INTRODUCTION
Intracranial aneurysmal subarachnoid hemorrhage (aSAH) remains a catastrophic cerebrovascular emergency, associated with high rates of early rebleeding, significant long-term neurological disability, and substantial mortality despite advances in neurocritical care [1,2]. Although microsurgical clipping and endovascular coiling are established treatment options, they have limited effectiveness in specific aneurysm subtypes such as blister-like, fusiform, or dissecting lesions, because of their fragile walls, broad necks, and unfavorable anatomical configurations [3]. In these cases, achieving durable occlusion while preserving parent vessel integrity remains challenging.
Flow-diverting stents (FDs) were originally developed for unruptured complex aneurysms, where they promote vessel wall remodeling and progressive aneurysm occlusion [4]. Their application in the acute rupture setting, however, remains controversial. The mandatory use of dual antiplatelet therapy (DAPT) raises concerns about rebleeding, EVD (extra ventricular drain)-related hemorrhage, and systemic bleeding events [5], yet FDs may offer a reconstructive solution when conventional options are not suitable.
DAPT is essential to prevent stent thrombosis, which remains one of the most feared complications in the acute setting due to its risk of abrupt vessel occlusion and ischemic stroke [6]. At the same time, DAPT increases the risk of rebleeding and EVD-related hemorrhage. Reported rates of thromboembolic and hemorrhagic complications with FDs in ruptured aneurysms vary widely from 7–12% and 6–10%, respectively [7,8]. Furthermore, some multicenter series have observed higher mortality when flow diversion was applied indiscriminately, underscoring the importance of meticulous patient selection and individualized antithrombotic protocols [9]. Recent clinical series and meta-analyses suggest that flow diversion in acute ruptured aneurysms can achieve high occlusion rates with complication profiles comparable to conventional therapies [10]. Despite growing global experience, most existing evidence originates from high-volume Western centers with advanced neurointerventional infrastructure. Data from resource-limited settings, where patient presentation, logistical constraints, and pharmacologic protocols differ substantially, remain sparse. Furthermore, outcomes in blister-like and dissecting aneurysms subtypes that are particularly fragile and difficult to treat are still not well defined.
The present study aims to evaluate the safety, efficacy, and clinical outcomes of early FD implantation in ruptured intracranial aneurysms, with a specific focus on small saccular, blister-like and dissecting morphologies treated within the first week after ictus. By providing real-world data from a single tertiary center in a developing region, this work seeks to contribute meaningful insight into the applicability of flow diversion in acute SAH under resource-constrained conditions.
MATERIALS AND METHODS
Study Design
This investigation was structured as a retrospective, observational, single-center study carried out at the Institute of Neurosciences, Hannah Joseph Hospital, Madurai, India. The study period extended from July 2021 to June 2025.
Patient Selection
All patients with aSAH who underwent early FD implantation, defined as placement within 7 days of ictus were included. Exclusion criteria were: (1) adjunctive coiling or surgical clipping during the index procedure; (2) FD performed after 7 days; (3) incomplete clinical or imaging data; and (4) saccular aneurysms >5 mm. This selection ensured a homogeneous cohort suitable for comparison with international series of early FD use in ruptured aneurysms.
Data Collection
Data were retrospectively extracted from electronic medical records, operative reports, and angiographic archives. Two investigators independently verified data entries for accuracy and completeness. Recorded variables included demographics, presenting grade (WFNS [World Federation of Neurosurgical Societies], Fisher), aneurysm morphology and location, device type, timing of intervention, procedural details, complications, and outcome measures. Functional outcomes (modified Rankin Scale [mRS] at 90 days) and angiographic results were coded using standardized definitions. Aneurysm occlusion was evaluated using the O’Kelly–Marotta (OKM) grading scale [9], which is specifically designed for assessing flow-diverted aneurysms. Follow-up data were obtained through in-person clinic visits and structured telephonic interviews. Follow-up was censored at the last clinical or imaging contact before December 2023. All data were anonymized and stored securely on an institutional database compliant with privacy regulations.
