The risk factors of intracranial aneurysm rupture and the assessing efficacy of CTA
- *Corresponding Author:
- Jia-Wei Tian
Medical Imaging Centre
Second Affiliated Hospital of Harbin Medical University, PR China
Accepted on May 22, 2017
Objective: The objective is to apply the Computed Tomographic Angiography (CTA) on assessing the risk factors of intracranial aneurysm rupture, providing the reference for the prevention of intracranial aneurysm rupture.
Methods: 252 intracranial aneurysm rupture patients admitted in our hospital between February 2014- February 2017 were selected for prospective study. The rate of intracranial aneurysm rupture was evaluated and calculated. The univariate analysis was used to evaluate the different clinical characteristics and CTA results of patients with intracranial aneurysm rupture patients, and then the factors with statistical difference were included in Logistic multivariate regression analysis to analyse the risk factors of intracranial aneurysm rupture.
Results: In 252 patients, 45 patients were confirmed as intracranial aneurysm rupture during the surgery, the rate of intracranial aneurysm rupture was 17.86%. Logistic multivariate regression analysis results showed that complicating with hypertension, the diameter of aneurysm ≥ 3.850 mm, the ratio of aneurysm depth to aneurysm neck width (aspect ratio, AR) ≥ 1.448, the ratio of tumor depth to patent artery diameter (size ratio, SR) ≥ 1.388, the ratio of aneurysm area to the patent artery area at aneurysm neck ≥ 1.192, irregular aneurysm wall and the aneurysm locating at posterior communicating artery, internal carotid artery or middle cerebral artery were the independent risk factors of intracranial aneurysm rupture. The age ≥ 60, male patient and complicating with diabetes were the protective factors (P<0.05).
Conclusion: Intracranial aneurysm rupture is closely related to clinical characteristics, aneurysm morphology and location. Based on the baseline characteristics, aneurysm diameter, AR, SR and area ratio in CTA image could be the reliable references of intracranial aneurysm rupture risk.
Intracranial aneurysm, Rupture, Risk factor, CT angiography, Evaluation.
Intracranial aneurysm is an acute cerebrovascular disease caused by cystic encephalocele of intracranial arterial wall in Neurosurgery Department [1,2]. It is also the premonitory symptom of subarachnoid hemorrhage, the disability rate and mortality of which are high. Hemorrhage caused by intracranial aneurysm rupture is the main reason of subarachnoid hemorrhage. Therefore, combining with the rapid diagnosis and treatment, accurately assessing the risk of aneurysm rupture and intervening timely is critical for improving the survival rate and prognosis of patients [3-5]. As a simple and non-invasive method, Computed Tomographic Angiography (CTA) is widely applied in the assessment of intracranial aneurysm size, structure and anatomical location.
Some researchers also have proposed that the advantage of CTA is hopeful to provide the reference for intracranial aneurysm rupture [6-8]. In this study, 252 intracranial aneurysm rupture patients were included and CTA was applied to assess the risk factors of aneurysm rupture.
Materials and Methods
252 intracranial aneurysm patients admitted in our hospital during February, 2014-February 2017 were selected as objects for the prospective study. Inclusion criteria: intracranial aneurysm was confirmed by medical imaging and surgery, and there were no criteria of intracranial aneurysm rupture when included; the clinical data were complete; the patients were informed about this study and accepted CTA voluntarily. Exclusion criteria: the patients were complicated with other hemorrhagic disease or vascular diseases such as hypertensive intracerebral hematoma, arteriovenous fistula, moyamoya disease, facial hemangioma and head trauma; infection or intracranial aneurysm caused by trauma; unconsciousness or unable to cooperate; the patients received vessel clamp or endovascular interventional therapy before inclusion; contrast agent allergy. The age of 252 patients was 24-79 y and the average age was (51.52 ± 11.38 y). There were 167 male patients and 85 female patients. The complications: 161 patients had hypertension, 78 patients had diabetes and 85 patients had hyperlipemia. The Ethics Committee of our hospital approved this study.
The baseline of patient characteristics: The baselines of patient characteristics were collected, including age, gender, past medical history, family history and personal history. The past medical history included hypertension, diabetes, hyperlipemia, coronary heart disease and polycystic kidney et al, the family history included intracranial aneurysm, subarachnoid hemorrhage, and the personal history included smoking and drinking history.
