Introduction

Due to more frequent use of cerebral MRI in the evaluation of minor symptoms, increasing numbers of patients are diagnosed with unruptured intracranial aneurysms (UIA) that prompt counselling. A recent MRI study of healthy volunteers identified a 1.8% prevalence of intracranial aneurysms [28]. Thus, the question of how we should deal with these incidentally found aneurysms poses a problem, and as of yet no solution has been found. Internationally, there is no consensus on how to manage UIAs [18]. As the effects of aneurysm rupture are potentially devastating [3, 23], information on all aspects of rupture risk is important in the counselling of patients with UIAs.

Over the years we have developed a clinical suspicion that there may be differences in the rupture rate of aneurysms depending on the aneurysm’s anatomical location. More specifically, it is our impression that anterior communicating artery aneurysms (AComA) present more frequently as the cause of an acute subarachnoid haemorrhage (SAH) compared with aneurysms in other locations. This observation seems to be in line with data underlying a Finnish study investigating the use of routine cerebral angiography after surgery for saccular aneurysms in which the ratio between ruptured and unruptured AComA was 2.5 [15]. If aneurysms in certain locations are more prone to rupture than others, it is important to clarify not only that such differences exist, but also to identify possible mechanisms behind them.

Reviewing the literature, we found conflicting data on the anatomical distribution of intracranial aneurysms, as well as ethnic differences [10, 11, 16, 22]. The majority of authors recognise female gender, smoking, and hypertension as independent risk factors for intracranial aneurysm formation [12–14, 29]. Much of the debate has also been centred on aneurysm size and if there is an ultimate threshold predicting increased rupture risk [20]. Some evidence also points to aneurysm location as an independent variable predicting rupture, in which basilar tip, AComA, and posterior communicating artery aneurysms (PComA) may all have an increased rupture risk [1, 6, 11, 30]. However, these observations have been made in populations known to have special risk factors for rupture (Japanese and Finnish), and in potentially biased cohorts [1], [7]. It is also possible that regional flow differences may contribute to aneurysm formation. Interestingly, it has been shown that unilateral ligation of the common carotid artery in hypertensive rats can produce AComA aneurysms [8]. In computer simulation studies of aneurysms factors like small impact zone, higher flow rate entering the aneurysm, elevated maximum wall shear stress (WSS), disturbed intra-aneurysmal flow, and narrow jets have been associated with increased risk of rupture [4, 5]. Regarding WSS, Shojima et al. found by mathematical simulation of 20 MCA vessels with aneurysms that maximum WSS occurred near the aneurysm neck and that a low WSS in the aneurysm tip may facilitate aneurysm growth and later rupture due to aneurysm wall degeneration[24].

In the current study of a stable population in a defined geographical region, we have compared unruptured with ruptured aneurysms with respect to anatomical location. The aim was to see if there was a different anatomical distribution of the aneurysms in the two patient groups.

Materials and methods

Hospital structure and population under study

The organisation of the neurosurgical services in Norway has been reported previously [9]. Briefly, in the study period, Norway had five university clinics with neurosurgical departments, each serving smaller local hospitals in one health region. A health region consisted of a geographical area with a well-defined population. There was no geographical overlap between the five health regions. Haukeland University Hospital was the university hospital on the southwestern coast of Norway, serving three counties. Our department was the only neurosurgical referral centre for all hospitals within this region. Thus, all patients that were diagnosed with an intracranial aneurysm in our health region, ruptured or not, were evaluated by our team. The patient leak from our region to other neurosurgical centres was negligible. During the study period the total population in our health region increased from 855,542 in 1991 to 908,589 in 1999 [26].

Patients

The patients included in this retrospective study were identified from the hospital database of diagnosis and treatment in the period from 1 January 1990 through 31 December 1999. The search was performed with registration of every patient in the period with diagnosis codes of 430 and 437.3 (International Classification of Diseases 9) or I60.0-I60.9 and I67.1 (International Classification of Diseases 10). These were the diagnostic codes assigned to patients with ruptured intracranial aneurysms (RIA) or UIAs in our hospital during the study period. Patients with subarachnoid haemorrhage from an arterio-venous malformation or from an unknown source, including perimesencephalic SAH, were excluded. Demographic data and clinical state on admission according to the Hunt and Hess score were registered for all patients. Angiographic data were extracted from the neuroradiology reports. The Koivisto categories [17] for aneurysm location were used:

  1. 1.

