Neurol Sci DOI 10.1007/s10072-015-2101-9
ORIGINAL ARTICLE
Observation of cerebral aneurysm wall thickness using intraoperative microscopy: clinical and morphological analysis of translucent aneurysm Jihye Song • Jung Eon Park • Hyoung Ryoul Kim Yong Sam Shin
•
Received: 22 September 2014 / Accepted: 29 January 2015 Ó Springer-Verlag Italia 2015
Abstract Intracranial aneurysms suffer various interactions between hemodynamics and pathobiology, and rupture when this balance disrupted. Aneurysm wall morphology is a result of these interactions and reflects the quality of the maturation. However, it is a poorly documented in previous studies. The purpose of this study is to observe aneurysm wall thickness and describe the characteristics of translucent aneurysm by analyzing clinical and morphological parameters. 253 consecutive patients who underwent clipping surgery in a single institute were retrospectively analyzed. Only middle cerebral artery aneurysms (MCA) which exposed most part of the dome during surgery were included. Aneurysms were categorized based on intraoperative video findings. Aneurysms more than 90 % of super-thin dome and any aneurysms with entirely super-thin-walled daughter sac were defined as translucent aneurysm. A total of 110 consecutive patients with 116 unruptured MCA aneurysms were included. Ninety-two aneurysms (79.3 %) were assigned to the nottranslucent group and 24 (20.7 %) to the translucent group. The relative proportion of translucent aneurysm in each age group was highest at ages 50–59 years and absent at ages J. Song Y. S. Shin (&) Department of Neurosurgery, Seoul St. Mary’s Hospital, Catholic University of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea e-mail: [email protected]; [email protected] J. E. Park Department of Neurosurgery, Ajou University School of Medicine and Hospital, Suwon, Korea H. R. Kim Department of Occupational and Environmental Medicine, Seoul St. Mary’s Hospital, Catholic University of Medicine, Seoul, Korea
30–39 and 70–79 years. There was a trend that translucent aneurysms were smaller in size (p = 0.019). Multivariate logistic analysis showed that translucent aneurysm was strongly correlated with height \3 mm (p = 0.003). We demonstrated that the translucent aneurysms were smaller in size and the aneurysm height \3 mm was related. These results may provide information in determining treatment strategies in patients with small size aneurysm. Keywords Intracranial aneurysm Translucent aneurysm Wall thickness
Introduction The natural history of intracranial aneurysm (IA) consists of three phases: initiation, growth, and either stabilization or rupture. IAs suffer various interactions between hemodynamics and pathobiology during its life, and rupture when this balance disrupted. Focal hemodynamic insult triggers endothelial dysfunction leads to activation of matrix metalloproteinase that mediate degradation of the extracellular matrix (ECM) and apoptosis of smooth muscle cells. These processes progressively weaken the arterial wall, resulting in aneurysm formation. After initiation, there are concurrent eutrophic changes (cell proliferation and ECM production) and destructive changes (cell death and ECM degradation) ongoing throughout the natural history of the IAs [1]. When these two processes are balanced, the intracranial aneurysm remains stable. When the balance is disrupted, an aneurysm may rupture. The net result of these interactions between hemodynamic stress and biologic processes is a modification in wall thickness [2]. So, wall morphology reflects the quality of the wall maturation and its resistance to rupture [3]. However,
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aneurysm dome wall thickness is poorly documented in previous studies. In this study, we examined aneurysm domes morphology using microscopy video during microsurgical clipping and describing the characteristics of translucent aneurysm by analyzing clinical and morphological parameters. We included only middle cerebral artery (MCA) aneurysms because MCA is the most frequent location for unruptured intracranial aneurysms, usually treated with clipping, and exposed most part of the aneurysmal dome during clipping surgery. So, the MCA aneurysm is the best candidate to design an aneurysm rupture risk evaluation based on intraoperative findings.