Endovascular Procedure and Periprocedural Management
All procedures were performed in a single-plane neuroangiography suite (Philips Allura Xper FD20; Philips Healthcare) under general anesthesia by experienced interventional neuroradiologists. A standard transfemoral approach was employed. Device selection (Pipeline Embolization Device, Medtronic; Surpass Evolve, Stryker Neurovascular; Silk Vista, Balt; Baby Silk Vista, Balt; or Silk Plus, Balt) was determined at the operator’s discretion based on aneurysm morphology and parent vessel anatomy.
Given the relatively high incidence of clopidogrel resistance, DAPT with aspirin and ticagrelor constituted the standard regimen. A loading dose of ticagrelor 180 mg and aspirin 300 mg was administered via Ryle’s tube immediately after intubation. Following stent deployment, a tirofiban bolus was administered as part of the institutional protocol to ensure adequate intraprocedural platelet inhibition. Tirofiban was administered as a weight-based bolus of 12 μg/kg (0.4 μg/kg/min over 20 minutes), followed by a maintenance infusion of 5 μg/kg/hour (0.1 μg/kg/min) for 6 hours.
Intraprocedural anticoagulation with intravenous unfractionated heparin was administered according to weightbased dosing protocols (100 U/kg; typically, 5,000 units after arterial access), with additional 1,000-unit boluses given hourly to maintain a target activated clotting time between 250 and 300 seconds throughout the procedure. Post-procedurally, patients were maintained on ticagrelor 90 mg every 12 hours and aspirin 75 mg once daily, starting from the time of loading.
None of the patients in this series required prior cerebrospinal fluid diversion or EVD, owing to the absence of significant hydrocephalus at presentation.
Periprocedural Hemodynamic Management
During the interval between ictus and definitive endovascular treatment, all ruptured aneurysm patients received standard neurocritical care. The observed treatment interval primarily reflected referral delays, neurological stabilization, and procedural logistics. Invasive arterial monitoring was used throughout the procedure and early recovery. Given that aneurysms treated with flow diversion remain unsecured until thrombosis occurs, systolic blood pressure (SBP) was maintained ≤140 mmHg before device deployment to minimize rebleeding risk. Following deployment and confirmation of reduced intra-aneurysmal flow, mean arterial pressure (MAP) was maintained between 80–100 mmHg in the absence of vasospasm. For angiographic or clinical vasospasm, induced hypertension was initiated with vasopressor support (typical targets: MAP 100–110 mmHg or SBP 160–180 mmHg), titrated to neurological response and cardiac tolerance. BP goals were individualized, balancing ischemic and hemorrhagic risks in accordance with guideline-based aSAH management principles [10,11]. These hemodynamic targets reflect institutional practice protocols developed in alignment with general aSAH management recommendations from published guidelines, in the absence of specific evidence for ruptured aneurysms treated with flow diversion [10,11].
Follow-Up Protocol
All patients were maintained on DAPT (aspirin and ticagrelor) for a minimum duration of 6 months following the procedure. In cases where follow-up angiography demonstrated in-stent stenosis or delayed endothelialization, DAPT was extended for an additional 6 months, after which patients were transitioned to lifelong single antiplatelet therapy with aspirin 150 mg daily. Clinical outcomes were evaluated using the mRS at 90 days, with scores of 0–2 classified as favorable. Angiographic follow-up was performed at a median of 12 months using digital subtraction angiography. The primary endpoint was functional outcome at 90 days. Secondary endpoints included delayed angiographic occlusion (OKM grading scale), ischemic or hemorrhagic complications, aneurysm rebleeding, and all-cause mortality.
Statistical Analysis
All statistical analyses were performed using IBM SPSS Statistics v26.0 (IBM Co.) and GraphPad Prism v10.0 (GraphPad Software). Continuous variables were summarized as mean±standard deviation or median [interquartile range] as appropriate. Categorical variables were reported as numbers and percentages. Exploratory group comparisons between favorable (mRS 0–2) and unfavorable (mRS 3–6) outcomes used the Mann–Whitney U-test for continuous data and Fisher’s exact test for categorical data. Multivariate analysis was not attempted because of the small cohort and retrospective design.
