Korean Journal of Cerebrovascular Surgery 2009;11(3):112-117.
Published online September 1, 2009.
Clinical Analysis of Intracranial Mirror-image Aneurysms: A 20-year Single Center Experience.
Jeong, Se Jin , Koh, Hyeon Song , Kwon, Hyon Jo , Choi, Seung Won , Kim, Seon Hwan , Kim, Youn
Department of Neurosurgery, School of Medicine, Chungnam National University, Daejeon, Korea. younkim@cnu.ac.kr
Abstract
OBJECTIVE
Detection of intracranial multiple aneurysms, including mirror-image aneurysms, have recently been increasing with the development of diagnostic techniques. However, studies of mirror-image aneurysms have been rare in South Korea. Thus, we intend to report our hospital's experience with mirror-image aneurysms during the past 20 years along with a review of relevant literature. METHODS: We analyzed medical records and image data from patients with cerebral aneurysms who had been admitted to our institution from January 1988 to June 2007. We divided the patients into three groups and investigated the clinical patterns of mirror-image aneurysms (Group 1). We then compared them with patients exhibiting non-mirror multiple aneurysms (Group 2) and the patients with solitary aneurysms (Group 3). We also statistically analyzed the age, sex, smoking habits, medical histories, and prognoses of the patients. RESULTS: Mirror-image aneurysms were found in 62 (5.1%) of the 1,209 patients admitted for cerebral aneurysms over the past 20 years. Of the mirror-image aneurysms, 48% were located in the posterior communicating artery (PcoA), and 40% were in the middle cerebral artery (MCA). Ruptures of aneurysms occurred slightly more frequently on the right side and when the aneurysm was larger and its shape was more irregular. Women, particularly menopausal women aged 50 and older, were shown to be at higher risk. Smoking was also a risk factor. However, there were no significant differences in prognoses among the three groups. CONCLUSION: We should pay attention to the possibility of mirror-image or multiple aneurysms when diagnosing and treating menopausal women and smokers, particularly if the cerebral aneurysm is located in the MCA or PcoA.
Key Words: Intracranial aneurysms, Mirror-image, Risk factors
 

Key Words : Intracranial aneurysms·Mirror-image·Risk factors.










Introduction


Detection of cerebral aneurysms, particularly multiple cerebral aneurysms, has been increasing with the recent development of diagnostic techniques. Multiple cerebral aneurysms account for about 10~30% of all cerebral aneurysms, and mirror-image aneurysms for 5~35% of all multiple cerebral aneurysms.4)8)16)25)33)

In South Korea, a small number of cases concerning mirror-image aneurysms have been reported,1)21) but no reports have analyzed for long-term clinical patterns. Therefore, we intend to report our hospital� experience with mirror-image aneurysms for the past 20 years by comparing them with cases of non-mirror multiple aneurysms and solitary aneurysms, including a review of related literature.


Materials and Methods


We retrospectively analyzed the medical records and image data for patients with cerebral aneurysms who were admitted to our hospital from January 1988 to June 2007. During this period, 1,209 patients were diagnosed with cerebral aneurysms. Among these, 174 (14.3%) had multiple aneurysms and 1,035 (85.7%) had solitary aneurysms. We divided the patients into three groups: patients with mirror-image aneurysms (62, Group 1), patients with non-mirror multiple aneurysms (99, Group 2), and patients with solitary aneurysms (200, Group 3). Of the 174 patients with multiple cerebral aneurysms, we included 161 patients but excluding 13 on the basis of insufficient records. Of the 1,035 patients with solitary aneurysms, we included the latest 200 patients based on the reliability of their recent medical records.

