The Role of Flow Diverter Stents in Treating Distal Middle Cerebral Artery Aneurysms: A Systematic Review and Meta-analysis

The Role of Flow Diverter Stents in Treating Distal Middle Cerebral Artery Aneurysms: A Systematic Review and Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review The Role of Flow Diverter Stents in Treating Distal Middle Cerebral Artery Aneurysms: A Systematic Review and Meta-analysis Luis Gustavo Biondi Soares, Murtaja Satea Shafeea, Guilherme Linha Secco, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6542820/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 Purpose Flow diversion has emerged as a key strategy in the treatment of intracranial aneurysms. However, its safety and efficacy in distal middle cerebral artery (MCA) aneurysms remain inadequately characterized. This study aims to update and synthesize the current literature by evaluating occlusion rates, procedural complications, and clinical outcomes associated with flow diversion in this subset. Methods A systematic review and meta-analysis were conducted according to the PRISMA guidelines. Relevant studies published through 2025 were identified through searches of major databases using predefined criteria. A random-effects proportional meta-analysis using R (version 4.4.2) was performed to assess pooled occlusion and complication rates. Heterogeneity was evaluated via I² statistics, and publication bias was assessed via funnel plots. Results Ten studies comprising 128 distal MCA aneurysms treated with flow diverter stents were included. The pooled complete occlusion rate was 87% (101/120; 95% CI: 80–93%), with no observed heterogeneity (I² = 0.0%, p = 0.7997). A sensitivity analysis excluding two large studies revealed an occlusion rate of 81% (48/61; 95% CI: 71–91%), with low heterogeneity. The overall complication rate was 14% (21/128; 95% CI: 8–21%), with the most frequent complications being thromboembolic events, in-stent stenosis, and hemorrhagic complications. Funnel plots did not reveal evidence of publication bias. Conclusion Flow diversion appears to be a promising treatment option for distal MCA aneurysms, offering high rates of complete occlusion with an acceptable complication profile. However, the data remain limited and heterogeneous. Larger prospective studies with standardized outcome reporting are needed to establish its definitive role in this challenging vascular territory. Flow diverter stent Intracranial aneurysm Middle cerebral artery Endovascular treatment Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Intracranial aneurysms (IAs) are focal dilatations of cerebral arteries that predominantly arise within the circle of Willis [1,2]. IA affects approximately 2–5% of the adult population and represents a significant public health issue because of its potential for rupture, which may result in subarachnoid hemorrhage (SAH) [2,3]. The pathogenesis of IAs involves maladaptive vascular remodeling triggered by hemodynamic stress and inflammatory responses [1,4]. Diagnosis typically involves imaging techniques such as magnetic resonance angiography (MRA) or computerized tomographic angiography (CTA) [1]. Management of unruptured IAs requires a careful balance between the risk of rupture and the procedural risks, with reported treatment-associated mortality and morbidity rates reaching up to 5% [3]. Microsurgical clipping and endovascular treatment are the primary approaches for managing IAs. Compared with endovascular techniques, clipping generally results in higher rates of complete occlusion and lower recurrence rates [5,6]. However, endovascular treatments are associated with lower periprocedural morbidity and better functional outcomes [5,7]. The choice between these modalities depends on factors such as aneurysm location, morphology, patient characteristics, and surgeon experience [8]. For middle cerebral artery aneurysms, clipping remains the standard treatment, although endovascular approaches are viable alternatives [6]. The field of IA treatment is rapidly evolving, with new endovascular techniques, such as flow diversion stent (FDS) and intrasaccular flow disruption. In complex cases, a combination of microsurgical and endovascular techniques may be necessary [8]. FDS has emerged as a revolutionary treatment for complex IAs, particularly those challenging conventional endovascular techniques [9,10]. FDS functions by altering hemodynamics, redirecting blood flow away from the aneurysm and along the parent vessel [11,12]. This flow modification induces gradual intra-aneurysmal thrombosis and promotes reendothelialization across the aneurysm neck [9,12]. The low porosity and high metal coverage of FDS are key properties enabling this mechanism [9]. Unlike traditional techniques that target the aneurysm sac, FDSs are implanted in the parent artery, representing a paradigm shift in IA treatment [9,10]. FDS has demonstrated favorable safety profiles with low complication rates compared with alternative treatments [13]. While FDSs have shown promise in treating complex IAs, they carry risks such as in-stent thrombosis and delayed hemorrhages. Nonetheless, FDS has become a new standard of care for selected IAs [10]. FDS is an effective treatment for intracranial aneurysms, particularly for small and complex cases. Studies have shown comparable occlusion rates and safety profiles for FDS use in small-caliber arteries (≤2.5 mm) to those in larger vessels, with complete occlusion rates of 73.6% at the 12.1-month follow-up. FDS has demonstrated efficacy in treating unruptured aneurysms, with 78% complete obliteration at 13 months and better outcomes for smaller aneurysms (<7 mm) [14]. Limited evidence suggests that FDS may be feasible for small (≤5 mm) ruptured aneurysms, achieving 100% occlusion in a small cohort [15]. However, complications can occur, including periprocedural, immediate postprocedural, and delayed events [10]. A previous study reported high aneurysm obliteration rates (>70%) and good clinical outcomes (97.4%) when various cerebral arteries were covered [16]. However, complications can occur, with an overall rate of 17% and neurological morbidity of 4.5% [17]. For carotid-ophthalmic aneurysms, FDSs achieve an 85% occlusion rate with only a 3% risk of new visual symptoms [18]. In tandem occlusions, nearly half of patients treated with mechanical thrombectomy have good neurological outcomes, with no significant differences between extracranial and intracranial approaches or between stenting and angioplasty [19]. Common FDSs include Pipeline and Silk, which have similar complication rates [17]. While effective, the risk of complications should be considered when deciding on FDS treatment. Recent studies have indicated that endovascular treatment is the preferred first-line approach for most ruptured and unruptured aneurysms, although microsurgical clipping remains favored for middle cerebral artery (MCA) aneurysms [20]. Treatment options have evolved to include traditional methods such as clipping and coiling, as well as newer techniques such as stent-assisted coiling and flow diversion [21]. The LEO stent, a braided self-expanding device, has shown promising results in treating wide-neck intracranial aneurysms. Compared with laser-cut stents, it offers greater metal coverage (14%) and radial force [22]. Clinical studies have demonstrated high technical success rates (97.5%) and favorable occlusion outcomes with LEO Baby stents, with complete occlusion observed in 85.7% of cases at follow-up [23]. Flow diverters are becoming the treatment of choice for large and complex internal carotid artery aneurysms [24]. Emerging technologies such as intrasaccular flow diverters (e.g., WEB devices) show promise for wide-neck bifurcation aneurysms [8]. Treatment decisions are based on factors such as patient characteristics, aneurysm features, and operator experience. While guidelines exist, there is considerable variability in patient selection, treatment strategies, and follow-up protocols among physicians [20]. Ongoing research and technological advancements continue to shape the landscape of intracranial aneurysm treatment. Studies have shown comparable safety and efficacy between FDS use in small- and large-calibrer vessels, with similar complication and occlusion rates [25]. The FRED device demonstrated low morbidity (2.0%) and mortality (1.0%) rates in a prospective study, whereas another study reported technical success in all patients with the same device [26,27]. However, the FIAT trial raised safety concerns, reporting death or dependency in 16% of patients treated with flow diversion [28]. Despite these mixed results, FDS has shown promise in treating diverse aneurysm types, including those in distal locations where other options pose a considerable risk [28]. More randomized trials are needed to definitively establish the role of flow diversion in aneurysm management [28]. The primary objective of this study was to systematically evaluate the efficacy and safety of FDSs in the treatment of distal MCA aneurysms, particularly those located in the M2 segment. Given the limited and conflicting evidence regarding the use of FDSs in distal intracranial vessels, this review aims to assess whether these stents offer a viable alternative to conventional treatment modalities, including microsurgical clipping, coiling, and balloon-assisted techniques. Additionally, this study compared the clinical and radiographic outcomes between FDSs and standard endovascular interventions, focusing on aneurysm occlusion rates, complication profiles, and long-term vascular remodeling. Special attention is given to the role of laser stents (e.g., Leo stent) and adjunctive balloon-assisted strategies to determine their potential in optimizing endovascular outcomes. By synthesizing available data through a systematic review and meta-analysis, this research seeks to bridge the existing knowledge gap and provide evidence-based insights into the feasibility of FDS for distal MCA aneurysm management, ultimately guiding future clinical decision-making and interventional strategies. Methods Search strategy This review followed the guidelines set by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [29], available in Figure 1 . A comprehensive search was performed across major databases, including PubMed (n = 119), Web of Science (n = 74), and Embase (n = 81), to identify relevant studies published up until 2025. Our search strategy utilized the following terms: flow diverter stent, flow diversion, MCA, middle cerebral artery, and M2. Four authors independently and collaboratively conducted the study selection, data extraction, and quality assessment (KW, RZ, GLS, PHK) on the basis of predefined criteria. ( This study was prospectively registered under the registration number CRD420251016691 ). Study selection - Inclusion and exclusion criteria Eligibility for inclusion required studies to meet predefined criteria. First, they needed to focus on the treatment of distal vessel aneurysms with a flow diverter stent or flow diversion as the primary treatment rather than other treatments, such as stent-assisted coiling, coiling alone, microsurgical clipping, and intrasaccular devices. Second, the studies had to provide data related to the aneurysm occlusion rate, procedural success rates, complication rates, functional outcomes (modified Rankin score (mRS)) and long-term durability of flow diversion. Studies that did not meet these requirements were excluded. These studies included studies that lacked clearly defined occlusion rates, procedural success, functional status, and complications. Additionally, studies focusing on patients under eighteen years of age, letters, comments, or