Intracranial aneurysm location: potential influencing factor in ruptures with internal carotid artery occlusion

Abstract

Background and purpose

Intracranial aneurysms combined with spontaneous internal carotid artery occlusion (ICAO) are a rare and serious vascular disorder. Currently, there is only limited information available on the clinical characteristics of these patients and the risk factors for aneurysm rupture. Our objective is to describe the clinical features of these patients and predict the risk factors for the rupture of unruptured intracranial aneurysms (UIAs) combined with ICAO.

Methods

We retrospectively analyzed cases of intracranial aneurysms with concurrent spontaneous ICAO from the Chinese Multicenter Aneurysm Database(CMAD). We collected population demographic characteristics and clinical data using a standardized case questionnaire from CMAD. Binary logistic regression analysis was used to identify risk factors for rupture of UIA associated with combined ICAO.

Results

We identified 93 patients with intracranial aneurysms combined with ICAO, including 38 females and 55 males, with an average age of 60.7 ± 9.5 years (ranging from 32 to 79 years old). Among those with ICAO, 52 had ruptured intracranial aneurysms (RIAs) and 41 had UIAs. Specifically, there were 81 cases of unilateral ICAO, with 16 aneurysms located on the same side as the ICAO, 22 in the midline (AcomA, Basilar tip), and 43 on the opposite side of the ICAO; 12 cases were bilateral ICAO. Binary logistic regression analysis indicated that risk factors associated with the rupture of UIAs with ICAO included bilateral internal carotid artery occlusion and aneurysms in the posterior circulation. Furthermore, multivariate analysis showed that posterior circulation aneurysms are an independent risk factor for the rupture of UIAs with ICAO.

Conclusion

We have described and analyzed the clinical characteristics and risk factors influencing the rupture of intracranial aneurysms in patients with ICAO. The study found that the location of the aneurysm is an important risk factor for the rupture of UIAs combined with ICAO.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12883-025-04362-7.

Introduction

SAH is an extremely serious and potentially fatal condition, with a high mortality and disability rate, most cases of non-traumatic SAH are attributed to the rupture of intracranial aneurysms [1–4]. With the widespread use of non-invasive imaging techniques, an increasing number of patients with spontaneous internal carotid artery occlusion (ICAO) are found to have intracranial aneurysms. ICAO is a relatively common cause of stroke and transient ischemic attacks (TIAs), accounting for about 10–15% of all cases [5]. Therefore, it is believed that the presence of both conditions can elevate the risk of mortality and morbidity even when collateral circulation is adequate. These conditions are more common in older patients who often have significant comorbidities and advanced atherosclerosis.

The management of IAs in the presence of ICAO poses a considerable challenge for neurosurgeons due to the potential treatment risks and high rupture probability. Current literature on IAs with ICAO is largely anecdotal [6–10], lacking definitive guidelines and consensus for optimal patient management.

Existing research has pinpointed potential risk factors for intracranial aneurysm rupture, including size, location, multiplicity, shape, smoking, age, hypertension, hypercholesterolemia, and a history of SAH [11–16]. Yet, data on rupture risks for UIAs in the context of ICAO remain unreported.

This study aims to deepen our understanding of the causes of intracranial aneurysm rupture in the context of ICAO and to improve treatment strategies and prognosis. The main objective is to analyze the clinical features associated with this rare condition and the impact of various risk factors on the rupture risk of unruptured intracranial aneurysms.

Materials and methods

Patients data

This study used data from the Chinese Multicenter Aneurysm Database (CMAD) (website: http://www.cmadtj.com; clinical trial No.:ChiCTR2200065083; Reg Date 2022-10-27). CMAD is a multicenter research project registered in China, led by Tianjin Medical University General Hospital. The collaborating centers, located in Tianjin, Hebei, Shandong, and Shanxi, have collectively registered over 10,000 cases of cerebral aneurysms. The CMAD data is sourced from medical records. This study was approved by the Ethics Committee of the Tianjin Medical University General Hospital (IRB2021-YX-178-01) and registered in the Chinese Clinical Trial Registry. All the procedures were performed in accordance with the World Medical Association Declaration of Helsinki [17]. After being approved, we cross-searched CMAD of patients combining the terms “intracranial aneurysms” and “internal carotid artery occlusion.” The inclusion criteria were as follows: diagnosis of aneurysms with spontaneous occlusion of the internal carotid artery confirmed by at least one examination—computed tomography angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA). The exclusion criteria were as follows: (1) comorbid Moyamoya disease, (2) acute carotid artery occlusion.