    ACA: anterior cerebral artery, anterior communicating artery, pericallosal artery

  2. 2.

    MCA: middle cerebral artery

  3. 3.

    ICA: internal carotid artery, ophthalmic artery, posterior communicating artery, anterior choroidal artery

  4. 4.

    VBA: vertebrobasilar arteries

Statistical analysis

All analyses were performed with SPSS 14.0 for Windows (SPSS, Inc., Chicago, IL). An α-level of 0.05 was used as the significance level in all tests. Group comparisons were performed with Student's t test for normally distributed continuous variables or Mann-Whitney U test for continuous or ordered categorical variables with abnormal distribution. Contingency tables were analysed with Fisher's exact test for dichotomized variables or χ2 statistics.

Results

General characteristics

The median crude rate of intracranial aneurysms referred to our centre was 5.7/100,000 per year, increasing from 3.5/100,000 in 1991 to 6.38/100,000 in 1999. The annual number of patients with SAH increased similarly in the study period from 18 (1990) to 50 (1999) (Table 1). The median number of SAH patients each year was 36.5. In total there were 483 intracranial aneurysms in 421 patients registered and evaluated in our hospital in the 10-year period. Three hundred sixty-one aneurysms had ruptured and caused SAH. The remaining 60 patients, all without a previous SAH history, had a total of 83 UIAs. We excluded 39 UIAs in patients that presented with SAH from another aneurysm, leaving 444 aneurysms eligible for analysis. These 444 aneurysms were found in 421 patients: 197 aneurysms in men (44.4%) and 247 aneurysms in women (55.6%). The female over-representation was statistically significant (p = 0.017). The median age of the patients was 50.9 (range 19.6-86.6 years); interestingly, men were significantly younger than women (48.2 years vs. 53.8 years, p < 0.0001).

Table 1 Number of intracranial aneurysms recorded each year in the 10-year period 1990–1999 at Haukeland University Hospital
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Ruptured aneurysms

The median age of the 361 SAH patients was 50.8 (range 19.6–86.6), with men being significantly younger than women (48.6 vs. 53.8 years, p < 0.0001). There were 170 aneurysms in men and 191 in women (p = 0.27). With the Koivisto categories the following distribution of aneurysms was found: ACA 36.0%, MCA 29.6%, ICA 24.4%, and VBA 10.0%. For the ACA, there were 121 (93.1%) AComA, 6 (4.6%) pericallosal, 1 A2 (0.8%), and 2 (1.6%) anterior aneurysms.

ACA aneurysms were over-represented among men (49 F, 81 M, p < 0.0001), and ICA aneurysms were over-represented among women (64 F, 24 M, p < 0.0001). For MCA and VBA aneurysms, there were no significant gender differences (Table 2).

Table 2 Gender distribution in patients with ruptured aneurysms in relation to location of the ruptured aneurysm
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Two-hundred nineteen of the aneurysms (60.7%) could be lateralised to the right or to the left of the anatomical midline. There was a significant difference in sidedness between aneurysms in the anterior and posterior circulation (p < 0.0001). This difference was caused solely by a left sidedness for ruptured VBA aneurysms (Table 3). Also, when comparing supra- and infratentorially located aneurysms, there was a significant difference in sidedness (Table 4).

Table 3 Sidedness of ruptured aneurysms according to aneurysm location
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Table 4 Sidedness for supra- and infratentorial ruptured aneurysms
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Unruptured aneurysms

The median age of the 60 patients with unruptured aneurysms was 49.1 years (range 22.9–80.4 years). Men were significantly younger than women (45.6 vs. 53.7 years, p = 0.005)

There were 27 aneurysms in men and 56 in women (p = 0.001). The distribution of aneurysms was: ACA 9.6%, MCA 51.8%, ICA 33.7%, and VBA 4.8%. Forty-seven (56.6%) of the unruptured aneurysms could be assigned to either the right or the left side in the intracranial circulation; there was however no significant sidedness present for these aneurysms.