reviews were excluded. Studies lacking full-text access or involving overlapping patient cohorts were also excluded. Studies that did not offer comprehensive outcome data were also excluded. In cases where patient cohorts overlapped from the same institution or database during the same period and involved at least one patient with similar procedural or baseline characteristics, priority was given to the more recent study or the study that presented data on the primary outcome. This study is an updated systematic review and meta-analysis built upon prior literature on flow diversion for distal MCA aneurysms. Two new studies published after the previous review were identified and included. These two studies contributed to the inclusion of 69 additional patients—59 patients from the first eight studies—thereby increasing the power and relevance of the pooled analysis. Data extraction During the analysis, the integrity of the data was maintained by thoroughly reviewing textual content, tables, images, and supplementary materials. Data extraction was carried out by two authors (KB, KW), each of whom focused on different aspects of the data. These aspects included publication details such as the first author, year of publication, and study design, as well as the baseline characteristics of the patients, including the number of patients, age, sex, complications, follow-up duration, complication rates, functional status, and success rates, along with any other relevant data. Quality assessment A bias assessment was conducted via the ROBINS-I tool [30] to evaluate the quality of the cohort studies included in the meta-analysis. This tool was used to identify potential concerns in the design and reporting of the included studies rather than serving as a criterion for inclusion. The decision to use this approach was based on the inherently high risk of bias in observational studies of exposures, in line with the guidelines provided by the tool. A summary of the results from the bias assessment is shown in Figure 2. Statistical analysis All the statistical analyses were performed via R (version 4.4.2, R Foundation for Statistical Computing, Vienna, Austria). Proportional meta-analyses were conducted with a random effects model to estimate pooled rates for complete occlusion and complications. Heterogeneity was assessed via I² statistics, and funnel plots were generated to evaluate publication bias. Results A summary of information regarding the included studies, including study type, number of patients/aneurysms, aneurysm morphology, complication type, follow-up duration in months, and number of recurrences/retreatments, is shown in Table 1. Table 1. Summary of information from the included studies. Study Reference number Study Type (Retrospective or prospective, and study design) No. of Patients/No. of aneurysms Aneurysm morphology Complication Type Follow up Duration (months) Recurrence and Retreatment Yavuz et al 2014 42 21 N/A N/A 3-30 3 Zanaty et al 2014 43 Retrospective 10 Fusiform 70% Saccular 30% N/A 7-12 0 Durst et al 2015 44 Case report 1 Fusiform N/A 3 0 Primiani et al 2018 45 Retrospective 65 Saccular 38 Fusiform 19 Dissecting 8 N/A 11.6 4 Cimflova et al 2020 46 Retrospective 23 Saccular 2 Sacculofusiform 8 Fusiform 13 Intraparenchymal hemorrhage Rerupture of the aneurysm 1-12 3 Aljuboori et al 2020 47 Case report 1 N/A N/A 6 N/A Sorenson et al 2020 48 Case report 1 N/A Occlusion N/A N/A Ma et al 2021 49 Retrospective 53 N/A Hemorrhage 2 Ischemic events 6 12 N/A Lauzier et al 2021 31 Singel center study 8 Fusiform 6 Saccular 2 N/A 6-12 Cao et al 2023 50 Retrospective 151 N/A Hemorrhagic 5 Thromboembolic 12 Iodine contrast intoxication Reperfusion syndrome 12 6-24 20 Ten studies encompassing 120 distal MCA aneurysms were included in the primary analysis of complete occlusion following flow diversion. The pooled complete occlusion rate was 87% (101/120; 95% CI: 80%–93%), with no observed heterogeneity across studies (I² = 0.0%, τ² = 0, p = 0.7997) (Figure 1). Two studies (Ma et al., 2021, and Cao et al., 2023) were included on the basis of their focus on distal cerebral circulation aneurysms and small-caliber vessels, respectively, which encompassed M2 segment aneurysms. While these studies did not separate occlusion outcomes by specific aneurysm sites, multiple distal MCA cases were identified in procedural descriptions and figures, justifying inclusion in the pooled analysis. Upon sensitivity analysis excluding these two studies and limiting them to those explicitly reporting distal MCA-specific occlusion data, the pooled occlusion rate was 81% (48/61; 95% CI: 71%–91%), with similarly low heterogeneity (I² = 0.0%, p = 0.833). This finding indicates that the results remain consistent across different analytical approaches. To assess potential publication bias in the complete occlusion analysis, a funnel plot was constructed using the full set of 10 studies (including Ma et al., 2021, and Cao et al., 2023) (Figure 4). The distribution of studies appeared relatively symmetrical around the pooled effect estimate, with no clear evidence of small-study effects or selective reporting. This visual assessment revealed a low likelihood of publication bias in the available literature on flow diversion for distal MCA aneurysms. All included studies reported complications, with a total of 21 complications among 128 treated aneurysms, yielding a pooled complication rate of 14% (95% CI: 8%–21%) (Figure 5). Heterogeneity was again low (I² = 0.0%, τ² = 0, p = 0.8133). Individual study complication rates ranged from 0% to 26%. The most frequently reported complications included thromboembolic events, in-stent stenosis, and hemorrhagic complications. The funnel plot assessing publication bias for complications (Figure 4) revealed a relatively balanced distribution of studies, with no strong visual indication of small-study effects or publication bias. Discussion Flow diverter stents (FDSs) have revolutionized the treatment of intracranial aneurysms, yet their use in M2 segment aneurysms of the middle cerebral artery (MCA) remains poorly understood and controversial [10, 15]. The literature has focused primarily on the efficacy of FDSs for proximal aneurysms, such as those in the anterior circulation and the M1 segment of the MCA, leaving a significant gap regarding their applicability in smaller caliber vessels and distal bifurcations [23, 24]. This study distinguishes itself through a systematic and quantitative evaluation of occlusion rates and complications associated with FDS use in the M2 segment, providing novel data on the feasibility and safety of FDS use. This systematic review included 10 studies comprising a total of 120 patients diagnosed with MCA-M2 aneurysms who underwent treatment with FDSs. Our analysis of the available evidence revealed an overall complication rate of 14% (95% CI: 8%–21%) and an occlusion rate of 87% (101/120; 95% CI: 80%–93%). Flow diverter stents (FDSs) have revolutionized the treatment of intracranial aneurysms, yet their use in M2 segment aneurysms of the middle cerebral artery (MCA) remains poorly understood and controversial [10, 15]. The literature has focused primarily on the efficacy of FDSs for proximal aneurysms, such as those in the anterior circulation and the M1 segment of the MCA, leaving a significant gap regarding their applicability in smaller caliber vessels and distal bifurcations [23, 24]. Our study stands out by conducting a systematic and quantitative analysis of occlusion rates and complications associated with FDS use in the M2 segment, providing novel data on the feasibility and safety of FDS use. Regarding occlusion rates, as mentioned above, our findings demonstrated a high occlusion rate for the treatment of FDSs. This finding correlates with the recent analysis of pipeline embolization from Lauzier et al., which demonstrated an occlusion rate of 80.1% (40/49; 95% CI: 69.4% - 90.7%) [31]. Although endovascular treatment of distal vessel aneurysms is a potential therapeutic option for patients, technical issues must be considered to improve those numbers. In addition, similar results were obtained by Cagnazzo et al. in 2021, who reported an occlusion rate of 79%, showing efficacy and a large field for the practical introduction of FDSs [32]. Additionally, the occlusion rates of flow diverter stents are similar to those of other techniques. In a recent multicenter cohort study, Leo stents demonstrated an occlusion rate of 84.6% at follow-up, whereas other analyses revealed different outcomes, with occlusion rates of 66.7% in the anterior cerebral artery and 95.5% for wide-necked intracranial bifurcations [33-35]. Although only two new studies were added in this update, they contributed a disproportionately large number of patients (69 of 128 total), exceeding the combined sample size of the previous eight studies. This substantial expansion of the dataset provided a more precise estimate of occlusion and complication rates, allowing a more representative and statistically robust analysis of current outcomes. As such, this update offers important clinical insights that were not possible in earlier analyses, especially given the evolving use of flow diversion in small-caliber distal vessels. The findings from our meta-analysis provide a more specific and comprehensive evaluation of the safety and efficacy of flow diverter stents in treating distal MCA aneurysms. While the broader literature reports thromboembolic complications ranging from 4% to 10% in flow diversion and in-stent stenosis occurring in up to 50% of cases [36-37], our meta-analysis revealed a lower pooled complication rate of 14% (95% CI: 8%–21%), with individual study complication rates ranging from 0% to 26%. These findings suggest that although complications associated with flow diverters are well documented, their incidence in distal MCA aneurysms specifically may be lower than that in more proximal aneurysms. Our analysis also revealed a high pooled complete occlusion rate of 87% (95% CI: 80%–93%), indicating strong efficacy in treating these lesions. Sensitivity analysis further reinforced these results, revealing an occlusion rate of 81% (95% CI: 71%–91%) when focusing strictly on explicitly reported distal MCA-specific outcomes. This contrasts with the general literature, which often does not stratify outcomes by aneurysm location. Hemorrhagic complications, cited at rates as low as 1.5% in broader studies [38-39], were included among the complications reported in our analysis but were not the dominant adverse events. These findings highlight that while flow diversion remains associated with procedural risks, the safety profile of distal MCA aneurysms appears favorable, reinforcing its role as a viable treatment strategy in selecting patients. The LEO stent, a self-expanding braided device, has been utilized in the endovascular treatment of intracranial aneurysms, including those in distal cerebral arteries. Studies have reported initial complete occlusion rates ranging from 60.1% to 76%, with follow-up occlusion rates improving to 70%–84.6%, demonstrating the stent's flow-diverting effect [40-41]. In terms of safety, the reported permanent morbidity rate is approximately 2.8%, with a mortality rate of 0.8% and complications such as parent artery narrowing (10.5%) and side branch injury (6.8%) [41]. Long-term studies also reported a recanalization rate of 11.3% and a retreatment rate of 6.2% [42]. Compared with our meta-analysis, which reported a pooled complete occlusion rate of 87% for flow diverters in distal MCA aneurysms and a complication rate of 14%, the Leo stent has comparable occlusion rates, particularly over extended follow-up periods, while