Clinical data

The following information was collected from patients with CMAD: patient demographics (age, sex), medical history (hypertension, type II diabetes, coronary heart disease, ischemic stroke, smoking, alcohol consumption), aneurysm characteristics (number, size and location), and internal carotid artery occlusion side (left, right, bilateral). We define the internal carotid artery supply system as the anterior circulation and the vertebrobasilar supply system as the posterior circulation. Posterior communicating artery aneurysms are categorized as anterior circulation aneurysms. Midline aneurysms are defined as those located along the midline of the circle of Willis, including anterior communicating artery aneurysms and basilar artery aneurysms. We identified < 140/90 mmHg as the target blood pressure for antihypertensive treatment, and blood pressure values above this target are considered uncontrolled hypertension.

Statistical analysis

Normally distributed continuous data are presented as the mean ± standard deviation (SD). When a patient has multiple aneurysms, ruptured aneurysms are classified according to the responsible aneurysm, while unruptured aneurysms are classified based on the largest aneurysm. We use logistic regression to identify risk factors for the rupture of UIA combined with ICAO in patients. In the univariate analysis, variables with p < 0.05 were entered into the multivariate analysis. We performed multivariable backward stepwise logistic regression analysis to identify independent factors associated with subarachnoid hemorrhage. Statistical analyses were performed using SPSS software (version 27.0, SPSS IBM), and a P-value < 0.05 was considered statistically significant.

Results

Patient characteristics

Table 1 baseline characteristics of intracranial aneurysms with ICAO and subgroups for comparing patients with RIA and UIA. Among 11,686 IA patients, 281 patients with ICAO. After excluding 181 Moyamoya disease patients and 7 with acute internal carotid artery occlusion, 93 (0.8%) patients were included in the study. The study cohort consisted of 55 males and 38 females, with an average age of 60.7 ± 9.5 years. This encompassed 52 cases of RIAs and 41 cases of UIAs. We found that 81 patients had unilateral ICAO, while 12 had bilateral ICAO. Among those with unilateral ICAO, aneurysms were located ipsilaterally in 16 patients, along the midline in 22 patients, and contralaterally in 43 patients. The 93 patients in our study had a total of 115 intracranial aneurysms, with 76 presenting a single aneurysm and 17 presenting multiple aneurysms. In patients with unilateral ICAO, a total of 99 aneurysms were identified: 21 aneurysms were located on the same side as the occluded carotid artery, 53 on the opposite side, and 25 along the midline (14 in the anterior communicating artery and 11 at the tip of the basilar artery). In patients with bilateral ICAO, 16 aneurysms were found, with 4 located in the anterior circulation and 12 in the posterior circulation (Table 2).

Table 1.

Baseline characteristics of intracranial aneurysms with ICAO and subgroups for comparing patients with RIA and UIA

Characteristic	All (n = 93)	RIA (n = 52)	UIA (n = 41)	P value
Sex				0.456
Male	55(59.1%)	29(55.8%)	26(63.4%)
Female	38(40.9%)	23(44.2%)	15(36.6%)
Age, year	60.7 ± 9.5y	61.3 ± 9.1y	60.0 ± 10.1y	0.158
<65	56(60.2%)	28(53.8%)	28(68.3%)
≥ 65	37(39.8%)	24(46.2%)	13(31.7%)
Medical history
Hypertension(yes)	55(59.1%)	33(63.5%)	22(53.7%)	0.340
Type II diabetes(yes)	12(12.9%)	8(15.4%)	4(9.8%)	0.421
Ischemic stroke(yes)	18(19.4%)	9(17.3%)	9(22.0%)	0.574
Smoking(yes)	25(26.9%)	15(28.8%)	10(24.4)	0.630
Alcohol consumption(yes)	11(11.8%)	7(13.5%)	4(9.8%)	0.583
Coronary heart disease(yes)	13(14.0%)	7(13.5%)	6(14.6%)	0.871
Number of ICAO				0.008
Unilateral	81(87.1%)	41(78.8%)	40(97.6%)
Bilateral	12(12.9%)	11(21.2%)	1(2.4%)
Number of aneurysms				0.178
Single aneurysm	76(81.7%)	40(76.9%)	36(87.8%)
Multiple aneurysms	17(18.3%)	12(23.1%)	5(12.2%)
Aneurysms site				0.001
ACA/AcomA	21(48.8%)	14(26.9%)	7(17.1%)
MCA	1(1.1%)	0(0%)	1(2.4%)
PcomA	16(17.2%)	7(13.5%)	9(21.95%)
ICA	19(20.4%)	4(7.7%)	15(36.6%)
Posterior circulation	36(38.7%)	27(51.9%)	9(21.95%)
Aneurysm size				0.491
<5 mm	53(57%)	28(53.8%)	25(61%)
≥ 5 mm	40(43%)	24(46.2%)	16(39%)

