Anterior Cerebral Artery Variants and Their Influence on Endovascular Outcomes: A propensity score matched analysis from the CRETA Registry

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Dmytriw, and 46 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9488266/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Anatomical variants of the anterior cerebral artery (ACA) may increase technical complexity during endovascular treatment of distal ACA aneurysms (DACA). However, their impact on treatment outcomes remains unclear. This study evaluated whether ACA variants influence angiographic and clinical outcomes following endovascular treatment. Methods : A retrospective multicenter analysis was conducted using data from the CRETA Registry, including patients with ruptured and unruptured DACA treated endovascularly. Patients were grouped according to ACA anatomy (variant vs conventional). Outcomes were compared after propensity score matching (PSM) to adjust for confounders including age, aneurysm rupture status, dome-to-neck ratio, branch origin, and treatment type. The primary outcome was aneurysm occlusion at last follow-up based on the Raymond–Roy classification. Secondary outcomes included ischemic and hemorrhagic complications, vasospasm, and clinical outcome measured by the modified Rankin Scale (mRS). Results : After PSM, 128 patients were included (64 per group). At a median imaging follow-up of 16.5 months, adequate occlusion rates were comparable between the variant and conventional ACA groups (81.5% vs 85.5%; p=0.6). No significant differences were observed in ischemic or hemorrhagic complications, vasospasm, or long-term clinical outcomes. Sensitivity analyses confirmed the robustness of the findings. Conclusions : ACA anatomical variants do not adversely affect the safety or efficacy of endovascular treatment for DACA. With appropriate anatomical assessment and treatment selection, endovascular therapy remains effective even in the presence of complex ACA configurations. Figures Figure 1 Figure 2 Introduction The endovascular management of ruptured and unruptured intracranial aneurysms has evolved during the last decades, being considered as a first-line treatment also in complex cases [1,2]. This has been due in part to the evolution of the techniques that allow the treatment of both the aneurysmal sac and the vessel wall [3]. However, the treatment of distal intracranial aneurysms can be challenging, because of the small caliber of the parent artery, the distal location and the presence of anatomical variations, which potentially may increase the procedural risk and technical demands [4,5]. Currently, no studies in the literature have investigated whether the presence of anatomical variations may represent an additional factor influencing the outcome of the endovascular treatment. The aim of this study was to assess whether the presence of anatomical variants of the anterior cerebral artery (ACA) may impact the outcome of different endovascular techniques for the treatment of distal anterior cerebral artery aneurysms (DACA), by analyzing data from the CRETA registry (Clinical and Radiological Evaluation of Endovascular Treatment of Distal Anterior Cerebral Artery Aneurysms) a multicenter, retrospective database that collects data on the endovascular management of DACA [6]. Methods Patients and treatment This is a retrospective, multicenter, observational study that included patients with ruptured and unruptured DACA aneurysms who underwent different endovascular treatments, analyzed as part of the CRETA Consortium study [6] (Figure 1). Data were collected on patient demographics, aneurysm characteristics, procedural details, complications, and clinical and radiographic outcomes. Endovascular treatments comprised simple coiling, balloon-assisted coiling, stent-assisted coiling, flow diverter stents (standalone or with coiling), and intrasaccular devices. We identified two study subgroups according to the presence (“ACA variant anatomy” subgroup) or absence of an anatomical variant of the ACA (ACA conventional anatomy). Anatomical variants of the ACA, specifically the azygos ACA and bihemispheric ACA subtypes, are uncommon but clinically significant configurations that require careful evaluation when planning endovascular treatment. According to Lasjaunias [7] the Azygos-type ACA is characterized by a single, unpaired artery arising from both the A1 segments throughout the ACA course and supplying both medial hemispheric surfaces. Despite the notion of an ACA variant according to these definition was available in the CRETA Registry, the subtype of the variant was not specified. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and was conducted under a nonprofit research protocol approved by the ethics committee of the coordinating center (Fondazione Policlinico Universitario A.Gemelli IRCCS, protocol ID 3583). Measures of outcome The primary outcome measure was aneurysm occlusion at last imaging follow-up assessed using digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA), and graded according to the Raymond-Roy Occlusion Classification (RROC) scale [8]. RR classes I and II were merged into a single variable indicating complete/near-complete occlusion, while IIIa and IIIb were defined as incomplete occlusion. Secondary outcome measures included the occurrence of ischemic or hemorrhagic complications and of vasospasm and the long-term clinical outcome measured with the modified Rankin Scale (mRS). Statistical analysis Descriptive statistics were used to summarize baseline characteristics. Continuous variables were expressed as means ± standard deviations (SD) or medians with interquartile ranges (IQR), while categorical variables were presented as counts and percentages. Fisher’s exact test was used to compare categorical variables, and either the Welch two-sample t-test or the Mann-Whitney U test was applied to continuous variables, depending on their distribution. The Shapiro-Wilk test was used to assess the normality of continuous variables. Missing data were not imputed, and significance was set at p<0.05. We used propensity score matching (PSM) with the optimal algorithm to estimate the difference in outcome measures between patients with the conventional ACA anatomy and those carrying the variant one. Covariates used in the PSM model were those with a potential effect on measured outcomes and included age, unruptured aneurysm status, the dome-to-neck ratio, the branch artery origin (classified as from the sack, the neck or the artery, respectively) and type of treatment. Covariates balance was assessed by examining standardized mean differences (SMD), with values <0.2 indicating acceptable balance. Odds ratio with 95% CI were calculated for each variable, with the variant ACA anatomy group serving as the reference (Supplemental Table 1). For missing clinical outcome data, a sensitivity analysis was conducted to evaluate the robustness of the results under three different scenarios: 1) the worst-case scenario (defined as the pro-variant ACA anatomy scenario: all missing cases with conventional ACA anatomy had the unfavorable angiographic outcome, all missing cases with the variant ACA anatomy had the favorable outcome), 2) the best-case scenario (defined as the pro-ACA normal anatomy: all missing cases with the conventional ACA anatomy had the favorable angiographic outcome, all missing cases carrying the variant ACA anatomy had the unfavorable outcome), and 3) the observed scenario (only cases with complete data). Odds ratios with 95% CI were calculated for each scenario (Supplemental Table 2 and Figure 1). Significance threshold was set at p<0.05. All analyses were performed using the R software v.4.3.2 with the MatchIt and tidyverse packages (https://www.r-project.org). No subgroup analysis was performed on the subtype of anatomical variation. Results We have analysed an initial cohort of 300 patients with conventional ACA anatomy and 64 patients harboring an ACA variant. After PSM, the final population included 128 patients, equally distributed between the two subgroups ACA normal anatomy and ACA variant anatomy. Detailed data according to each subgroup were summarized in Tables 1-2. We report here only the overall results. The majority were female (85/128, 66.4%) with a median age of 62 years (IQR 54–70). Hypertension was the most common risk factor, present in 79/126 (62.7%), followed by dyslipidemia in 30/126 (23.8%) and diabetes in 17/126 (13.5%). Only 15/125 (12.0%) were current smokers. A family history of aneurysms was reported in 20/122 (16.4%). Previous SAH occurred in 13/127 (10.2%), due to the index aneurysm in 10/126 (7.9%) and to another aneurysm in 3/126 (2.4%). Ruptured aneurysms were observed in 62/128 (48,4%), with irregular morphology in 81/128 (63.3%). Branch artery origin involved the sac in 25/128 (19.5%), the neck in 61/128 (47.7%), and the artery in 42/128 (32.8%). Transradial access was performed in 9/128 (7%) and in 79/125 (63%) cases a tri-axial system was used. The most frequently used techniques were standalone coiling in 57/128 cases (44.5%) and flow-diverter in 34/128 (26.6%) (Figure 2). According to the CRETA registry the median radiological follow-up was 16.5 months (IQR 7–24) (6). The clinical and procedural outcomes were summarized in Table 3. We did not observe any statistical difference concerning the adequate occlusion rate (81.5% vs 85.5%, OR 1.3; 95% CI 0.5–3.7; p=0.6) and the intra-procedural complications (ischemic: 7.8% vs. 14.1%, p=0.7; hemorrhagic: 3.2% vs. 7.8%, p=0.5). Clinical outcomes did not significantly differ between two subgroups. The sensitivity analysis showed no significant modification of the primary and second endpoints (Supplemental Figure 1 and Table 1). Angiographic outcomes of the covered vessel by Flow-Diverter (FD) stents at the last follow-up in the two study subgroups, before PSM, were reported in Supplemental Table 3. No ischemic complications related to the vessel covered by the FD stent were observed in both subgroups. Discussion Our statistical analysis showed no significant difference in terms of adequate occlusion (RR I-II) at the latest follow-up of the treated aneurysms in patients with and without an ACA variant. Furthermore, the complication rates were comparable in the two subgroups. These results indicate that the presence of an anatomical variant does not adversely affect the outcome of the endovascular treatment. Effectiveness of EVT according to anatomical variations The effectiveness of the endovascular treatment for distal anterior cerebral aneurysms has already been shown in previous studies. In particular, the meta-analysis by Vilardo et al [9] concluded that the use of Flow-Diverter stents seems to be safe and effective in the treatment of distal aneurysms and that this is associated with high occlusion rates. Although previous studies have reported similar rates of effectiveness of EVT in distal ACA aneurysms (DACA), none specifically accounted for the presence of anatomical variants. Cagnazzo et al. [10] reported an overall rate of adequate occlusion (OKM C–D) of 79% (19/24 aneurysm) in a series of 25 unruptured DACA treated with flow diverters. These results are in line with those reported in the same subgroup in a previous meta-analysis, focusing on the treatment of distal aneurysms of the anterior circulation [11]. In our cohort, the occlusion rates were similar or higher. However, in this study we have included different endovascular techniques, and our findings are not limited to the FD stents. Porto et al. [12] reported high occlusion rates (>90%) at the end of the follow-up in a cohort of 84 patients with DACA treated in 5 institutions through primary coiling (60/84) or FD stents (24/84). Interestingly, in their series about 60% of the patients (61.9%, 52/84) had ruptured aneurysms and among them 11 were treated by FD stents. The effectiveness of flow diverters in the management of ruptured DACA aneurysms has also been supported by Salsano et al.[13], who reported an adequate occlusion rate of 95.2% in an analysis of 21 ruptured DACA treated by FD stents. Nevertheless, poor data are available concerning the impact of the ACA variants on the endovascular outcomes. In our study, we reported comparable occlusion rates at the last follow-up in both the variant (81.5%) and non-variant (85.5%) sub-groups and these are in line with the aforementioned ones. These results underline the effectiveness of the different endovascular approaches even in case of potentially challenging anatomical conditions. In our study no significative difference was observed in terms of arterial branches arising from the sac or the neck. Indeed, it had been previously shown that this factor may negatively affect the occlusion rates [14,15] particularly when they originate from the aneurysm dome [16]. This mechanism has been supported by experimental evidence where neointimal growth effectively seals the aneurysm neck but spares the origin of the branch, since the efferent flow through the incorporated branch prevents the intra-aneurysmal stasis required for complete sac thrombosis [17]. This may be particularly relevant in the context of the treatment of DACA with FD stents in the setting of ACA variants, where the origin, vessel caliber, and distribution of leptomeningeal anastomoses may differ from the normal anatomical configuration. In our study, within the group of patients with ACA variants, a branch originated from the aneurysm neck in 30 out of 64 cases (46.9%) and from the aneurysm sac in 12 out of 64 cases (18.7%). Despite the presence of a branch arising from the aneurysm in more than half of the cases, the endovascular outcome was not adversely affected. This finding had already been reported by Cagnazzo et al., probably related to the presence of collateral circulation in the frontal and orbitofrontal regions [10], and further confirmed in the analysis of the CRETA registry [6]. Finally, the size and the dome-to-neck ratio did not influence the occlusion rates in both variant and non-variant subgroups, although the mean size of the aneurysm was <6 mm in this analysis. Safety profile according to anatomical variations In our series, the presence of an ACA anatomical variant was not associated with a higher rate of procedural complications. On the contrary, both ischemic and hemorrhagic complications occurred less frequently in the variant group compared to the non-variant group, although these differences did not reach statistical significance. These results are consistent with prior studies reporting overall treatment-related complication rates of approximately 5–7.5% for DACA aneurysms treated with flow diverters [6,11,18] and up to 13% for DACA treated with different endovascular devices [12]. Anatomical variants such as azygos or bihemispheric ACA may theoretically represent a higher thromboembolic risk due to the presence of a single dominant or unpaired arterial segment. However, in our cohort, ischemic complications occurred in only 5 patients within the ACA variant group, and all were asymptomatic. Although ACA variants may lead to a different disposition of the origin and caliber of the cortical branches raising from A2–A3 segments [19], no acute thromboembolic occlusion of these vessels was observed. This suggests that the presence of an anatomical variant does not increase the ischemic risk compared to the normal anatomy, particularly in case of usage of flow-diverter stents. As far as the rate of hemorrhagic complications is concerned, in the ACA variant subgroup this was lower than in the subgroup with conventional anatomy. These results could be explained using different endovascular techniques, in particular unassisted coiling and intrasaccular devices, with the choice of respecting the vascular anatomy of the parent vessel when possible. In our study, no ischemic complications related to covered side vessels from the FD stent were observed in either the normal ACA anatomy group or the ACA variant anatomy group. This finding is consistent with previous studies reporting a very low rate of symptomatic ischemic events associated with vessel occlusion [10,20]. In the systematic review by Gunkan et al., 30/372 covered vessels were occluded, but only 3 cases were symptomatic [21]. Cagnazzo et al. attributed this phenomenon to the presence of collateral circulation in the frontal and orbitofrontal regions, which may account for asymptomatic occlusion or flow remodelling of the covered branches [10]. As we have shown with our results, this mechanism may also apply in the setting of ACA anatomical variants. Overall, these findings support the assumption that ACA anatomical variants do not adversely impact the safety of the endovascular treatment for distal aneurysms and that the procedural