potentially having a lower overall complication rate. Nevertheless, the observed recanalization and retreatment rates underscore the need for vigilant long-term monitoring in aneurysm management. Stent-assisted coiling (SAC) is widely used for intracranial aneurysm treatment, with laser-cut and braided stents showing comparable thromboembolic event rates (4.33% vs. 5.05%, p = 0.288), in-stent stenosis rates (2.94% vs. 2.84%, p = 0.909), and mortality rates (1.22% vs. 1.12%, p = 0.868), although laser-cut stents had a higher deployment success rate (98.69% vs. 97.07%, p = 0.003) and a lower rate of periprocedural intracranial hemorrhage (1.13% vs. 1.85%, p = 0.048), whereas braided stents reduced permanent morbidity (1.58% vs. 2.92%, p = 0.015) (43). In ruptured wide-necked aneurysms, LVIS (braided) stents had a lower perioperative complication rate (5.6% vs. 14%, p = 0.028) and a lower intraprocedural rupture rate (0.7% vs. 6.5%, p = 0.016), although the incidence of ischemic complications was similar (2.1% vs. 6.5%, p = 0.161) [44]. Low-profile laser-cut stents were associated with thromboembolic events in 10.7% of the patients, with symptomatic ischemic stroke in 1.5%, and Y-stenting was identified as a potential risk factor (OR = 3.9, 95% CI: 1.0–16.5; p = 0.08) [45]. Compared with our meta-analysis on flow diverters for distal MCA aneurysms, which reported a complete occlusion rate of 87% and a complication rate of 14%, while stent-assisted techniques provide acceptable safety profiles, flow diversion remains a compelling alternative for specific cases because of its high occlusion rates. This study has several limitations. First, although our primary analysis included 10 studies, only eight of those studies explicitly reported occlusion outcomes, specifically for distal MCA aneurysms. Two studies (Ma et al., 2021; Cao et al., 2023) contributed substantially to the dataset but did not separate outcomes by precise aneurysm location. While these were included in the main analysis on the basis of their anatomical relevance and detailed procedural descriptions, this required the assumption that reported occlusion rates applied to the distal MCA subgroup, which may introduce bias. Second, clinical and anatomical heterogeneity across studies—such as variations in aneurysm size, morphology, flow diverter type, adjunctive coiling, and antiplatelet regimens—has not been consistently reported or stratified. This limits the ability to perform subgroup analyses and assess how these factors influence outcomes. Finally, follow-up durations varied between studies, and in some cases, the precise time points for imaging follow-up were not clearly defined. This may have impacted the comparability of occlusion and complication rates across studies. Conclusion The treatment of aneurysms located in distal vessels, especially in the M2 segment of the middle cerebral artery, is still lacking, but many techniques have shown potential in practice. Within this clinical context, flow diverter stents represent a potentially efficient and reliable therapeutic option. Thus, given the difficulty of treating this pathology, further well-designed studies are warranted to elucidate the definitive role of this technology. Abbreviations IA: Intracranial Aneurysm SAH: Subarachnoid Hemorrhage FDS: Flow Diverter Stent MCA: Middle Cerebral Artery mRS: Modified Rankin Scale MRA: Magnetic Resonance Angiography CTA: Computed Tomographic Angiography SAC: Stent-Assisted Coiling LVIS: Low-profile Visualized Intraluminal Support WEB: Woven EndoBridge Declarations Compliance with journal guidelines: This manuscript complies with all the author instructions provided by the journal. Authorship and approval: All authors meet the authorship criteria as per the ICMJE guidelines. The final version of the manuscript has been reviewed and approved by all the authors prior to submission. Originality statement: We confirm that this manuscript has not been published elsewhere and is not under consideration for publication in any other journal. Use of reporting checklist: This systematic review follows the PRISMA reporting guidelines to ensure methodological transparency and rigor. Conflict of interest (COI): The authors declare that they have no conflicts of interest related to this study. COI disclosure forms have been collected in accordance with ICMJE guidelines and are available upon request. Ethical considerations: As this study is a systematic review based on previously published data, it does not require ethical approval or informed consent. Funding statement: This study did not receive any financial support. References Zhou S, Dion PA, Rouleau GA. Genetics of intracranial aneurysms. Stroke. 2018;49(3):780-787. doi:10.1161/strokeaha.117.018152 Xu Z, Rui YN, Hagan JP, Kim DH. Intracranial aneurysms: pathology, genetics, and molecular mechanisms. NeuroMolecular Medicine. 2019;21(4):325-343. doi:10.1007/s12017-019-08537-7 Frączek MJ, Krzyżewski RM, Kliś KM, Kwinta BM, Popiela TJ, Stachura K. Unruptured intracranial aneurysms: Why should we focus on small aneurysms? A comprehensive update of recent findings. Polish Journal of Radiology. 2024;89:13-23. doi:10.5114/pjr.2024.134424 Diagbouga MR, Morel S, Bijlenga P, Kwak BR. Role of hemodynamics in initiation/growth of intracranial aneurysms. European Journal of Clinical Investigation. 2018;48(9). doi:10.1111/eci.12992 Rodriguez-Calienes A, Borjas-Calderón NF, Vivanco-Suarez J, et al. Endovascular Treatment and Microsurgical clipping for the Management of paraclinoid intracranial aneurysms: A Systematic Review and Meta-Analysis. World Neurosurgery. 2023;178:e489-e509. doi:10.1016/j.wneu.2023.07.108 Pflaeging M, Kabbasch C, Schlamann M, et al. Microsurgical Clipping versus Advanced Endovascular Treatment of Unruptured Middle Cerebral Artery Bifurcation Aneurysms After a “Coil-First” Policy. World Neurosurgery. 2021;149:e336-e344. doi:10.1016/j.wneu.2021.02.027 Kim JE, Xu R, Jackson CM, et al. Open microsurgical versus endovascular management of unruptured and ruptured brain aneurysms. Operative Neurosurgery. November 2024. doi:10.1227/ons.0000000000001448 Lee KS, Zhang JJY, Nguyen V, et al. The evolution of intracranial aneurysm treatment techniques and future directions. Neurosurgical Review. 2021;45(1):1-25. doi:10.1007/s10143-021-01543-z Alghamdi F, Morais R, Scillia P, Lubicz B. The Silk flow-diverter stent for endovascular treatment of intracranial aneurysms. Expert Review of Medical Devices. 2015;12(6):753-762. doi:10.1586/17434440.2015.1093413 Al-Mufti F, Amuluru K, Gandhi CD, Prestigiacomo CJ. Flow diversion for Intracranial Aneurysm Management: a new standard of care. Neurotherapeutics. 2016;13(3):582-589. doi:10.1007/s13311-016-0436-4 Chua MMJ, Silveira L, Moore J, Pereira VM, Thomas AJ, Dmytriw AA. Flow diversion for treatment of intracranial aneurysms: Mechanism and implications. Annals of Neurology. 2019;85(6):793-800. doi:10.1002/ana.25484 Ravindran K, Casabella AM, Cebral J, Brinjikji W, Kallmes DF, Kadirvel R. Mechanism of action and biology of flow diverters in the treatment of intracranial aneurysms. Neurosurgery. 2019;86(Supplement_1):S13-S19. doi:10.1093/neuros/nyz324 Chancellor B, Raz E, Shapiro M, et al. Flow diversion for Intracranial Aneurysm treatment: Trials involving flow diverters and Long-Term Outcomes. Neurosurgery. 2019;86(Supplement_1):S36-S45. doi:10.1093/neuros/nyz345 Feng SW, Luo CB, Lee CH, Chang FC, Lin CJ. Flow-diverter stent to manage intracranial aneurysms: A single center experience. Journal of the Chinese Medical Association. 2021;85(3):358-363. doi:10.1097/jcma.0000000000000619 Bhogal P, Henkes E, Schob S, et al. The use of flow diverters to treat small (≤5 mm) ruptured, saccular aneurysms. Surgical Neurology International. 2018;9(1):216. doi:10.4103/sni.sni_243_18 Liu J, Cao F, Zhenmei N, et al. Flow-diverter stents in intracranial aneurysm treatment: impact on covered cerebral artery branches. International Journal of Surgery. October 2023. doi:10.1097/js9.0000000000000762 Zhou G, Su M, Yin YL, Li MH. Complications associated with the use of flow-diverting devices for cerebral aneurysms: a systematic review and meta-analysis. Neurosurgical FOCUS. 2017;42(6):E17. doi:10.3171/2017.3.focus16450 Touzé R, Gravellier B, Rolla-Bigliani C, et al. Occlusion rate and visual complications with Flow-Diverter stent placed across the ophthalmic artery’s origin for Carotid-Ophthalmic aneurysms: A Meta-Analysis. Neurosurgery. 2019;86(4):455-463. doi:10.1093/neuros/nyz202 Wilson MP, Murad MH, Krings T, et al. Management of tandem occlusions in acute ischemic stroke – intracranial versus extracranial first and extracranial stenting versus angioplasty alone: a systematic review and meta-analysis. Journal of NeuroInterventional Surgery. 2018;10(8):721-728. doi:10.1136/neurintsurg-2017-013707 Fargen KM, Soriano-Baron HE, Rushing JT, et al. A survey of intracranial aneurysm treatment practices among United States physicians. Journal of NeuroInterventional Surgery. 2017;10(1):44-49. doi:10.1136/neurintsurg-2016-012808 Zhao J, Lin H, Summers R, Yang M, Cousins BG, Tsui J. Current treatment strategies for intracranial aneurysms: An overview. Angiology. 2017;69(1):17-30. doi:10.1177/0003319717700503 Cho SH, Jo WI, Jo YE, Yang KH, Park JC, Lee DH. Bench-top comparison of physical properties of 4 Commercially Available Self-Expanding intracranial stents. Neurointervention. 2017;12(1):31-39. doi:10.5469/neuroint.2017.12.1.31 Aydin K, Arat A, Sencer S, Barburoglu M, Men S. Stent-Assisted Coiling of Wide-Neck Intracranial aneurysms using Low-Profile LEO Baby stents: Initial and midterm results. American Journal of Neuroradiology. 2015;36(10):1934-1941. doi:10.3174/ajnr.a4355 Sorenson T, Brinjikji W, Lanzino G. Newer endovascular tools: a review of experimental and clinical aspects. J Neurosurg Sci. 2016;60(1):116-125. Sweid A, Starke RM, Herial N, et al. Flow diversion for small caliber vessel aneurysms: efficacy, safety, and functional outcome. Journal of Neurosurgical Sciences. 2020;63(6). doi:10.23736/s0390-5616.19.04734-9 Pierot L, Spelle L, Berge J, et al. Feasibility, complications, morbidity, and mortality results at 6 months for aneurysm treatment with the Flow Re-Direction Endoluminal Device: report of SAFE study. Journal of NeuroInterventional Surgery. 2018;10(8):765-770. doi:10.1136/neurintsurg-2017-013559 Möhlenbruch MA, Herweh C, Jestaedt L, et al. The FRED Flow-Diverter Stent for intracranial aneurysms: Clinical Study to assess safety and efficacy. American Journal of Neuroradiology. 2015;36(6):1155-1161. doi:10.3174/ajnr.a4251 Raymond J, Gentric JC, Darsaut TE, et al. Flow diversion in the treatment of aneurysms: a randomized care trial and registry. Journal of Neurosurgery. 2016;127(3):454-462. doi:10.3171/2016.4.jns152662 Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021;134:178-189. doi: 10.1016/j.jclinepi.2021.03.001 Sterne J A, Hernán M A, Reeves B C, Savović J, Berkman N D, Viswanathan M et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions BMJ 2016; 355 :i4919 doi:10.1136/bmj.i4919 Lauzier DC, Root BK, Yasha Kayan, Delgado E, Osbun JW, Chatterjee AR, et al. Pipeline embolization of MCA aneurysms in the M2-M4 segment: Dual center study and meta-analysis. Clinical Neurology and Neurosurgery. 