Angiographic occlusion and complication rates were expressed as proportions with 95% confidence intervals (CI) calculated by the Clopper–Pearson method. Descriptive visualizations explored relationships between time to treatment and outcome, and between aneurysm morphology and ischemic complications.
All tests were two-tailed with statistical significance set at P<0.05. The analytical framework followed prior single-center studies of early flow diversion in ruptured aneurysms to allow transparent comparison with published literature.
RESULTS
Patient, Aneurysm, and Subarachnoid Haemorrhage Characteristics
A total of 26 patients were included (Table 1). The mean age was 47.3±12.1 years (range 16–71), and 16 (61.5%) were male. The mean WFNS and Fisher grades were 2.3 and 3.0, respectively. Aneurysm morphology was saccular in 11 (42.3%), blister-like in 9 (34.6%), and fusiform or dissecting in 6 (23.1%). Seventeen aneurysms (65.4%) arose from the anterior circulation—paraclinoid/ophthalmic internal carotid artery (ICA) (n=8), anterior choroidal ICA (n=2), posterior communicating artery (n=2), anterior communicating artery (n=3), and middle cerebral artery (n=2). Nine (34.6%) were in the posterior circulation, involving the posterior cerebral artery (n=4), V4 vertebral artery (n=3), and basilar artery (n=2).
Procedural Characteristics
The mean time from ictus to FD implantation was 3.9±1.8 days (median 3, range 2–8). A single FD device was used in all cases. Devices included Pipeline (n=13, 50.0%), Surpass Evolve (n=7, 26.9%), Silk Vista (n=3, 11.5%), Baby Silk Vista (n=2, 7.7%), and Silk Plus (n=1, 3.8%). All procedures achieved technical success with no deployment failures, intraprocedural rupture, or mortality. No adjunctive coiling was performed in this cohort (Table 2).
Exploratory Analysis by Treatment Timing
Patients treated earlier and later within the acute phase (2–7 days) showed no obvious differences in functional outcome, ischemic events, or angiographic occlusion; however, the limited sample size precluded statistically robust comparison.
Clinical Outcomes
At 90 days, 22 out of 26 patients (84.6%) achieved a favorable functional outcome (mRS 0–2). Mortality occurred in 4 patients (15.4%), all due to secondary causes. Two patients (7.7%) died from fatal vasospasm, while the remaining 2 (7.7%) succumbed to systemic complications, including cardiac arrest and pulmonary edema. All 4 deaths were attributed to neurological and systemic causes secondary to aSAH. Importantly, there were no procedure-related deaths, aneurysm rebleeds, or stent thrombosis related major ischemic strokes noted during post-operative period or following discharge (Table 2).
Angiographic Outcome
At a median follow-up of 12 months (range, 6–18 months), complete occlusion (OKM grading scale D) was documented in all 21 patients (100%) who had imaging follow-up available. One patient was lost to imaging follow-up. The notably high occlusion rate in this cohort may be attributed, at least in part, to the relatively longer median follow-up duration (1 year) compared with previous studies (Table 2). A representative example of early FD deployment with complete occlusion is shown in Fig. 1.
Complications
Procedure-related ischemic complications occurred in 3 out of 26 patients (11.5%). Among them, 1 patient (3.8%) developed left hemiparesis due to a pontine perforator infarct (Fig. 2), with a residual deficit at 3 months (mRS 3). Two patients (7.7%) experienced procedure-related microembolic infarcts, which improved over 3 months without significant neurological morbidity (mRS 2). No procedure-related hemorrhagic complications or aneurysm rebleeds were observed. Additionally, no hemorrhages attributable to DAPT and no cases requiring EVD placement were recorded (Table 3).
Comparison of Clinical and Procedural Parameters by Outcome
Exploratory comparison between patients with favorable (mRS 0–2) and unfavorable (mRS 3–6) outcomes revealed no statistically significant differences in clinical or procedural parameters. Trends such as higher age and WFNS/Fisher grades in the unfavorable group were observed, but the small sample size limits the ability to draw definitive conclusions (Supplementary Table 1). Larger studies are needed to identify potential predictors of outcome following FD treatment.