Comparison between ruptured and unruptured aneurysms

There was no difference in gender for ruptured aneurysms, but men were under-represented among the UIAs (p = 0.0196). Median age was similar (50.8 and 49.1, p = 0.85) in the two groups (RIA and UIA), but men were significantly younger in both categories (p < 0.0001 and p = 0.005, respectively). Anatomically, ACA aneurysms were much more frequent in the RIA group (36.0% vs. 9.6%, p < 0.0001), while MCA aneurysms were more frequent in the UIA group (51.8% vs. 29.6%, p < 0.0002). For the ICA and VBA locations, no significant differences were found between the RIAs and the UIAs aneurysms (Table 5 for details).

Table 5 Distribution of gender, age, and anatomical location for ruptured and unruptured aneurysms
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Discussion

In the present population-based study of 444 intracranial aneurysms, we found a significant over-representation of ACA aneurysms in SAH patients in comparison to patients with UIAs. In fact, the frequency of ACA aneurysms was more than three times higher in the RIA than in the UIA group of aneurysms. MCA aneurysms, on the other hand, were clearly over-represented in the UIA group. For SAH patients, ACA aneurysms were over-represented in men, and ICA aneurysms in women. These results support our clinical suspicion, namely that ACA aneurysms seem to have a higher rupture risk, and thus possibly should be treated more aggressively than MCA aneurysms when found incidentally. The findings in our study are in line with data underlying a Finnish study [15]. In this study of more than 800 aneurysms, the distribution of ruptured and unruptured ACA and MCA aneurysms was 41% vs. 18% and 29% vs. 51%, respectively. Further, a three-dimensional angiography study of 155 consecutive aneurysms found the same over-representation (44.9 vs. 20.4%) of ACA aneurysms in ruptured vs. unruptured aneurysms [2]. Thus, evidence from different sources points to ACA aneurysms as being more prone to rupture than MCA aneurysms.

Furthermore, our study showed that ruptured VBA aneurysms were much more often found on the left side. This left-sided dominance in the posterior circulation may be explained by systematic differences in the intraluminal haemodynamics between the two sides, caused by asymmetries of the precerebral artery tree. It is a puzzling fact that in a study of 1,413 brains, only 34.5% had a balanced configuration of the circulus Willisi [27]. For the vertebral arteries, some interesting side differences between the right and the left side have been described, with the left side usually being the dominant. This applies both to normal variations in diameter and pathologically narrowed vessels [19, 21, 25]. Based on our results, we therefore hypothesise that dominant vertebral arteries on the left side may explain the observed left sidedness for ruptured VBA aneurysms. Correspondingly, one might ask whether such differences in vessel calibre could explain why ACA aneurysms were more frequent in the SAH group and MCA aneurysms in the UIA group. Could it be that a greater dimension of the feeding vessel would add to the flow and turbulence in the aneurysm? However, due to the design of the study we have no available data from the angiography investigations to enlighten this issue.

Men were significantly younger at diagnosis than women. The median difference was 5.2 years in the SAH group and 8.1 years in the UIA group. We have not identified any explanations for this age difference. With the anatomical distribution present in this study in mind, one might therefore argue that the indication for treating young men with ACA aneurysms is particularly strong.

Bearing in mind that this study was population-based from a single centre, we have identified a number of limitations. Although all patients diagnosed with an intracranial aneurysm in our region were routinely evaluated and treated in our department, there were some patients that never came to our attention. We have no information on the number of sudden deaths caused by SAH; however, intuitively this number should be low. Furthermore, some moribund SAH patients might not have been referred to our institution, since it is the medical team at the local community hospitals that decides whether to refer or not. In the studied period there was also a more conservative treatment policy for the older age groups. For SAH patients above 70 years, angiography and clipping were routinely not performed in the first part of the study period. Gradually, this regimen was changed and thus the oldest SAH patient in the material was 86.6 years. Nevertheless, the number of patients above 70 years should be low and thus conceivably not alter the main results of the study.

In conclusion, this retrospective, population-based study showed that there were anatomical differences in the distribution of intracranial aneurysms between SAH and UIA patients. The results indicate that laterality and vessel of origin are important factors contributing to the pathophysiology behind aneurysm formation and rupture. Finally, the study emphasises the importance of treating patients with incidentally found ACA aneurysms.