2021 Nov 24;212:107063–3. Cagnazzo, F., Fanti, A., Lefevre, P. H., Derraz, I., Dargazanli, C., Gascou, G., Riquelme, C., Ahmed, R., Bonafe, A., & Costalat, V. (2021). Distal anterior cerebral artery aneurysms treated with flow diversion: experience of a large-volume center and systematic review of the literature. Journal of neurointerventional surgery, 13(1), 42–48. https://doi.org/10.1136/neurintsurg-2020-015980 Duan, Y., Xu, B., Qin, X., Mao, R., Hu, Y., Zhou, B., Li, J., & Chen, G. (2022). Flow diversion effect of the leo braided stent for aneurysms in the posterior and distal anterior circulations: A multicenter cohort study. Frontiers in neurology, 13, 957709. https://doi.org/10.3389/fneur.2022.957709 Zhang, G., Shen, Y., Ni, H., Jia, Z., Liu, X., Wang, B., Lu, G., Shi, H., Zhao, L., & Liu, S. (2025). Safety and efficacy of stent-assisted coiling of unruptured distal anterior cerebral artery aneurysms with low-profile braided stents. Clinical radiology, 84, 106848. Advance online publication. https://doi.org/10.1016/j.crad.2025.106848 Suleyman, K., Korkmazer, B., Kocer, N., Islak, C., & Kızılkılıc, O. (2023). Evaluation of short- and long-term results of Y-stent-assisted coiling with Leo stents in endovascular treatment of wide-necked intracranial bifurcation aneurysms. Neuroradiology, 65(4), 785–791. https://doi.org/10.1007/s00234-023-03116-x Dowlati E, Pasko KBD, Liu J, Miller CA, Felbaum DR, Sur S, et al. Treatment of In-Stent Stenosis Following Flow Diversion of Intracranial Aneurysms with Cilostazol and Clopidogrel. Neurointervention. 2021 Sep 10; Georgi Vladev, Sirakov A, Svetozar Matanov, Sirakova K, Ninov K, Stanimir Sirakov. An increase in flow-diverter oversizing values as an independent risk factor for developing more severe in-stent stenosis. A retrospective single-center study based on flow diversion of supraclinoid internal carotid artery aneurysms. Frontiers in Neurology. 2025 Jan 8;15. Efe Soydemir, Cemal Aydın Gündoğmuş, Derya Türeli, Nurten Andaç Baltacıoğlu, Yaşar Bayri, Feyyaz Baltacıoğlu. Safety and efficacy of flow diverter stents in the treatment of middle cerebral artery aneurysms: a single-center experience and follow-up data. Diagnostic and Interventional Radiology [Internet]. 2023 Jan 13;29(2):350–8. Available from: https://pubmed.ncbi.nlm.nih.gov/36988000/ Enriquez-Marulanda A, Young MM, Taussky P. Flow diversion: a disruptive technology coming of age. Lessons learned and challenges for the future. Journal of Neurosurgery [Internet]. 2023 Apr 28;139(5):1317–27. Available from: https://thejns.org/view/journals/j-neurosurg/139/5/article-p1317.xml Lubicz, B., Kadou, A., Morais, R., & Mine, B. (2017). Leo stent for endovascular treatment of intracranial aneurysms: very long-term results in 50 patients with 52 aneurysms and literature review. Neuroradiology , 59 (3), 271–276. https://doi.org/10.1007/s00234-017-1805-3 Duan Y, Xu B, Qin X, Mao R, Hu Y, Zhou B, et al. Flow diversion effect of the leo braided stent for aneurysms in the posterior and distal anterior circulations: A multicenter cohort study. Frontiers in neurology [Internet]. 2022;13:957709. Available from: https://pubmed.ncbi.nlm.nih.gov/36237608/ Pumar JM, Sucasas P, Mosqueira A, Vega P, Murias E. Five-Years Angiographic Follow-Up of Wide-Neck Intracranial Aneurysms Treated With LEO Plus Stent. Front Neurol. 2021 Nov 26;12:744962. doi: 10.3389/fneur.2021.744962. PMID: 34899568; PMCID: PMC8661051. Zhang L, Chen X, Dong L, Liu P, Jia L, Zhang Y, et al. Clinical and Angiographic Outcomes After Stent-Assisted Coiling of Cerebral Aneurysms With Laser-Cut and Braided Stents: A Comparative Analysis of the Literatures. Frontiers in Neurology. 2021 Apr 29;12. Xue G, Zuo Q, Zhang X, Tang H, Zhao R, Li Q, et al. Safety and efficacy of stent-assisted coiling for acutely ruptured wide-necked intracranial aneurysms: comparison of LVIS stents with laser-cut stents. Chinese Neurosurgical Journal. 2021 Mar 3;7(1). Goertz L, Smyk MA, Siebert E, Turowski B, Borggrefe J, Mpotsaris A, et al. Low-Profile Laser-Cut Stents for Endovascular Treatment of Intracranial Aneurysms : Incidence, Clinical Presentation and Risk Factors of Thromboembolic Events. Clinical neuroradiology [Internet]. 2021 Mar;31(1):107–15. Available from: https://pubmed.ncbi.nlm.nih.gov/31970465/ Yavuz K, Serdar Geyik, Isil Saatci, Saruhan Cekirge. Endovascular Treatment of Middle Cerebral Artery Aneurysms with Flow Modification with the Use of the Pipeline Embolization Device. 2014 Mar 1;35(3):529–35. ‌Zanaty M, Chalouhi N, Tjoumakaris SI, Gonzalez LF, Rosenwasser R, Jabbour P. Flow diversion for complex middle cerebral artery aneurysms. Neuroradiology. 2014 Feb 18;56(5):381–7. ‌Durst CR, Hixson HR, Schmitt P, Gingras JM, Crowley RW. Endovascular Treatment of a Fusiform Aneurysm at the M3-M4 Junction of the Middle Cerebral Artery Using the Pipeline Embolization Device. World Neurosurgery. 2016 Feb;86:511.e1–4. ‌Primiani CT, Ren Z, Kan P, et al. J NeuroIntervent Surg 2019;11:903–907. Cimflova P, Özlük E, Korkmazer B, et al. J NeuroIntervent Surg 2021;13:631–636. Aljuboori Z, Meyer K, Ding D, James R. Endovascular Treatment of a Traumatic Middle Cerebral Artery Pseudoaneurysm with the Pipeline Flex Embolization Device. World Neurosurgery. 2020 Jan;133:201–4. ‌Sorenson TJ, Klein JP, Rangel-Castilla L, Lanzino G. Flow Diversion of an Incompletely-Treated Fusiform Middle Cerebral Artery Aneurysm: 2-Dimensional Operative Video. Operative Neurosurgery. 2019 Aug 2;18(4):E125–6. ‌Ma C, Zhu H, Liang S, Liang F, Han J, Jia Z, et al. Pipeline for the treatment of distal cerebral circulation aneurysms: A multicenter study focusing on periprocedural Complications. Interventional neuroradiology. 2021 Dec 16;28(6):708–18. ‌Cao R, Mattar A, Torche E, Riva R, Laubacher M, Moreno-Gomez R, et al. Clinical and angiographic characteristics of ruptured and unruptured distal cerebral aneurysms: a review of a large series of cases in a high-volume center. Journal of NeuroInterventional Surgery. 2024 Mar 5;jnis-021164. Lauzier DC, Root BK, Yasha Kayan, Delgado E, Osbun JW, Chatterjee AR, et al. Pipeline embolization of MCA aneurysms in the M2-M4 segment: Dual center study and meta-analysis. Clinical Neurology and Neurosurgery. 2021 Nov 24;212:107063–3. Additional Declarations No competing interests reported. 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01:08:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6542820/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6542820/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83319605,"identity":"db0c67f1-5c47-4101-b0cf-50a9d7c8eeba","added_by":"auto","created_at":"2025-05-23 03:10:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":274319,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram for study selection.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6542820/v1/a2587b879f581a77bf7a420d.png"},{"id":83319610,"identity":"8f43027b-c21f-4bd5-b0ff-07ac5f07953a","added_by":"auto","created_at":"2025-05-23 03:10:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":277533,"visible":true,"origin":"","legend":"\u003cp\u003eROBINS-I summary results.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6542820/v1/9c8d6f3885f4070951fca8a8.png"},{"id":83319606,"identity":"18be7a6b-2020-4d06-90d6-a250de7a17dd","added_by":"auto","created_at":"2025-05-23 03:10:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":256925,"visible":true,"origin":"","legend":"\u003cp\u003eProportional analysis for complete occlusion.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6542820/v1/e05db1baaa13e8a3eacf46cd.png"},{"id":83319607,"identity":"7fbdcb26-e9fb-4393-bc8f-44aac252bf80","added_by":"auto","created_at":"2025-05-23 03:10:50","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":56752,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot for complete occlusion.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6542820/v1/26c50052b2285f06f88a790c.png"},{"id":83319726,"identity":"ba64c098-0443-430a-8b2b-7160cf82c4c0","added_by":"auto","created_at":"2025-05-23 03:18:50","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":253574,"visible":true,"origin":"","legend":"\u003cp\u003eProportional analysis of complications.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6542820/v1/ef4e045e329c2486eda92d0e.png"},{"id":83320618,"identity":"237c5b4c-031f-47f6-9add-c212d7050116","added_by":"auto","created_at":"2025-05-23 03:42:50","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":41783,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot for complications\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6542820/v1/14929b047e471d2eeff4ebf8.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Role of Flow Diverter Stents in Treating Distal Middle Cerebral Artery Aneurysms: A Systematic Review and Meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIntracranial aneurysms (IAs) are focal dilatations of cerebral arteries that predominantly arise within the circle of Willis [1,2]. IA affects approximately 2\u0026ndash;5% of the adult population and represents a significant public health issue because of its potential for rupture, which may result in subarachnoid hemorrhage (SAH) [2,3]. The pathogenesis of IAs involves maladaptive vascular remodeling triggered by hemodynamic stress and inflammatory responses [1,4]. Diagnosis typically involves imaging techniques such as magnetic resonance angiography (MRA) or computerized tomographic angiography (CTA) [1]. Management of unruptured IAs requires a careful balance between the risk of rupture and the procedural risks, with reported treatment-associated mortality and morbidity rates reaching up to 5% [3].\u003c/p\u003e\n\u003cp\u003eMicrosurgical clipping and endovascular treatment are the primary approaches for managing IAs. Compared with endovascular techniques, clipping generally results in higher rates of complete occlusion and lower recurrence rates [5,6]. However, endovascular treatments are associated with lower periprocedural morbidity and better functional outcomes [5,7]. The choice between these modalities depends on factors such as aneurysm location, morphology, patient characteristics, and surgeon experience [8]. For middle cerebral artery aneurysms, clipping remains the standard treatment, although endovascular approaches are viable alternatives [6]. The field of IA treatment is rapidly evolving, with new endovascular techniques, such as flow diversion stent (FDS) and intrasaccular flow disruption. In complex cases, a combination of microsurgical and endovascular techniques may be necessary [8].\u003c/p\u003e\n\u003cp\u003eFDS has emerged as a revolutionary treatment for complex IAs, particularly those challenging conventional endovascular techniques [9,10]. FDS functions by altering hemodynamics, redirecting blood flow away from the aneurysm and along the parent vessel [11,12]. This flow modification induces gradual intra-aneurysmal thrombosis and promotes reendothelialization across the aneurysm neck [9,12]. The low porosity and high metal coverage of FDS are key properties enabling this mechanism [9]. Unlike traditional techniques that target the aneurysm sac, FDSs are implanted in the parent artery, representing a paradigm shift in IA treatment [9,10]. FDS has demonstrated favorable safety profiles with low complication rates compared with alternative treatments [13]. While FDSs have shown promise in treating complex IAs, they carry risks such as in-stent thrombosis and delayed hemorrhages. Nonetheless, FDS has become a new standard of care for\u0026nbsp;selected IAs [10].\u003c/p\u003e\n\u003cp\u003eFDS is an effective treatment for intracranial aneurysms, particularly for small and complex cases. Studies have shown comparable occlusion rates and safety profiles for FDS use in small-caliber arteries (\u0026le;2.5 mm) to those in larger vessels, with complete occlusion rates of 73.6% at the 12.1-month follow-up. FDS has demonstrated efficacy in treating unruptured aneurysms, with 78% complete obliteration at 13 months\u0026nbsp;and better outcomes for smaller aneurysms (\u0026lt;7 mm) [14]. Limited evidence suggests that FDS may be feasible for small (\u0026le;5 mm) ruptured aneurysms, achieving 100% occlusion in a small cohort [15]. However, complications can occur, including periprocedural, immediate postprocedural, and delayed events [10].