risks remain comparable to those described in the literature for conventional ACA anatomy. Anatomical Considerations and Procedural Technical Aspects The hypothesis of this study focused on the potential role of anatomical variation of ACA in determining different outcomes of the endovascular treatment of DACA. The Azygos type is different from the Unpaired type of Anterior cerebral artery, where both A1 segments join at the midline and immediately divide into two main trunks at the level of the genu of the corpus callosum [22]. In the bihemispheric-type ACA, a dominant A2 segment crosses the midline, perfusing both hemispheres, often in association with hypoplasia or aplasia of the contralateral A2 [7,19,22]. Despite these major anatomical differences, our study showed no statistically significant difference in the mean diameter of the parent vessel from which the aneurysm originated between the ACA variant group and the group with normal anatomy (2 mm [IQR 1.6-2.4]; 1.9mm [IQR 1.6-2.2]; p=0.1). This finding is consistent with previously published data reporting an average vessel diameter of approximately 2 mm [10,11,18,23], suggesting that standard stent sizing remains appropriate even in the presence of ACA anatomical variants. Compared to the conventional ACA anatomical pattern, these variants present notable morphological differences, which have been correlated with an increased susceptibility to the development of aneurysmal formations [24], particularly at sites of altered hemodynamic stress and vessel wall weakness. This is further supported by our findings, which showed a statistically significant difference in aneurysm morphology after PSM: irregularly shaped aneurysms were more frequently observed in the ACA variant group compared to the normal anatomy group (45/64, 70.3% vs. 36/64, 56.2%; p = 0.005). However, despite the association between ACA anatomical variants and an increased risk of irregular aneurysm morphology, we demonstrated that endovascular treatment remains both effective and safe in these cases. Conversely, in the ACA variants, the dominant vessel may give rise to a greater number of cortical and perforating branches to supply both hemispheres compared to a standard A2 [7,19], which may theoretically increase the complexity of stent placement, particularly in the context of flow diverter placement, compromising the perfusion of cortical arterial branches [25]. Moreover, although in ACA variants a single vessel supplies both hemispheres, this could raise concerns that procedural complications such as thromboembolism or in-stent thrombosis could result in more extensive neurological deficits. However, in our study such events were not observed. Limitations This study presented some limitations. First, its retrospective and multicenter design introduces potential heterogeneity due to differences in endovascular techniques and operator preferences across centers, which may have influenced the outcomes. In addition, there was no centralized imaging analysis for the definition of ACA variants, which may have introduced heterogeneity in variant classification across centers and in the CRETA registry the specific subtype of the variant was not specified, limiting the specificity of this analysis. Additionally, although anatomical variations of the anterior cerebral artery are relatively rare, the sample size of patients with these variants remains limited. Larger, prospective studies are therefore needed to confirm our findings and better define the impact of ACA anatomical variants on treatment outcomes. Conclusion Our results demonstrate that the presence of ACA variants did not adversely affect the efficacy and safety of the endovascular treatment of DACA. The comparable rates of adequate occlusion and procedural complications observed in patients with and without ACA variants suggest that, when meticulous anatomical assessment and appropriate device selection are performed, these variants do not constitute a further risk factor for unfavorable outcomes. Declarations Funding No funding was received for this research. Competing Interests: LS: unrelated to the current study, Penumbra (paid lectures). FS: Outside the submitted work received lecturer’s fee from Idorsia Pharmaceuticals for the past 36 months. OG: Outside the submitted work, MicroVention proctor for the WEB device, Stryker consultant, Route 92 consultant. ML: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. AMA: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AP: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AEH: Consultant/Speaker: Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Shockwave, Toro and Xcath. Principal Investigator: COMPLETE study – Penumbra, LVO SYNCHRONISE – Viz.ai, MARRS - Perfuze, RESCUE - ICAD - Medtronic. Steering Committee/Publication committee member: SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. DSMB - COMAND trial. ML Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. FC reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board) ; all not directly related to the present work. CC consultant for Medtronic, Microvention, Cerenovus, Stryker, Anaconda, unrelated to the current study. Availability of data and material Data are available upon reasonable request to the Principal Investigator. Ethics approval All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study is part of a nonprofit research protocol approved by the ethics committee of the coordinating center (Fondazione Policlinico Universitario A.Gemelli IRCCS, protocol ID 3583). Informed consent Informed consent was waived in consideration of the retrospective nature of this study. References Hoh BL, Ko NU, Amin-Hanjani S, Hsiang-Yi Chou S, Cruz-Flores S, Dangayach NS, et al. (2023) Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke 54(7):E314–70. Thompson BG, Brown RD, Amin-Hanjani S, Broderick JP, Cockroft KM, Connolly ES, et al. (2015). Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation 46(8):2368–400. Pierot L, Wakhloo AK. Endovascular treatment of intracranial aneurysms: Current status. (2013) Stroke 44(7):2046–54. Atallah E, Saad H, Mouchtouris N, Bekelis K, Walker J, Chalouhi N, et al. (2019). Pipeline for distal cerebral circulation aneurysms. Clin Neurosurg. 85(3):E477–84. Ma C, Zhu H, Liang S, Liang F, Han J, Jia Z, et al. (2022). Pipeline for the treatment of distal cerebral circulation aneurysms: A multicenter study focusing on periprocedural Complications. Interventional Neuroradiology 28(6):708–18. Scarcia L, Clarençon F, Dmytriw AA, Shotar E, Premat K, Jabbour P, et al. (2024). Flow-diverting stents for the treatment of unruptured distal anterior cerebral artery aneurysms: analysis of the CRETA Registry. J Neurointerv Surg 17(12):1270-1276. doi: 10.1136/jnis-2024-022315. Lasjaunias PBA ter BKG. (2001) Surgical Neuroangiography. Volume 1: Functional Anatomy of Craniofacial Arteries. 2nd ed. Vol. 1. Berlin: Springer. Mascitelli JR, Moyle H, Oermann EK, Polykarpou MF, Patel AA, Doshi AH, et al. (2015). An update to the Raymond–Roy Occlusion Classification of intracranial aneurysms treated with coil embolization. J Neurointerv Surg 7:496–502. Vilardo M, Günkan A, Dmytriw AA, Elek A, Scarramal JPL, Bocanegra-Becerra JE, et al. (2025). Efficacy and Safety of Flow Diversion for Distal Anterior Cerebral Aneurysms: A Systematic Review and Proportional Meta-Analysis. American Journal of Neuroradiology. 