CTA: The patients in both groups received CTA on the day admitted; the equipment used for the examination was LightSpeed 64 slice CT scanner (GE Healthcare, California, USA). Scanning parameters: the diameter was 64 mm × 0.5 mm, the pitch was 0.641, reconstructed slice thickness was 0.5 mm, the interval was 0.3 mm, the bulb rotation time was 0.5 s/ circle, the matrix was 512 × 512; scanning range: from calvarium to the lower edge of atlas; 60-80 ml non-ionic contrast agent iohexol and 100 ml normal saline were injected through cubital vein with speed of 4 ml/s, the threshold was set as 100 Hu at aortic arch. After scanning, the three dimensional image was reconstructed by several methods including multiplane reconstruction, maximal intensity projection and volume rendering technique, ADW 4.5 workstation was applied for image post-processing. In addition to aneurysm location and aneurysm wall, the aneurysm parameters were also assessed including aneurysm depth (Hmax, the maximal distance from the midpoint of aneurysm neck to aneurysm peak), height (Hp, the vertical distance from aneurysm peak to aneurysm neck plane), aneurysm width (W, the maximal vertical diameter from aneurysm to Hp), aneurysm neck width (N, the maximal vertical diameter from aneurysm neck to Hp), and the diameter of patent artery (Dv). Based on above parameters, the ratio of aneurysm depth to aneurysm neck width (aspect ratio, AR=Hmax/N), the ratio of tumor depth to patent artery diameter (size ratio, SR=Hmax/Dv), the ratio of aneurysm neck width to patent artery diameter (NPR, NPR=N/Dv) and the ratio of aneurysm area to the patent artery area at aneurysm neck (area ratio=Hp × W/(Dv × N)) were calculated.
Diagnosis of intracranial aneurysm rupture: According to the references [9-11], the intracranial aneurysm rupture was diagnosed, the criteria were as the following: the location where subarachnoid hemorrhage is concentrated or the location of hematoma; the ruptured aneurysm indicated by parent artery spasm; surgery results. The rupture rate of 252 patients was calculated.
Analysis of risk factors: The rates of intracranial aneurysm rupture in patients with different clinical characteristics and CTA results were calculated, and the factors with statistical difference were included in Logistics multivariate analysis to conclude the factors that affect intracranial aneurysm rupture.
SPSS18.0 (International Business Machines Corp., New York, USA) was used to analyse the clinical data in this clinical study. The numeration data were presented as (n/%) and χ2 test was used for analysis. The measurement data were presented as (͞x ± s), if the data fit normal distribution t-test was used for analysis and if the data don’t fit normal distribution modified t-test was used for analysis. The factors that affected intracranial aneurysm rupture were included in Logistic multivariate analysis, P<0.05 was considered as statistically significant.
The general data of intracranial aneurysm rupture
In 252 patients, 45 patients were confirmed as intracranial aneurysm rupture during the surgery. The rate of intracranial aneurysm rupture was 17.86%.
Baseline characteristics: The rates of intracranial aneurysm rupture in patients with different age, gender, hypertension and diabetes were statistically different (P<0.05), as shown in Table 1.
|Baseline characteristics||Case number||Case number of intracranial aneurysm rupture (n)||Occurrence rate (%)||P value|
Table 1. Analysis of intracranial aneurysm rupture in patients with different baseline characteristics (n=252).
CTA parameters: The rates of intracranial rupture in patients with different aneurysm diameter, AR, SR, area ratio, aneurysm diameter and irregular aneurysm wall were statistically different (P<0.05), as shown in Table 2.
|CTA parameter*||Case number||Case number of intracranial aneurysm rupture (n)||Occurrence rate (%)||P value|
|Aneurysm neck||<3.151 mm||173||31||17.92||>0.05|
|≥ 3.151 mm||79||14||17.72|
|Aneurysm diameter||<3.850 mm||85||8||9.41||<0.05|
|≥ 3.850 mm||167||37||22.16|
|≥ 2.081 mm||236||42||17.80|
|Irregular aneurysm wall||Yes||125||38||30.40||<0.05|
|Aneurysm location||Posterior Communicating artery||89||18||20.22||<0.05|
|Internal carotid artery||37||9||24.32|
|Anterior cerebral artery||51||5||9.80|
|Middle cerebral artery||59||12||20.34|
|Posterior cerebral circulation artery||16||1||6.25|
|*Note: the mean CTA parameters of 252 were selected as cut-off value.|
Table 2. The relation between CTA parameter and intracranial aneurysm rupture (n=252).