DISCUSSION
In aSAH, coil embolization is often the go-to endovascular treatment. Yet, aneurysms with broad necks, blister-like configurations, or dissecting features present a formidable therapeutic challenge, as both surgical clipping and traditional coiling are frequently inadequate [8,12]. FDs, featuring a dense metallic lattice and low porosity, reroute blood along the parent artery, fostering blood stagnation within the aneurysm sac [12]. This environment encourages progressive thrombosis and vessel wall reconstruction over time [8,12,13]. Unlike surgeries or endovascular coiling that immediately secure an aneurysm, FDs gradually produce occlusion and mandate DAPT to mitigate the high risk of in-stent clot formation, even during the early post-deployment phase. This requirement complicates treatment in the acute rupture context, where the risk of rebleeding must be weighed carefully [13,14].
Our cohort was predominantly middle-aged, with a mean age of approximately 47 years (range 16–71), and a male preponderance (61.5%), a slight departure from general aSAH demographics where females typically account for a greater proportion, particularly post-menopause. Remarkably, a substantial fraction of aneurysms in our series displayed anatomically aggressive morphologies: blister-like lesions composed 34.6%, and fusiform/dissecting aneurysms represented 23.1%, whereas saccular types accounted for only 42.3%. We deliberately included small (<5 mm) saccular aneurysms in our cohort despite their lower overall prevalence, because endovascular coiling of such tiny lesions carries a notably elevated rate of intra-procedural rupture, reported at approximately 8.3% (95% CI: 6.0–11.4%) in some series and up to 10.7% (95% CI: 7.4–15.1%) in ruptured aneurysms, making flow diversion a safer alternative in these fragile cases [15,16]. These lesions, often located in the supraclinoid ICA, pose considerable challenges due to their fragile walls and propensity for rupture, making both surgical clipping and endovascular coiling high risk [16]. Additionally, ruptured blister aneurysms have been associated with complicated clinical courses, including delayed cerebral ischemia, particularly in those with higher Fisher grades [17,18]. Therefore, the predominance of these complex aneurysm subtypes in our patient population underscores the rigor of our case selection and emphasizes the practical significance of demonstrating favorable outcomes in scenarios where traditional interventions are often inadequate or hazardous. All patients in this cohort were selected in the absence of significant hydrocephalus requiring EVD, which likely contributed to the favorable hemorrhagic safety profile under DAPT.
Although treatment timing varied within the defined early window, most patients were treated within the first 3 days. The small cohort size limits assessment of the impact of precise timing on outcome, and this variability should be considered when interpreting the results.
Functional Outcomes and Angiographic Success
Our cohort achieved outstanding clinical and angiographic outcomes: 84.6% of patients attained a favorable 90-day mRS score (0–2), and all patients with follow-up imaging achieved complete aneurysm occlusion. These results resonate strongly with recent high-quality studies. A retrospective analysis of 76 patients treated within 4 days of SAH reported an 81.6% rate of mRS 0–2 at 90 days and 95.5% complete or near-complete occlusion by 3–6 months, with no aneurysm rebleeding, confirming the protective value of early flow diversion coupled with rigorous antiplatelet management [19]. Similarly, another single-center study implementing a standardized antithrombotic protocol found that post-protocol patients experienced zero re-ruptures and comparable functional outcomes, despite higher use of glycoprotein IIb/IIIa inhibitors and earlier DAPT [20]. Additionally, a retrospective series of 30 consecutive ruptured cases showed favorable mRS outcomes in approximately two-thirds of patients with angiographic occlusion rates approaching those seen in our cohort [21].
Safety Profile: Rebleeding, Ischemic Events, and Dual Antiplatelet Therapy Considerations
No patient experienced aneurysm rebleeding. Procedure-related ischemic events occurred in 11.5%, all transient or with minimal residual deficits. No hemorrhagic complications were attributed to DAPT. A meta-analysis reported ~12% composite complications, including 5% rebleeding and 4% other hemorrhages, likely influenced by larger aneurysms and heterogeneous DAPT regimens [18]. A retrospective series on DAPT safety in SAH similarly showed more EVD-related bleeds under DAPT but without clinical significance, alongside reduced ischemic events [21]. Together, these findings support that meticulous periprocedural DAPT and BP control can ensure FD safety even in the acute rupture setting. However, these favorable outcomes should be interpreted in the context of our institution’s structured and relatively aggressive antiplatelet protocol, and may not be directly generalizable to centers employing different antithrombotic strategies. Our ischemic event rate (11.5%) is within expected limits and lower in morbidity severity, with no permanent neurological deficit.
