Surg Neural 1990;34:361-5
361
Autopsy Study of Unruptured Incidental Intracranial Aneurysms Tetsuji Department Department
Inagawa, M.D.,
and Asao Hirano,
M.D.
of Neurosurgery, Shimane Prefectural Central Hospital, Izumo, Japan, and Division of Neuropathology, of Pathology, Montefiore Medical Center, Bronx, New York
Inagawa T, Hirano A. Autopsy study of unruptured incidental intracranial aneurysms. Surg Neural 1990;34:361-5. The autopsy files and preparations of unruptured incidental intracranial aneurysms seen at the Montefiore Medical Center between 195 1 and 1987 were reviewed. There were 84 patients with 102 unruptured aneurysms in a total of 10,259 autopsies, giving a prevalence of 0.8%. Sixteen of the 84 (19%) had multiple aneurysms. The thickness of walls of aneurysms could be estimated in 78 of 102 aneurysms, and was determined to be either thin or thin and thick in 71 aneurysms. In this study, four noteworthy factors were found: (1) the incidence of unruptured aneurysms was higher in elderly patients aged 60 years or older, and the peak percentage was 1.2% in the seventh decade; (2) aneurysms occurred more frequently in females than males, with a ratio of 53: 31; (3) the most common site
of aneurysms was the middle cerebral artery; 37 of 102 aneurysms (36%) occurred on it; and (4) the rate of small aneurysms was very high; 50 of 93 aneurysms (54%) were 4 mm or less in diameter, and 33 aneurysms (35%) were 5-9 mm in diameter. However, relationships could not be found between age distribution and location, size, or thickness of walls; between gender and size or thickness of walls; between location and size or thickness of walls; or between size and thickness of walls. Based on published statistics on subarachnoid hemorrhage and this study, the rupture rate of unruptured aneurysms seems to be very low. Although the risk of rupture may be relatively low in small aneurysms, its low risk probably cannot be explained adequately by morphological examination only. KEY WORDS: Unruptured rupture; Autopsy
aneurysm; Aneurysm
size; Risk of
Despite the dramatic improvement in surgical results for ruptured intracranial aneurysm, the overall management mortality for this disorder still remains high [3,15,19,22]. The high mortality is attributed, in part, to the fact that about one half of the patients suffering
A&ireu reprint requests to: Tetsuji Inagawa, M.D., Department of Neurosurgery, Shimane Prefectural Central Hospital, 116 Imaichicho, Izumo, Shimane 693, Japan. Received October 16, 1989; accepted 0 1990 by Else&r
May 25, 1990.
Science Publishing Co., Inc.
from aneurysmal subarachnoid hemorrhage (SAH) cannot be treated surgically because of severe brain damage after SAH [ 14,15,19,22]. One method of overcoming this dismal disease is to operate on the aneurysms before they rupture; that is, to treat unruptured aneurysms. There are several reports concerning the surgical results of unruptured incidental aneurysms [11,34,35,44]. However, to operate on such patients, it is important to know what kind of unruptured aneurysms are likely to rupture. The natural history of unruptured aneurysms, especially the risk of rupture, is not precisely known [6,10,17,41-431. Jane et aI [17J and Winn et aI 1431 speculated that the annual risk of rupture of an unruptured asymptomatic aneurysm was similar to the natural history of the healed ruptured aneurysm; that is, a hemorrhage rate of 3%4% per year. In patients with multiple aneurysms, the risk of bleeding from a previously unruptured aneurysm was reported to be 10%-170/o [7,28]. However, they are mainly discussing unruptured aneurysms discovered clinically by angiography and other methods. In this paper, unruptured incidental aneurysms found in autopsy series were investigated to search for a clue as to what factors regarding unruptured aneurysms can be correlated to the risk of rupture.
Materials
and Methods
The autopsy files of patients with intracranial aneurysms seen at the Montefiore Medical Center during the 37year period between 1951 and 1987 were reviewed. During this period a total of 10,259 autopsies, including examination of the cranial contents, were performed. For this report, 84 patients with unruptured incidental saccular aneurysm were studied. One hundred thirtythree patients with ruptured saccular aneurysm [13], 14 patients with fusiform aneurysm, and seven patients with mycotic aneurysm were excluded from this study. Unruptured aneurysms in patients with SAH were not analyzed. Classification of aneurysm size was based on the dimension of greatest diameter. The thickness of walls of aneurysms was estimated by reviewing the thin-sectioned aneurysms placed on coverglass preparation, and dividing it into three basic types: thin, thin and thick, 0090-3019/90/$3.50
Table
Inagawa and Hirano
Surg Neurol 1990;34:361-5
362
1. Cause of Death in 84 Autopsy Patients with
Vnrubtured
Aneurvsms No. of cases
Cause of death
9 3
Cerebral disease Cerebral infarction
Intracerebral hematoma
4
Brain tumor Other
2
causes
Cancer Cardiovascular Pneumonia Gastric ulcer
75 29 29 4 1
disease
Liver cirrhosis Renal failure Sepsis Aplastic anemia
3 4 4 1
Total
84
and thick. If it was almost the same thickness as the parent vessel wall or thicker, it was designated as thick. If the wall was uniformly thin, it was designated as thin. If it was mixed with both thin and thick parts, it was designated as thin and thick.