Logistic multivariate analysis
Logistic multivariate regression analysis results showed that complicating with hypertension, the diameter of aneurysm ≥ 3.850 mm, AR ≥ 1.448, SR ≥ 1.388, the area ratio ≥ 1.192, irregular aneurysm wall and the aneurysm locating at posterior communicating artery, internal carotid artery or middle cerebral artery were the independent risk factors of intracranial aneurysm rupture. The age ≥ 60, male patient, complicating with diabetes were the protective factors (P<0.05), as shown in Table 3.
|Risk factor||β||SE (β)||Wald χ2 value||P value||OR||95% CI|
|Age ≥ 60 y||-1.325||0.118||126.086||0.000||0.266||0.211~0.335|
|Aneurysm diameter ≥ 3.850 mm||0.781||0.339||5.308||0.000||2.184||1.124~4.244|
|AR ≥ 1.448||0.265||0.111||5.700||0.000||1.303||1.049~1.620|
|SR ≥ 1.388||0.994||0.135||54.213||0.000||2.702||2.074~3.520|
|Area ratio ≥ 1.192||1.032||0.241||18.337||0.000||2.807||1.750~4.501|
|Irregular aneurysm wall||2.597||0.582||19.911||0.000||13.423||4.290~42.002|
|Location at posterior communicating artery/internal carotid artery/middle cerebral artery||0.891||0.147||36.738||0.000||2.438||1.827~3.252|
Table 3. The multivariate regression analysis of factors that affect intracranial aneurysm rupture.
Intracranial aneurysm is prone to locate at posterior communicating artery or anterior communicating artery branch in Willis circle and this area is located around the subarachnoid space [12,13]. Thus, once there is intracranial aneurysm rupture, there is high risk of spontaneous subarachnoid hemorrhage, which causes high mortality and disability rate [4,14,15]. Therefore, risk assessment of intracranial aneurysm rupture in the early stage is critical in determining the surgical regimen and timing.
Previously most of the studies regarding the risk factor of intracranial aneurysm rupture focused on the baseline characteristics of patients . In this study, the results showed that the patients with age ≥ 60 y, male patient and complicating with diabetes had lower risk of intracranial aneurysm rupture, and the patients complicating with hypertension had higher risk of intracranial aneurysm rupture, which is in accordance with the previous studies [17-19]. Compared with young people, older people's cerebrovascular autoregulation ability is relatively slow, which may lead to intracranial aneurysms more likely to rupture in the elderly ones. The main reasons are: Although among the elderly population the compliance and elasticity of artery are decreased and there is high morbidity of aneurysm in elderly population, the risk of rupture is lower. As the age increases the rupture risk is decreased. It is considered that the decreased risk is related to several protective factors such as decreased blood flow and decreased external stimuli [20,21]. In this study, the risk of intracranial aneurysm rupture in male patients was only 0.671 times of female patients, that is to say, the risk in female patients was 1.5 times higher than male patients, which might be related to that most of female patients were in menopausal status, and menopause is considered to be related to increased risk of intracranial aneurysm rupture. This may be related to endocrine factors. Postmenopausal estrogen levels decreased, causing the content of collagen in tissues to reduce, and thus increasing the brittleness of the vessel wall, so the aneurysm is easy to form and develop. There is also study proposes that estrogenreplacement therapy can effectively decrease the rate of intracranial aneurysm rupture [22,23]; in diabetes patients, there are some pathophysiological changes such as glucose, lipid and protein metabolism disorder, the above changes can cause thickening of capillary basement membrane and atherosclerosis which further increases the risk of intracranial aneurysm. Hyperglycemia is conducive to mononuclear cells into the intima and into foam cells, eventually leading to atherosclerosis, contributing to the occurrence of aneurysms, but the role of aneurysm rupture is not clear. However, in this study, complicating with diabetes was the protective factor of intracranial aneurysm rupture, that is to say, although diabetes can increase the occurrence rate of intracranial aneurysm, it can decrease the risk of intracranial aneurysm rupture. This may be related to that diabetes patients have higher self-management awareness, and there is better timing for the early diagnosis and treatment of intracranial aneurysm. Furthermore, the regular diet and exercise of diabetes patients are helpful to the stability of aneurysm, and the complications in diabetes patients can also cause vicious events before intracranial aneurysm rupture, which can also cause error in statistical results [24-27]; hypertension caused thickening of vessel wall, arteriole hyaline change, smooth muscle cell proliferation of vascular wall, and endothelium damage can decrease the tolerance of vascular wall to blood pressure, and repetitive blood pressure fluctuation impact can gradually cause aneurysm rupture [28-30].