Materials and methods Patients We retrospectively selected all patients who underwent microsurgical clipping in our institute between January 2012 and October 2013. 253 consecutive patients were collected and 143 consecutive patients with 151 middle cerebral artery (MCA) aneurysms were enrolled. Only patients with MCA aneurysms who had an available intraoperative video file, distal subtraction angiography (DSA) data and medical records were included. Aneurysms that were fusiform, dissection, partially dissected, and clipped after coil embolization were excluded. Ruptured or intraoperative premature ruptured aneurysms were excluded because blood obscured visualization of the aneurysm dome. A total of 116 aneurysms in 110 patients were selected. Their clinical, radiographic and video file data were prospectively registered at the time into neurosurgical databases and then analyzed retrospectively by the authors. Institutional Review Board approval was obtained before data collection. Intraoperative video data All intraoperative images were captured through a Pentero 900 or Pentero surgical microscope video (Carl Zeiss, Oberkochen, Germany) at 1,920 9 1,080 or 720 9 480 pixels during aneurysm clipping procedures. Aneurysms were assessed for their wall thickness based on color translucence and divided into two groups. The aneurysms that were more than 90 % of transparent and super-thin dome and any aneurysms with an entirely transparent and super-thin-walled daughter sac (Fig. 1) were classified to translucent group and others to thick-walled group. Superthin regions were defined based on color intensity with respect to the parent vessel wall. Randomly selected 20 microscopic videos were reviewed together by two
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neurosurgeons (J. Song and J.E. Park) to minimize interobserver bias of the aneurysm grouping. Then they reviewed the rests of 96 microscopic videos independently. There was no discrepancy between the two surgeon’s groupings of the aneurysms. Demographic and angiographic data Demographic data of patient age, sex, history of medical comorbidities, smoking status, and the family history of stroke were reviewed from medical records. Aneurysm size was defined as previously described [4]. Angiographic data collected from 3D DSA images included maximal diameter (Dmax; defined as the largest of all cross sections along the height of the aneurysm), maximal width (Wmax; defined as the largest parallel diameter to the Dneck), neck diameter (Dneck; defined as the average neck diameter), height (H; defined as the maximum perpendicular distance of the dome from the neck plane), aspect ratio (H/Dneck), bottle neck factor (Wmax/Dneck), and height–width ratio (H/Wmax). Statistics The continuous data were expressed as mean ± SD. v2 test or Fishers exact test was used to compare medical comorbidities and dichotomized morphological parameters between the translucent and not-translucent groups. An unpaired t test was used for continuous variable statistical analyses. To identify the independent parameters that had significant correlations with translucent aneurysm, univariate and multivariate logistic regression analyses were separately performed for all of the aneurysms. Factors found to have a marginal association (defined as p \ 0.10) with the translucent aneurysms in the univariate analysis were entered into the multivariate analysis. For dichotomization of continuous parameters, median value (height, BNF and HWR) or previously suggested values (AR and Dmax) were applied. The odds ratio (OR) and 95 % confidence interval (CI) were calculated. A p \ 0.05 was considered significant. Statistical analysis was performed using SPSS software (SPSS, Chicago, IL).
Results Of the 116 aneurysms, 92 (79.3 %) cases were assigned to the thick-walled group and 24 (20.6 %) cases were assigned to the translucent group. The relative proportion of translucent aneurysm in each age group was highest in patients aged 50–59 years. No translucent aneurysms were detected in patients aged 30–39 and 70–79 years. Table 1 summarizes the demographic characteristics. Family history, multiplicity, sex, or other previously suggested risk
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Fig. 1 Intraoperative microscopic image of translucent aneurysms. a Aneurysms that were more than 90 % of transparent and super-thin dome. b Aneurysms with an entirely transparent and super-thin-walled daughter sac
Table 1 Clinical characteristics with translucent and nottranslucent aneurysms
Characteristics
Aneurysm groups (N = 116) Not-translucent (n = 92)
Age (years)
p value Translucent (n = 24)
56.07 ± 8.6
55.88 ± 6.3
0.062
30–39
3 (100 %)
0 (0 %)
0.384
40–49
18 (81.8 %)
4 (18.2 %)
50–59
32 (71.1 %)
13 (28.9 %)
60–69
35 (83.3 %)
7 (16.7 %)
70–79
4 (100 %)
0 (0 %)
25 (83.3 %) 67 (77.9 %)
5 (16.7 %) 19 (22.1 %)
Hypertension
43 (79.6 %)
11 (20.4 %)
Diabetes
7 (70.0 %)
3 (30.0 %)
Smoking
6 (85.7 %)
1 (14.3 %)
0.555
Family history
16 (80.0 %)
4 (20.0 %)
0.601
Multiplicity
37 (78.7 %)
10 (21.3 %)
0.538
Gender Male Female
0.364
factor showed no significant difference between the two groups. Unpaired t test showed a trend that translucent MCA aneurysms were smaller in size (5.2 vs 4.5 mm, p = 0.019, OR 1.655) and had larger BNF (1.3 vs 1.5, p = 0.004, OR 16.483) (Table 2). Larger AR was related with translucent aneurysms, but did not remain significant after multivariate analysis. To evaluate the predictive factor of translucent aneurysm, statistical analyses were performed with dichotomized value (Table 3). Univariate logistic regression analysis revealed that height\3 mm (p = 0.028) and BNF C 1.7 (p = 0.018) were significantly related to translucent aneurysms. Multivariate regression analysis demonstrated height \3 mm (p = 0.003; OR 10.679; 95 % CI 2.259–50.489) and AR C 1.2 (p = 0.013; OR 7.970; 95 % CI 1.553–40.897) were significantly associated to translucent aneurysm.