Results The ages of the 84 patients with unruptured aneurysms ranged from 31 to 89 years, with a mean of 66.9 years (men 66.8 years, women 66.9 years). The causes of death are shown in Table 1. The incidence of unruptured aneurysms was 0.8% for all ages, and 0.9% for the 30-89 age group (Table 2). It was higher in elderly patients aged 60 years or older. The peak percentage was 1.2% in the seventh decade. Of the 84 subjects, 31 (37%) were men and 53 (64%) were women. There was no correlation between gender and age. Atherosclerosis of the circle of Willis was found in 60 of 73 patients (82%), but no correlation could be found between the degree of sclerosis and age. A total of 102 unruptured aneurysms was found. tif the 84 patients, 68 (81oJo) had a single aneurysm and 16 (19%), three men and 13 women, had multiple aneurysms. The latter group consisted of 14 patients with two aneurysms and two patients
Table
2.
Incidence of Vnruptured
Aneurysms
with three aneurysms (Table 3). There was no correlation between the incidence of multiple aneurysms and age. There were 28 anterior communicating artery (AComA) aneurysms (27%), 29 internal carotid artery (ICA) aneurysms (28%), 37 middle cerebral artery (MCA) aneurysms (36%), and eight vertebrobasilar artery (VBA) aneurysms (8%). The MCA was the most common site. Of the 93 aneurysms, 50 (54%) were 4 mm or less in diameter, 33 (35%) were 5-9 mm, and 10 (11%) were 10 mm or larger. The thickness of walls of aneurysms could be estimated in 78 of 102 aneurysms; it was thin in 19 aneurysms (24%), mix&d thin and thick in 52 (67%), and thick in seven (9%). Relationships of the patient’s age to location, size, or thickness of walls of aneurysms could not be demonstrated. Of 68 aneurysms in women, both ICA and MCA aneurysms accounted for 23 (34%) each, while of 34 aneurysms in men, 14 (4 1%) were MCA aneurysms and 13 (38%) were AComA aneurysms (Table 4). Relationships of gender to size (Table 5) and thickness of walls of aneurysms could not be found. Relationships of location of aneurysms to size are shown in Table 6. Twenty of 27 AComA aneurysms (74%), 10 of 25 ICA aneurysms (40%), and 19 of 35 MCA aneurysms (54%) were 4 mm or smaller in diameter. Six of 27 AComA aneurysms (22%), 10 of 25 ICA aneurysms (4070), and 12 of 35 MCA aneurysms (3470) were 5-9 mm in diameter. A relationship of the location of aneurysms to the thickness of walls could not be demonstrated. Relationships of size of aneurysms to thickness of walls are shown in Table 7. In seven of the 36 aneurysms (19%) that were 4 mm or smaller in diameter, the thickness of walls of aneurysms was thin; and in 24 of 36 (67%), it was thin and thick. In 10 of 39 aneurysms (26%) that were 5 mm or larger in diameter, the thickness of walls of aneurysms was thin; and in 27 of 39 (69%), it was thin and thick. A total of 31 of 36 aneurysms (86%), which were 4 mm or smaller in diameter, had a thin portion in the walls; and a total of 37 of 39 aneurysms (95%), which were 5 mm or larger in diameter, had a thin portion. Other studies have indicated a possible link between polycystic kidney disease and intracranial aneurysm. The following is a summary bf associated conditions and is
Found at Autopsy by Age Age (years)
O-29
No. of autopsies No. of cases with aneurysm Incidence (%)
903 0 0
30-39
40-49
50-59
60-O
70-79
80-89
290
Total
438 2 0.46
921 3 0.32
1868 13 0.70
2663 33 1.24
2290 22 0.96
1052 11 1.05
124 0 0
10,259 84 0.82
Unruptured
Table
Intracranial
Surg Neurol 1990;34:361-5
Aneurysms
363
3. Age Distribution of Patients with Multiple Unruptured Aneurysms Age
Aneurysms found
30-39
40-49
50-59
1
1 1 0
1 2 0
10 2 1
2. 3
included for information only. The examination reports indicated polycystic kidney disease in six of 10,259 autopsies, and the coexistence of polycystic kidney disease and intracranial aneurysm in three patients: a 64-yearold man with an unruptured AComA aneurysm, a 31year-old man with a ruptured MCA aneurysm, and a 13year-old girl with a ruptured basilar artery aneurysm. An association of tumor and intracranial aneurysm was found in three patients: a 6%year-old woman with an unruptured fusiform anterior cerebral artery (ACA) aneurysm and a spinal meningioma, a 69year-old woman with an unruptured ICA aneurysm coexisting with both a falx meningioma and a pituitary microadenoma, and a 64-year-old man with a ruptured ACA aneurysm with a pituitary microadenoma.