\u003c/p\u003e\n\u003cp\u003eA previous study reported high aneurysm obliteration rates (\u0026gt;70%) and good clinical outcomes (97.4%) when various cerebral arteries were covered [16]. However, complications can occur, with an overall rate of 17% and neurological morbidity of 4.5% [17]. For carotid-ophthalmic aneurysms, FDSs achieve an 85% occlusion rate with only a 3% risk of new visual symptoms [18]. In tandem occlusions, nearly half of patients treated with mechanical thrombectomy have good neurological outcomes, with no significant differences between extracranial and intracranial approaches or between stenting and angioplasty [19]. Common FDSs include Pipeline and Silk, which have similar complication rates [17]. While effective, the risk of complications should be considered when deciding on FDS treatment.\u003c/p\u003e\n\u003cp\u003eRecent studies have indicated that endovascular treatment is the preferred first-line approach for most ruptured and unruptured aneurysms, although microsurgical clipping remains favored for middle cerebral artery (MCA) aneurysms [20]. Treatment options have evolved to include traditional methods such as clipping and coiling, as well as newer techniques such as stent-assisted coiling and flow diversion [21]. The LEO stent, a braided self-expanding device, has shown promising results in treating wide-neck intracranial aneurysms. Compared with laser-cut stents, it offers greater metal coverage (14%) and radial force [22]. Clinical studies have demonstrated high technical success rates (97.5%) and favorable occlusion outcomes with LEO Baby stents, with complete occlusion observed in 85.7% of cases at follow-up [23]. Flow diverters are becoming the treatment of choice for large and complex internal carotid artery aneurysms [24]. Emerging technologies such as intrasaccular flow diverters (e.g., WEB devices) show promise for wide-neck bifurcation aneurysms [8]. Treatment decisions are based on factors such as patient characteristics, aneurysm features, and operator experience. While guidelines exist, there is considerable variability in patient selection, treatment strategies, and follow-up protocols among physicians [20]. Ongoing research and technological advancements continue to shape the landscape of intracranial aneurysm treatment.\u003c/p\u003e\n\u003cp\u003eStudies have shown comparable safety and efficacy between FDS use in small- and large-calibrer vessels, with similar complication and occlusion rates [25]. The FRED device demonstrated low morbidity (2.0%) and mortality (1.0%) rates in a prospective study, whereas another study reported technical success in all patients with the same device [26,27]. However, the FIAT trial raised safety concerns, reporting death or dependency in 16% of patients treated with flow diversion [28]. Despite these mixed results, FDS has shown promise in treating diverse aneurysm types, including those in distal locations where other options pose a considerable risk [28]. More randomized trials are needed to definitively establish the role of flow diversion in aneurysm management [28].\u003c/p\u003e\n\u003cp\u003eThe primary objective of this study was to systematically evaluate the efficacy and safety of FDSs in the treatment of distal MCA aneurysms, particularly those located in the M2 segment. Given the limited and conflicting evidence regarding the use of FDSs in distal intracranial vessels, this review aims to assess whether these stents offer a viable alternative to conventional treatment modalities, including microsurgical clipping, coiling, and balloon-assisted techniques. Additionally, this study compared the clinical and radiographic outcomes between FDSs and standard endovascular interventions, focusing on aneurysm occlusion rates, complication profiles, and long-term vascular remodeling. Special attention is given to the role of laser stents (e.g., Leo stent) and adjunctive balloon-assisted strategies to determine their potential in optimizing endovascular outcomes. By synthesizing available data through a systematic review and meta-analysis, this research seeks to bridge the existing knowledge gap and provide evidence-based insights into the feasibility of FDS for distal MCA aneurysm management, ultimately guiding future clinical decision-making and interventional strategies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSearch strategy\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis review followed the guidelines set by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [29], available in \u003cstrong\u003eFigure 1\u003c/strong\u003e.\u0026nbsp;A comprehensive search was performed across major databases, including PubMed (n = 119), Web of Science (n = 74), and Embase (n = 81), to identify relevant studies published up until 2025. Our search strategy utilized the following terms: flow diverter stent, flow diversion, MCA, middle cerebral artery, and M2.\u0026nbsp;Four authors independently and collaboratively conducted the study selection, data extraction, and quality assessment\u0026nbsp;(KW, RZ, GLS, PHK) on the basis of predefined criteria.\u0026nbsp;(\u003cstrong\u003eThis study was prospectively registered under the registration number CRD420251016691\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy selection - Inclusion and exclusion criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEligibility for inclusion required studies to meet predefined criteria. First, they needed to focus on the treatment of distal vessel aneurysms with a flow diverter stent or flow diversion as the primary treatment rather than other treatments, such as stent-assisted coiling, coiling alone, microsurgical clipping, and intrasaccular devices. Second, the studies had to provide data related to the aneurysm occlusion rate, procedural success rates, complication rates, functional outcomes (modified Rankin score (mRS)) and long-term durability of flow diversion. Studies that did not meet these requirements were excluded. These studies included studies that lacked clearly defined occlusion rates, procedural success, functional status, and complications. Additionally, studies focusing on patients under eighteen years of age, letters, comments, or reviews were excluded. Studies lacking full-text access or involving overlapping patient cohorts were also excluded.\u003c/p\u003e\n\u003cp\u003eStudies that did not offer comprehensive outcome data were also excluded. In cases where patient cohorts overlapped from the same institution or database during the same period and involved at least one patient with similar procedural or baseline characteristics, priority was given to the more recent study or the study that presented data on the primary outcome.\u003c/p\u003e\n\u003cp\u003eThis study is an updated systematic review and meta-analysis built upon prior literature on flow diversion for distal MCA aneurysms. Two new studies published after the previous review were identified and included. These two studies contributed to the inclusion of 69 additional patients\u0026mdash;59 patients from the first eight studies\u0026mdash;thereby increasing the power and relevance of the pooled analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData extraction\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the analysis, the integrity of the data was maintained by thoroughly reviewing textual content, tables, images, and supplementary materials. Data extraction was carried out by two authors (KB, KW), each of whom focused on different aspects of the data. These aspects included publication details such as the first author, year of publication, and study design, as well as the baseline characteristics of the patients, including the number of patients, age, sex, complications, follow-up duration, complication rates, functional status, and success rates, along with any other relevant data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eQuality assessment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA bias assessment was conducted via the ROBINS-I tool [30] to evaluate the quality of the cohort studies included in the meta-analysis. This tool was used to identify potential concerns in the design and reporting of the included studies rather than serving as a criterion for inclusion. The decision to use this approach was based on the inherently high risk of bias in observational studies of exposures, in line with the guidelines provided by the tool. A summary of the results from the bias assessment is shown in \u003cstrong\u003eFigure 2.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the statistical analyses were performed via R (version 4.4.2, R Foundation for Statistical Computing, Vienna, Austria). Proportional meta-analyses were conducted with a random effects model to estimate pooled rates for complete occlusion and complications. Heterogeneity was assessed via I\u0026sup2; statistics, and funnel plots were generated to evaluate publication bias.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA summary of information regarding the included studies, including study type, number of patients/aneurysms, aneurysm morphology, complication type, follow-up duration in months, and number of recurrences/retreatments, is shown in Table 1.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 1.\u003c/strong\u003e Summary of information from the included studies.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"602\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003eReference number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eStudy Type (Retrospective or prospective, and study design)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003eNo. of Patients/No. of aneurysms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eAneurysm morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eComplication Type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003eFollow up Duration (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003eRecurrence and Retreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eYavuz et al 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e3-30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eZanaty et al 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e\u0026nbsp;43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eRetrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eFusiform 70%\u003c/p\u003e\n \u003cp\u003eSaccular 30%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e7-12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eDurst et al 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eCase report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eFusiform\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003ePrimiani et al 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eRetrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eSaccular 38 Fusiform 19\u003c/p\u003e\n \u003cp\u003eDissecting 8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eCimflova et al 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e\u0026nbsp;46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eRetrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eSaccular 2\u003c/p\u003e\n \u003cp\u003eSacculofusiform 8\u003c/p\u003e\n \u003cp\u003eFusiform 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eIntraparenchymal hemorrhage\u003c/p\u003e\n \u003cp\u003eRerupture of the aneurysm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e1-12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eAljuboori et al 