0.463
Discussion The prevalence of unruptured IAs in the general population ranges between 3 and 7 % [5]. The incidence of ruptured aneurysm is low, with approximately 0.5 % per year [5]. Aneurysm rupture occurs at a relatively young age and has high case fatality and morbidity rates up to 60 % [6]. Estimation of the rupture risk for an unruptured intracranial aneurysm(IA) is critical for clinical decision-making because the majority of unruptured IAs remain asymptomatic and never rupture [3] and preventive treatment carries a risk up to 5 % [7]. The International Study of Unruptured Intracranial Aneurysms (ISUIA) demonstrated an association between size and risk of rupture [8]. The Small Unruptured Intracranial Aneurysm Verification (SUAVe) study demonstrated the risk
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Neurol Sci Table 2 Analysis to evaluate trends of translucent and not-translucent aneurysm [mm, mean (SD)] Not-translucent (n = 92)
Translucent (n = 24)
Univariate analysis
Wmax
5.1 (2.2)
4.3 (1.4)
p = 0.100
Dmax
5.2 (5.2)
4.5 (1.2)
p = 0.052
Height
3.7 (1.8)
3.0 (1.2)
p = 0.303 p = 0.045
AR
0.9 (0.3)
1.0 (0.5)
BNF
1.3 (0.3)
1.5 (0.5)
p = 0.001
HWR
0.7 (0.2)
0.7 (0.3)
p = 0.513
Multivariate analysis
OR (95 % CI)
p = 0.019
1.655 (1.087–2.518)
p = 0.004
16.483 (2.434–111.611)
Dmax maximal diameter, Wmax maximal width, AR aspect ratio, BNF bottle neck factor, HWR height waist ratio
Table 3 Univariate and multivariate analysis of angiographic characteristics of translucent and not-translucent aneurysm Aneurysm group Not-translucent (n = 92)
Univariate analysis
Multivariate analysis
OR (95 % CI)
Translucent (n = 24)
Wmax C 5
53 (57.6 %)
17 (70.8 %)
p = 0.173
Dmax C 5
52 (56.5 %)
17 (70.8 %)
p = 0.149
height \ 3
35 (38.0 %)
15 (62.5 %)
p = 0.028
p = 0.003
10.679 (2.259–50.489)
AR C 1.2
74 (80.4 %)
15 (62.5 %)
p = 0.061
p = 0.013
7.970 (1.553–40.897)
BNF C 1.7
81 (88.0 %)
16 (66.7 %)
p = 0.018
HWR C 0.7
46 (50.0 %)
13 (54.2 %)
p = 0.447
Dmax maximal diameter, Wmax maximal width, AR aspect ratio, BNF bottle neck factor, HWR height waist ratio
of rupture for aneurysms \5 mm was 0.34 % per year [9]. However, it is noteworthy that a large number of patients have subarachnoid hemorrhages (SAH) as a result of the rupture of aneurysms with diameters \5 mm [10]. Other factors besides aneurysm, size affects its rupture [11]. IAs are initiated, growing and either be stabilized or ruptured by various interactions between hemodynamics and biological process and wall thickness reflect the net result of these interactions. Therefore, aneurysm wall thickness may provide insight into the adaptive mechanism of aneurysms. Aneurysm wall thickness has been a poorly documented feature in studies of aneurysm pathogenesis. To the best of our knowledge, this is the first attempt to investigate clinical and morphologic characteristics of super-thin-walled aneurysm and the largest analysis based on intraoperative findings of aneurysms. Wall thickness and aneurysm rupture Previous studies reported that thin portion of aneurysm dome correlated with point of rupture [12]. Aneurysms with a clearly defined foci of translucency suggest focal weakness by influencing local stiffness and predisposes these regions to rupture [13]. In histologic assessment, Kataoka et al. [14] found that aneurysms with very thin and degenerated walls with hyaline deposits mostly ruptured, and aneurysms with thick intima-like walls are mostly unruptured. Frosen et al. [15] identified four histologic aneurysm
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wall types and described morphologic changes in the aneurysm walls that correlated with rupture. They showed that the aneurysms with thin and hypocellular wall were 100 % ruptured. Based on these previous reports, we could hypothesize that translucent aneurysms which is entirely super-thin wall or with super-thin daughter sac may be prone to rupture. Previous studies on aneurysm rupture risk assessment have focused on size and morphology without integrated information about the heterogeneous wall thickness distribution across aneurysm types [8]. Aneurysm size and rupture risk We found that the aneurysm height \3 mm was significantly associated with the translucent group, with Dmax showing a negative trend in the multivariate analysis. Previous analysis with wall thickness based on intraoperative microscopy reported a similar result, but different morphologic parameter and cut-off value (Dmax \ 7 mm) [16]. Aneurysms increase in size by wall maturation, not just by stretching, which attenuates the wall [17]. Thus, aneurysm size provides information on how much the wall has grown. Aneurysms discovered in younger persons are much more likely to rupture than not rupture, and the reverse is true among elderly patients [18]. The average size of aneurysms, both ruptured and unruptured, does not significantly increase progressively with the age of the patient. This suggests that aneurysms are more likely to rupture the more
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recently they have formed [18]. Aneurysms with super-thin wall, which are significantly smaller than other aneurysms, may be in the early phase of their natural history when they are vulnerable to rupture. And this result might provide an information in the pre-operative planning strategies for patient with small size aneurysm.