47(1):66-72. doi: 10.3174/ajnr.A8926. Cagnazzo F, Fanti A, Lefevre PH, Derraz I, Dargazanli C, Gascou G, et al. (2021). Distal anterior cerebral artery aneurysms treated with flow diversion: experience of a large-volume center and systematic review of the literature. J Neurointerv Surg 13(1):42–8. Cagnazzo F, Perrini P, Dargazanli C, Lefevre PH, Gascou G, Morganti R, et al. (2019). Treatment of Unruptured Distal Anterior Circulation Aneurysms with Flow-Diverter Stents: A Meta-Analysis. American Journal of Neuroradiology 40(4):687-693. doi: 10.3174/ajnr.A6002. Porto GBF, Al Kasab S, Sattur MG, Almallouhi E, Lajthia O, Casey MA, et al. (2021). Endovascular Management of Distal Anterior Cerebral Artery Aneurysms: A Multicenter Retrospective Review. World Neurosurg. Oct;154:e421–7. Salsano G, Scarcia L, Clarençon F, Shotar E, Russo R, Bergui M, et al. (2025). Flow diverter stent for the treatment of ruptured distal anterior cerebral artery: A retrospective multicenter analysis from CRETA registry. Interventional Neuroradiology. Aug 4:15910199251348514. doi: 10.1177/15910199251348514. Cagnazzo F, Lefevre PH, Mantilla D, Rouchaud A, Morganti R, Perrini P, et al. (2019). Patency of the supraclinoid internal carotid artery branches after flow diversion treatment. A meta-analysis. Journal of Neuroradiology Feb;46(1):9–14. Daou B, Valle-Giler EP, Chalouhi N, Starke RM, Tjoumakaris S, Hasan D, et al. (2017). Patency of the posterior communicating artery following treatment with the Pipeline Embolization Device. J Neurosurg. Feb;126(2):564–9. Dibas M, Vivanco‐Suarez J, Galecio‐Castillo M, Lopes DK, Hanel RA, Rodriguez‐Calienes A, et al. (2024). Flow Diversion for Intracranial Aneurysms With Incorporated Branch: A Subanalysis From the SEASE International Registry. Stroke: Vascular and Interventional Neurology Oct 25;4(6):e001448. doi: 10.1161/SVIN.124.001448. Darsaut TE, Bing F, Salazkin I, Gevry G, Raymond J. (2012). Flow Diverters Can Occlude Aneurysms and Preserve Arterial Branches: A New Experimental Model. American Journal of Neuroradiology Nov;33(10):2004–9. Khanafer A, Henkes H, Cohen J, Albiña-Palmarola P, Gomori JM, Forsting M, et al. (2024). Endovascular treatment of distal anterior cerebral artery aneurysms using flow modulation devices: mid- and long-term results from a two-center study. Front Neurol. Mar 11;15:1368612. doi: 10.3389/fneur.2024.1368612. Cilliers K, Page BJ. (2016). Detailed description of the anterior cerebral artery anomalies observed in a cadaver population. Annals of Anatomy - Anatomischer Anzeiger. Nov;208:1–8. Scarcia L, Clarençon F, Dmytriw AA, Shotar E, Jabbour P, Psychogios M, et al. (2025). Silk Vista Baby for the treatment of distal anterior cerebral artery aneurysms. Neuroradiology Aug;67(8):2167-2177. doi: 10.1007/s00234-025-03678-y. Günkan A, Vilardo M, Scarramal JPL, Elek A, Bocanegra-Becerra JE, Cardoso LJC, et al. (2025). Flow diversion for distal cerebral aneurysms: a systematic review and meta-analysis. J Neurointerv Surg. May 13;jnis-2025-023362. Baptista AG. (1963) Studies on the arteries of the brain. Neurology. Oct;13(10):825–825. Nossek E, Zumofen DW, Setton A, Potts MB, Raz E, Shapiro M, et al. (2017). Treatment of distal anterior cerebral artery aneurysms with the Pipeline Embolization Device. Journal of Clinical Neuroscience Jan;35:133–8. Triantafyllou G, Paschopoulos I, Kamoutsis K, Papadopoulos-Manolarakis P, Valenzuela-Fuenzalida JJ, Sanchis-Gimeno J, et al. (2025). Morphological Variations of the Anterior Cerebral Artery: A Systematic Review with Meta-Analysis of 85,316 Patients. Diagnostics Jul 28;15(15):1893. Michelozzi C, Darcourt J, Guenego A, Januel AC, Tall P, Gawlitza M, et al. (2019). Flow diversion treatment of complex bifurcation aneurysms beyond the circle of Willis: complications, aneurysm sac occlusion, reabsorption, recurrence, and jailed branch modification at follow-up. J Neurosurg. Dec;131(6):1751–62. Tables Tables are available in the Supplementary Files section. Additional Declarations Competing interest reported. LS: unrelated to the current study, Penumbra (paid lectures). FS: Outside the submitted work received lecturer’s fee from Idorsia Pharmaceuticals for the past 36 months. OG: Outside the submitted work, MicroVention proctor for the WEB device, Stryker consultant, Route 92 consultant. ML: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. AMA: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AP: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AEH: Consultant/Speaker: Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Shockwave, Toro and Xcath. Principal Investigator: COMPLETE study – Penumbra, LVO SYNCHRONISE – Viz.ai, MARRS - Perfuze, RESCUE - ICAD - Medtronic. Steering Committee/Publication committee member: SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. DSMB - COMAND trial. ML Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. FC reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board) ; all not directly related to the present work. CC consultant for Medtronic, Microvention, Cerenovus, Stryker, Anaconda, unrelated to the current study. Supplementary Files Table1.docx Table2.docx Table3.docx Supplementalmaterial.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9488266","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635120207,"identity":"fba12e62-b500-4f38-a8d3-0cfc975ef132","order_by":0,"name":"Arturo Consoli","email":"","orcid":"","institution":"Hôpital Foch","correspondingAuthor":false,"prefix":"","firstName":"Arturo","middleName":"","lastName":"Consoli","suffix":""},{"id":635120209,"identity":"429debde-7ea8-4ce0-9b0a-4a7ca43ad509","order_by":1,"name":"Raffaele Tortora","email":"","orcid":"","institution":"Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona","correspondingAuthor":false,"prefix":"","firstName":"Raffaele","middleName":"","lastName":"Tortora","suffix":""},{"id":635120210,"identity":"aed7426a-2021-4967-bfd5-da1086d22451","order_by":2,"name":"Frédéric Clarençon","email":"","orcid":"","institution":"Pitié-Salpêtrière Hospital","correspondingAuthor":false,"prefix":"","firstName":"Frédéric","middleName":"","lastName":"Clarençon","suffix":""},{"id":635120212,"identity":"ef9dab6c-6740-4bc9-b36e-f5af02058acd","order_by":3,"name":"Adam A. 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The aneurysm was treated through unassisted coiling with complete occlusion of the sac (C). The 4-years MRI 3D-TOF follow-up shows the persistent and complete occlusion of the aneurysm. In the same picture it is possible to observe the left hypoplasic A2 segment (D, white arrow). \u003cstrong\u003eIllustrative case 2\u003c/strong\u003e \u003cstrong\u003e(E-H)\u003c/strong\u003e: 3D-Rotational angiography showing a 6x4 mm, irregular, unruptured, aneurysm at the origin of the left pericallosal artery (E) without any anatomical variant of the ACA. The aneurysm was treated using a Fred jr. 2.5x18mm FD stent (F). The final angiogram at the end of the procedure shows the correct deployment of the stent and the reduction of the filling of the aneurysmal sac (G). The 1-year DSA follow-up shows the complete occlusion of the aneurysm, the patency of the stent and of the covered callosomarginal artery (H).\u003c/p\u003e","description":"","filename":"Figure2tiff.png","url":"https://assets-eu.researchsquare.com/files/rs-9488266/v1/3d4915a6fdec639bc3dd5fd1.png"},{"id":108979772,"identity":"39d14797-c816-495c-82c7-32a51f6c1141","added_by":"auto","created_at":"2026-05-11 12:01:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6821268,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9488266/v1/01e9e04e-8a5a-40df-b700-eadd27f79f71.pdf"},{"id":108978117,"identity":"e8f7add1-9009-43a2-9e2f-04dbdc96bb63","added_by":"auto","created_at":"2026-05-11 11:34:10","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":21995,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9488266/v1/0657dd52f0047897f75ca949.docx"},{"id":108977846,"identity":"858f707f-54bb-4c1e-b914-a46d68ad9403","added_by":"auto","created_at":"2026-05-11 11:33:11","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18646,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-9488266/v1/e84266f1fe9c599458d6927f.docx"},{"id":108941762,"identity":"4a79e345-eb20-4178-ac0b-dba74674bfa2","added_by":"auto","created_at":"2026-05-11 05:37:58","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17187,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-9488266/v1/651577b15ba7ddb9763d9897.docx"},{"id":108977481,"identity":"8fc05575-acf9-44cb-8d1a-75f5dff1c2c4","added_by":"auto","created_at":"2026-05-11 11:31:52","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":131847,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementalmaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-9488266/v1/9811bf565a3621a7e0de1125.docx"}],"financialInterests":"Competing interest reported. LS: unrelated to the current study, Penumbra (paid lectures). FS: Outside the submitted work received lecturer’s fee from Idorsia Pharmaceuticals for the past 36 months. OG: Outside the submitted work, MicroVention proctor for the WEB device, Stryker consultant, Route 92 consultant. ML: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. AMA: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AP: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AEH: Consultant/Speaker: Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Shockwave, Toro and Xcath. Principal