Discussion In autopsy studies, the incidence of intracranial aneurysms including not only unruptured but also ruptured aneurysms was reported to be 0.2%-8.1% [2,4, 13,24-26,31,37]. According to Berry et al [2), unruptured incidental asymptomatic aneurysms were found in 1% of the brains examined in 6686 autopsy series. In a planned autopsy study of 2786 consecutive necropsies, at least one unruptured aneurysm was observed in 2% of them [4]. McCormick [24] reported that, in a prospective and consecutive autopsy series of 2276 patients, the percentages of patients with unruptured aneurysm were 5 .O@ for all ages and 6.1% for those 20 years and older. Riggs and Rupp 1321 discovered miliary aneurysms measuring 5 mm or less in 13 1 of 1437 consecutive autopsy patients (9%). In the present autopsy series of 10,259 patients, unruptured saccular aneurysms were found in 84 patients, and 16 of these (19%) had multiple aneurysms. The incidence of unruptured incidental aneurysms was 0.8% for all ages, and
(yews)
60-O
Artery affected
Male
Female
Total
Anterior communicating Internal carotid Middle cerebral Vertebrobasilar
13 6 14 1
15 23 23 7
28 29 37 8
80-89
Total
18 4 0
11 0 0
68
27 5 1
14 2
0.9% for the 30-89 age group. Therefore, if the incidence of unruptured aneurysms were estimated as 1%9% in- patients of all ages, and if the annual incidence of aneurysmal SAH were estimated as 6-21 per 100,000 population [12,13,22,29,30,33], the annual risk of rupture of unruptured aneurysms could be calculated as roughly 0.1~?-2.1~Z. Which factors cause an unruptured aneurysm to rupture? In this autopsy study, four noteworthy factors were found. (1) The incidence of unruptured aneurysms was higher in elderly patients aged 60 years or older. (2) Female patients outnumbered males 5 : 3. (3) The most common site of aneurysms was the MCA. (4) The percentage of small aneurysms was very high. The peak incidence of unruptured incidental aneurysms was 1.2% in the seventh decade. McCormick’s I241 autopsy series recorded the peak incidence as being in the seventh decade. However, in this study, we could not find a correlation between atherosclerosis of vessels of the circle of Willis and the patient’s age. The relationship of the patient’s age to location, size, and thickness of walls of aneurysms could not be found either. In published epidemiological studies, the incidence of aneurysmal SAH increased almost linearly with the increase in age [8,18,21,30,33}. Therefore, there seems to be no difference in the degree of risk of rupture of unruptured aneurysms between those in young patients and in elderly patients. Second, females outnumbered males in a ratio of 53 : 31, or 63% to 37%. The highest incidence for both sexes was in the seventh decade. Some epidemiological studies reported that the annual incidence of SAH was higher in males 19,361, whereas others reported the incidence to be higher in females [1,3,8,21,29,30). There is no consistent trend of incidence by gender [14]. In our study, a relationship of gender to size of aneurysms or
Table Table 4. Location and Gender of 102 Unruptured Aneurysms
70-79
5. Size and Gender of 9.3 Unruptured Aneurysms’
Size (mm) 54 5-9 10-14 15-19 ’ Nine aneurysms
Male
Female
Total
20 8 1 3
30 25 4 2
50 33 5 5
had undetermined
sizes.
Inagawa and Hirano
Surg Neural 1990;34:361-5
364
Table 6. Relationship of Location to Size in 93 Unruptured Aneurysms” Size (mm) Arterv affected Anterior communicating Internal carotid Middle cerebral Vertebrobasilar
54
5-9
10-14
15-19
Total
20 10 19 1
6 10 12 5
1 2 2 0
0 3 2 0
27 25 35 6
8 Nine aneurysms had undetermined sizes
thickness of walls could not be found. There seems to be no relationship between gender and risk of aneurysm rupture. Third, 37 of the total of 102 aneurysms (36%) occurred on the MCA, while 28 (27%) occurred on the AComA, 29 (28%) on the ICA, and eight (8%) on the VBA. In clinical studies, it has been shown that MCA aneurysms account for about 20oJ0-30% of all ruptured aneurysms [14,16,20,22,23,39]. In general, MCA aneurysms usually preponderate in autopsy material [38], whereas in clinical material, AComA aneurysms are more frequent than MCA aneurysms. McKissock et al [27] found that 27 aneurysms had not been diagnosed during the lives of 20 of 100 complete necropsy patients, and that the most common site of these was the MCA. Therefore, the rate of rupture of unruptured aneurysms seems to be lower in MCA aneurysms than in AComA or ICA aneurysms. In our study, there were no relevant differences in the size of aneurysms as well as in the thickness of walls between the MCA aneurysms and the other aneurysms. Crompton {5] said that, when combinations of MCA and ICA aneurysms were present on the same side, the proximal aneurysm was ruptured more frequently. The lower risk of rupture in unruptured MCA aneurysms may be attributable to other factors, such as hemodynamic stress. Fourth, of 93 unruptured incidental aneurysms, 50 (54%) were 4 mm or less in diameter, and 33 (35%) were 5-9 mm in diameter. Wiebers et al [41,42), in a clinical study, reported that unruptured saccular aneurysms of less than 10 mm in diameter had a very low