We investigated the occurrence of mirror-image aneurysms, location of ruptures, and difference in ruptures according to size and shape, and prognosis. We also statistically analyzed the age, sex, and histories of hypertension, smoking, diabetes mellitus, and prognosis for all three groups. Diagnosis of cerebral aneurysms was performed by using conventional digital subtraction angiogram (DSA) before April 2004 and by using three-dimensional computed tomography angiogram (3D-CTA) with DSA after April 2004. Two neurosurgeons collaborated in determining the locations, sizes and shapes of mirror-image aneurysms. Regarding the sizes of cerebral aneurysms, many old records did not have sufficient descriptions about the unruptured cerebral aneurysms. Therefore, we only included the data of cases with sufficient descriptions, and in each case we measured the largest diameter of the dome for this study. For shapes, we divided and compared those cases with simple shapes and those with more complex shapes. We used the Hunt-Hess grade (H-H grade) to assess the preoperative neurologic status of patients, and the Glasgow outcome scale (GOS) to assess the prognosis. The histories of hypertension were determined through previous diagnosis before admission or continuous administration of antihypertensive drugs after hospitalization. Statistical analysis for the comparison of the three groups was performed using the chi-square and cross tab test. A p-value of < 0.05 was considered statistically significant.


Results


Locations, sizes, shapes and ruptures of mirror-image aneurysms

For mirror-image aneurysms, 30 pairs (48.0%) were observed in the posterior communicating artery (PcoA), 25 pairs (40.0%) in the middle cerebral artery (MCA), four pairs (6.5%) in the anterior choroidal artery (AchA), and one pair (1.6%) in the ophthalmic artery, pericallosal artery and paraclinoid portion of internal carotid artery (ICA). Thirty-three patients (57.0%) were ruptured on the right side, and 25 patients (43.0%) on the left. More ruptures occurred on the right side in the PcoA patients (62.0%) and AchA patients (66.0%), while more ruptures occurred on the left side in the MCA patients (54.0%) (Table 1).

The sizes of both sides of the mirror-image aneurysms could be measured in 32 patients (ruptured: 29, unruptured: 3; MCA: 14, PcoA: 16, others: 2). The sizes of MCA aneurysms on the right side were 6.08 ± 2.98mm, and 6.71 ± 3.01mm on the left. For the PcoA patients, sizes on the right side were 6.78 ± 4.34mm, and 6.32 ± 3.36mm on the left (Table 2). In the ruptured 29 patients, 18 patients (62.1%) had a rupture in the larger side, while 7 patients (24.1%) had a rupture on the smaller side. In four patients (13.8%), the sizes were similar.

The shapes of both sides of the mirror-image aneurysms could be compared in 30 patients (ruptured: 30, unruptured: 0; MCA: 12, PcoA: 17, others: 1), 20 patients (66.7%) had a rupture in the cerebral aneurysms with a more complex shape, while 8 patients (26.7%) had a rupture in the simple saccular-shaped aneurysms. Two patients (6.6%) had almost identical aneurysm shapes on both sides (Table 3).


Differences in age, sex, and treatments among the groups

The mean age of all the patients was 55.3 ± 12.1. The mean ages of Groups 1, 2, and 3 were 55.1 ± 9.4, 53.7 ± 10.2, and 56.1 ± 10.4, respectively, so there were no significant differences. Age distributions were also similar among three groups. In all of the patients, the male-to-female ratio was 1:1.91 (124 men and 237 women). It was 1:3.13, 1:2.00, and 1:1.63 for Groups 1, 2, and 3, respectively. For Group 1, in particular, the ratio of women aged 50 and older (1:4.25) was higher than that of women aged under 50 (1:1.86) (Table 4).

Fifty-eight (93.5%) of 62 patients in Group 1 visited our hospital with subarachnoid hemorrhage (SAH), and the total number of detected cerebral aneurysms was 146. Initially 81 of them underwent neck clipping (67, 82.7%) and coil embolization (14, 17.3%). Fourteen unruptured aneurysms underwent additional neck clipping (7, 50.0%) and coil embolization (7, 50.0%). We could not perform clipping or coiling for all remaining unruptured aneurysm, because the patients or their family refused the additional surgery. For Group 2, 93 (93.9%) of 99 patients visited because of SAH, and 120 (54.8%) of 219 aneurysms underwent aneurysmal neck clipping (106, 88.3%) and coil embolization (14, 11.7%). For Group 3, 193 (96.5%) of 200 patients were admitted for SAH, and 171 (85.5%) of 200 patients underwent neck clipping (154, 90.1%) and coil embolization (17, 9.9%).