Investigator: COMPLETE study – Penumbra, LVO SYNCHRONISE – Viz.ai, MARRS - Perfuze, RESCUE - ICAD - Medtronic. Steering Committee/Publication committee member: SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. DSMB - COMAND trial. ML Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. FC reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board) ; all not directly related to the present work. CC consultant for Medtronic, Microvention, Cerenovus, Stryker, Anaconda, unrelated to the current study.","formattedTitle":"\u003cp\u003eAnterior Cerebral Artery Variants and Their Influence on Endovascular Outcomes: A propensity score matched analysis from the CRETA Registry\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe endovascular management of ruptured and unruptured intracranial aneurysms has evolved during the last decades, being considered as a first-line treatment also in complex cases [1,2]. \u003csup\u003e\u0026nbsp;\u003c/sup\u003eThis has been due in part to the evolution of the techniques that allow the treatment of both the aneurysmal sac and the vessel wall [3]. However, the treatment of distal intracranial aneurysms can be challenging, because of the small caliber of the parent artery, the distal location and the presence of anatomical variations, which potentially may increase the procedural risk and technical demands [4,5]. Currently, no studies in the literature have investigated whether the presence of anatomical variations may represent an additional factor influencing the outcome of the endovascular treatment. The aim of this study was to assess whether the presence of anatomical variants of the anterior cerebral artery (ACA) may impact the outcome of different endovascular techniques for the treatment of distal anterior cerebral artery aneurysms (DACA), by analyzing data from the CRETA registry (Clinical and Radiological Evaluation of Endovascular Treatment of Distal Anterior Cerebral Artery Aneurysms) a multicenter, retrospective database that collects data on the endovascular management of \u0026nbsp;DACA [6].\u0026nbsp;\u003c/p\u003e\n"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003ePatients and treatment\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis is a retrospective, multicenter, observational study that included patients with ruptured and unruptured DACA aneurysms who underwent different endovascular treatments, analyzed as part of the CRETA Consortium study [6] (Figure 1). Data were collected on patient demographics, aneurysm characteristics, procedural details, complications, and clinical and radiographic outcomes. Endovascular treatments comprised simple coiling, balloon-assisted coiling, stent-assisted coiling, flow diverter stents (standalone or with coiling), and intrasaccular devices.\u003c/p\u003e\n\u003cp\u003eWe identified two study subgroups according to the presence (\u0026ldquo;ACA variant anatomy\u0026rdquo; subgroup) or absence of an anatomical variant of the ACA (ACA conventional anatomy). Anatomical variants of the ACA, specifically the azygos ACA and bihemispheric ACA subtypes, are uncommon but clinically significant configurations that require careful evaluation when planning endovascular treatment. According to Lasjaunias [7] the Azygos-type ACA is characterized by a single, unpaired artery arising from both the A1 segments throughout the ACA course and supplying both medial hemispheric surfaces. Despite the notion of an ACA variant according to these definition was available in the CRETA Registry, the subtype of the variant was not specified.\u003c/p\u003e\n\u003cp\u003eThe study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and was conducted under a nonprofit research protocol approved by the ethics committee of the coordinating center (Fondazione Policlinico Universitario A.Gemelli IRCCS, protocol ID 3583).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasures of outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome measure was aneurysm occlusion at last imaging follow-up assessed using digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA), and graded according to the Raymond-Roy Occlusion Classification (RROC) scale [8]. RR classes I and II were merged into a single variable indicating complete/near-complete occlusion, while IIIa and IIIb were defined as incomplete occlusion. Secondary outcome measures included the occurrence of ischemic or hemorrhagic complications and of vasospasm and the long-term clinical outcome measured with the modified Rankin Scale (mRS). \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive statistics were used to summarize baseline characteristics. Continuous variables were expressed as means \u0026plusmn; standard deviations (SD) or medians with interquartile ranges (IQR), while categorical variables were presented as counts and percentages. Fisher\u0026rsquo;s exact test was used to compare categorical variables, and either the Welch two-sample t-test or the Mann-Whitney U test was applied to continuous variables, depending on their distribution. The Shapiro-Wilk test was used to assess the normality of continuous variables. Missing data were not imputed, and significance was set at p\u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003eWe used propensity score matching (PSM) with the optimal algorithm to estimate the difference in outcome measures between patients with the conventional ACA anatomy and those carrying the variant one. Covariates used in the PSM model were those with a potential effect on measured outcomes and included age, unruptured aneurysm status, the dome-to-neck ratio, the branch artery origin (classified as from the sack, the neck or the artery, respectively) and type of treatment. Covariates balance was assessed by examining standardized mean differences (SMD), with values \u0026lt;0.2 indicating acceptable balance. Odds ratio with 95% CI were calculated for each variable, with the variant ACA anatomy group serving as the reference (Supplemental Table 1). For missing clinical outcome data, a sensitivity analysis was conducted to evaluate the robustness of the results under three different scenarios: 1) the worst-case scenario (defined as the pro-variant ACA anatomy scenario: all missing cases with conventional ACA anatomy had the unfavorable angiographic outcome, all missing cases with the variant ACA anatomy had the favorable outcome), 2) the best-case scenario (defined as the pro-ACA normal anatomy: all missing cases with the conventional ACA anatomy had the favorable angiographic outcome, all missing cases carrying the variant ACA anatomy had the unfavorable outcome), and 3) the observed scenario (only cases with complete data). Odds ratios with 95% CI were calculated for each scenario (Supplemental Table 2 and Figure 1). Significance threshold was set at p\u0026lt;0.05. All analyses were performed using the R software v.4.3.2 with the \u003cem\u003eMatchIt\u003c/em\u003e and \u003cem\u003etidyverse\u003c/em\u003e packages (https://www.r-project.org). No subgroup analysis was performed on the subtype of anatomical variation.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe have analysed an initial cohort of 300 patients with conventional ACA anatomy and 64 patients harboring an ACA variant. After PSM, the final population included 128 patients, equally distributed between the two subgroups ACA normal anatomy and ACA variant anatomy. Detailed data according to each subgroup were summarized in Tables 1-2. We report here only the overall results. The majority were female (85/128, 66.4%) with a median age of 62 years (IQR 54\u0026ndash;70). Hypertension was the most common risk factor, present in 79/126 (62.7%), followed by dyslipidemia in 30/126 (23.8%) and diabetes in 17/126 (13.5%). Only 15/125 (12.0%) were current smokers. A family history of aneurysms was reported in 20/122 (16.4%). Previous SAH occurred in 13/127 (10.2%), due to the index aneurysm in 10/126 (7.9%) and to another aneurysm in 3/126 (2.4%). Ruptured aneurysms were observed in 62/128 (48,4%), with irregular morphology in 81/128 (63.3%). Branch artery origin involved the sac in 25/128 (19.5%), the neck in 61/128 (47.7%), and the artery in 42/128 (32.8%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTransradial access was performed in 9/128 (7%) and in 79/125 (63%) cases a tri-axial system was used. The most frequently used techniques were standalone coiling in 57/128 cases (44.5%) and flow-diverter in 34/128 (26.6%) (Figure 2). According to the CRETA registry the median radiological follow-up was 16.5 months (IQR 7\u0026ndash;24) (6).