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Objective: Thromboembolic (TE) events are among the most feared complications after flow diversion (FD) and have been reported to occur even with adequate dual antiplatelet therapy. Herein, the authors characterize thrombotic and embolic events that developed after FD, focusing on the morbidity of each of these events and the predisposing factors associated with their development., Methods: A retrospective analysis of aneurysms treated with FD at a single institution in the US between 2013 and 2023 was performed. The authors documented the emergence of intraprocedural and postoperative TE events. A survival analysis and a Cox regression model was conducted to identify predictors associated with these events., Results: The authors included 651 procedures performed in 591 patients to treat 746 aneurysms. TE events occurred in 38 of the procedures performed (5.8%), causing permanent deficit in 20 patients and death in 4 patients. Eleven cases presented with acute stent thrombosis, 11 with large-vessel occlusion, and 9 with perforator strokes. At a median follow-up of 9.5 months, 73.0% of patients with an ischemic event had a modified Rankin Scale score ≤ 2. Three of the deaths were secondary to occlusion at the basilar trunk and vertebral artery. In patients with TE events in the anterior circulation, 7 of 11 patients with middle cerebral artery occlusion and 9 of 12 patients with internal carotid artery occlusion achieved independence. Time-to-event Cox regression analysis demonstrated that TE events were more frequent in patients exhibiting aspirin resistance (hazard ratio 2.66; 95% CI 1.10-6.70)., Conclusions: TE events after FD result from multiple factors, including age, aneurysm characteristics, aneurysm location, antiplatelet resistance, and procedural factors. In our cohort, we found the highest morbidity for patients with TE events presenting with large-vessel occlusion at the middle cerebral artery, and vertebrobasilar system.

Objective: Anterior choroidal artery (AChA) aneurysms account for 2%-5% of all intracranial aneurysms. Treatment considerations include microsurgical clipping, flow diversion, or coiling with or without adjunctive devices. AChA aneurysms pose challenges in treatment due to the origination of the aneurysm from the origin or proximal segment of the AChA. The AChA is particularly susceptible to vasospasm and occlusion during treatment with devastating neurological deficits, including hemiparesis, hemianesthesia, lethargy, neglect, and hemianopia. In this study, the authors performed a meta-analysis to quantify the outcomes and complication rates across treatment modalities for AChA aneurysms and to identify risk factors reported in the literature., Methods: The authors performed a systematic review of AChA aneurysms treated with surgical clipping, endovascular coiling, or flow diversion and reported in the PubMed, Embase, Scopus, and Cochrane search databases. Single-arm meta-analyses of the selected outcomes were performed in RStudio., Results: Literature review yielded 25 studies that met the inclusion criteria. In total, 1627 patients were included in the analysis, with 554 males, 1009 females, and 64 unspecified. The rate of any complication in the full cohort was 11.6%, with a rate of ischemic complications of 5.5% and a favorable recovery rate of 90.3% of all patients treated. In total, 1064 patients underwent surgical clipping, 443 were treated with coiling, and 120 patients with flow diversion. In clipped patients, the rate of total surgical complications was 17.6%, with an ischemic complication rate of 9.4%. The rate of good functional recovery, defined on the basis of a Glasgow Outcome Scale score of 4-5 or modified Rankin Scale score of 0-2, was 88.0%, and complete obliteration was achieved in 84.5% of surgically clipped aneurysms. The complication rate in coiled patients was 10.3%, with an ischemic complication rate of 3.0%. Good functional recovery was achieved in 88.6% of coiled patients and complete aneurysm obliteration in 74.1%. Flow diversion resulted in a complication rate of 1.3%, with 0.7% rate of ischemic complications. Good functional recovery was achieved in 98.4% of patients and complete aneurysm obliteration in 79.0% in the flow diversion group. Aneurysm morphological features that impacted the complication rate were also identified to augment quantitative data and to help guide treatment selection for AChA aneurysms., Conclusions: Flow diversion showed significantly lower total and ischemic complications and improved outcomes compared to clipping and coiling. There may be differences in outcomes between treatment types, especially when considering the varied patient presentations that guide treatment selection.