Based on the baseline characteristics, the value of CTA parameters in assessing aneurysm rupture risk was discussed. The results showed that aneurysm diameter ≥ 3.850 mm, AR ≥ 1.448, SR ≥ 1.388, area ratio ≥ 1.192, irregular aneurysm or the aneurysm located at posterior communicating artery/ internal carotid artery/middle cerebral artery could provide reliable reference for assessing the risk of aneurysm rupture. The above characteristics can not only help to assess the aneurysm itself, but also judge some parameters including the blood volume in aneurysm, blood flow speed and average shear stress within the aneurysm, and further predict the rupture risk based on the patent artery. Besides, Huang et al.  found that CTA parameters were independent risk factors from baseline characteristics, thus, CTA parameters combined with patients baseline characteristics can provide more accurate assessment, and further provide a timing and reliable indication for the diagnosis and treatment of intracranial aneurysm.
In conclusion, intracranial aneurysm rupture is closely related to patient age, gender and complication, and CTA parameters can also be applied in predicting the risk of intracranial aneurysm rupture. Thus, the above parameters are hopeful to be applied in predicting the risk of intracranial aneurysm rupture more accurately, however larger sample size is needed to verify the efficacy.
- Aoki T. Future prospects for the development of a novel medical therapy for intracranial aneurysm. Nihon Yakurigaku Zasshi 2016; 148: 86-91.
- Fernandes ST, Alves RV, Doria-Netto HL, Puglia Junior P, Rivau FR, Jory M. Treatment of complex intracranial aneurysm: Case report of the simultaneous use of endovascular and microsurgical techniques. Surg Neurol Int 2016; 7: 1060-1064.
- Al-Jehani H, Najjar A, Sheikh BY. Determining the critical size of intracranial aneurysm predisposing to subarachnoid hemorrhage in the Saudi population. Asian J Neurosurg 2014; 9: 193-195.
- Farag E, Ebrahim Z, Traul D, Katzan I, Manno E. Perioperative management of intracranial aneurysm and subarachnoid hemorrhage. Curr Pharm Des 2013; 19: 5792-5808.
- Kimura H, Akutsu N, Shiomi R, Kohmura E. Subarachnoid hemorrhage caused by ruptured intracranial fusiform aneurysm associated with microscopic polyangiitis. Neurol Med Chir (Tokyo) 2012; 52: 495-498.
- Illies T, Saering D, Kinoshita M, Fujinaka T, Bester M, Fiehler J, Tomiyama N, Watanabe Y. Feasibility of quantification of intracranial aneurysm pulsation with 4D CTA with manual and computer-aided post-processing. PLoS One 2016; 11: 0166810.
- Kapsas G, Budai C, Toni F, Patruno F, Federica Marliani A, Leonardi M, Cirillo L. Evaluation of CTA, time-resolved 4D CE-MRA and DSA in the follow-up of an intracranial aneurysm treated with a flow diverter stent: Experience from a single case. Interv Neuroradiol 2015; 21: 69-71.
- Vaphiades MS, Cure J, Kline L. Management of intracranial aneurysm causing a third cranial nerve palsy: MRA, CTA or DSA? Semin Ophthalmol 2008; 23: 143-150.
- Bui JT, Jajko R, Zivin SP. Massive hemorrhage from arterial access during intracranial aneurysm stent-assisted embolization: endovascular diagnosis and therapy. Semin Intervent Radiol 2015; 32: 14-17.
- Kannoth S, Thomas SV. Intracranial microbial aneurysm (infectious aneurysm): current options for diagnosis and management. Neurocrit Care 2009; 11: 120-129.
- Klepaczko A, Szczypinski P, Strzelecki M, Materka A. Numerical modeling of MR angiography for validation of image-driven quantitative diagnosis of intracranial aneurysm and carotid stenosis. EJNMMI Phys 2014; 1: 63.
- Dengler J, Maldaner N, Bijlenga P, Burkhardt JK, Graewe A, Guhl S, Hong B, Hohaus C, Kursumovic A, Mielke D, Schebesch KM, Wostrack M, Rufenacht D, Vajkoczy P, Schmidt NO, Giant Intracranial Aneurysm Study Group. Perianeurysmal edema in giant intracranial aneurysms in relation to aneurysm location, size, and partial thrombosis. J Neurosurg 2015; 123: 446-452.
- Mackey J, Brown RD, Moomaw CJ, Sauerbeck L, Hornung R, Gandhi D, Woo D, Kleindorfer D, Flaherty ML, Meissner I, Anderson C, Connolly ES, Rouleau G, Kallmes DF, Torner J, Huston J, Broderick JP. Unruptured intracranial aneurysms in the familial intracranial aneurysm and international study of unruptured intracranial aneurysms cohorts: differences in multiplicity and location. J Neurosurg 2012; 117: 60-64.