may provide information in determining treatment strategies in patients with small size aneurysm. Conflict of interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Age-specific incidence of aneurysmal SAH References Aneurysms are rarely found in patients younger than 30 years of age. The decennial age distribution displays a bell-shaped curve for both ruptured and unruptured aneurysms between the age of 30 and 70 years, with the most common decades being 50–59 years for ruptured aneurysms [19]. The average age of patients was 51 years in a very large series of ruptured lesion [20]. The ratio of ruptured aneurysms to the total number of aneurysms decreases progressively with increasing age of patient; a previous study reported the percentage of aneurysm ruptures was 0 % in subjects C80 years of age [19]. In our study, the relative proportion of translucent aneurysms in each age group was similar to previous report concerning ruptured aneurysms. Presently, the proportion of translucent aneurysms in each age group was highest at ages 50–59 years and was 0 % at ages 30–39 and 70–79 years. These findings may help in deciding whether to treat or not, especially in elderly patients who have a short life expectancy and usually a higher morbidity rate under general anesthesia. However, it is difficult to apply in clinical practice because only 4 patients were included at ages 70–79 years. Large series studies are needed. Limitation Main limitation is that the categorization of super-thin or translucent aneurysm is based on two neurosurgeon’s subjective observation. We tried to reduce subjectivity of this study by analyzing intraoperative video together for 20 cases at first, reviewed separately the rests 96 cases and matched its results. Another limitation of this analysis was based on intraoperative findings and included only surgical cases. Unclippable, very small-sized aneurysms were excluded and the study mainly included aneurysms involving anterior circulation, particularly the middle cerebral artery (MCA). This analysis was retrospective and included only MCA surgical cases for dome visualization. These may have introduced a potential selection bias.
Conclusions We demonstrated that the translucent aneurysms were smaller in size and the aneurysm height\3 mm. This result
1. Meng H, Tutino VM, Xiang J, Siddiqui A (2013) High wss or low wss? Complex interactions of hemodynamics with intracranial aneurysm initiation, growth, and rupture: toward a unifying hypothesis. Am J Neuroradiol 2. Kadasi LM, Dent WC, Malek AM (2013) Colocalization of thinwalled dome regions with low hemodynamic wall shear stress in unruptured cerebral aneurysms. J Neurosurg 119(1):172–179 3. Elsharkawy A, Lehecka M, Niemela M et al (2013) Anatomic risk factors for middle cerebral artery aneurysm rupture: computed tomography angiography study of 1009 consecutive patients. Neurosurgery 73(5):825–837 discussion 836–827 4. Raghavan ML, Ma B, Harbaugh RE (2005) Quantified aneurysm shape and rupture risk. J Neurosurg 102(2):355–362 5. Costalat V, Sanchez M, Ambard D et al (2011) Biomechanical wall properties of human intracranial aneurysms resected following surgical clipping (irras project). J Biomech 44(15):2685–2691 6. Ingall T, Asplund K, Mahonen M, Bonita R (2000) A multinational comparison of subarachnoid hemorrhage epidemiology in the who monica stroke study. Stroke 31(5):1054–1061 7. Naggara ON, White PM, Guilbert F, Roy D, Weill A, Raymond J (2010) Endovascular treatment of intracranial unruptured aneurysms: systematic review and meta-analysis of the literature on safety and efficacy. Radiology 256(3):887–897 8. Wiebers DO, Whisnant JP, Huston J 3rd et al (2003) Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362(9378):103–110 9. Sonobe M, Yamazaki T, Yonekura M, Kikuchi H (2010) Small unruptured intracranial aneurysm verification study: suave study, Japan. Stroke 41(9):1969–1977 10. Forget TR Jr, Benitez R, Veznedaroglu E et al (2001) A review of size and location of ruptured intracranial aneurysms. Neurosurgery 49(6):1322–1325 discussion 1325–1326 11. Dhar S, Tremmel M, Mocco J et al (2008) Morphology parameters for intracranial aneurysm rupture risk assessment. Neurosurgery 63(2):185–196 discussion 196–187 12. Asari S, Ohmoto T (1994) Growth and rupture of unruptured cerebral aneurysms based on the intraoperative appearance. Acta Med Okayama 48(5):257–262 13. Steiger HJ, Aaslid R, Keller S, Reulen HJ (1989) Strength, elasticity and viscoelastic properties of cerebral aneurysms. Heart Vessels 5(1):41–46 14. Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R (1999) Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke 30(7):1396–1401 15. Frosen J, Piippo A, Paetau A et al (2004) Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35(10):2287–2293 16. Sherif C, Kleinpeter G, Mach G et al (2014) Evaluation of cerebral aneurysm wall thickness in experimental aneurysms: comparison of 3t-mr imaging with direct microscopic measurements. Acta Neurochir (Wien) 156(1):27–34