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e\u0026nbsp;47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eCase report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eSorenson et al 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eCase report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eOcclusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eMa et al 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eRetrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eHemorrhage 2\u003c/p\u003e\n \u003cp\u003eIschemic events 6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eLauzier et al 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e\u0026nbsp;31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eSingel center study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eFusiform 6\u003c/p\u003e\n \u003cp\u003eSaccular 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e6-12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1498%;\"\u003e\n \u003cp\u003eCao et al 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4825%;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.1431%;\"\u003e\n \u003cp\u003eRetrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9817%;\"\u003e\n \u003cp\u003e151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.807%;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6389%;\"\u003e\n \u003cp\u003eHemorrhagic 5\u003c/p\u003e\n \u003cp\u003eThromboembolic 12\u003c/p\u003e\n \u003cp\u003eIodine contrast intoxication\u003c/p\u003e\n \u003cp\u003eReperfusion syndrome 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.65058%;\"\u003e\n \u003cp\u003e6-24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1464%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTen studies encompassing 120 distal MCA aneurysms were included in the primary analysis\u0026nbsp;of complete occlusion following flow diversion. The pooled complete occlusion rate was 87% (101/120; 95% CI: 80%\u0026ndash;93%), with no observed heterogeneity across studies (I\u0026sup2; = 0.0%, \u0026tau;\u0026sup2; = 0, p = 0.7997) (Figure 1).\u003c/p\u003e\n\u003cp\u003eTwo studies (Ma et al., 2021, and Cao et al., 2023) were included on the basis of their focus on distal cerebral circulation aneurysms and small-caliber vessels, respectively, which encompassed M2 segment aneurysms. While these studies did not separate occlusion outcomes by specific aneurysm sites, multiple distal MCA cases were identified in procedural descriptions and figures, justifying inclusion in the pooled analysis.\u003c/p\u003e\n\u003cp\u003eUpon sensitivity analysis excluding these two studies and limiting them to those explicitly reporting distal MCA-specific occlusion data, the pooled occlusion rate was 81% (48/61; 95% CI: 71%\u0026ndash;91%), with similarly low heterogeneity (I\u0026sup2; = 0.0%, p = 0.833). This finding indicates that the results remain consistent across different analytical approaches.\u003c/p\u003e\n\u003cp\u003eTo assess potential publication bias in the complete occlusion analysis, a funnel plot was constructed using the full set of 10 studies (including Ma et al., 2021, and Cao et al., 2023) (Figure 4). The distribution of studies appeared relatively symmetrical around the pooled effect estimate, with no clear evidence of small-study effects or selective reporting. This visual assessment revealed a low likelihood of publication bias in the available literature on flow diversion for distal MCA aneurysms.\u003c/p\u003e\n\u003cp\u003eAll included studies reported complications, with a total of 21 complications among 128 treated aneurysms, yielding a pooled complication rate of 14% (95% CI: 8%\u0026ndash;21%) (Figure 5). Heterogeneity was again low (I\u0026sup2; = 0.0%, \u0026tau;\u0026sup2; = 0, p = 0.8133). Individual study complication rates ranged from 0% to 26%. The most frequently reported complications included thromboembolic events, in-stent stenosis, and hemorrhagic complications.\u003c/p\u003e\n\u003cp\u003eThe funnel plot assessing publication bias for complications (Figure 4) revealed a relatively balanced distribution of studies, with no strong visual indication of small-study effects or publication bias.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFlow diverter stents (FDSs) have revolutionized the treatment of intracranial aneurysms, yet their use in M2 segment aneurysms of the middle cerebral artery (MCA) remains poorly understood and controversial [10, 15]. The literature has focused primarily on the efficacy of FDSs for proximal aneurysms, such as those in the anterior circulation and the M1 segment of the MCA, leaving a significant gap regarding their applicability in smaller caliber vessels and distal bifurcations [23, 24]. This study distinguishes itself through a systematic and quantitative evaluation of occlusion rates and complications associated with FDS use in the M2 segment, providing novel data on the feasibility and safety of FDS use. This systematic review included 10 studies comprising a total of 120 patients diagnosed with MCA-M2 aneurysms who underwent treatment with FDSs. Our analysis of the available evidence revealed an overall complication rate of 14% (95% CI: 8%\u0026ndash;21%) and an occlusion rate of 87% (101/120; 95% CI: 80%\u0026ndash;93%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFlow diverter stents (FDSs) have revolutionized the treatment of intracranial aneurysms, yet their use in M2 segment aneurysms of the middle cerebral artery (MCA) remains poorly understood and controversial [10, 15]. The literature has focused primarily on the efficacy of FDSs for proximal aneurysms, such as those in the anterior circulation and the M1 segment of the MCA, leaving a significant gap regarding their applicability in smaller caliber vessels and distal bifurcations [23, 24]. Our study stands out by conducting a systematic and quantitative analysis of occlusion rates and complications associated with FDS use in the M2 segment, providing novel data on the feasibility and safety of FDS use.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding occlusion rates, as mentioned above, our findings demonstrated a high occlusion rate for the treatment of FDSs. This finding correlates with the recent analysis of pipeline embolization from Lauzier et al., which demonstrated an occlusion rate of 80.1% (40/49; 95% CI: 69.4% - 90.7%) [31]. Although endovascular treatment of distal vessel aneurysms is a potential therapeutic option for patients, technical issues must be considered to improve those numbers. In addition, similar results were obtained by Cagnazzo et al. in 2021, who reported an occlusion rate of 79%, showing efficacy and a large field for the practical introduction of FDSs [32]. Additionally, the occlusion rates of flow diverter stents are similar to those of other techniques. In a recent multicenter cohort study, Leo stents demonstrated an occlusion rate of 84.6% at follow-up, whereas other analyses revealed different outcomes, with occlusion rates of 66.7% in the anterior cerebral artery and 95.5% for wide-necked intracranial bifurcations [33-35].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough only two new studies were added in this update, they contributed a disproportionately large number of patients (69 of 128 total), exceeding the combined sample size of the previous eight studies. This substantial expansion of the dataset provided a more precise estimate of occlusion and complication rates, allowing a more representative and statistically robust analysis of current outcomes. As such, this update offers important clinical insights that were not possible in earlier analyses, especially given the evolving use of flow diversion in small-caliber distal vessels.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe findings from our meta-analysis provide a more specific and comprehensive evaluation of the safety and efficacy of flow diverter stents in treating distal MCA aneurysms. While the broader literature reports thromboembolic complications ranging from 4% to 10% in flow diversion and in-stent stenosis occurring in up to 50% of cases [36-37], our meta-analysis revealed a lower pooled complication rate of 14% (95% CI: 8%\u0026ndash;21%), with individual study complication rates ranging from 0% to 26%. These findings suggest that although complications associated with flow diverters are well documented, their incidence in distal MCA aneurysms specifically may be lower than that in more proximal aneurysms. Our analysis also revealed a high pooled complete occlusion rate of 87% (95% CI: 80%\u0026ndash;93%), indicating strong efficacy in treating these lesions. Sensitivity analysis further reinforced these results, revealing an occlusion rate of 81% (95% CI: 71%\u0026ndash;91%) when focusing strictly on explicitly reported distal MCA-specific outcomes. This contrasts with the general literature, which often does not stratify outcomes by aneurysm location. Hemorrhagic complications, cited at rates as low as 1.5% in broader studies [38-39], were included among the complications reported in our analysis but were not the dominant adverse events. These findings highlight that while flow diversion remains associated with procedural risks, the safety profile of distal MCA aneurysms appears favorable, reinforcing its role as a viable treatment strategy in selecting patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe LEO stent, a self-expanding braided device, has been utilized in the endovascular treatment of intracranial aneurysms, including those in distal cerebral arteries. Studies have reported initial complete occlusion rates ranging from 60.1% to 76%, with follow-up occlusion rates improving to 70%\u0026ndash;84.6%, demonstrating the stent\u0026apos;s flow-diverting effect [40-41]. In terms of safety, the reported permanent morbidity rate is approximately 2.8%, with a mortality rate of 0.8% and complications such as parent artery narrowing (10.5%) and side branch injury (6.8%) [41]. Long-term studies also reported a recanalization rate of 11.3% and a retreatment rate of 6.2% [42]. Compared with our meta-analysis, which reported a pooled complete occlusion rate of 87% for flow diverters in distal MCA aneurysms and a complication rate of 14%, the Leo stent has comparable occlusion rates, particularly over extended follow-up periods, while potentially having a lower overall complication rate. Nevertheless, the observed recanalization and retreatment rates underscore the need for vigilant long-term monitoring in aneurysm management.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStent-assisted coiling (SAC) is widely used for intracranial aneurysm treatment, with laser-cut and braided stents showing comparable thromboembolic event rates (4.33% vs. 5.05%, p = 0.288), in-stent stenosis rates (2.94% vs. 2.84%, p = 0.909), and mortality rates (1.22% vs. 1.12%, p = 0.868), although laser-cut stents had a higher deployment success rate (98.69% vs. 97.07%, p = 0.003) and a lower rate of periprocedural intracranial hemorrhage (1.13% vs. 1.85%, p = 0.048), whereas braided stents reduced permanent morbidity (1.58% vs. 2.92%, p = 0.015) (43). In ruptured wide-necked aneurysms, LVIS (braided) stents had a lower perioperative complication rate (5.6% vs. 14%, p = 0.028) and a lower intraprocedural rupture rate (0.7% vs. 6.5%, p = 0.016), although the incidence of ischemic complications was similar (2.1% vs. 6.5%, p = 0.161) [44]. Low-profile laser-cut stents were associated with thromboembolic events in 10.7% of the patients, with symptomatic ischemic stroke in 1.5%, and Y-stenting was identified as a potential risk factor (OR = 3.9, 95% CI: 1.0\u0026ndash;16.5; p = 0.08) [45]. Compared with our meta-analysis on flow diverters for distal MCA aneurysms, which reported a complete occlusion rate of 87% and a complication rate of 14%, while stent-assisted techniques provide acceptable safety profiles, flow diversion remains a compelling alternative for specific cases because of its high occlusion rates.