Introduction

Since the International Study of Unruptured Intracranial Aneurysms (ISUIA) in 1998, it has been generally accepted that unruptured small aneurysms <10mm in diameter have an extremely low rupture rate.9) However, in our experience, the majority of aneurysmal subarachnoid hemorrhage (SAH) patients have aneurysms <10 mm in diameter. To elucidate these contradictory results, we reviewed the medical records of the ruptured aneurysmal patients.

Materials and Methods

Two hundred and forty four cerebral aneurysmal patients who were treated at our hospital from January 2004 to December 2006 were analyzed. To elucidate the proportion of small aneurysms, each aneurysmal group was divided9)11)22)23)25)30) into five groups according to their longest diameter : Group 1, tiny aneurysm (<3 mm); Group 2, very small aneurysm (3~5 mm); Group 3, small aneurysm (5~7 mm); Group 4, medium aneurysm (7~10 mm); Group 5, large aneurysm (>10 mm). All patients were diagnosed by computerized tomography (CT) and CT angiography.12)15) Clinical features and radiological findings of the ruptured aneurysms were studied. As clinical factors, Hunt and Hess grade and Glasgow outcome scale (GOS) score were recorded and the size of the aneurysms, locations and the extent of the SAH were measured. In the cases of multiple aneurysms, the aneurysms thought to be ruptured were selected first, and then the largest one was selected. To measure the extent and amount of SAH, Hijdra’s SAH score and Fisher grade were used.8)

For the statistical analysis, correlation coefficient was used to evaluate the relationship between the aneurysmal size and the other factors. Categorical variables such as aneurysmal size with the SAH score were compared using the one-way analysis of variables (ANOVA). P-value <0.05 was considered statistically significant.

Results

The 244 enrolled patients comprised 93 males and 151 females (mean age 54.6 ± 12.8 years). There were 31 multiple aneurysms. Mean Hunt and Hess Grade was 2.8 ± 0.9. Mean Fisher grade and SAH score were 3.1 ± 0.9 and 16.6 ± 8.2, respectively. The mean GOS was 3.6 ± 1.6. The mean aneurysmal size was 6.8 ± 4.9 mm (Table 1).

The proportions of the five ruptured aneurysmal groups were 7.8% (Group 1), 30.7% (Group 2), 25.4% (Group 3), 19.3% (Group 4) and 16.8% (Group 5). The proportion of small ruptured aneurysms was 7.8% (<3 mm), 38.5% (<5 mm)and 63.9% (<7 mm). The clinical factors represented by Hunt-Hess Grade and GOS, and the radiological findings represented by Fisher Grade and SAH score were significantly correlated with the aneurysmal size (P<0.05) (Tables 2, 3).

According to the aneurysmal location, mean size of anterior communicating artery aneurysm (ACoA), posterior communicating artery aneurysm (PCoA), middle cerebral artery aneurysm (MCA), posterior circulation aneurysm (including basilar, cerebellar and posterior cerebellar), paraclinoid aneurysm, and anterior cerebral artery aneurysm (ACA) were 4.9 ± 2.1, 6.4 ± 4.7, 8.6 ± 5.9, 8.1 ± 5.1, 12.2 ± 10.2 and 6.4 ± 4.5, respectively. There were significant differences of ruptured aneurysmal sizes according to their location. Regarding the location and the size of the aneurysms, the mean size of ACoA was smallest (4.9 ± 2.1) and the paraclinoid aneurysms were largest (12.2 ± 10.2). (p<0.05) However, there was no difference of the proportions for less than 3mm according to the aneurysmal location (P=0.000). The existences of intracerebral hemorrhage and intraventricular hemorrhage were different according to the aneurysmal location (P<0.05) (Table 4).

Discussion

The population-based incidence of aneurysmal SAH is about 10 out of 100,000 but the incidence of unruptured aneurysms is known to be much higher.3)7)20)22) Since screening of cerebral vessels has become more popular, the detection rate of small unruptured cerebral aneurysm has sharply increased.17) Consequently, clinicians are increasingly confronted with the management of small unruptured aneurysms.