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Neurol Sci 17. Ujiie H, Tamano Y, Sasaki K, Hori T (2001) Is the aspect ratio a reliable index for predicting the rupture of a saccular aneurysm? Neurosurgery 48(3):495–502 discussion 502–493 18. Weir B (2002) Unruptured aneurysms. J Neurosurg 97(5): 1011–1012 discussion 1012–1013
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19. Weir B (2002) Unruptured intracranial aneurysms: a review. J Neurosurg 96(1):3–42 20. Allcock JM, Canham PB (1976) Angiographic study of the growth of intracranial aneurysms. J Neurosurg 45(6):617–621
ORIGINAL ARTICLE
Observation of cerebral aneurysm wall thickness using intraoperative microscopy: clinical and morphological analysis of translucent aneurysm Jihye Song • Jung Eon Park • Hyoung Ryoul Kim Yong Sam Shin
•
Received: 22 September 2014 / Accepted: 29 January 2015 Ó Springer-Verlag Italia 2015
Abstract Intracranial aneurysms suffer various interactions between hemodynamics and pathobiology, and rupture when this balance disrupted. Aneurysm wall morphology is a result of these interactions and reflects the quality of the maturation. However, it is a poorly documented in previous studies. The purpose of this study is to observe aneurysm wall thickness and describe the characteristics of translucent aneurysm by analyzing clinical and morphological parameters. 253 consecutive patients who underwent clipping surgery in a single institute were retrospectively analyzed. Only middle cerebral artery aneurysms (MCA) which exposed most part of the dome during surgery were included. Aneurysms were categorized based on intraoperative video findings. Aneurysms more than 90 % of super-thin dome and any aneurysms with entirely super-thin-walled daughter sac were defined as translucent aneurysm. A total of 110 consecutive patients with 116 unruptured MCA aneurysms were included. Ninety-two aneurysms (79.3 %) were assigned to the nottranslucent group and 24 (20.7 %) to the translucent group. The relative proportion of translucent aneurysm in each age group was highest at ages 50–59 years and absent at ages J. Song Y. S. Shin (&) Department of Neurosurgery, Seoul St. Mary’s Hospital, Catholic University of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea e-mail: [email protected]; [email protected] J. E. Park Department of Neurosurgery, Ajou University School of Medicine and Hospital, Suwon, Korea H. R. Kim Department of Occupational and Environmental Medicine, Seoul St. Mary’s Hospital, Catholic University of Medicine, Seoul, Korea
30–39 and 70–79 years. There was a trend that translucent aneurysms were smaller in size (p = 0.019). Multivariate logistic analysis showed that translucent aneurysm was strongly correlated with height \3 mm (p = 0.003). We demonstrated that the translucent aneurysms were smaller in size and the aneurysm height \3 mm was related. These results may provide information in determining treatment strategies in patients with small size aneurysm. Keywords Intracranial aneurysm Translucent aneurysm Wall thickness
Introduction The natural history of intracranial aneurysm (IA) consists of three phases: initiation, growth, and either stabilization or rupture. IAs suffer various interactions between hemodynamics and pathobiology during its life, and rupture when this balance disrupted. Focal hemodynamic insult triggers endothelial dysfunction leads to activation of matrix metalloproteinase that mediate degradation of the extracellular matrix (ECM) and apoptosis of smooth muscle cells. These processes progressively weaken the arterial wall, resulting in aneurysm formation. After initiation, there are concurrent eutrophic changes (cell proliferation and ECM production) and destructive changes (cell death and ECM degradation) ongoing throughout the natural history of the IAs [1]. When these two processes are balanced, the intracranial aneurysm remains stable. When the balance is disrupted, an aneurysm may rupture. The net result of these interactions between hemodynamic stress and biologic processes is a modification in wall thickness [2]. So, wall morphology reflects the quality of the wall maturation and its resistance to rupture [3]. However,
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aneurysm dome wall thickness is poorly documented in previous studies. In this study, we examined aneurysm domes morphology using microscopy video during microsurgical clipping and describing the characteristics of translucent aneurysm by analyzing clinical and morphological parameters. We included only middle cerebral artery (MCA) aneurysms because MCA is the most frequent location for unruptured intracranial aneurysms, usually treated with clipping, and exposed most part of the aneurysmal dome during clipping surgery. So, the MCA aneurysm is the best candidate to design an aneurysm rupture risk evaluation based on intraoperative findings.