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, although our primary analysis included 10 studies, only eight of those studies explicitly reported occlusion outcomes, specifically for distal MCA aneurysms. Two studies (Ma et al., 2021; Cao et al., 2023) contributed substantially to the dataset but did not separate outcomes by precise aneurysm location. While these were included in the main analysis on the basis of their anatomical relevance and detailed procedural descriptions, this required the assumption that reported occlusion rates applied to the distal MCA subgroup, which may introduce bias. Second, clinical and anatomical heterogeneity across studies\u0026mdash;such as variations in aneurysm size, morphology, flow diverter type, adjunctive coiling, and antiplatelet regimens\u0026mdash;has not been consistently reported or stratified. This limits the ability to perform subgroup analyses and assess how these factors influence outcomes. Finally, follow-up durations varied between studies, and in some cases, the precise time points for imaging follow-up were not clearly defined. This may have impacted the comparability of occlusion and complication rates across studies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe treatment of aneurysms located in distal vessels, especially in the M2 segment of the middle cerebral artery, is still lacking, but many techniques have shown potential in practice.\u003c/p\u003e\n\u003cp\u003eWithin this clinical context, flow diverter stents represent a potentially efficient and reliable therapeutic option. Thus, given the difficulty of treating this pathology, further well-designed studies are warranted to elucidate the definitive role of this technology.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIA: Intracranial Aneurysm\u003c/p\u003e\n\u003cp\u003eSAH: Subarachnoid Hemorrhage\u003c/p\u003e\n\u003cp\u003eFDS: Flow Diverter Stent\u003c/p\u003e\n\u003cp\u003eMCA: Middle Cerebral Artery\u003c/p\u003e\n\u003cp\u003emRS: Modified Rankin Scale\u003c/p\u003e\n\u003cp\u003eMRA: Magnetic Resonance Angiography\u003c/p\u003e\n\u003cp\u003eCTA: Computed Tomographic Angiography\u003c/p\u003e\n\u003cp\u003eSAC: Stent-Assisted Coiling\u003c/p\u003e\n\u003cp\u003eLVIS: Low-profile Visualized Intraluminal Support\u003c/p\u003e\n\u003cp\u003eWEB: Woven EndoBridge\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompliance with journal guidelines:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript complies with all the author instructions provided by the journal.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship and approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors meet the authorship criteria as per the ICMJE guidelines. The final version of the manuscript has been reviewed and approved by all the authors prior to submission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOriginality statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe confirm that this manuscript has not been published elsewhere and is not under consideration for publication in any other journal.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUse of reporting checklist:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic review follows the PRISMA reporting guidelines to ensure methodological transparency and rigor.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest (COI):\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest related to this study. COI disclosure forms have been collected in accordance with ICMJE guidelines and are available upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this study is a systematic review based on previously published data, it does not require ethical approval or informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any financial support.\u003c/p\u003e"},{"header":"References","content":"\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eZhou S, Dion PA, Rouleau GA. Genetics of intracranial aneurysms. Stroke. 2018;49(3):780-787. doi:10.1161/strokeaha.117.018152\u003c/li\u003e\n \u003cli\u003eXu Z, Rui YN, Hagan JP, Kim DH. Intracranial aneurysms: pathology, genetics, and molecular mechanisms. NeuroMolecular Medicine. 2019;21(4):325-343. doi:10.1007/s12017-019-08537-7\u003c/li\u003e\n \u003cli\u003eFrączek MJ, Krzyżewski RM, Kliś KM, Kwinta BM, Popiela TJ, Stachura K. Unruptured intracranial aneurysms: Why should we focus on small aneurysms? A comprehensive update of recent findings. Polish Journal of Radiology. 2024;89:13-23. doi:10.5114/pjr.2024.134424\u003c/li\u003e\n \u003cli\u003eDiagbouga MR, Morel S, Bijlenga P, Kwak BR. Role of hemodynamics in initiation/growth of intracranial aneurysms. European Journal of Clinical Investigation. 2018;48(9). doi:10.1111/eci.12992\u003c/li\u003e\n \u003cli\u003eRodriguez-Calienes A, Borjas-Calder\u0026oacute;n NF, Vivanco-Suarez J, et al. Endovascular Treatment and Microsurgical clipping for the Management of paraclinoid intracranial aneurysms: A Systematic Review and Meta-Analysis. World Neurosurgery. 2023;178:e489-e509. doi:10.1016/j.wneu.2023.07.108\u003c/li\u003e\n \u003cli\u003ePflaeging M, Kabbasch C, Schlamann M, et al. Microsurgical Clipping versus Advanced Endovascular Treatment of Unruptured Middle Cerebral Artery Bifurcation Aneurysms After a \u0026ldquo;Coil-First\u0026rdquo; Policy. World Neurosurgery. 2021;149:e336-e344. doi:10.1016/j.wneu.2021.02.027\u003c/li\u003e\n \u003cli\u003eKim JE, Xu R, Jackson CM, et al. Open microsurgical versus endovascular management of unruptured and ruptured brain aneurysms. Operative Neurosurgery. November 2024. doi:10.1227/ons.0000000000001448\u003c/li\u003e\n \u003cli\u003eLee KS, Zhang JJY, Nguyen V, et al. The evolution of intracranial aneurysm treatment techniques and future directions. Neurosurgical Review. 2021;45(1):1-25. doi:10.1007/s10143-021-01543-z\u003c/li\u003e\n \u003cli\u003eAlghamdi F, Morais R, Scillia P, Lubicz B. The Silk flow-diverter stent for endovascular treatment of intracranial aneurysms. Expert Review of Medical Devices. 2015;12(6):753-762. doi:10.1586/17434440.2015.1093413\u003c/li\u003e\n \u003cli\u003eAl-Mufti F, Amuluru K, Gandhi CD, Prestigiacomo CJ. Flow diversion for Intracranial Aneurysm Management: a new standard of care. Neurotherapeutics. 2016;13(3):582-589. doi:10.1007/s13311-016-0436-4\u003c/li\u003e\n \u003cli\u003eChua MMJ, Silveira L, Moore J, Pereira VM, Thomas AJ, Dmytriw AA. Flow diversion for treatment of intracranial aneurysms: Mechanism and implications. Annals of Neurology. 2019;85(6):793-800. doi:10.1002/ana.25484\u003c/li\u003e\n \u003cli\u003eRavindran K, Casabella AM, Cebral J, Brinjikji W, Kallmes DF, Kadirvel R. Mechanism of action and biology of flow diverters in the treatment of intracranial aneurysms. Neurosurgery. 2019;86(Supplement_1):S13-S19. doi:10.1093/neuros/nyz324\u003c/li\u003e\n \u003cli\u003eChancellor B, Raz E, Shapiro M, et al. Flow diversion for Intracranial Aneurysm treatment: Trials involving flow diverters and Long-Term Outcomes. Neurosurgery. 2019;86(Supplement_1):S36-S45. doi:10.1093/neuros/nyz345\u003c/li\u003e\n \u003cli\u003eFeng SW, Luo CB, Lee CH, Chang FC, Lin CJ. Flow-diverter stent to manage intracranial aneurysms: A single center experience. Journal of the Chinese Medical Association. 2021;85(3):358-363. doi:10.1097/jcma.0000000000000619\u003c/li\u003e\n \u003cli\u003eBhogal P, Henkes E, Schob S, et al. The use of flow diverters to treat small (\u0026le;5 mm) ruptured, saccular aneurysms. Surgical Neurology International. 2018;9(1):216. doi:10.4103/sni.sni_243_18\u003c/li\u003e\n \u003cli\u003eLiu J, Cao F, Zhenmei N, et al. Flow-diverter stents in intracranial aneurysm treatment: impact on covered cerebral artery branches. International Journal of Surgery. October 2023. doi:10.1097/js9.0000000000000762\u003c/li\u003e\n \u003cli\u003eZhou G, Su M, Yin YL, Li MH. Complications associated with the use of flow-diverting devices for cerebral aneurysms: a systematic review and meta-analysis. Neurosurgical FOCUS. 2017;42(6):E17. doi:10.3171/2017.3.focus16450\u003c/li\u003e\n \u003cli\u003eTouz\u0026eacute; R, Gravellier B, Rolla-Bigliani C, et al. Occlusion rate and visual complications with Flow-Diverter stent placed across the ophthalmic artery\u0026rsquo;s origin for Carotid-Ophthalmic aneurysms: A Meta-Analysis. Neurosurgery. 2019;86(4):455-463. doi:10.1093/neuros/nyz202\u003c/li\u003e\n \u003cli\u003eWilson MP, Murad MH, Krings T, et al. Management of tandem occlusions in acute ischemic stroke \u0026ndash; intracranial versus extracranial first and extracranial stenting versus angioplasty alone: a systematic review and meta-analysis. Journal of NeuroInterventional Surgery. 2018;10(8):721-728. doi:10.1136/neurintsurg-2017-013707\u003c/li\u003e\n \u003cli\u003eFargen KM, Soriano-Baron HE, Rushing JT, et al. A survey of intracranial aneurysm treatment practices among United States physicians. Journal of NeuroInterventional Surgery. 2017;10(1):44-49. doi:10.1136/neurintsurg-2016-012808\u003c/li\u003e\n \u003cli\u003eZhao J, Lin H, Summers R, Yang M, Cousins BG, Tsui J. Current treatment strategies for intracranial aneurysms: An overview. Angiology. 2017;69(1):17-30. doi:10.1177/0003319717700503\u003c/li\u003e\n \u003cli\u003eCho SH, Jo WI, Jo YE, Yang KH, Park JC, Lee DH. Bench-top comparison of physical properties of 4 Commercially Available Self-Expanding intracranial stents. Neurointervention. 2017;12(1):31-39. doi:10.5469/neuroint.2017.12.1.31\u003c/li\u003e\n \u003cli\u003eAydin K, Arat A, Sencer S, Barburoglu M, Men S. Stent-Assisted Coiling of Wide-Neck Intracranial aneurysms using Low-Profile LEO Baby stents: Initial and midterm results. American Journal of Neuroradiology. 2015;36(10):1934-1941. doi:10.3174/ajnr.a4355\u003c/li\u003e\n \u003cli\u003eSorenson T, Brinjikji W, Lanzino G. Newer endovascular tools: a review of experimental and clinical aspects. J Neurosurg Sci. 2016;60(1):116-125.\u003c/li\u003e\n \u003cli\u003eSweid A, Starke RM, Herial N, et al. Flow diversion for small caliber vessel aneurysms: efficacy, safety, and functional outcome. Journal of Neurosurgical Sciences. 2020;63(6). doi:10.23736/s0390-5616.19.04734-9\u003c/li\u003e\n \u003cli\u003ePierot L, Spelle L, Berge J, et al. Feasibility, complications, morbidity, and mortality results at 6 months for aneurysm treatment with the Flow Re-Direction Endoluminal Device: report of SAFE study. Journal of NeuroInterventional Surgery. 2018;10(8):765-770. doi:10.1136/neurintsurg-2017-013559\u003c/li\u003e\n \u003cli\u003eM\u0026ouml;hlenbruch MA, Herweh C, Jestaedt L, et al. The FRED Flow-Diverter Stent for intracranial aneurysms: Clinical Study to assess safety and efficacy. American Journal of Neuroradiology. 2015;36(6):1155-1161. doi:10.3174/ajnr.a4251\u003c/li\u003e\n \u003cli\u003eRaymond J, Gentric JC, Darsaut TE, et al. Flow diversion in the treatment of aneurysms: a randomized care trial and registry. Journal of Neurosurgery. 2016;127(3):454-462. doi:10.3171/2016.4.jns152662\u003c/li\u003e\n \u003cli\u003ePage MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021;134:178-189. doi: 10.1016/j.jclinepi.2021.03.001\u003c/li\u003e\n \u003cli\u003eSterne J A, Hern\u0026Atilde;\u0026iexcl;n M A, Reeves B C, Savovi\u0026Auml;\u0026Dagger; J, Berkman N D, Viswanathan M et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions BMJ 2016; 355 :i4919 doi:10.1136/bmj.i4919\u003c/li\u003e\n \u003cli\u003eLauzier DC, Root BK, Yasha Kayan, Delgado E, Osbun JW, Chatterjee AR, et al. Pipeline embolization of MCA aneurysms in the M2-M4 segment: Dual center study and meta-analysis. Clinical Neurology and Neurosurgery. 