Before the International Study of Unruptured Intracranial Aneurysms (ISUIA) Investigators in 1998, cerebral arterial aneurysms were all considered to have a very high rupture risk, regardless of their sizes. However, this study revealed that small aneurysms (<10 mm) in fact may exhibit a negligible rupture rate. The ISUIA study was soon criticized on the basis of various aspects including selection bias. Nevertheless, it has become the general consensus that very small aneurysms are not so dangerous as previously thought.1)2)4)6)9)28)

The management strategy of unruptured aneurysms has changed, but is still controversial. Once, only aneurysms exceeding 10 mm in size were recommended for active treatment. However, this treatment strategy has changed to include aneurysms 5 mm or 7 mm in size.9)22)23)25)30)

Since 1985, when we began aneurysm surgery in our hospital, most of the ruptured aneurysms encountered were 5~10 mm (mean 6.8 ± 4.9 mm) in size, contrary to the ISUIA findings. Given this prevalence, our view became that aneurysms <7 mm or <10 mm should not just be observed, but should be dealt with surgically. From our retrospective review of patient records, the mean size of ruptured aneurysms was 6.8 mm, slightly larger than the 5.6 mm of unruptured aneurysm reported by the Korean Society of Cerebrovascular Surgery (KSCVS).17) Considering that ruptured aneurysms <5 mm comprised 38.5% of the total in the present study, even the 5.6 mm figure of KSCVS may not represent a safe limit. Consistent with this view, aneurysms <7 mm in size have not been safe from rupture.13,14) In some countries, 5 mm is indicative for surgery or coiling. In a study of 70 patients with aneurysmal rupture reported that 18 cases involved aneuryms that were <5 mm, reinforcing the view that careful attention should be required for unruptured aneurysms < 5 mm.11)27) However, this convention is by no means universal. It has been recommended that small, incidental aneurysms <5 mm in diameter should be managed conservatively in virtually all cases.18) Other studies, including an autopsy study, reported that ruptured aneurysmal size of 8.2 mm and 14.5 mm.16)21) The mean size of the ruptured aneurysms of our patients (6.8 ± 4.9) was much smaller than the latter two series. The fact that the proportion of ruptured aneurysms 3~5 mm (very small aneurysms) constituted 30.7% of the total is noteworthy and is evidence that small aneurysms should be regarded as dangerous and dealt with appropriately.

There are various other factors related with aneurysmal rupture in addition to the size of the aneurysm.5)10)20)29) Aneurysms with a daughter sac, multilobulated aneurysms and blister aneurysms present a high rupture risk. The location of the aneurysm should be considered in decision making. An aneurysm of the cavernous internal carotid artery has an extremely low rupture risk, but an aneurysm located at hemodynamically vulnerable location such as basilar bifurcation or anterior communicating artery has a relatively higher rupture risk.

Race also seems to influence on the rupture risk. Ruptured mean aneurysmal sizes from Korea, Japan, Hong Kong and China have been reported as 6.3 mm, 7.6 mm, 5.8 mm and 5.9 mm, respectively.11)13)14)19)23)24)26)

However, the most important factors that must be considered in managing patients with small unruptured aneurysms are age and general health status. After considering all these factors, active treatment is recommended for very small aneurysms and tiny aneurysms. Although the percentage of ruptured and unruptured tiny aneurysms (<3 mm) was 7.8% and 21.8%, respectively, in our study, these are still quite significant numbers, considering the unruptured aneurysms in the population. There is still very limited data about ruptured tiny aneurysms to permit a rigorous evaluation. However, it is our belief that even though the tiny aneurysms (<3 mm) have a very low rupture rate, close follow-up is necessary, since even these aneurysms are not absolutely safe from rupture.

Conclusion

The proportion of very small ruptured aneurysms (3~5 mm) was presently significant, and necessitated surgery or endovascular coiling. Although tiny aneurysms (<3 mm) may have a very low rupture risk, close follow-up is prudent.

REFERENCES

1) Berenstein A, Flamm ES, Kupersmith MJ. Unruptured intracranial aneurysms. N Engl J Med 340:1439-40; author reply 1432-41, 1999

2) Brett A. Unruptured intracranial aneurysms. N Engl J Med 340: 1441-2, 1999

3) Brisman JL, Song JK, Newell DW. Cerebral aneurysms. N Engl J Med 355:928-39, 2006

4) Caplan LR. Should intracranial aneurysms be treated before they rupture? N Engl J Med 339:1774-5, 1998

5) Clarke G, Mendelow AD, Mitchell P. Predicting the risk of rupture of intracranial aneurysms based on anatomical location. Acta Neurochir (Wien) 147:259-63; discussion 263, 2005

6) Connolly ES, Jr., Mohr JP, Solomon RA. Unruptured intracranial aneurysms. N Engl J Med 340:1440-41; author reply 1441-42, 1999

7) de Rooij NK, Linn FH, van der Plas JA, Algra A, Rinkel GJ. Incidence of subarachnoid haemorrhage: A systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry 78:1365-72, 2007

8) Hijdra A, Brouwers PJ, Vermeulen M, Van Gijn J. Grading the amount of blood on computed tomograms after subarachnoid hemorrhage. Stroke 21:1156-61, 1990

9) The International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms--risk of rupture and risks of surgical intervention. N Engl J Med 339:1725-33, 1998