 

Differences in risk factors and prognoses among the groups

With regard to hypertension, 28 (45.2%) of 62 patients in Group 1, 51 (51.5%) of 99 patients in Group 2, and 74 (37.0%) of 200 patients in Group 3 had hypertension. There were no significant differences among the groups. Smokers in Group 1 numbered 31 (50.0%) of 62 patients; in Group 2, 47 (47.5%) of 99 patients; and in Group 3, 19 (9.5%) of 200 patients. No significant statistical difference in smoking as a risk factor was evident between Groups 1 and 2 , but between Groups 1 and 3, smoking history was significantly higher in Group 1 (p=0.028). For diabetes mellitus, in Group 1, 1 (1.6%) of 62 patients; in Group 2, 7 (7.1%) of 99 patients; and in Group 3, 19 (9.5%) of 200 patients were diagnosed. There was no significant statistical difference between Groups 1 and 2, but between Groups 1 and 3, diabetes mellitus was statistically higher in Group 3 (p=0.041) (Table 5).

When looking at all of the prognoses, the higher the Hunt-Hess grade at admission the worse the prognosis. However, no significant differences existed among the groups (Table 6).


Discussion


Locations, sizes, shapes, and ruptures of mirror-image aneurysms

Mirror-image aneurysms occurred most commonly in the PcoA (48.0%) and MCA (40.0%) in our study, and this was also reported by Juvela.11) In our cases, none were of mirror-image aneurysms in the anterior communicating artery (AcoA), as previously reported by Kong et al.15)

Clinically, when an SAH occurs in patients with mirror-image aneurysms, it is critical to find the ruptured aneurysm. It is generally known that the possibility of a rupture is higher on the side with a large amount of localized clots in a computed tomography (CT) image, and on the side where there is a local vasospasm in the cerebral angiography, and on the side where the aneurysm is larger and the shape is more irregular.3)8)35) Radaelli et al27) reported that ruptures occur mainly on the left side in patients with mirror-image aneurysms. While the left ICA directly branches from the aortic arch, the right ICA branches from the brachiocephalic trunk, which branches off from the aortic arch. It is assumed that this difference influences the blood flow to the aneurysm and its rupture. In our study, 33 (57.0%) of the all patients had a rupture on the right side, with 25 (43.0%) occurring on the left. In PcoA patients, more ruptures occurred on the right (62.0%), whereas in MCA patients, ruptures occurred on the left side (54.0%) slightly more. No definite differences between ruptures on both sides were evident. Regarding the sizes and shapes of ruptures, Wood35) noted that the size of an aneurysm was important in determining the ruptured site in patients with multiple aneurysms. However, Nehls et al.22) reported that irregularities of contours were more important than size in identifying the site of a rupture because ruptures occurred in 83.3% of cases of large aneurysms, while ruptures occurred in 93.3% of aneurysms with irregular shapes. They explained that this was related to the decrease in size after the rupture of an aneurysm. In our study, as in other reports, more ruptures occurred in larger aneurysms (62.1%) and more complex-shaped aneurysms (66.7%). However, no significant difference between the influences of an aneurysm� size and shape on a rupture was noted.


The influence of age and sex on mirror-image aneurysms

In the past, many authors have reported that, as with a solitary aneurysm, most multiple aneurysms occur in women.2)5)12)14)18)19)22)23)26)28) Our study also showed higher incidences for women in all groups. This was particularly significant among people aged 50 and older (the age of menopause for women), considering the ratio of mirror-image aneurysms in men to women was 1:4.25. This was much higher than that of multiple aneurysms (1:2.42) and solitary aneurysms (1:2.04). Considering the fact that most mirror-image aneurysms were discovered at the menopausal age, we can infer that the reduction of hormones, such as estrogen, play a role in the rupture of aneurysms as well as in the occurrence of mirror-image aneurysms. However, in order to understand the influence of hormones on the rupture of mirror-image aneurysms accurately, we need a comparative study with patients having unruptured mirror-image aneurysms on both sides.