Materials and methods Patients We retrospectively selected all patients who underwent microsurgical clipping in our institute between January 2012 and October 2013. 253 consecutive patients were collected and 143 consecutive patients with 151 middle cerebral artery (MCA) aneurysms were enrolled. Only patients with MCA aneurysms who had an available intraoperative video file, distal subtraction angiography (DSA) data and medical records were included. Aneurysms that were fusiform, dissection, partially dissected, and clipped after coil embolization were excluded. Ruptured or intraoperative premature ruptured aneurysms were excluded because blood obscured visualization of the aneurysm dome. A total of 116 aneurysms in 110 patients were selected. Their clinical, radiographic and video file data were prospectively registered at the time into neurosurgical databases and then analyzed retrospectively by the authors. Institutional Review Board approval was obtained before data collection. Intraoperative video data All intraoperative images were captured through a Pentero 900 or Pentero surgical microscope video (Carl Zeiss, Oberkochen, Germany) at 1,920 9 1,080 or 720 9 480 pixels during aneurysm clipping procedures. Aneurysms were assessed for their wall thickness based on color translucence and divided into two groups. The aneurysms that were more than 90 % of transparent and super-thin dome and any aneurysms with an entirely transparent and super-thin-walled daughter sac (Fig. 1) were classified to translucent group and others to thick-walled group. Superthin regions were defined based on color intensity with respect to the parent vessel wall. Randomly selected 20 microscopic videos were reviewed together by two
123
neurosurgeons (J. Song and J.E. Park) to minimize interobserver bias of the aneurysm grouping. Then they reviewed the rests of 96 microscopic videos independently. There was no discrepancy between the two surgeon’s groupings of the aneurysms. Demographic and angiographic data Demographic data of patient age, sex, history of medical comorbidities, smoking status, and the family history of stroke were reviewed from medical records. Aneurysm size was defined as previously described [4]. Angiographic data collected from 3D DSA images included maximal diameter (Dmax; defined as the largest of all cross sections along the height of the aneurysm), maximal width (Wmax; defined as the largest parallel diameter to the Dneck), neck diameter (Dneck; defined as the average neck diameter), height (H; defined as the maximum perpendicular distance of the dome from the neck plane), aspect ratio (H/Dneck), bottle neck factor (Wmax/Dneck), and height–width ratio (H/Wmax). Statistics The continuous data were expressed as mean ± SD. v2 test or Fishers exact test was used to compare medical comorbidities and dichotomized morphological parameters between the translucent and not-translucent groups. An unpaired t test was used for continuous variable statistical analyses. To identify the independent parameters that had significant correlations with translucent aneurysm, univariate and multivariate logistic regression analyses were separately performed for all of the aneurysms. Factors found to have a marginal association (defined as p \ 0.10) with the translucent aneurysms in the univariate analysis were entered into the multivariate analysis. For dichotomization of continuous parameters, median value (height, BNF and HWR) or previously suggested values (AR and Dmax) were applied. The odds ratio (OR) and 95 % confidence interval (CI) were calculated. A p \ 0.05 was considered significant. Statistical analysis was performed using SPSS software (SPSS, Chicago, IL).