\u003c/p\u003e\n\u003cp\u003eThe clinical and procedural outcomes were summarized in Table 3. We did not observe any statistical difference concerning the adequate occlusion rate (81.5% vs 85.5%, OR 1.3; 95% CI 0.5\u0026ndash;3.7; p=0.6) and the intra-procedural complications (ischemic: 7.8% vs. 14.1%, p=0.7; hemorrhagic: 3.2% vs. 7.8%, p=0.5). Clinical outcomes did not significantly differ between two subgroups. The sensitivity analysis showed no significant modification of the primary and second endpoints (Supplemental Figure 1 and Table 1).\u003c/p\u003e\n\u003cp\u003eAngiographic outcomes of the covered vessel by Flow-Diverter (FD) stents at the last follow-up in the two study subgroups, before PSM, were reported in Supplemental Table 3. No ischemic complications related to the vessel covered by the FD stent were observed in both subgroups.\u003c/p\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eOur statistical analysis showed no significant difference in terms of adequate occlusion (RR I-II) at the latest follow-up of the treated aneurysms in patients with and without an ACA variant. Furthermore, the complication rates were comparable in the two subgroups. These results indicate that the presence of an anatomical variant does not adversely affect the outcome of the endovascular treatment. \u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eEffectiveness of EVT according to anatomical variations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe effectiveness of the endovascular treatment for distal anterior cerebral aneurysms has already been shown in previous studies. In particular, the meta-analysis by Vilardo et al [9] concluded that the use of Flow-Diverter stents seems to be safe and effective in the treatment of distal aneurysms and that this is associated with high occlusion rates.\u003c/p\u003e\n\u003cp\u003eAlthough previous studies have reported similar rates of effectiveness of EVT in distal ACA aneurysms (DACA), none specifically accounted for the presence of anatomical variants. Cagnazzo et al. [10] reported an overall rate of adequate occlusion (OKM C\u0026ndash;D) of 79% (19/24 aneurysm) in a series of 25 unruptured DACA treated with flow diverters. These results are in line with those reported in the same subgroup in a previous meta-analysis, focusing on the treatment of distal aneurysms of the anterior circulation [11]. \u003c/p\u003e\n\u003cp\u003eIn our cohort, the occlusion rates were similar or higher. However, in this study we have included different endovascular techniques, and our findings are not limited to the FD stents. \u003c/p\u003e\n\u003cp\u003ePorto et al. [12] reported high occlusion rates (\u0026gt;90%) at the end of the follow-up in a cohort of 84 patients with DACA treated in 5 institutions through primary coiling (60/84) or FD stents (24/84). Interestingly, in their series about 60% of the patients (61.9%, 52/84) had ruptured aneurysms and among them 11 were treated by FD stents. The effectiveness of flow diverters in the management of ruptured DACA aneurysms has also been supported by Salsano et al.[13], who reported an adequate occlusion rate of 95.2% in an analysis of 21 ruptured DACA treated by FD stents. \u003c/p\u003e\n\u003cp\u003eNevertheless, poor data are available concerning the impact of the ACA variants on the endovascular outcomes. \u003c/p\u003e\n\u003cp\u003eIn our study, we reported comparable occlusion rates at the last follow-up in both the variant (81.5%) and non-variant (85.5%) sub-groups and these are in line with the aforementioned ones. These results underline the effectiveness of the different endovascular approaches even in case of potentially challenging anatomical conditions. \u003c/p\u003e\n\u003cp\u003eIn our study no significative difference was observed in terms of arterial branches arising from the sac or the neck. Indeed, it had been previously shown that this factor may negatively affect the occlusion rates [14,15] particularly when they originate from the aneurysm dome [16]. This mechanism has been supported by experimental evidence where neointimal growth effectively seals the aneurysm neck but spares the origin of the branch, since the efferent flow through the incorporated branch prevents the intra-aneurysmal stasis required for complete sac thrombosis [17]. This may be particularly relevant in the context of the treatment of DACA with FD stents in the setting of ACA variants, where the origin, vessel caliber, and distribution of leptomeningeal anastomoses may differ from the normal anatomical configuration.\u003c/p\u003e\n\u003cp\u003eIn our study, within the group of patients with ACA variants, a branch originated from the aneurysm neck in 30 out of 64 cases (46.9%) and from the aneurysm sac in 12 out of 64 cases (18.7%). Despite the presence of a branch arising from the aneurysm in more than half of the cases, the endovascular outcome was not adversely affected. This finding had already been reported by Cagnazzo et al., probably related to the presence of collateral circulation in the frontal and orbitofrontal regions [10], and further confirmed in the analysis of the CRETA registry [6]. Finally, the size and the dome-to-neck ratio did not influence the occlusion rates in both variant and non-variant subgroups, although the mean size of the aneurysm was \u0026lt;6 mm in this analysis.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eSafety profile according to anatomical variations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn our series, the presence of an ACA anatomical variant was not associated with a higher rate of procedural complications. On the contrary, both ischemic and hemorrhagic complications occurred less frequently in the variant group compared to the non-variant group, although these differences did not reach statistical significance. These results are consistent with prior studies reporting overall treatment-related complication rates of approximately 5\u0026ndash;7.5% for DACA aneurysms treated with flow diverters [6,11,18] and up to 13% for DACA treated with different endovascular devices [12].\u003c/p\u003e\n\u003cp\u003eAnatomical variants such as azygos or bihemispheric ACA may theoretically represent a higher thromboembolic risk due to the presence of a single dominant or unpaired arterial segment. However, in our cohort, ischemic complications occurred in only 5 patients within the ACA variant group, and all were asymptomatic. Although ACA variants may lead to a different disposition of the origin and caliber of the cortical branches raising from A2\u0026ndash;A3 segments [19], no acute thromboembolic occlusion of these vessels was observed. This suggests that the presence of an anatomical variant does not increase the ischemic risk compared to the normal anatomy, particularly in case of usage of flow-diverter stents. As far as the rate of hemorrhagic complications is concerned, in the ACA variant subgroup this was lower than in the subgroup with conventional anatomy. \u003c/p\u003e\n\u003cp\u003eThese results could be explained using different endovascular techniques, in particular unassisted coiling and intrasaccular devices, with the choice of respecting the vascular anatomy of the parent vessel when possible.\u003c/p\u003e\n\u003cp\u003eIn our study, no ischemic complications related to covered side vessels from the FD stent were observed in either the normal ACA anatomy group or the ACA variant anatomy group. This finding is consistent with previous studies reporting a very low rate of symptomatic ischemic events associated with vessel occlusion [10,20]. In the systematic review by Gunkan et al., 30/372 covered vessels were occluded, but only 3 cases were symptomatic [21]. Cagnazzo et al. attributed this phenomenon to the presence of collateral circulation in the frontal and orbitofrontal regions, which may account for asymptomatic occlusion or flow remodelling of the covered branches [10]. As we have shown with our results, this mechanism may also apply in the setting of ACA anatomical variants.\u003c/p\u003e\n\u003cp\u003eOverall, these findings support the assumption that ACA anatomical variants do not adversely impact the safety of the endovascular treatment for distal aneurysms and that the procedural risks remain comparable to those described in the literature for conventional ACA anatomy.