2021 Nov 24;212:107063\u0026ndash;3.\u003c/li\u003e\n \u003cli\u003eCagnazzo, F., Fanti, A., Lefevre, P. H., Derraz, I., Dargazanli, C., Gascou, G., Riquelme, C., Ahmed, R., Bonafe, A., \u0026amp; Costalat, V. (2021). Distal anterior cerebral artery aneurysms treated with flow diversion: experience of a large-volume center and systematic review of the literature. Journal of neurointerventional surgery, 13(1), 42\u0026ndash;48.\u003ca href=\"https://doi.org/10.1136/neurintsurg-2020-015980\"\u003e\u0026nbsp;\u003c/a\u003e\u003ca href=\"https://doi.org/10.1136/neurintsurg-2020-015980\"\u003ehttps://doi.org/10.1136/neurintsurg-2020-015980\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eDuan, Y., Xu, B., Qin, X., Mao, R., Hu, Y., Zhou, B., Li, J., \u0026amp; Chen, G. (2022). Flow diversion effect of the leo braided stent for aneurysms in the posterior and distal anterior circulations: A multicenter cohort study. Frontiers in neurology, 13, 957709.\u003ca href=\"https://doi.org/10.3389/fneur.2022.957709\"\u003e\u0026nbsp;\u003c/a\u003e\u003ca href=\"https://doi.org/10.3389/fneur.2022.957709\"\u003ehttps://doi.org/10.3389/fneur.2022.957709\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eZhang, G., Shen, Y., Ni, H., Jia, Z., Liu, X., Wang, B., Lu, G., Shi, H., Zhao, L., \u0026amp; Liu, S. (2025). Safety and efficacy of stent-assisted coiling of unruptured distal anterior cerebral artery aneurysms with low-profile braided stents. Clinical radiology, 84, 106848. Advance online publication.\u003ca href=\"https://doi.org/10.1016/j.crad.2025.106848\"\u003e\u0026nbsp;\u003c/a\u003e\u003ca href=\"https://doi.org/10.1016/j.crad.2025.106848\"\u003ehttps://doi.org/10.1016/j.crad.2025.106848\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eSuleyman, K., Korkmazer, B., Kocer, N., Islak, C., \u0026amp; Kızılkılıc, O. (2023). Evaluation of short- and long-term results of Y-stent-assisted coiling with Leo stents in endovascular treatment of wide-necked intracranial bifurcation aneurysms. Neuroradiology, 65(4), 785\u0026ndash;791.\u003ca href=\"https://doi.org/10.1007/s00234-023-03116-x\"\u003e\u0026nbsp;\u003c/a\u003e\u003ca href=\"https://doi.org/10.1007/s00234-023-03116-x\"\u003ehttps://doi.org/10.1007/s00234-023-03116-x\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eDowlati E, Pasko KBD, Liu J, Miller CA, Felbaum DR, Sur S, et al. Treatment of In-Stent Stenosis Following Flow Diversion of Intracranial Aneurysms with Cilostazol and Clopidogrel. Neurointervention. 2021 Sep 10;\u003c/li\u003e\n \u003cli\u003eGeorgi Vladev, Sirakov A, Svetozar Matanov, Sirakova K, Ninov K, Stanimir Sirakov. An increase in flow-diverter oversizing values as an independent risk factor for developing more severe in-stent stenosis. A retrospective single-center study based on flow diversion of supraclinoid internal carotid artery aneurysms. Frontiers in Neurology. 2025 Jan 8;15.\u003c/li\u003e\n \u003cli\u003eEfe Soydemir, Cemal Aydın G\u0026uuml;ndoğmuş, Derya T\u0026uuml;reli, Nurten Anda\u0026ccedil; Baltacıoğlu, Yaşar Bayri, Feyyaz Baltacıoğlu. Safety and efficacy of flow diverter stents in the treatment of middle cerebral artery aneurysms: a single-center experience and follow-up data. Diagnostic and Interventional Radiology [Internet]. 2023 Jan 13;29(2):350\u0026ndash;8. Available from:\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/36988000/\"\u003e\u0026nbsp;\u003c/a\u003e\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/36988000/\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/36988000/\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eEnriquez-Marulanda A, Young MM, Taussky P. Flow diversion: a disruptive technology coming of age. Lessons learned and challenges for the future. Journal of Neurosurgery [Internet]. 2023 Apr 28;139(5):1317\u0026ndash;27. Available from: https://thejns.org/view/journals/j-neurosurg/139/5/article-p1317.xml\u003c/li\u003e\n \u003cli\u003eLubicz, B., Kadou, A., Morais, R., \u0026amp; Mine, B. (2017). Leo stent for endovascular treatment of intracranial aneurysms: very long-term results in 50 patients with 52 aneurysms and literature review. \u003cem\u003eNeuroradiology\u003c/em\u003e, \u003cem\u003e59\u003c/em\u003e(3), 271\u0026ndash;276.\u003ca href=\"https://doi.org/10.1007/s00234-017-1805-3\"\u003e\u0026nbsp;\u003c/a\u003e\u003ca href=\"https://doi.org/10.1007/s00234-017-1805-3\"\u003ehttps://doi.org/10.1007/s00234-017-1805-3\u003c/a\u003e\u003c/li\u003e\n \u003cli\u003eDuan Y, Xu B, Qin X, Mao R, Hu Y, Zhou B, et al. Flow diversion effect of the leo braided stent for aneurysms in the posterior and distal anterior circulations: A multicenter cohort study. Frontiers in neurology [Internet]. 2022;13:957709. Available from: https://pubmed.ncbi.nlm.nih.gov/36237608/\u003c/li\u003e\n \u003cli\u003ePumar JM, Sucasas P, Mosqueira A, Vega P, Murias E. Five-Years Angiographic Follow-Up of Wide-Neck Intracranial Aneurysms Treated With LEO Plus Stent. Front Neurol. 2021 Nov 26;12:744962. doi: 10.3389/fneur.2021.744962. PMID: 34899568; PMCID: PMC8661051.\u003c/li\u003e\n \u003cli\u003eZhang L, Chen X, Dong L, Liu P, Jia L, Zhang Y, et al. Clinical and Angiographic Outcomes After Stent-Assisted Coiling of Cerebral Aneurysms With Laser-Cut and Braided Stents: A Comparative Analysis of the Literatures. Frontiers in Neurology. 2021 Apr 29;12.\u003c/li\u003e\n \u003cli\u003eXue G, Zuo Q, Zhang X, Tang H, Zhao R, Li Q, et al. Safety and efficacy of stent-assisted coiling for acutely ruptured wide-necked intracranial aneurysms: comparison of LVIS stents with laser-cut stents. Chinese Neurosurgical Journal. 2021 Mar 3;7(1).\u003c/li\u003e\n \u003cli\u003eGoertz L, Smyk MA, Siebert E, Turowski B, Borggrefe J, Mpotsaris A, et al. Low-Profile Laser-Cut Stents for Endovascular Treatment of Intracranial Aneurysms : Incidence, Clinical Presentation and Risk Factors of Thromboembolic Events. Clinical neuroradiology [Internet]. 2021 Mar;31(1):107\u0026ndash;15. Available from: https://pubmed.ncbi.nlm.nih.gov/31970465/\u003c/li\u003e\n \u003cli\u003eYavuz K, Serdar Geyik, Isil Saatci, Saruhan Cekirge. Endovascular Treatment of Middle Cerebral Artery Aneurysms with Flow Modification with the Use of the Pipeline Embolization Device. 2014 Mar 1;35(3):529\u0026ndash;35.\u003c/li\u003e\n \u003cli\u003e\u0026zwnj;Zanaty M, Chalouhi N, Tjoumakaris SI, Gonzalez LF, Rosenwasser R, Jabbour P. Flow diversion for complex middle cerebral artery aneurysms. Neuroradiology. 2014 Feb 18;56(5):381\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003e\u0026zwnj;Durst CR, Hixson HR, Schmitt P, Gingras JM, Crowley RW. Endovascular Treatment of a Fusiform Aneurysm at the M3-M4 Junction of the Middle Cerebral Artery Using the Pipeline Embolization Device. World Neurosurgery. 2016 Feb;86:511.e1\u0026ndash;4.\u003c/li\u003e\n \u003cli\u003e\u0026zwnj;Primiani CT, Ren Z, Kan P, et al. J NeuroIntervent Surg 2019;11:903\u0026ndash;907.\u003c/li\u003e\n \u003cli\u003eCimflova P, \u0026Ouml;zl\u0026uuml;k E, Korkmazer B, et al. J NeuroIntervent Surg 2021;13:631\u0026ndash;636.\u003c/li\u003e\n \u003cli\u003eAljuboori Z, Meyer K, Ding D, James R. Endovascular Treatment of a Traumatic Middle Cerebral Artery Pseudoaneurysm with the Pipeline Flex Embolization Device. World Neurosurgery. 2020 Jan;133:201\u0026ndash;4.\u003c/li\u003e\n \u003cli\u003e\u0026zwnj;Sorenson TJ, Klein JP, Rangel-Castilla L, Lanzino G. Flow Diversion of an Incompletely-Treated Fusiform Middle Cerebral Artery Aneurysm: 2-Dimensional Operative Video. Operative Neurosurgery. 2019 Aug 2;18(4):E125\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003e\u0026zwnj;Ma C, Zhu H, Liang S, Liang F, Han J, Jia Z, et al. Pipeline for the treatment of distal cerebral circulation aneurysms: A multicenter study focusing on periprocedural Complications. Interventional neuroradiology. 2021 Dec 16;28(6):708\u0026ndash;18.\u003c/li\u003e\n \u003cli\u003e\u0026zwnj;Cao R, Mattar A, Torche E, Riva R, Laubacher M, Moreno-Gomez R, et al. Clinical and angiographic characteristics of ruptured and unruptured distal cerebral aneurysms: a review of a large series of cases in a high-volume center. Journal of NeuroInterventional Surgery. 2024 Mar 5;jnis-021164.\u003c/li\u003e\n \u003cli\u003eLauzier DC, Root BK, Yasha Kayan, Delgado E, Osbun JW, Chatterjee AR, et al. Pipeline embolization of MCA aneurysms in the M2-M4 segment: Dual center study and meta-analysis. Clinical Neurology and Neurosurgery. 2021 Nov 24;212:107063\u0026ndash;3.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":false,"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":"Flow diverter stent, Intracranial aneurysm, Middle cerebral artery, Endovascular treatment, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-6542820/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6542820/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eFlow diversion has emerged as a key strategy in the treatment of intracranial aneurysms. However, its safety and efficacy in distal middle cerebral artery (MCA) aneurysms remain inadequately characterized. This study aims to update and synthesize the current literature by evaluating occlusion rates, procedural complications, and clinical outcomes associated with flow diversion in this subset.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA systematic review and meta-analysis were conducted according to the PRISMA guidelines. Relevant studies published through 2025 were identified through searches of major databases using predefined criteria. A random-effects proportional meta-analysis using R (version 4.4.2) was performed to assess pooled occlusion and complication rates. Heterogeneity was evaluated via I\u0026sup2; statistics, and publication bias was assessed via funnel plots.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTen studies comprising 128 distal MCA aneurysms treated with flow diverter stents were included. The pooled complete occlusion rate was 87% (101/120; 95% CI: 80\u0026ndash;93%), with no observed heterogeneity (I\u0026sup2; = 0.0%, p\u0026thinsp;=\u0026thinsp;0.7997). A sensitivity analysis excluding two large studies revealed an occlusion rate of 81% (48/61; 95% CI: 71\u0026ndash;91%), with low heterogeneity. The overall complication rate was 14% (21/128; 95% CI: 8\u0026ndash;21%), with the most frequent complications being thromboembolic events, in-stent stenosis, and hemorrhagic complications. Funnel plots did not reveal evidence of publication bias.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eFlow diversion appears to be a promising treatment option for distal MCA aneurysms, offering high rates of complete occlusion with an acceptable complication profile. However, the data remain limited and heterogeneous. Larger prospective studies with standardized outcome reporting are needed to establish its definitive role in this challenging vascular territory.\u003c/p\u003e","manuscriptTitle":"The Role of Flow Diverter Stents in Treating Distal Middle Cerebral Artery Aneurysms: A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-23 03:10:45","doi":"10.21203/rs.3.rs-6542820/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":"59014483-2cef-4ad6-847b-d7fb52269991","owner":[],"postedDate":"May 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-23T03:10:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-23 03:10:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6542820","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6542820","identity":"rs-6542820","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}