Abbreviations: ACA Anterior cerebral artery, AcomA Anterior communicating artery, ICA Internal cerebral artery, MCA Middle cerebral artery, PcomA Posterior communicating artery

Table 2.

Frequency of posterior circulation aneurysms in RIA and UIA patients

Posterior circulation aneurysms	All (n = 36)	RIA (n = 27)	UIA (n = 9)
BA	16(44.4%)	14(51.9%)	2(22.2%)
PCA	13(36.1%)	9(33.3%)	4(44.4%)
SCA	1(2.8%)	1(3.7%)	0(0)
PICA	3(8.3%)	2(7.4%)	1(11.1%)
VA	3(8.3%)	1(3.7%)	2(22.2%)

Abbreviations: BA Basilar artery, SCA Superior cerebellar artery, AICA Anterior inferior cerebellar artery, PICA Posterior inferior cerebellar artery, VA Vertebral artery

Table 3 the distribution frequencies of the relationship between ICAO lateralization and intracranial aneurysm location between the two groups. After excluding 12 patients with bilateral internal carotid artery occlusion, a comparison was made among 81 patients with unilateral internal carotid artery occlusion to assess the relationship between the side of internal carotid artery occlusion and the location of intracranial aneurysms. A chi-square test indicated a statistically significant difference between the two groups (p = 0.009).

Table 3.

Comparison of the relationship between aneurysm location and side of ICAO between the RIA and UIA groups

Groups	All (n = 81)	RIA (n = 41)	UIA (n = 40)
Ipsilateral	16(19.8%)	8(19.5%)	8(20.0%)
Contralateral	43(53.1%)	16(39.0%)	27(67.5%)
Midline	22(27.2%)	17(41.5%)	5(12.5%)
P value	0.009

Table 4 comparison of arterial aneurysm location between unilateral ICAO and bilateral ICAO. Merging unilateral and bilateral internal carotid artery occlusions for intracranial aneurysm location grouping revealed a significant statistical difference (p < 0.001). Bilateral occlusions are more prone to posterior circulation aneurysms.

Table 4.

Comparison of arterial aneurysm location between unilateral ICAO and bilateral ICAO

Groups	All(n = 93)	Anterior circulation aneurysm(n = 57)	Posterior circulation aneurysm(n = 36)
Unilateral occlusion	81(87.1%)	55(67.9%)	26(32.1%)
Bilateral occlusion	12(12.9%)	2(16.7%)	10(83.3%)
P value	<0.001

Risk factors for ICAO combined with UIA rupture

Results of a univariable and multivariable analysis of factors related to ICAO combined with UIA rupture in patient are summarized in Table 5. The statistical results showed that the following variables were associated with aneurysm rupture based on the univariable analysis: Bilateral internal carotid artery occlusion (ORs 10.732; 1.323–87.021 95% CI; P = 0.026), posterior circulation aneurysms (ORs 3.84; 1.533–9.617 95% CI; P = 0.004). Further multivariable analysis revealed that posterior circulation aneurysms (ORs 2.874; 1.101–7.497 95% CI; P = 0.031) were an independent risk factor for UIA rupture combined with ICAO. Although hypertension is not a risk factor for UIA rupture combined with ICAO in the multivariable regression analysis, further analysis of the hypertensive patient group reveals that uncontrolled blood pressure control increases the risk of aneurysm rupture. See supplementary materials for details.