Objective: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications., Methods: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values., Results: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51., Conclusions: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.

Objective: The placement of flow-diverting devices has become a common method of treating unruptured intracranial aneurysms of the internal carotid artery. The progressive improvement of aneurysm occlusion after treatment-with low complication and rupture rates-has led to a dilemma regarding the management of aneurysms in which occlusion has not occurred within 6-24 months. The authors aimed to identify clinical consensus regarding management of intracranial aneurysms displaying persistent filling 6-24 months after flow diversion and to ascertain questions that may drive future investigation., Methods: An international panel of 67 experts was invited to participate in a multistep Delphi consensus process on the treatment of intracranial aneurysms after failed flow diversion., Results: Of the 67 experts invited, 23 (34%) participated. Qualitative analysis of an initial survey with open-ended questions resulted in 51 statements regarding management of aneurysms showing persistent filling after flow diversion. The statements were grouped into 8 categories, and in the second round, respondents rated the degree of their agreement with each statement on a 5-point Likert scale. Flow diverters with surface modifiers did not influence administration of dual-antiplatelet therapy according to 83%. Consensus was also reached regarding the definition of treatment failure at specific time points, including at 6 months if there is aneurysm growth or persistent rapid flow through the entirety of the aneurysm (96%), at 12 months if there is aneurysm growth or symptom onset (78%), and at 24 months if there is persistent filling regardless of size and filling characteristics (74%). Although experts agreed that the degree of intimal hyperplasia or in-device stenosis could not be ascertained by noninvasive imaging alone (83%), only 65% chose digital subtraction angiography as the preferred modality. At 6 and 12 months, retreatment is preferred if there is persistent filling with aneurysm growth (96%, 96%), device malposition (48%, 87%), or a history of subarachnoid hemorrhage (65%, 70%), respectively, and at 24 months if there is persistent filling without reduction in aneurysm size (74%). Experts favored treatment with an additional flow diverter (87%) over aneurysm clipping, applying the same principles for follow-up (83%) and treatment failure (91%) as for the first flow diverter., Conclusions: The authors present the consensus practices of experts in the management of intracranial aneurysms without occlusion 6-24 months after treatment with a flow-diverting device.

Objective: Treatment of intracranial aneurysms by flow diversion is safe and effective and is increasingly popular. However, the correct treatment paradigm for aneurysms incompletely treated by initial placement of a flow diverter has not been established, nor have the subsequent natural history and occlusion rates of such aneurysms. The authors sought to outline the natural history of such aneurysms, which to date have been considered partially treated., Methods: The authors retrospectively reviewed consecutive cases from 6 high-volume neurointerventional services, including all cases in which the first follow-up imaging after placement of a flow diverter showed incomplete occlusion of the aneurysm, and for which subsequent clinical and/or radiological follow-up was available. All included patients were treated with the Pipeline Flex embolization device or the Pipeline Flex embolization device with Shield Technology. Subsequent radiographic and clinical outcome data were collected and analyzed using the Kaplan-Meier survival function., Results: A total of 263 patients with persistently patent aneurysms on first follow-up imaging after flow diversion were identified. Of these, 204 had clinical follow-up and 152 had additional imaging follow-up. Of this final cohort, 148 aneurysms were unruptured, and 4 were ruptured. The average aneurysm size by maximum dimension was 10.8 mm. The average recorded follow-up was 27.8 months in the cohort, with some patients followed for as long as 9 years from treatment. Over the course of 403 person-years of follow-up, no delayed aneurysm ruptures were recorded. Both with and without retreatment, aneurysms showed a trend toward progressive occlusion over time. Complications related to device placement were low., Conclusions: Aneurysms that have been incompletely treated by flow diversion have a benign natural history with progression toward occlusion over time, with or without retreatment.