Results Of the 116 aneurysms, 92 (79.3 %) cases were assigned to the thick-walled group and 24 (20.6 %) cases were assigned to the translucent group. The relative proportion of translucent aneurysm in each age group was highest in patients aged 50–59 years. No translucent aneurysms were detected in patients aged 30–39 and 70–79 years. Table 1 summarizes the demographic characteristics. Family history, multiplicity, sex, or other previously suggested risk
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Fig. 1 Intraoperative microscopic image of translucent aneurysms. a Aneurysms that were more than 90 % of transparent and super-thin dome. b Aneurysms with an entirely transparent and super-thin-walled daughter sac
Table 1 Clinical characteristics with translucent and nottranslucent aneurysms
Characteristics
Aneurysm groups (N = 116) Not-translucent (n = 92)
Age (years)
p value Translucent (n = 24)
56.07 ± 8.6
55.88 ± 6.3
0.062
30–39
3 (100 %)
0 (0 %)
0.384
40–49
18 (81.8 %)
4 (18.2 %)
50–59
32 (71.1 %)
13 (28.9 %)
60–69
35 (83.3 %)
7 (16.7 %)
70–79
4 (100 %)
0 (0 %)
25 (83.3 %) 67 (77.9 %)
5 (16.7 %) 19 (22.1 %)
Hypertension
43 (79.6 %)
11 (20.4 %)
Diabetes
7 (70.0 %)
3 (30.0 %)
Smoking
6 (85.7 %)
1 (14.3 %)
0.555
Family history
16 (80.0 %)
4 (20.0 %)
0.601
Multiplicity
37 (78.7 %)
10 (21.3 %)
0.538
Gender Male Female
0.364
factor showed no significant difference between the two groups. Unpaired t test showed a trend that translucent MCA aneurysms were smaller in size (5.2 vs 4.5 mm, p = 0.019, OR 1.655) and had larger BNF (1.3 vs 1.5, p = 0.004, OR 16.483) (Table 2). Larger AR was related with translucent aneurysms, but did not remain significant after multivariate analysis. To evaluate the predictive factor of translucent aneurysm, statistical analyses were performed with dichotomized value (Table 3). Univariate logistic regression analysis revealed that height\3 mm (p = 0.028) and BNF C 1.7 (p = 0.018) were significantly related to translucent aneurysms. Multivariate regression analysis demonstrated height \3 mm (p = 0.003; OR 10.679; 95 % CI 2.259–50.489) and AR C 1.2 (p = 0.013; OR 7.970; 95 % CI 1.553–40.897) were significantly associated to translucent aneurysm.
0.463
Discussion The prevalence of unruptured IAs in the general population ranges between 3 and 7 % [5]. The incidence of ruptured aneurysm is low, with approximately 0.5 % per year [5]. Aneurysm rupture occurs at a relatively young age and has high case fatality and morbidity rates up to 60 % [6]. Estimation of the rupture risk for an unruptured intracranial aneurysm(IA) is critical for clinical decision-making because the majority of unruptured IAs remain asymptomatic and never rupture [3] and preventive treatment carries a risk up to 5 % [7]. The International Study of Unruptured Intracranial Aneurysms (ISUIA) demonstrated an association between size and risk of rupture [8]. The Small Unruptured Intracranial Aneurysm Verification (SUAVe) study demonstrated the risk
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Neurol Sci Table 2 Analysis to evaluate trends of translucent and not-translucent aneurysm [mm, mean (SD)] Not-translucent (n = 92)
Translucent (n = 24)
Univariate analysis
Wmax
5.1 (2.2)
4.3 (1.4)
p = 0.100
Dmax
5.2 (5.2)
4.5 (1.2)
p = 0.052
Height
3.7 (1.8)
3.0 (1.2)
p = 0.303 p = 0.045
AR
0.9 (0.3)
1.0 (0.5)
BNF
1.3 (0.3)
1.5 (0.5)
p = 0.001
HWR
0.7 (0.2)
0.7 (0.3)
p = 0.513
Multivariate analysis
OR (95 % CI)
p = 0.019
1.655 (1.087–2.518)
p = 0.004
16.483 (2.434–111.611)
Dmax maximal diameter, Wmax maximal width, AR aspect ratio, BNF bottle neck factor, HWR height waist ratio
Table 3 Univariate and multivariate analysis of angiographic characteristics of translucent and not-translucent aneurysm Aneurysm group Not-translucent (n = 92)
Univariate analysis
Multivariate analysis
OR (95 % CI)
Translucent (n = 24)
Wmax C 5
53 (57.6 %)
17 (70.8 %)
p = 0.173
Dmax C 5
52 (56.5 %)
17 (70.8 %)
p = 0.149
height \ 3
35 (38.0 %)
15 (62.5 %)
p = 0.028
p = 0.003
10.679 (2.259–50.489)
AR C 1.2
74 (80.4 %)
15 (62.5 %)
p = 0.061
p = 0.013
7.970 (1.553–40.897)
BNF C 1.7
81 (88.0 %)
16 (66.7 %)
p = 0.018
HWR C 0.7
46 (50.0 %)
13 (54.2 %)
p = 0.447
Dmax maximal diameter, Wmax maximal width, AR aspect ratio, BNF bottle neck factor, HWR height waist ratio