Table 5.

Risk factors associated with rupture: univariable and multivariable analysis

Characteristics	Univariate			Multivariate
	HR	95% CI	P value	HR	95% CI	P value
Sex(fmale)	1.375	0.265–2.087	0.457	—	—	—
Age(≥ 65y)	1.846	0.786–4.338	0.160	—	—	—
Medical history
Hypertension(Yes)	1.500	0.652–3.453	0.341	—	—	—
Type II diabetes(Yes)	1.682	0.469–6.033	0.425	—	—	—
Ischemic stroke(Yes)	0.744	0.265–2.087	0.574	—	—	—
Smoking(Yes)	1.257	0.495–3.191	0.631	—	—	—
Alcohol consumption(Yes)	1.439	0.391–5.297	0.584	—	—	—
Coronary heart disease(Yes)	0.907	0.280–2.943	0.871	—	—	—
Occlusion number
Single	1	Reference	—	1	Reference	—
Double	10.732	1.323–87.021	0.026	6.663	0.778–57.097	0.084
Location of aneurysm
Anterior circulation	1	Reference	—	1	Reference	—
Posterior circulation	3.84	1.533–9.617	0.004	2.874	1.101–7.497	0.031
Number of aneurysm
Single aneurysm	1	Reference	—	—	—	—
Multiple aneurysms	2.160	0.693–6.729	0.184	—	—	—
Aneurysm size
<5 mm	1	Reference	—	—	—	—
≥ 5 mm	1.339	0.583–3.075	0.491	—	—	—

Discussion

We conducted a comprehensive study on 93 patients with cerebral aneurysms and concurrent internal carotid artery occlusion to investigate their clinical characteristics and risk factors influencing aneurysm rupture. To our knowledge, this is the largest multicenter study to date on intracranial aneurysms in the setting of internal carotid artery occlusion.

Baseline characteristics of patients with ICAO combined with intracranial aneurysms

Hemodynamics play a crucial role in the formation and rupture of intracranial aneurysms (IAs), and its research has gained significant clinical attention. Hemodynamic parameter analysis based on computational fluid dynamics (CFD) has become an essential tool for assessing the rupture risk of IAs [18, 19]. Anatomically, IAs commonly occur at arterial bifurcations, branch points, and regions with geometric shape changes, where disturbed blood flow patterns lead to elevated hemodynamic stresses and vascular wall remodeling [20]. Pathophysiologically, sustained shear stress from abnormal intra-aneurysmal flow patterns induces endothelial dysfunction in localized arterial wall regions, ultimately contributing to IA rupture events [21]. Key hemodynamic parameters, including Wall Shear Stress (WSS), Oscillatory Shear Index (OSI), and Low Shear Area (LSA), have been identified as critical indicators in this process.

WSS, which represents the tangential frictional force exerted by blood flow on the vascular endothelium, is closely linked to IA pathology. Low WSS promotes inflammation and wall remodeling in large aneurysms, while high WSS accelerates the formation and rupture of small aneurysms [22–24]. The OSI reflects changes in blood flow direction and intensity, helping to assess local flow stability. Ruptured IAs typically exhibit higher OSI levels, indicating more frequent changes in WSS direction, which leads to greater oscillatory forces on the aneurysmal wall and eventual rupture [25–27]. Additionally, LSA, defined as the cumulative area where WSS is below 10% of the average WSS, is positively correlated with IA rupture, further highlighting the importance of WSS in aneurysm rupture risk [28, 29].

The Circle of Willis, as an important bridge and flow regulator of intracranial vascular connections, is crucial for maintaining stable cerebral circulation [30]. However, due to structural abnormalities of cerebral vessels, especially congenital variations in the region of the Circle of Willis, changes in intracranial hemodynamics may occur, leading to the formation of intracranial aneurysms [31, 32]. A study by Shakur et al. [33] revealed that patients with concurrent internal carotid artery occlusion and intracranial aneurysms exhibit a significant increase in blood flow velocity and wall shear stress in the anterior communicating artery. Furthermore, new or enlarged aneurysms are frequently observed on collateral vessels following internal carotid artery occlusion.