Objective: By providing a more physiological approach to the treatment of intracranial aneurysms, the Pipeline embolization device (PED) has revolutionized the endovascular treatment of aneurysms. Although there are many flow diverters on the market, the authors report their experience with the PED, the first flow diverter to be approved by the Food and Drug Administration. They aimed to assess the efficacy and safety of PED flow diversion for the treatment of a wide range of aneurysms, as well as to look at factors affecting occlusion., Methods: This is a retrospective study of a prospectively maintained database of patients treated with the PED between January 2011 and December 2019. Charts were reviewed for patient, aneurysm, and procedure characteristics. The primary outcomes of interest were complication rates, occlusion outcomes (O'Kelly-Marotta grading scale), and functional outcomes (modified Rankin Scale [mRS]). Secondary outcomes included predictors of incomplete occlusion at 6 and 24 months of follow-up., Results: The study cohort included 581 patients with 674 aneurysms. Most aneurysms (90.5%) were in the anterior circulation and had a saccular morphology (85.6%). Additionally, 638 aneurysms (94.7%) were unruptured, whereas 36 (5.3%) were acutely ruptured. The largest mean aneurysm diameter was 8.3 ± 6.1 mm. Complications occurred at a rate of 5.5% (n = 32). The complete occlusion rate was 89.3% at 24 months' follow-up, and 94.8% of patients had a favorable neurological outcome (mRS score 0-2) at the last follow-up. On multivariate analysis, predictors of incomplete aneurysm occlusion at 6 months were hypertension (OR 1.7, p = 0.03), previous aneurysm treatment (OR 2.4, p = 0.001), and increasing aneurysm neck diameter (OR 1.2, p = 0.02), whereas a saccular morphology was protective (OR 0.5, p = 0.05). Predictors of incomplete occlusion at 24 months were increasing aneurysm neck diameter (OR 1.2, p = 0.01) and previous aneurysm treatment (OR 2.3, p = 0.01)., Conclusions: The study findings are corroborated by those of previous studies and trials. The complete occlusion rate was 89.3% at 24 months' follow-up, with 94.8% of patients having favorable functional outcomes (mRS score 0-2). Aneurysm treatment before PED deployment and an increasing aneurysm neck diameter increase the risk of incomplete occlusion at 6 and 24 months.

Objective: Intracranial saccular aneurysms are vascular malformations responsible for 80% of nontraumatic brain hemorrhage. Recently, flow diverters have been used as a less invasive therapeutic alternative for surgery. However, they fail to achieve complete occlusion after 6 months in 25% of cases. In this study, the authors built a tool, using machine learning (ML), to predict the aneurysm occlusion outcome 6 months after treatment with flow diverters., Methods: A total of 667 aneurysms in 616 patients treated with the Pipeline embolization device at a tertiary referral center between January 2011 and December 2017 were included. To build the predictive tool, two experiments were conducted. In the first experiment, six ML algorithms (support vector machine [SVM], decision tree, random forest [RF], k-nearest neighbor, XGBoost, and CatBoost) were trained using 26 features related to patient risk factors and aneurysm morphological characteristics, and the results were compared with logistic regression (LR) modeling. In the second experiment, the models were trained using the top 10 features extracted by Shapley additive explanation (SHAP) analysis performed on the RF model., Results: The results showed that the authors' tool can better predict the occlusion outcome than LR (accuracy of 89% for the SVM model vs 62% for the LR model), even when trained using a subset of the features (83% accuracy). SHAP analysis revealed that age, hypertension, smoking status, branch vessel involvement, aneurysm neck, and larger diameter dimensions were among the most important features contributing to accurate predictions., Conclusions: In this study, an ML-based tool was developed that successfully predicts outcome in intracranial aneurysms treated with flow diversion, thus helping neurosurgeons to practice a more refined approach and patient-tailored medicine.