10) Ishibashi T, Murayama Y, Urashima M, Saguchi T, Ebara M, Arakawa H, et al. Unruptured intracranial aneurysms: Incidence of rupture and risk factors. Stroke 40:313-16, 2009

11) Isobe N, Sato H, Murakami T, Kurokawa Y, Seyama G, Oki S. Evaluation of ruptured cerebral aneurysms under 5 mm in size on 3D-rotation angiography. No Shinkei Geka 36:775-80, 2008

12) Jayaraman MV, Mayo-Smith WW, Tung GA, Haas RA, Rogg JM, Mehta NR, et al. Detection of intracranial aneurysms: Multi-detector row CT angiography compared with DSA. Radiology 230:510-8, 2004

13) Jeong YG, Jung YT, Kim MS, Eun CK, Jang SH. Size and location of ruptured intracranial aneurysms. J Korean Neurosurg Soc 45:11-5, 2009

14) Joo SW, Lee SI, Noh SJ, Jeong YG, Kim MS, Jeong YT. What is the significance of a large number of ruptured aneurysms smaller than 7 mm in diameter? J Korean Neurosurg Soc 45: 85-9, 2009

15) Karamessini MT, Kagadis GC, Petsas T, Karnabatidis D, Kons- tantinou D, Sakellaropoulos GC, et al. CT angiography with three-dimensional techniques for the early diagnosis of intracranial aneurysms. Comparison with intra-arterial DSA and the surgical findings. Eur J Radiol 49:212-23, 2004

16) Kassell NF, Torner JC. Size of intracranial aneurysms. Neurosurgery 12:291-7, 1983

17) Kim JE, Lim DJ, Hong CK, Joo SP, Yoon SM, Kim BT. Treatment of unruptured intracranial aneurysms in South Korea in 2006: A nationwide multicenter survey from the Korean Society of Cerebrovascular Surgery. J Korean Neurosurg Soc 47:112-8, 2010

18) Komotar RJ, Mocco J, Solomon RA. Guidelines for the surgical treatment of unruptured intracranial aneurysms: The first annual J. Lawrence pool memorial research symposium-controversies in the management of cerebral aneurysms. Neurosurgery 62:183-93; discussion 184-93, 2008

19) Lai HP, Cheng KM, Yu SC, Au Yeung KM, Cheung YL, Chan CM, et al. Size, location, and multiplicity of ruptured intracranial aneurysms in the Hong Kong Chinese population with sub- arachnoid haemorrhage. Hong Kong Med J 15:262-6, 2009

20) Lall RR, Eddleman CS, Bendok BR, Batjer HH. Unruptured intracranial aneurysms and the assessment of rupture risk based on anatomical and morphological factors. Sifting through the sands of data. Neurosurg Focus 26:E2, 2009

21) McCormick WF, Acosta-Rua GJ. The size of intracranial saccular aneurysms. An autopsy study. J Neurosurg 33:422-7, 1970

22) Mitchell P, Gholkar A, Vindlacheruvu RR, Mendelow AD. Un- ruptured intracranial aneurysms. Benign curiosity or ticking bomb? Lancet Neurol 3:85-92, 2004

23) Morita A, Fujiwara S, Hashi K, Ohtsu H, Kirino T. Risk of rupture associated with intact cerebral aneurysms in the Japanese population. A systematic review of the literature from Japan. J Neurosurg 102:601-6, 2005

24) Ohashi Y, Horikoshi T, Sugita M, Yagishita T, Nukui H. Size of cerebral aneurysms and related factors in patients with subarachnoid hemorrhage. Surg Neurol 61:239-45; discussion 237-45, 2004

25) Raymond J, Meder JF, Molyneux AJ, Fox AJ, Johnston SC, Collet JP, et al. Unruptured intracranial aneurysms: The unreliability of clinical judgment, the necessity for evidence, and reasons to participate in a randomized trial. J Neuroradiol 33: 211-9, 2006

26) Song J, Mao Y, Song D, Leng B, Gu Y. Relationship between characteristic geometry and risk of rupture in cerebral saccular aneurysm. Zhonghua Yi Xue Za Zhi 24:732-5, 2009

27) Sonobe M, Yamazaki T, Yonekura M, Kikuchi H. Small un- ruptured intracranial aneurysm verification study: Suave study, japan. Stroke: 41;1966-77, 2010

28) Stieg PE, Friedlander R. Unruptured intracranial aneurysms. N Engl J Med 340:1441; author reply 1441-2, 1999

29) Wermer MJ, van der Schaaf IC, Algra A, Rinkel GJ. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: An updated meta-analysis. Stroke 38:1404-10, 2007

30) Wiebers DO, Whisnant JP, Huston J, 3rd, Meissner I, Brown RD, Jr., Piepgras DG, et al. Unruptured intracranial aneurysms: Natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:103-10, 2003