Table 7. Relationship of Size to Thickness of Walls in 75 Unruptured Aneurysms’
probability of subsequent rupture. On the contrary, Kassell and Torner [20} stressed that unruptured aneurysms of less than 10 mm in diameter could not be considered innocuous, and that operation should be considered for lesions more than 5 mm in diameter. In an autopsy study, Crompton [5] found that the critical size for risk of rupture of unruptured aneurysms was a maximum external diameter of 4 mm. McCormick and Acosta-Rua {25f found in their autopsy series that 130 of the 137 unruptured aneurysms (95%) were less than 10 mm in diameter. However, they demonstrated that the unfixed size of the unruptured aneurysms was 30%-60% greater in maximal diameter during infusion of the cerebral arteries with a 0.9% saline solution under 70 mm Hg pressure. They stated, therefore, that an aneurysm measuring 1 cm in the living patient would measure only about 6-7 mm at autopsy. In addition, the same authors demonstrated that there was a decrease in size of 6%-12% following formalin fixation. Allowing for all these factors affecting the size of aneurysms, the size of aneurysms 10 mm in diameter while the patient is alive would decrease to 5.5-7.2 mm in autopsy material. In our series, assuming that the critical size of aneurysms found at autopsy is 5 mm or larger in diameter, 43 of 93 unruptured incidental aneurysms (46%) seem to have had a risk of rupture. However, even if the 50 aneurysms (54%) smaller than 5 mm in diameter are excluded, the rupture rate of unruptured incidental aneurysms is still very low. With respect to the thickness of walls of aneurysms, Suzuki and Ohara 140) stressed that, when aneurysms grew larger than 4 mm, the walls became collagenous and extremely thin portions developed in their domes. However, in our study, correlation could not be found between the size of aneurysms and the thickness of walls. Although there is little doubt that aneurysm size is a very important factor in the risk of aneurysm rupture ES, 13,20,4 1,421, the discrepancy between the incidence of unruptured incidental aneurysms in autopsy series and the incidence of ruptured aneurysms in clinical studies may not be explained adequately by the relationship of the size of aneurysms to the thickness of walls. In the present study, the question as to why the vast majority of unruptured aneurysms do not rupture could not be explained adequately by the morphological examination. Other studies, such as a hemodynamic study, may be necessary to explain the rarity of rupture in unruptured aneurysms.
Thickness of walls Size bxrn) 14
5-9
10-14 15-19
Thin
:
0 1
Thin and thick
Thick
Total
24 20 3 4
5 2 0 0
36 31 3 5
1 Twenty-seven aneurysms had undetermined site and/or thickness of walls.
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4. Chason JL, Hindman Results of a planned
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WM. Berry aneurysms of the circle of Willis. autopsy study. Neurology 1958;8:41-4.
MR. Mechanism of growth and rupture 5. Crompton berry aneurysms. Br Med J 1966;1:1138-42. 6. Dell S. Asymptomatic rupture. Neurosurgery
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of subarachnoid 7. Drake CG, Girvin JP. The surgical treatment hemorrhage with multiple aneurysms. In: Morley TP, ed. Current controversies in neurosurgery. Philadelphia: WB Saunders, 1976~274-6.
27. McKissock W, Richardson cranial aneurysms. Lancet
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S. Incidence, haemorrhage.
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30. Phillips LH II, Whisnant JP, O’FaIlon M, Sundt TM Jr. The unchanging pattern of subarachnoid hemorrhage in a community. Neurology 1980;30:1034-40.
G. Primary 7. Gudmundsson Stroke 1973;4:764-7.
31. Pitt GN.
subarachnoid
hemorrhage
10. Heiskanen 0. Risk of bleeding from unruptured cases with multiple intracranial aneurysms. 1981;55:524-6. 11. Heiskanen 0, Poranen A. Surgery of incidental rysms. Surg Neural 1987;28:432-6. 12. Inagawa T. Incidence Neural Med (Tokyo)
of subarachnoid 1988;28:105-7.
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33. Sacco RL, Wolf PA, Bharucha NE, Meeks SL, Kannel WB, Charette LJ, McNamara PM, Palmer EP, D’Agostino R. Subarachnoid and intracerebral hemorrhage: natural history, prognosis, and precursive factors in the Framingham study. Neurology 1984;34:847-54. and incidental 34. SaIazar JL. Surgical treatment of asymptomatic tracranial aneurysms. J Neurosurg 1980;53:20-1.
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of 35. Samson DS, Hodosh RM, Clark WK. Surgical management unruptured asymptomatic aneurysms. J Neurosurg 1977;46:731-4.