of rupture for aneurysms \5 mm was 0.34 % per year [9]. However, it is noteworthy that a large number of patients have subarachnoid hemorrhages (SAH) as a result of the rupture of aneurysms with diameters \5 mm [10]. Other factors besides aneurysm, size affects its rupture [11]. IAs are initiated, growing and either be stabilized or ruptured by various interactions between hemodynamics and biological process and wall thickness reflect the net result of these interactions. Therefore, aneurysm wall thickness may provide insight into the adaptive mechanism of aneurysms. Aneurysm wall thickness has been a poorly documented feature in studies of aneurysm pathogenesis. To the best of our knowledge, this is the first attempt to investigate clinical and morphologic characteristics of super-thin-walled aneurysm and the largest analysis based on intraoperative findings of aneurysms. Wall thickness and aneurysm rupture Previous studies reported that thin portion of aneurysm dome correlated with point of rupture [12]. Aneurysms with a clearly defined foci of translucency suggest focal weakness by influencing local stiffness and predisposes these regions to rupture [13]. In histologic assessment, Kataoka et al. [14] found that aneurysms with very thin and degenerated walls with hyaline deposits mostly ruptured, and aneurysms with thick intima-like walls are mostly unruptured. Frosen et al. [15] identified four histologic aneurysm
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wall types and described morphologic changes in the aneurysm walls that correlated with rupture. They showed that the aneurysms with thin and hypocellular wall were 100 % ruptured. Based on these previous reports, we could hypothesize that translucent aneurysms which is entirely super-thin wall or with super-thin daughter sac may be prone to rupture. Previous studies on aneurysm rupture risk assessment have focused on size and morphology without integrated information about the heterogeneous wall thickness distribution across aneurysm types [8]. Aneurysm size and rupture risk We found that the aneurysm height \3 mm was significantly associated with the translucent group, with Dmax showing a negative trend in the multivariate analysis. Previous analysis with wall thickness based on intraoperative microscopy reported a similar result, but different morphologic parameter and cut-off value (Dmax \ 7 mm) [16]. Aneurysms increase in size by wall maturation, not just by stretching, which attenuates the wall [17]. Thus, aneurysm size provides information on how much the wall has grown. Aneurysms discovered in younger persons are much more likely to rupture than not rupture, and the reverse is true among elderly patients [18]. The average size of aneurysms, both ruptured and unruptured, does not significantly increase progressively with the age of the patient. This suggests that aneurysms are more likely to rupture the more
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recently they have formed [18]. Aneurysms with super-thin wall, which are significantly smaller than other aneurysms, may be in the early phase of their natural history when they are vulnerable to rupture. And this result might provide an information in the pre-operative planning strategies for patient with small size aneurysm.
may provide information in determining treatment strategies in patients with small size aneurysm. Conflict of interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Age-specific incidence of aneurysmal SAH References Aneurysms are rarely found in patients younger than 30 years of age. The decennial age distribution displays a bell-shaped curve for both ruptured and unruptured aneurysms between the age of 30 and 70 years, with the most common decades being 50–59 years for ruptured aneurysms [19]. The average age of patients was 51 years in a very large series of ruptured lesion [20]. The ratio of ruptured aneurysms to the total number of aneurysms decreases progressively with increasing age of patient; a previous study reported the percentage of aneurysm ruptures was 0 % in subjects C80 years of age [19]. In our study, the relative proportion of translucent aneurysms in each age group was similar to previous report concerning ruptured aneurysms. Presently, the proportion of translucent aneurysms in each age group was highest at ages 50–59 years and was 0 % at ages 30–39 and 70–79 years. These findings may help in deciding whether to treat or not, especially in elderly patients who have a short life expectancy and usually a higher morbidity rate under general anesthesia. However, it is difficult to apply in clinical practice because only 4 patients were included at ages 70–79 years. Large series studies are needed. Limitation Main limitation is that the categorization of super-thin or translucent aneurysm is based on two neurosurgeon’s subjective observation. We tried to reduce subjectivity of this study by analyzing intraoperative video together for 20 cases at first, reviewed separately the rests 96 cases and matched its results. Another limitation of this analysis was based on intraoperative findings and included only surgical cases. Unclippable, very small-sized aneurysms were excluded and the study mainly included aneurysms involving anterior circulation, particularly the middle cerebral artery (MCA). This analysis was retrospective and included only MCA surgical cases for dome visualization. These may have introduced a potential selection bias.
Conclusions We demonstrated that the translucent aneurysms were smaller in size and the aneurysm height\3 mm. This result
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