This study revealed that the majority of intracranial aneurysms associated with concurrent internal carotid artery occlusion are located on the contralateral collateral circulation and midline, particularly in regions with higher hemodynamic loads such as the anterior communicating artery, posterior communicating artery, basilar artery, and the junction of the basilar artery and posterior cerebral artery. The higher incidence of intracranial aneurysms in the anterior communicating artery and posterior communicating artery is also attributed to compensatory changes in the cerebral Willis circle following internal carotid artery occlusion, with these arteries being considered as the primary collateral pathways after internal carotid artery occlusion [34, 35].

The majority of the literature on the coexistence of ICAO and intracranial aneurysms is derived from prospective studies investigating aneurysm formation, growth, and rupture post internal carotid artery ligation, as well as isolated case reports [36–40]. These aneurysms predominantly affect the anterior communicating artery and posterior communicating artery.In the study conducted by Crobeddu et al., it was found that the majority of intracranial aneurysms in patients with concomitant internal carotid artery occlusion were located in the anterior communicating artery, with a lower incidence observed in the posterior circulation [41].Nevertheless, our retrospective study using CMAD demonstrated a notable association between internal carotid artery occlusion and concomitant posterior circulation aneurysms. The incidence of posterior circulation aneurysms was found to be 38.7%, with a strikingly higher rate of 51.9% observed in cases of ruptured aneurysms. This incidence far surpasses the occurrence rate of posterior circulation aneurysms in the absence of concurrent ICAO [42, 43].

Our study revealed that in patients with intracranial aneurysms and concurrent unilateral ICAO, aneurysms were more frequently located on the contralateral side and in the midline position of the ICAO. Additionally, our comparison between unilateral and bilateral internal carotid artery occlusions demonstrated a higher propensity for developing posterior circulation aneurysms in cases of bilateral occlusion. These findings collectively suggest that the establishment of major collateral circulation and hemodynamic alterations following internal carotid artery occlusion may play a critical role in the pathogenesis and progression of cerebral aneurysms.

Risk factors for ICAO combined with UIA rupture

In past and current research, it has been found that the location of an aneurysm is a significant risk factor for its rupture [11, 14, 16]. Aneurysms in the posterior circulation are believed to be associated with a higher risk of rupture [14, 44–46]. In our study, aneurysms located in the posterior circulation were identified as an independent risk factor for the rupture of UIA in patients with concurrent ICAO, consistent with previous research findings. Currently, there are numerous predictive models for assessing the rupture risk of UIA [47–49]. In terms of intracranial aneurysm characteristics, our study results suggest that the location of the aneurysm may be a potential influencing factor to consider in stratifying rupture risk.

Investigating such cases contributes to a better understanding of the pivotal role of hemodynamic alterations in the processes of aneurysm formation, growth, and rupture. In the presence of internal carotid artery occlusion, the vertebral-basilar system can compensate for cerebral blood supply through collateral circulation pathways, such as the posterior communicating artery. The increased vulnerability to rupture and hemorrhage in posterior circulation aneurysms, particularly those located in the basilar artery, in the context of internal carotid artery occlusion, can be elucidated by hemodynamic. The risk of formation and rupture of vertebral-basilar artery aneurysms may be related to the direction of blood flow perpendicular to the inflow direction of the aneurysm [50].Furthermore, animal experiments conducted by Gao L et al. [51] indicated that after carotid artery ligation, there was a significant increase in the maximum blood flow velocity in the basilar artery by 105–900%. All rabbits subjected to carotid artery ligation developed de novo aneurysms, characterized by a bulging near the terminal segment of the basilar artery, thinning of the media, and absence of the internal elastic lamina. Patients with carotid artery occlusive disease may be at risk for rapid progression of residual intracranial aneurysms. The proposed mechanism involves compensatory increases in blood flow that exert detrimental hemodynamic stress on the arterial wall, promoting aneurysm formation. For example, van Everdingen et al. observed increased blood flow in the contralateral internal carotid artery (ICA) and basilar artery in patients with symptomatic unilateral ICA occlusion [52]. Additionally, the vertebrobasilar system acts as a major source of collateral circulation, and increased flow in this system can further elevate hemodynamic stress on the arterial wall, potentially leading to saccular aneurysms. Therefore, the compensatory role of the vertebrobasilar system in carotid occlusion is critical, particularly in cases of bilateral ICA occlusion [53]. The hemodynamic changes in bilateral ICA occlusion resemble those in moyamoya disease, where the basilar artery becomes the primary source of cerebral blood supply and is more prone to aneurysm formation [54–56].

