms (ISUIA), evaluated the natural history of 1937 unruptured aneurysms in 1449 patients. Patients harboring at least one unruptured aneurysm were divided into two groups: those with no history of subarachnoid hemorrhage (group 1) and those with a history of subarachnoid hemorrhage from another aneurysm (group 2). Patients in these two groups were not selected for surgical repair for various and often unknown reasons. The mean duration of follow-up was 8.3 years. As shown in Table 42.2 , for aneurysms smaller than 10 mm, the annual rupture rate was 0.05% in group 1 (727 patients) and 0.5% in group 2 (722 patients). For aneurysms 10 to 24 mm in size, the annual rupture rate was approximately 1% in both groups. For giant aneurysms (25 mm or larger), the rupture rate was 6% in the first year and declined thereafter. Aneurysms of the posterior circulation (the vertebrobasilar system) were significantly more likely to rupture than aneurysms of the anterior circulation, with basilar apex aneurysms carrying a relative risk of 13.8 compared to other locations. The study concluded that small unruptured aneurysms, particularly those in the anterior circulation with no history of prior aneurysmal subarachnoid hemorrhage, should be left untreated, especially when the morbidity and mortality rates of surgical repair were considered. This study generated significant controversy because its results were substantially different from previously published reports of a 1% to 2% annual rupture risk. ^,

In 2003, prospective data from the ISUIA was published as Phase II. Aneurysms in this study were categorized by size into four groups: under 7 mm, 7 to 12 mm, 13 to 24 mm, and 25 mm or larger. Noncavernous anterior circulation aneurysms had 5-year cumulative rupture rates of 0% to 1.5%, 2.6%, 14.5%, and 40%, by size category, respectively. Posterior circulation aneurysms (including [Pcom] aneurysms, which are usually considered part of the anterior circulation) had cumulative 5-year rupture rates of 2.5%, 14%, 18.4%, and 50%. Although the two ISUIA studies stratified aneurysm size differently, ISUIA II reported rupture rates that were generally higher than ISUIA I (see Table 42.2 ). For aneurysms in the 7- to 10-mm size range, ISUIA II suggested an annual rupture risk (0.5% to 2.9%) that was several-fold greater than the rate of 0.05% to 0.5% purported by ISUIA I, which grouped together all aneurysms under 10 mm in size for the analysis.

Both ISUIA studies have been widely criticized for underestimating the true rupture risk of intracranial aneurysms, and certain limitations may have affected their results:

• 1.

  Selection bias: To be included in either study, a patient first had to be recommended for conservative management by a neurosurgeon. It is quite possible that those aneurysms included in the studies were judged to be very low risk, based on their benign morphology or location (i.e., intracavernous). In ISUIA I, internal carotid artery (ICA) aneurysms represented 42% of the total in group 1 and 27% in group 2; of these, cavernous-segment ICA aneurysms represented 16.9% in group 1 and 9.5% in group 2. In addition, a significant number of patients (32.7% in group 1 and 61.2% in group 2) had very small aneurysms (2 to 5 mm in size) which could also carry a lower rupture risk. Thus the ISUIA I study population included large numbers of patients who harbored intracranial aneurysms considered to have little risk of rupture, at least during the study duration.

• 2.

  Crossover: In both ISUIA phases I and II, some patients who were initially chosen for observation were later advised to have treatment. In phase II, of the 1692 patients in the observation cohort, 534 patients were switched to therapeutic intervention. It is possible that the management strategy changed because of new symptoms or increased aneurysm size, both of which are risk factors for rupture. If those patients were left untreated, the observation cohort rupture rate may have been much higher.

• 3.

  Incomplete follow-up: Mean follow-up for the retrospective phase I study was 8.3 years, and for the prospective phase II study was 4.1 years. Of the 193 patients (11%) who died of causes other than subarachnoid hemorrhage, 52 patients died of intracranial hemorrhage. These patients were excluded from the analysis. It is unknown how these hemorrhages were determined to result from causes other than aneurysm rupture.

Given the disparity between the ISUIA data and other published reports, a population analysis based on prevalence of unruptured aneurysms and incidence of subarachnoid hemorrhage would be helpful. To estimate the prevalence of aneurysms, Winn and colleagues reviewed 3684 cerebral angiography studies performed at the University of Virginia between April 1969 and January 1980. During the pre-CT era, the cerebral angiogram was a commonly performed neuroimaging test for a variety of indications. The authors found 24 asymptomatic unruptured aneurysms in 3684 patients, yielding a prevalence rate of 0.65%. Nearly 80% of the aneurysms were smaller than 10 mm. Because only 53% of the patients underwent a complete angiography study, the authors estimated that the true prevalence ranged from 0.65% to 1.3%. That would mean that in a population of 100,000, between 650 and 1300 people would have an unruptured intracranial aneurysm. Given an annual incidence of subarachnoid hemorrhage of 11 per 100,000 people, a person with an unruptured aneurysm can be estimated to have a 0.85% to 1.7% yearly risk of rupture.

Since ISUIA, a number of other prospective studies on unruptured intracranial aneurysms have been completed. The Unruptured Cerebral Aneurysm Study (UCAS) from Japan prospectively evaluated 5720 patients with unruptured saccular brain aneurysms larger than 3 mm. While this study confirmed findings from ISUIA in terms of aneurysm size and location being predictive of rupture risk, it also demonstrated that anterior communicating artery (ACA) location and presence of a daughter sac increased the likelihood of rupture. This study was significant as it showed that aneurysms in both anterior and posterior communicating arteries ruptured at a relatively high rate even when they were less than 7 mm. While this data pertains to a Japanese population only, it sheds important light on unruptured aneurysm epidemiology.

Another prospective study from Japan (SUAVe: Small Unruptured Aneurysm Verification Study) looked at small unruptured intracranial aneurysms less than 5 mm in 374 patients with 448 aneurysms. Seven patients ruptured during the ensuing 3 and a half years leading to a rupture risk of 0.34% per year in patients with single aneurysms and 0.95% in those with multiple aneurysms. This study found aneurysm multiplicity (with diameter ≥4 mm) to be an independent predictor of rupture in addition to aneurysm diameter, age greater than 50 years, and hypertension.

Lee et al. performed a prospective study in the South Korean population of 7404 patients with unruptured intracranial aneurysms by following them over 3 years. Rupture events occurred in 163 of the 5963 untreated patients leading to a rupture rate of 0.9 cases/100 person years. This study demonstrated highest rupture rate in the first year after unruptured intracranial aneurysm diagnosis and confirmed older age as a risk factor for rupture.

Scoring Schemes for Rupture Risk Prediction of Unruptured Intracranial Aneurysms

A number of scoring systems have been devised that can be used in clinical practice by incorporating all the risk factors described above. The two most common ones are the PHASES score and the Unruptured Intracranial Aneurysm Treatment Score (UIATS).