M, Aoki H, Ishikawa S, Yoshimoto H. 15. Inagawa T, Takahashi Aneurysmal subarachnoid hemorrhage in Izumo City and Shimane Prefecture of Japan. Outcome. Stroke 1988; 19: 176-80.
36. Sivenius J, Heinonen incidence of stroke 1985;16:188-92.
16. Inagawa T, Yamamoto M, Kamiya K, Ogasawara H. Management of elderly patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 1788;67:332-9.
and anatomical 37. Stehbens WE. Aneurysms arteries. Arch Path01 1963;75:45-64.
17. Jane JA, Winn RH, Richardson AE. The natural history of intracranial aneurysms: rebleeding rates during the acute and long term period and implication for surgical management. Clin Neurosurg 1977;24:176-84. 18. Joensen P. Subarachnoid Incidence on the Faroes 1984;15:438-40. 17. Kassell NF, Drake gery 1982;10:514-9. 20.
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CG. Timing
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JC. Size of intracranial
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21. Kiyohara Y, Ueda K, Hasuo Y, Wada J, Kawano H, Kato I, Sinkawa A, Ohmura T, Iwamoto H, Omae T, Fujishima M. Incidence and prognosis of subarachnoid hemorrhage in a Japanese rural community. Stroke 1989;20:1150-5. 22. Ljunggren B, S&eland H, Brandt L, Zygmunt S. Early operation and overall outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg 1985;62:547-51. study of intracranial 23. Locksley HB. Report on the cooperative aneurysms and subarachnoid hemorrhage. Section V, part II. Natural history of subarachnoid hemorrhage, intracranial aneurysms
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JP, Sundt TM Jr, O’Fallon WM. The intracranial saccular aneurysms. J Neu-
AE, Jane JA. The long-term prognosis in 43. Winn HR. Richardson untreated cerebral aneurysms: I. The incidence oflate hemorrhage in cerebral aneurysm: a IO-year evaluation of 364 patients. Ann Neural 1977;1:358-70. 44
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D, Scott RM. Surgical treatment Neurosurgery aneurysms.
361
Autopsy Study of Unruptured Incidental Intracranial Aneurysms Tetsuji Department Department
Inagawa, M.D.,
and Asao Hirano,
M.D.
of Neurosurgery, Shimane Prefectural Central Hospital, Izumo, Japan, and Division of Neuropathology, of Pathology, Montefiore Medical Center, Bronx, New York
Inagawa T, Hirano A. Autopsy study of unruptured incidental intracranial aneurysms. Surg Neural 1990;34:361-5. The autopsy files and preparations of unruptured incidental intracranial aneurysms seen at the Montefiore Medical Center between 195 1 and 1987 were reviewed. There were 84 patients with 102 unruptured aneurysms in a total of 10,259 autopsies, giving a prevalence of 0.8%. Sixteen of the 84 (19%) had multiple aneurysms. The thickness of walls of aneurysms could be estimated in 78 of 102 aneurysms, and was determined to be either thin or thin and thick in 71 aneurysms. In this study, four noteworthy factors were found: (1) the incidence of unruptured aneurysms was higher in elderly patients aged 60 years or older, and the peak percentage was 1.2% in the seventh decade; (2) aneurysms occurred more frequently in females than males, with a ratio of 53: 31; (3) the most common site
of aneurysms was the middle cerebral artery; 37 of 102 aneurysms (36%) occurred on it; and (4) the rate of small aneurysms was very high; 50 of 93 aneurysms (54%) were 4 mm or less in diameter, and 33 aneurysms (35%) were 5-9 mm in diameter. However, relationships could not be found between age distribution and location, size, or thickness of walls; between gender and size or thickness of walls; between location and size or thickness of walls; or between size and thickness of walls. Based on published statistics on subarachnoid hemorrhage and this study, the rupture rate of unruptured aneurysms seems to be very low. Although the risk of rupture may be relatively low in small aneurysms, its low risk probably cannot be explained adequately by morphological examination only. KEY WORDS: Unruptured rupture; Autopsy
aneurysm; Aneurysm
size; Risk of
Despite the dramatic improvement in surgical results for ruptured intracranial aneurysm, the overall management mortality for this disorder still remains high [3,15,19,22]. The high mortality is attributed, in part, to the fact that about one half of the patients suffering
A&ireu reprint requests to: Tetsuji Inagawa, M.D., Department of Neurosurgery, Shimane Prefectural Central Hospital, 116 Imaichicho, Izumo, Shimane 693, Japan. Received October 16, 1989; accepted 0 1990 by Else&r
May 25, 1990.