Nonetheless, the precise underlying mechanisms remain elusive, warranting further investigation to elucidate this phenomenon. Previous studies have also revealed a higher mortality rate associated with posterior circulation aneurysms compared to anterior circulation aneurysms [57–60]. Therefore, when treating posterior circulation aneurysms concomitant with internal carotid artery occlusion, it is imperative to carefully select treatment modalities and closely monitor the risk of rupture. Further research is needed to elucidate the specific mechanisms, enhance treatment decision-making, and prevent rupture.

Numerous studies have highlighted age as a critical risk factor for aneurysm rupture, with the risk escalating as individuals grow older [11, 61, 62]. Although this study indicates that age may not be an independent risk factor for the rupture of UIA in the presence of concomitant ICAO, statistical analysis reveals a positive association between increasing age and the risk of aneurysm rupture, aligning with previous research findings.

While hemodynamic and anatomical characteristics play a crucial role in the formation and rupture of aneurysms, environmental factors also contribute significantly. Factors such as smoking history, multiple aneurysms, and hypertension have been established as independent risk factors for rupture in other studies [14, 45, 62, 63]. However, in our cohort, these factors did not show a significant impact on aneurysm rupture.

Furthermore, the size and shape of an aneurysm play a critical role in assessing the risk of rupture in UIA. Larger aneurysms and irregular shapes are often associated with a higher risk of rupture. Therefore, a comprehensive assessment of the risk of aneurysm rupture should take into account hemodynamic, anatomical, and environmental factors.

Limitations

This study has some limitations. Firstly, the study design is retrospective, which may introduce information retrieval biases and issues with incomplete data. Future research should consider using prospective study designs to address these limitations. Secondly, the sample size of this study is relatively small, which may limit the statistical power and generalizability of the study findings. Future studies should include larger and more diverse samples to enhance the robustness of these results. Thirdly, during our research process, we overlooked the impact of anatomical variations in the Willis circle on cerebral hemodynamics. This oversight may have led to an exaggerated emphasis on the influence of changes in cerebral hemodynamics following internal carotid artery occlusion on the development and rupture of intracranial aneurysms. In future research, revising the study plan, collecting new data, or employing novel analytical methods may be necessary to analyze how variations in Willis circle anatomy combined with ICAO impact the formation and rupture of intracranial aneurysms.

Conclusion

We conducted a comprehensive retrospective analysis to investigate the clinical characteristics of intracranial aneurysms associated with ICAO and identify key factors that may increase the risk of rupture in UIA. Our study found that aneurysm location, particularly in the posterior circulation, is a significant risk factor for rupture in UIA associated with ICAO. Furthermore, we identified a notable association between ICAO and an increased risk of aneurysmal rupture. This highlights the importance of not only focusing on the ischemic stroke risks associated with ICAO but also considering the hemodynamic changes caused by ICAO that may contribute to the risk of aneurysm rupture. This provides valuable insights for the management of ICAO.

Authors’ contributions

L and B contributed to drafting the initial manuscript or provided significant academic contributions. M was involved in the revision and editing of the manuscript, particularly providing feedback on the hemodynamics of intracranial aneurysms. G, D, Z, Y, Z, and W were responsible for data processing, statistical analysis, and assisting with chart design, among other tasks. L, Y, and Z provided support during the revision and editing process, particularly regarding the theoretical framework, data interpretation, or methodology. All authors reviewed the manuscript.

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Declarations

Ethics approval nd consent to participate

This study was approved by the Ethics Committee of the Tianjin Medical University General Hospital [IRB2021-YX-178-01] and registered in the Chinese Clinical Trial Registry [registration number: ChiCTR2200065083].

All participants provided informed consent, and their personal information and privacy have been thoroughly safeguarded. This study adheres to the principles outlined in the Declaration of Helsinki, ensuring that all research activities are conducted in accordance with ethical standards.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.