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eAnatomical Considerations and Procedural Technical Aspects\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe hypothesis of this study focused on the potential role of anatomical variation of ACA in determining different outcomes of the endovascular treatment of DACA. The Azygos type is different from the Unpaired type of Anterior cerebral artery, where both A1 segments join at the midline and immediately divide into two main trunks at the level of the genu of the corpus callosum [22]. In the bihemispheric-type ACA, a dominant A2 segment crosses the midline, perfusing both hemispheres, often in association with hypoplasia or aplasia of the contralateral A2 [7,19,22]. Despite these major anatomical differences, our study showed no statistically significant difference in the mean diameter of the parent vessel from which the aneurysm originated between the ACA variant group and the group with normal anatomy (2 mm [IQR 1.6-2.4]; 1.9mm [IQR 1.6-2.2]; p=0.1). This finding is consistent with previously published data reporting an average vessel diameter of approximately 2 mm [10,11,18,23], suggesting that standard stent sizing remains appropriate even in the presence of ACA anatomical variants.\u003c/p\u003e\n\u003cp\u003eCompared to the conventional ACA anatomical pattern, these variants present notable morphological differences, which have been correlated with an increased susceptibility to the development of aneurysmal formations [24], particularly at sites of altered hemodynamic stress and vessel wall weakness. This is further supported by our findings, which showed a statistically significant difference in aneurysm morphology after PSM: irregularly shaped aneurysms were more frequently observed in the ACA variant group compared to the normal anatomy group (45/64, 70.3% vs. 36/64, 56.2%; p = 0.005). However, despite the association between ACA anatomical variants and an increased risk of irregular aneurysm morphology, we demonstrated that endovascular treatment remains both effective and safe in these cases.\u003c/p\u003e\n\u003cp\u003eConversely, in the ACA variants, the dominant vessel may give rise to a greater number of cortical and perforating branches to supply both hemispheres compared to a standard A2 [7,19], which may theoretically increase the complexity of stent placement, particularly in the context of flow diverter placement, compromising the perfusion of cortical arterial branches [25]. \u003c/p\u003e\n\u003cp\u003eMoreover, although in ACA variants a single vessel supplies both hemispheres, this could raise concerns that procedural complications such as thromboembolism or in-stent thrombosis could result in more extensive neurological deficits. However, in our study such events were not observed. \u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLimitations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study presented some limitations. First, its retrospective and multicenter design introduces potential heterogeneity due to differences in endovascular techniques and operator preferences across centers, which may have influenced the outcomes. In addition, there was no centralized imaging analysis for the definition of ACA variants, which may have introduced heterogeneity in variant classification across centers and in the CRETA registry the specific subtype of the variant was not specified, limiting the specificity of this analysis. Additionally, although anatomical variations of the anterior cerebral artery are relatively rare, the sample size of patients with these variants remains limited. Larger, prospective studies are therefore needed to confirm our findings and better define the impact of ACA anatomical variants on treatment outcomes.\u003c/p\u003e\n"},{"header":"Conclusion","content":"\u003cp\u003eOur results demonstrate that the presence of ACA variants did not adversely affect the efficacy and safety of the endovascular treatment of DACA. The comparable rates of adequate occlusion and procedural complications observed in patients with and without ACA variants suggest that, when meticulous anatomical assessment and appropriate device selection are performed, these variants do not constitute a further risk factor for unfavorable outcomes.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this research. \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLS: unrelated to the current study, Penumbra (paid lectures). FS: Outside the submitted work received lecturer’s fee from Idorsia Pharmaceuticals for the past 36 months. OG: Outside the submitted work, MicroVention proctor for the WEB device, Stryker consultant, Route 92 consultant. ML: Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. AMA: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AP: educational grants from Medtronic, Stryker, Balt and Microvention/Terumo unrelated to the current study. AEH: Consultant/Speaker: Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Shockwave, Toro and Xcath. Principal Investigator: COMPLETE study – Penumbra, LVO SYNCHRONISE – Viz.ai, MARRS - Perfuze, RESCUE - ICAD - Medtronic. Steering Committee/Publication committee member: SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. DSMB - COMAND trial. ML Unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, AIDoc and Arsenal Medical; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. FC reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board) ; all not directly related to the present work. CC consultant for Medtronic, Microvention, Cerenovus, Stryker, Anaconda, unrelated to the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available upon reasonable request to the Principal Investigator.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003eThis study is part of a nonprofit research protocol approved by the ethics committee of the coordinating center (Fondazione Policlinico Universitario A.Gemelli IRCCS, protocol ID 3583).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was waived in consideration of the retrospective nature of this study.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHoh BL, Ko NU, Amin-Hanjani S, Hsiang-Yi Chou S, Cruz-Flores S, Dangayach NS, et al. (2023) Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke 54(7):E314\u0026ndash;70. \u003c/li\u003e\n\u003cli\u003eThompson BG, Brown RD, Amin-Hanjani S, Broderick JP, Cockroft KM, Connolly ES, et al. (2015). Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation 46(8):2368\u0026ndash;400. \u003c/li\u003e\n\u003cli\u003ePierot L, Wakhloo AK. Endovascular treatment of intracranial aneurysms: Current status. (2013) Stroke 44(7):2046\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eAtallah E, Saad H, Mouchtouris N, Bekelis K, Walker J, Chalouhi N, et al. (2019). Pipeline for distal cerebral circulation aneurysms. Clin Neurosurg. 85(3):E477\u0026ndash;84. \u003c/li\u003e\n\u003cli\u003eMa C, Zhu H, Liang S, Liang F, Han J, Jia Z, et al. (2022). Pipeline for the treatment of distal cerebral circulation aneurysms: A multicenter study focusing on periprocedural Complications. Interventional Neuroradiology 28(6):708\u0026ndash;18. \u003c/li\u003e\n\u003cli\u003eScarcia L, Claren\u0026ccedil;on F, Dmytriw AA, Shotar E, Premat K, Jabbour P, et al. (2024). Flow-diverting stents for the treatment of unruptured distal anterior cerebral artery aneurysms: analysis of the CRETA Registry. J Neurointerv Surg 17(12):1270-1276. doi: 10.1136/jnis-2024-022315.\u003c/li\u003e\n\u003cli\u003eLasjaunias PBA ter BKG. (2001) Surgical Neuroangiography. Volume 1: Functional Anatomy of Craniofacial Arteries. 2nd ed. Vol. 1. Berlin: Springer.\u003c/li\u003e\n\u003cli\u003eMascitelli JR, Moyle H, Oermann EK, Polykarpou MF, Patel AA, Doshi AH, et al. (2015). An update to the Raymond\u0026ndash;Roy Occlusion Classification of intracranial aneurysms treated with coil embolization. J Neurointerv Surg 7:496\u0026ndash;502. \u003c/li\u003e\n\u003cli\u003eVilardo M, G\u0026uuml;nkan A, Dmytriw AA, Elek A, Scarramal JPL, Bocanegra-Becerra JE, et al. (2025). Efficacy and Safety of Flow Diversion for Distal Anterior Cerebral Aneurysms: A Systematic Review and Proportional Meta-Analysis. American Journal of Neuroradiology. 47(1):66-72. doi: 10.3174/ajnr.A8926.