The mean treatment interval of 3.9 days post-ictus supports the feasibility of early FD placement in carefully selected ruptured aneurysms. Under structured DAPT and hemodynamic management, FDs provide an effective reconstructive solution for blister-like, dissecting, and small saccular aneurysms (<5 mm). Our results reaffirm that, even in resource-limited environments, early flow diversion can match or surpass global benchmarks for both occlusion and safety.
In the absence of a control group, we compared our outcomes with representative contemporary series of alternative treatments for ruptured blister-like and very small aneurysms (Supplementary Table 2). While direct comparison is limited by heterogeneity of study design and outcome definitions, our results demonstrate comparable or improved functional outcomes, high occlusion rates, and absence of rebleeding when flow diversion is applied in carefully selected patients. Importantly, this analysis supports the feasibility and safety of early flow diversion rather than implying superiority over other established treatment strategies.
Exploratory subgroup analysis was performed according to aneurysm morphology (small saccular, blister-like, and fusiform/ dissecting; Table 4) [22-25]. Although numerical differences in functional outcomes, angiographic occlusion rates, and ischemic complication rates were observed among the 3 groups, no statistically significant differences were identified. These comparisons were underpowered due to the small number of patients in each subgroup and should therefore be interpreted as descriptive and hypothesis-generating.
Clinical Implications
The mean treatment interval of 3.9 days after ictus supports the feasibility of early FD placement in carefully selected ruptured aneurysms. Under structured dual antiplatelet and hemodynamic management, FDs provide an effective reconstructive option for blister-like, dissecting, and small saccular aneurysms (<5 mm). Indeed, a recent meta-analysis of ruptured blood-blister-like aneurysms found that long-term complete occlusion rates were significantly higher with FDs (89.3%) compared with stent-assisted coiling (70.3%), while recanalization rates were markedly lower (4.5% vs. 25.4%) [26]. These findings reaffirm that, with strict selection and standardized protocols, early flow diversion can achieve excellent clinical and angiographic outcomes, comparable or superior to contemporary benchmarks.
Limitations
This study has several limitations. First, the sample size was small, and the retrospective design introduces selection and information biases. Second, the cohort was deliberately selected and excluded patients with acute hydrocephalus requiring EVD, which may have influenced the observed hemorrhagic safety profile and limits generalizability. Third, aneurysm morphology heterogeneity introduces biological and clinical variability, and the exploratory subgroup analysis performed to address this was underpowered and should be interpreted as descriptive. Fourth, inclusion of small saccular aneurysms measuring >3 mm and <5 mm although often amenable to conventional treatment introduces additional heterogeneity when focusing on difficult-to-treat lesions; however, inclusion of very small aneurysms (≤3 mm), which carry a non-negligible risk of iatrogenic rupture during coiling, preserves the clinical relevance of the findings. Fifth, incomplete long-term angiographic follow-up may limit assessment of delayed stent related complications. Finally, the single-center design may introduce analytical bias. Despite these limitations, our findings support the feasibility and safety of early flow diversion in carefully selected ruptured aneurysms.
CONCLUSION
Early flow diversion in carefully selected ruptured intracranial aneurysms was associated with high functional recovery, complete angiographic occlusion, and a low rate of procedure-related complications, including in morphologies traditionally unsuitable for conventional therapy. The favorable safety profile reflects stringent patient selection, absence of acute hydrocephalus requiring EVD, experienced operators, and standardized antithrombotic and hemodynamic protocols. Under these conditions, FD stents represent a feasible and effective reconstructive strategy for complex ruptured aneurysms, even in resource-limited settings. Larger prospective multicenter studies are needed to confirm these findings and refine management strategies.
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