Science Publishing Co., Inc.
from aneurysmal subarachnoid hemorrhage (SAH) cannot be treated surgically because of severe brain damage after SAH [ 14,15,19,22]. One method of overcoming this dismal disease is to operate on the aneurysms before they rupture; that is, to treat unruptured aneurysms. There are several reports concerning the surgical results of unruptured incidental aneurysms [11,34,35,44]. However, to operate on such patients, it is important to know what kind of unruptured aneurysms are likely to rupture. The natural history of unruptured aneurysms, especially the risk of rupture, is not precisely known [6,10,17,41-431. Jane et aI [17J and Winn et aI 1431 speculated that the annual risk of rupture of an unruptured asymptomatic aneurysm was similar to the natural history of the healed ruptured aneurysm; that is, a hemorrhage rate of 3%4% per year. In patients with multiple aneurysms, the risk of bleeding from a previously unruptured aneurysm was reported to be 10%-170/o [7,28]. However, they are mainly discussing unruptured aneurysms discovered clinically by angiography and other methods. In this paper, unruptured incidental aneurysms found in autopsy series were investigated to search for a clue as to what factors regarding unruptured aneurysms can be correlated to the risk of rupture.
Materials
and Methods
The autopsy files of patients with intracranial aneurysms seen at the Montefiore Medical Center during the 37year period between 1951 and 1987 were reviewed. During this period a total of 10,259 autopsies, including examination of the cranial contents, were performed. For this report, 84 patients with unruptured incidental saccular aneurysm were studied. One hundred thirtythree patients with ruptured saccular aneurysm [13], 14 patients with fusiform aneurysm, and seven patients with mycotic aneurysm were excluded from this study. Unruptured aneurysms in patients with SAH were not analyzed. Classification of aneurysm size was based on the dimension of greatest diameter. The thickness of walls of aneurysms was estimated by reviewing the thin-sectioned aneurysms placed on coverglass preparation, and dividing it into three basic types: thin, thin and thick, 0090-3019/90/$3.50
Table
Inagawa and Hirano
Surg Neurol 1990;34:361-5
362
1. Cause of Death in 84 Autopsy Patients with
Vnrubtured
Aneurvsms No. of cases
Cause of death
9 3
Cerebral disease Cerebral infarction
Intracerebral hematoma
4
Brain tumor Other
2
causes
Cancer Cardiovascular Pneumonia Gastric ulcer
75 29 29 4 1
disease
Liver cirrhosis Renal failure Sepsis Aplastic anemia
3 4 4 1
Total
84
and thick. If it was almost the same thickness as the parent vessel wall or thicker, it was designated as thick. If the wall was uniformly thin, it was designated as thin. If it was mixed with both thin and thick parts, it was designated as thin and thick.
Results The ages of the 84 patients with unruptured aneurysms ranged from 31 to 89 years, with a mean of 66.9 years (men 66.8 years, women 66.9 years). The causes of death are shown in Table 1. The incidence of unruptured aneurysms was 0.8% for all ages, and 0.9% for the 30-89 age group (Table 2). It was higher in elderly patients aged 60 years or older. The peak percentage was 1.2% in the seventh decade. Of the 84 subjects, 31 (37%) were men and 53 (64%) were women. There was no correlation between gender and age. Atherosclerosis of the circle of Willis was found in 60 of 73 patients (82%), but no correlation could be found between the degree of sclerosis and age. A total of 102 unruptured aneurysms was found. tif the 84 patients, 68 (81oJo) had a single aneurysm and 16 (19%), three men and 13 women, had multiple aneurysms. The latter group consisted of 14 patients with two aneurysms and two patients
Table
2.
Incidence of Vnruptured
Aneurysms
with three aneurysms (Table 3). There was no correlation between the incidence of multiple aneurysms and age. There were 28 anterior communicating artery (AComA) aneurysms (27%), 29 internal carotid artery (ICA) aneurysms (28%), 37 middle cerebral artery (MCA) aneurysms (36%), and eight vertebrobasilar artery (VBA) aneurysms (8%). The MCA was the most common site. Of the 93 aneurysms, 50 (54%) were 4 mm or less in diameter, 33 (35%) were 5-9 mm, and 10 (11%) were 10 mm or larger. The thickness of walls of aneurysms could be estimated in 78 of 102 aneurysms; it was thin in 19 aneurysms (24%), mix&d thin and thick in 52 (67%), and thick in seven (9%). Relationships of the patient’s age to location, size, or thickness of walls of aneurysms could not be demonstrated. Of 68 aneurysms in women, both ICA and MCA aneurysms accounted for 23 (34%) each, while of 34 aneurysms in men, 14 (4 1%) were MCA aneurysms and 13 (38%) were AComA aneurysms (Table 4). Relationships of gender to size (Table 5) and thickness of walls of aneurysms could not be found. Relationships of location of aneurysms to size are shown in Table 6. Twenty of 27 AComA aneurysms (74%), 10 of 25 ICA aneurysms (40%), and 19 of 35 MCA aneurysms (54%) were 4 mm or smaller in diameter. Six of 27 AComA aneurysms (22%), 10 of 25 ICA aneurysms (4070), and 12 of 35 MCA aneurysms (3470) were 5-9 mm in diameter. A relationship of the location of aneurysms to the thickness of walls could not be demonstrated. Relationships of size of aneurysms to thickness of walls are shown in Table 7. In seven of the 36 aneurysms (19%) that were 4 mm or smaller in diameter, the thickness of walls of aneurysms was thin; and in 24 of 36 (67%), it was thin and thick. In 10 of 39 aneurysms (26%) that were 5 mm or larger in diameter, the thickness of walls of aneurysms was thin; and in 27 of 39 (69%), it was thin and thick. A total of 31 of 36 aneurysms (86%), which were 4 mm or smaller in diameter, had a thin portion in the walls; and a total of 37 of 39 aneurysms (95%), which were 5 mm or larger in diameter, had a thin portion. Other studies have indicated a possible link between polycystic kidney disease and intracranial aneurysm. The following is a summary bf associated conditions and is