- Griessenauer CJ, Poston TL, Shoja MM, Mortazavi MM, Falola M, Tubbs RS, Fisher WS. The impact of temporary artery occlusion during intracranial aneurysm surgery on long-term clinical outcome: part I. Patients with subarachnoid hemorrhage. World Neurosurg 2014; 82: 140-148.
- Kimball D, Ples H, Kimball H, Miclaus GD, Matusz P, Loukas M. Fusiform aneurysm of a persistent trigeminal artery associated with rare intracranial arterial variations and subarachnoid hemorrhage. Surg Radiol Anat 2015; 37: 115-118.
- Zhang LT, Wei FJ, Zhao Y, Zhang Z, Dong WT, Jin ZN, Gao F, Gao NN, Cai XW, Li NX, Wei W, Xiao FS, Yue SY, Zhang JN, Yang SY, Li WD, Yang XY. Intracranial aneurysm risk factor genes: relationship with intracranial aneurysm risk in a Chinese Han population. Genet Mol Res 2015; 14: 6865-6878.
- Park J, Son W, Park KS, Kang DH, Shin IH. Intraoperative premature rupture of middle cerebral artery aneurysms: risk factors and sphenoid ridge proximation sign. J Neurosurg 2016; 125: 1235-1241.
- Chen JX, Lai LF, Zheng K, Li GX, He XY, Li LP, Duan CZ. Influencing factors of immediate angiographic results in intracranial aneurysms patients after endovascular treatment. J Neurol 2015; 262: 2115-2123.
- Schneiders JJ, Marquering HA, van den Berg R, Van Bavel E, Velthuis B, Rinkel GJ, Majoie CB. Rupture-associated changes of cerebral aneurysm geometry: high-resolution 3D imaging before and after rupture. AJNR Am J Neuroradiol 2014; 35: 1358-1362.
- Ben Mrad M, Derbel B. An infected false aneurysm of the subclavian artery in a 41-year old drug abuser. Pan Afr Med J 2015; 22: 211.
- Fathi NQ, Syahrilfazli AJ, Azizi AB, Redzuan IM, Sobri M, Kumar R. Ruptured giant left distal anterior cerebral artery aneurysm in a two-month-old baby. Pediatr Neurosurg 2015; 50: 275-280.
- Harrod CG, Batjer HH, Bendok BR. Deficiencies in estrogen-mediated regulation of cerebrovascular homeostasis may contribute to an increased risk of cerebral aneurysm pathogenesis and rupture in menopausal and postmenopausal women. Med Hypotheses 2006; 66: 736-756.
- Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Shikat F, Pena Silva RA, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T. Estrogen protects against intracranial aneurysm rupture in ovariectomized mice. Hypertension 2014; 63: 1339-1344.
- Takagi H, Takuya U. Association of diabetes mellitus with presence, expansion, and rupture of abdominal aortic aneurysm: Curiouser and curiouser! cried ALICE. Semin Vasc Surg 2016; 29: 18-26.
- Takagi H, Umemoto T. Negative association of diabetes with rupture of abdominal aortic aneurysm. Diab Vasc Dis Res 2016; 13: 341-347.
- Theivacumar NS, Stephenson MA, Mistry H, Valenti D. Diabetes mellitus and aortic aneurysm rupture: a favorable association? Vasc Endovascular Surg 2014; 48: 45-50.
- Tsai CL, Lin CL, Wu YY, Shieh DC, Sung FC, Kao CH. Advanced complicated diabetes mellitus is associated with a reduced risk of thoracic and abdominal aortic aneurysm rupture: a population-based cohort study. Diabetes Metab Res Rev 2015; 31: 190-197.
- Hosaka K, Downes DP, Nowicki KW, Hoh BL. Modified murine intracranial aneurysm model: aneurysm formation and rupture by elastase and hypertension. J Neurointerv Surg 2014; 6: 474-479.
- Tsai FY, Yen A, Guo WY, Wu CC. Venous hypertension and cerebral aneurysm rupture. Neuroradiol J 24, 137-144
- Hu P, Wang J, Fan XC, Hu B, Lu L. Hypertension triggers the rupture of coronary artery aneurysm in an 8-year-old boy with Kawasaki disease. J Clin Hypertens (Greenwich) 2014; 16: 766-767.
- Huang ZQ, Meng ZH, Hou ZJ, Huang SQ, Chen JN, Yu H, Feng LJ, Wang QJ, Li PA, Wen ZB. Geometric parameter analysis of ruptured and unruptured aneurysms in patients with symmetric bilateral intracranial aneurysms: a multicenter CT angiography study. AJNR Am J Neuroradiol 2016; 37: 1413-1417.