\u003c/li\u003e\n\u003cli\u003eCagnazzo F, Fanti A, Lefevre PH, Derraz I, Dargazanli C, Gascou G, et al. (2021). Distal anterior cerebral artery aneurysms treated with flow diversion: experience of a large-volume center and systematic review of the literature. J Neurointerv Surg 13(1):42\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eCagnazzo F, Perrini P, Dargazanli C, Lefevre PH, Gascou G, Morganti R, et al. (2019). Treatment of Unruptured Distal Anterior Circulation Aneurysms with Flow-Diverter Stents: A Meta-Analysis. American Journal of Neuroradiology 40(4):687-693. doi: 10.3174/ajnr.A6002.\u003c/li\u003e\n\u003cli\u003ePorto GBF, Al Kasab S, Sattur MG, Almallouhi E, Lajthia O, Casey MA, et al. (2021). Endovascular Management of Distal Anterior Cerebral Artery Aneurysms: A Multicenter Retrospective Review. World Neurosurg. Oct;154:e421\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSalsano G, Scarcia L, Claren\u0026ccedil;on F, Shotar E, Russo R, Bergui M, et al. (2025). Flow diverter stent for the treatment of ruptured distal anterior cerebral artery: A retrospective multicenter analysis from CRETA registry. Interventional Neuroradiology. Aug 4:15910199251348514. doi: 10.1177/15910199251348514.\u003c/li\u003e\n\u003cli\u003eCagnazzo F, Lefevre PH, Mantilla D, Rouchaud A, Morganti R, Perrini P, et al. (2019). Patency of the supraclinoid internal carotid artery branches after flow diversion treatment. A meta-analysis. Journal of Neuroradiology Feb;46(1):9\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eDaou B, Valle-Giler EP, Chalouhi N, Starke RM, Tjoumakaris S, Hasan D, et al. (2017). Patency of the posterior communicating artery following treatment with the Pipeline Embolization Device. J Neurosurg. Feb;126(2):564\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eDibas M, Vivanco‐Suarez J, Galecio‐Castillo M, Lopes DK, Hanel RA, Rodriguez‐Calienes A, et al. (2024). Flow Diversion for Intracranial Aneurysms With Incorporated Branch: A Subanalysis From the SEASE International Registry. Stroke: Vascular and Interventional Neurology Oct 25;4(6):e001448. doi: 10.1161/SVIN.124.001448.\u003c/li\u003e\n\u003cli\u003eDarsaut TE, Bing F, Salazkin I, Gevry G, Raymond J. (2012). Flow Diverters Can Occlude Aneurysms and Preserve Arterial Branches: A New Experimental Model. American Journal of Neuroradiology Nov;33(10):2004\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eKhanafer A, Henkes H, Cohen J, Albi\u0026ntilde;a-Palmarola P, Gomori JM, Forsting M, et al. (2024). Endovascular treatment of distal anterior cerebral artery aneurysms using flow modulation devices: mid- and long-term results from a two-center study. Front Neurol. Mar 11;15:1368612. doi: 10.3389/fneur.2024.1368612.\u003c/li\u003e\n\u003cli\u003eCilliers K, Page BJ. (2016). Detailed description of the anterior cerebral artery anomalies observed in a cadaver population. Annals of Anatomy - Anatomischer Anzeiger. Nov;208:1\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eScarcia L, Claren\u0026ccedil;on F, Dmytriw AA, Shotar E, Jabbour P, Psychogios M, et al. (2025). Silk Vista Baby for the treatment of distal anterior cerebral artery aneurysms. Neuroradiology Aug;67(8):2167-2177. doi: 10.1007/s00234-025-03678-y.\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;nkan A, Vilardo M, Scarramal JPL, Elek A, Bocanegra-Becerra JE, Cardoso LJC, et al. (2025). Flow diversion for distal cerebral aneurysms: a systematic review and meta-analysis. J Neurointerv Surg. May 13;jnis-2025-023362. \u003c/li\u003e\n\u003cli\u003eBaptista AG. (1963) Studies on the arteries of the brain. Neurology. Oct;13(10):825\u0026ndash;825. \u003c/li\u003e\n\u003cli\u003eNossek E, Zumofen DW, Setton A, Potts MB, Raz E, Shapiro M, et al. (2017). Treatment of distal anterior cerebral artery aneurysms with the Pipeline Embolization Device. Journal of Clinical Neuroscience Jan;35:133\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eTriantafyllou G, Paschopoulos I, Kamoutsis K, Papadopoulos-Manolarakis P, Valenzuela-Fuenzalida JJ, Sanchis-Gimeno J, et al. (2025). Morphological Variations of the Anterior Cerebral Artery: A Systematic Review with Meta-Analysis of 85,316 Patients. Diagnostics Jul 28;15(15):1893. \u003c/li\u003e\n\u003cli\u003eMichelozzi C, Darcourt J, Guenego A, Januel AC, Tall P, Gawlitza M, et al. (2019). Flow diversion treatment of complex bifurcation aneurysms beyond the circle of Willis: complications, aneurysm sac occlusion, reabsorption, recurrence, and jailed branch modification at follow-up. J Neurosurg. Dec;131(6):1751\u0026ndash;62. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9488266/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9488266/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Anatomical variants of the anterior cerebral artery (ACA) may increase technical complexity during endovascular treatment of distal ACA aneurysms (DACA). However, their impact on treatment outcomes remains unclear. This study evaluated whether ACA variants influence angiographic and clinical outcomes following endovascular treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A retrospective multicenter analysis was conducted using data from the CRETA Registry, including patients with ruptured and unruptured DACA treated endovascularly. Patients were grouped according to ACA anatomy (variant vs conventional). Outcomes were compared after propensity score matching (PSM) to adjust for confounders including age, aneurysm rupture status, dome-to-neck ratio, branch origin, and treatment type. The primary outcome was aneurysm occlusion at last follow-up based on the Raymond–Roy classification. Secondary outcomes included ischemic and hemorrhagic complications, vasospasm, and clinical outcome measured by the modified Rankin Scale (mRS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: After PSM, 128 patients were included (64 per group). At a median imaging follow-up of 16.5 months, adequate occlusion rates were comparable between the variant and conventional ACA groups (81.5% vs 85.5%; p=0.6). No significant differences were observed in ischemic or hemorrhagic complications, vasospasm, or long-term clinical outcomes. Sensitivity analyses confirmed the robustness of the findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: ACA anatomical variants do not adversely affect the safety or efficacy of endovascular treatment for DACA. With appropriate anatomical assessment and treatment selection, endovascular therapy remains effective even in the presence of complex ACA configurations.\u003c/p\u003e","manuscriptTitle":"Anterior Cerebral Artery Variants and Their Influence on Endovascular Outcomes: A propensity score matched analysis from the CRETA Registry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 05:37:53","doi":"10.21203/rs.3.rs-9488266/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5b32ffff-41f0-4cd6-ac75-8e669b964b0e","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"114004016830598289770801048440773352699","date":"2026-05-17T11:52:40+00:00","index":87,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-17T06:30:14+00:00","index":86,"fulltext":""},{"type":"reviewerAgreed","content":"138004509719792057836944613453475128192","date":"2026-05-17T06:23:27+00:00","index":85,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T18:02:40+00:00","index":84,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-14T07:25:21+00:00","index":82,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T15:42:06+00:00","index":81,"fulltext":""},{"type":"reviewerAgreed","content":"151304878159102674074424787146816567023","date":"2026-05-12T11:08:09+00:00","index":80,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T08:33:19+00:00","index":79,"fulltext":""},{"type":"reviewerAgreed","content":"189486012135304098562918665937986078019","date":"2026-05-12T08:26:49+00:00","index":78,"fulltext":""},{"type":"reviewerAgreed","content":"172386699454544191006077287131464547324","date":"2026-05-12T06:36:13+00:00","index":74,"fulltext":""},{"type":"reviewerAgreed","content":"79688777021224247833065687064121337417","date":"2026-05-12T06:24:26+00:00","index":73,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T05:37:54+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 05:37:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9488266","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9488266","identity":"rs-9488266","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}