Found at Autopsy by Age Age (years)
O-29
No. of autopsies No. of cases with aneurysm Incidence (%)
903 0 0
30-39
40-49
50-59
60-O
70-79
80-89
290
Total
438 2 0.46
921 3 0.32
1868 13 0.70
2663 33 1.24
2290 22 0.96
1052 11 1.05
124 0 0
10,259 84 0.82
Unruptured
Table
Intracranial
Surg Neurol 1990;34:361-5
Aneurysms
363
3. Age Distribution of Patients with Multiple Unruptured Aneurysms Age
Aneurysms found
30-39
40-49
50-59
1
1 1 0
1 2 0
10 2 1
2. 3
included for information only. The examination reports indicated polycystic kidney disease in six of 10,259 autopsies, and the coexistence of polycystic kidney disease and intracranial aneurysm in three patients: a 64-yearold man with an unruptured AComA aneurysm, a 31year-old man with a ruptured MCA aneurysm, and a 13year-old girl with a ruptured basilar artery aneurysm. An association of tumor and intracranial aneurysm was found in three patients: a 6%year-old woman with an unruptured fusiform anterior cerebral artery (ACA) aneurysm and a spinal meningioma, a 69year-old woman with an unruptured ICA aneurysm coexisting with both a falx meningioma and a pituitary microadenoma, and a 64-year-old man with a ruptured ACA aneurysm with a pituitary microadenoma.
Discussion In autopsy studies, the incidence of intracranial aneurysms including not only unruptured but also ruptured aneurysms was reported to be 0.2%-8.1% [2,4, 13,24-26,31,37]. According to Berry et al [2), unruptured incidental asymptomatic aneurysms were found in 1% of the brains examined in 6686 autopsy series. In a planned autopsy study of 2786 consecutive necropsies, at least one unruptured aneurysm was observed in 2% of them [4]. McCormick [24] reported that, in a prospective and consecutive autopsy series of 2276 patients, the percentages of patients with unruptured aneurysm were 5 .O@ for all ages and 6.1% for those 20 years and older. Riggs and Rupp 1321 discovered miliary aneurysms measuring 5 mm or less in 13 1 of 1437 consecutive autopsy patients (9%). In the present autopsy series of 10,259 patients, unruptured saccular aneurysms were found in 84 patients, and 16 of these (19%) had multiple aneurysms. The incidence of unruptured incidental aneurysms was 0.8% for all ages, and
(yews)
60-O
Artery affected
Male
Female
Total
Anterior communicating Internal carotid Middle cerebral Vertebrobasilar
13 6 14 1
15 23 23 7
28 29 37 8
80-89
Total
18 4 0
11 0 0
68
27 5 1
14 2
0.9% for the 30-89 age group. Therefore, if the incidence of unruptured aneurysms were estimated as 1%9% in- patients of all ages, and if the annual incidence of aneurysmal SAH were estimated as 6-21 per 100,000 population [12,13,22,29,30,33], the annual risk of rupture of unruptured aneurysms could be calculated as roughly 0.1~?-2.1~Z. Which factors cause an unruptured aneurysm to rupture? In this autopsy study, four noteworthy factors were found. (1) The incidence of unruptured aneurysms was higher in elderly patients aged 60 years or older. (2) Female patients outnumbered males 5 : 3. (3) The most common site of aneurysms was the MCA. (4) The percentage of small aneurysms was very high. The peak incidence of unruptured incidental aneurysms was 1.2% in the seventh decade. McCormick’s I241 autopsy series recorded the peak incidence as being in the seventh decade. However, in this study, we could not find a correlation between atherosclerosis of vessels of the circle of Willis and the patient’s age. The relationship of the patient’s age to location, size, and thickness of walls of aneurysms could not be found either. In published epidemiological studies, the incidence of aneurysmal SAH increased almost linearly with the increase in age [8,18,21,30,33}. Therefore, there seems to be no difference in the degree of risk of rupture of unruptured aneurysms between those in young patients and in elderly patients. Second, females outnumbered males in a ratio of 53 : 31, or 63% to 37%. The highest incidence for both sexes was in the seventh decade. Some epidemiological studies reported that the annual incidence of SAH was higher in males 19,361, whereas others reported the incidence to be higher in females [1,3,8,21,29,30). There is no consistent trend of incidence by gender [14]. In our study, a relationship of gender to size of aneurysms or
Table Table 4. Location and Gender of 102 Unruptured Aneurysms
70-79
5. Size and Gender of 9.3 Unruptured Aneurysms’
Size (mm) 54 5-9 10-14 15-19 ’ Nine aneurysms
Male
Female
Total
20 8 1 3
30 25 4 2
50 33 5 5
had undetermined
sizes.