Risk factors and prognosis of mirror-image aneurysms

Smoking is a well-known risk factor in cerebral aneurysms. Although no significant difference between Groups 1 and 2 was found in this study, a significant difference was observed between Groups 1 and 3 (p=0.028). Thus, smoking was found to contribute to the occurrence of mirror-image or multiple aneurysms. The main impact of smoking with regard to aneurysms is that it restricts the activity of alpha-1-antitrypsin that suppresses the protease that accelerates the decomposition of collagens so as to reduce elastins in the blood and increase the expansion of the arterial wall during systole.30)32) Furthermore, it is known that in a mechanism similar to atherosclerotic changes, smoking damages endothelial cells, accelerating the formation of atheroma by suppressing the enzymes involved in the functions of platelets and the restoration system for vessel walls, thereby causing an aneurysm at the bifurcation point that is affected by blood pressure.29)33) Smoking is also known to have anti-estrogen features and promotes the formation of an aneurysm in menopausal women.24) This fact agrees with the higher occurrence of mirror-image aneurysms in women aged 50 and older in this study. Even though there are many reports that hypertension is also related to the occurrence of cerebral aneurysms,2)7)24)28) this study found no significant correlations between Groups 1 and 2 or between Groups 1 and 3. We suspect that these findings are related to the recent increase of patients who receive antihypertensive drugs, as reported by Qureshi et al.26) Diabetes mellitus was most related to solitary cerebral aneurysms in our study. This result was presumably caused by the situation that the diagnosis rate of diabetes was high in recent patients with relatively complete medial records, while many past patients were undiagnosed or overlooked in their medical records.

It has been reported that the perioperative complication rate is higher and prognosis is worse for multiple aneurysms than for solitary aneurysms.13)15)17)31)32)36) However, this study found no difference among the groups, and the initial neurologic grade of patients was most important same as the patients with solitary aneurysms.


Treatment of unruptured cerebral aneurysms

In this study, only 14 unruptured aneurysms underwent operations additionally. The main reason was that we were not active in the treatment of unruptured aneurysms in the past, or many patients and their family refused the second operation for unruptured aneurysms due to many factors. Heiskanen9) reported that ruptures occurred in 16.4% of previously unruptured aneurysms, and the mortality rate after rebleeding was 11.5%. Vajda34) insisted that aneurysms needed to be treated by bilateral simultaneous operations if the shape of unruptured aneurysms is irregular, if the aneurysm is located at the center of cranial cavity, or if it is accompanied by hypertension. Aggressive treatment of the remnant aneurysm is also recommended if it is difficult to ascertain the location of the rupture or the location is inaccurately determined before an operation.6)10)20)31) Considering our recent experience of a spontaneous rupture occurring in the opposite unruptured MCA aneurysm, 10 days after an operation for a ruptured one, it can be helpful to consider early treatment for the opposite unruptured aneurysm in cases of mirror-image or multiple aneurysms. By recent development of coil embolization techniques, we can treat the opposite unruptured aneurysm with much less physical burden to the patient.


Limitations of this study

In this study, there are patients who have another aneurysms in additional to their mirror-image aneurysms in Group 1. For a more accurate analysis of mirror-image aneurysms, we need to study the patients with pure mirror-image aneurysms only in Group 1. We could not estimate the precise sizes and shapes of all mirror-image aneurysms because of insufficient data in the past. Furthermore, we only sampled recent 200 patients with solitary aneurysms, and there can be differences in the disease patterns over time, which may have affected the results of this study.


Conclusion


Mirror-image aneurysms were most commonly found in the PcoA and MCA. Aneurysm ruptures occurred slightly more frequently on the right side and in the larger aneurysms with irregular shapes. Generally, mirror-image aneurysms had similar characteristics with non-mirror multiple aneurysms. Menopause in women and smokers were found to be risk factors, and the neurologic grade of a patient at admission was important for the prognosis. If a cerebral aneurysm is found in the MCA or PcoA in menopausal women and smokers, we should pay attention to the possibility of mirror-image or multiple aneurysms during diagnosis and treatment.


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