Inagawa and Hirano
Surg Neural 1990;34:361-5
364
Table 6. Relationship of Location to Size in 93 Unruptured Aneurysms” Size (mm) Arterv affected Anterior communicating Internal carotid Middle cerebral Vertebrobasilar
54
5-9
10-14
15-19
Total
20 10 19 1
6 10 12 5
1 2 2 0
0 3 2 0
27 25 35 6
8 Nine aneurysms had undetermined sizes
thickness of walls could not be found. There seems to be no relationship between gender and risk of aneurysm rupture. Third, 37 of the total of 102 aneurysms (36%) occurred on the MCA, while 28 (27%) occurred on the AComA, 29 (28%) on the ICA, and eight (8%) on the VBA. In clinical studies, it has been shown that MCA aneurysms account for about 20oJ0-30% of all ruptured aneurysms [14,16,20,22,23,39]. In general, MCA aneurysms usually preponderate in autopsy material [38], whereas in clinical material, AComA aneurysms are more frequent than MCA aneurysms. McKissock et al [27] found that 27 aneurysms had not been diagnosed during the lives of 20 of 100 complete necropsy patients, and that the most common site of these was the MCA. Therefore, the rate of rupture of unruptured aneurysms seems to be lower in MCA aneurysms than in AComA or ICA aneurysms. In our study, there were no relevant differences in the size of aneurysms as well as in the thickness of walls between the MCA aneurysms and the other aneurysms. Crompton {5] said that, when combinations of MCA and ICA aneurysms were present on the same side, the proximal aneurysm was ruptured more frequently. The lower risk of rupture in unruptured MCA aneurysms may be attributable to other factors, such as hemodynamic stress. Fourth, of 93 unruptured incidental aneurysms, 50 (54%) were 4 mm or less in diameter, and 33 (35%) were 5-9 mm in diameter. Wiebers et al [41,42), in a clinical study, reported that unruptured saccular aneurysms of less than 10 mm in diameter had a very low
Table 7. Relationship of Size to Thickness of Walls in 75 Unruptured Aneurysms’
probability of subsequent rupture. On the contrary, Kassell and Torner [20} stressed that unruptured aneurysms of less than 10 mm in diameter could not be considered innocuous, and that operation should be considered for lesions more than 5 mm in diameter. In an autopsy study, Crompton [5] found that the critical size for risk of rupture of unruptured aneurysms was a maximum external diameter of 4 mm. McCormick and Acosta-Rua {25f found in their autopsy series that 130 of the 137 unruptured aneurysms (95%) were less than 10 mm in diameter. However, they demonstrated that the unfixed size of the unruptured aneurysms was 30%-60% greater in maximal diameter during infusion of the cerebral arteries with a 0.9% saline solution under 70 mm Hg pressure. They stated, therefore, that an aneurysm measuring 1 cm in the living patient would measure only about 6-7 mm at autopsy. In addition, the same authors demonstrated that there was a decrease in size of 6%-12% following formalin fixation. Allowing for all these factors affecting the size of aneurysms, the size of aneurysms 10 mm in diameter while the patient is alive would decrease to 5.5-7.2 mm in autopsy material. In our series, assuming that the critical size of aneurysms found at autopsy is 5 mm or larger in diameter, 43 of 93 unruptured incidental aneurysms (46%) seem to have had a risk of rupture. However, even if the 50 aneurysms (54%) smaller than 5 mm in diameter are excluded, the rupture rate of unruptured incidental aneurysms is still very low. With respect to the thickness of walls of aneurysms, Suzuki and Ohara 140) stressed that, when aneurysms grew larger than 4 mm, the walls became collagenous and extremely thin portions developed in their domes. However, in our study, correlation could not be found between the size of aneurysms and the thickness of walls. Although there is little doubt that aneurysm size is a very important factor in the risk of aneurysm rupture ES, 13,20,4 1,421, the discrepancy between the incidence of unruptured incidental aneurysms in autopsy series and the incidence of ruptured aneurysms in clinical studies may not be explained adequately by the relationship of the size of aneurysms to the thickness of walls. In the present study, the question as to why the vast majority of unruptured aneurysms do not rupture could not be explained adequately by the morphological examination. Other studies, such as a hemodynamic study, may be necessary to explain the rarity of rupture in unruptured aneurysms.
Thickness of walls Size bxrn) 14
5-9
10-14 15-19
Thin
:
0 1
Thin and thick
Thick
Total
24 20 3 4
5 2 0 0
36 31 3 5
1 Twenty-seven aneurysms had undetermined site and/or thickness of walls.
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