Over the last 2 decades, the field of transcriptomics has emerged as a major subdiscipline in biology. Transcriptomic techniques have been used by many groups over this time to better understand intracranial aneurysm development, rupture, and treatment. However, only a few studies have applied transcriptomics to understand the mechanisms behind flow diversion (FD) specifically, despite its increasing importance in the neurointerventional armamentarium. FD is an increasingly safe and effective treatment option for intracranial aneurysms. However, the clinical understanding and use of FD has far outpaced the understanding of the underlying mechanisms. To make FD more predictable, clinically efficacious, and safe, it is important to understand the biological mechanisms at play that lead to successful and unsuccessful FD. In this review, the authors focus on the current understanding of FD biology, the recent advances in transcriptomics, and what future studies could be performed to deepen the understanding of FD. They propose the new concept of the FD microenvironment to be studied, which may unlock a deeper biological understanding. This review provides the background for prospective studies into the development of targeted aneurysm therapy, whether by modified devices or by medical adjuncts.

Objective: Flow diversion created a paradigm shift in the treatment of intracranial aneurysms. The new flow redirection endoluminal device with X technology (FRED X) is the latest update of the recent Food and Drug Administration-approved FRED. The FRED X is engineered to reduce material thrombogenicity and enhance vessel healing. In this study, the authors aimed to evaluate the feasibility and early safety and efficacy of the new FRED X., Methods: The authors retrospectively collected and analyzed data from patients who had undergone flow diversion with the new FRED X at four tertiary cerebrovascular centers in the United States from February 2022 through July 2022., Results: Forty-four patients with 45 aneurysms treated using 46 devices comprised the overall study cohort and were divided into two groups: 39 patients with unruptured aneurysms and 5 patients with ruptured aneurysms. The mean patient age was 57.7 ± 9.1 years, and most patients were female (84%). Ninety-one percent of the aneurysms were saccular, with the majority (93%) located in the anterior circulation, specifically the posterior communicating (27%) and carotid ophthalmic (27%) territories. The mean maximum aneurysm diameter was 5.6 ± 4.6 mm, and 20% of the lesions had been previously treated. The mean procedure time was 61.6 minutes, with a mean cumulative fluoroscopy time of 24.6 minutes. Additionally, 7% of the lesions received adjunct treatment. Stent placement was successful in 100% of cases, achieving good wall apposition and complete neck coverage. Further, immediate aneurysm contrast stasis > 90% was observed in 61% of cases. Symptomatic postoperative complications occurred in 3 patients in the unruptured cohort and 1 patient in the ruptured cohort. All patients in the study were discharged on dual antiplatelet regimens with a modified Rankin Scale score of 0. At 6 months after treatment, 89% of cases had adequate occlusion, with < 6% of cases having asymptomatic in-stent stenosis. All patients had excellent functional outcomes., Conclusions: FRED X for the treatment of an intracranial aneurysm is technically feasible alone or in conjunction with intrasaccular embolization. In addition, the study results showed very promising early safety and efficacy. Follow-up studies should establish the long-term safety and efficacy profiles of this new stent.

Objective: The object of this study was to compare the efficacy and safety profile of the Pipeline embolization device (PED)/Pipeline Flex embolization device (PED Flex) with that of the Pipeline Flex embolization device with Shield Technology (PED Shield). After introducing the first-generation PED and the second-generation PED Flex with its updated delivery system, the PED Shield was launched with a synthetic layer of phosphorylcholine surface modification to reduce thrombogenicity., Methods: This is a retrospective review of unruptured aneurysms treated with PED/PED Flex versus PED Shield between 2017 and 2022 at the authors' institution. Patients with ruptured aneurysms, adjunctive treatment, failed flow diverter deployment, and prior treatment of the target aneurysm were excluded. Baseline characteristics were collected for all patients, including age, sex, past medical history (hypertension, hyperlipidemia, diabetes mellitus), smoking status, aneurysm location, and aneurysm dimensions (neck, width, height) and morphology (saccular, nonsaccular). The primary outcome was procedural and periprocedural complication rates., Results: The study cohort comprised 200 patients with 200 aneurysms, including 150 aneurysms treated with the PED/PED Flex and 50 treated with the PED Shield. With respect to intraprocedural and periprocedural complications, length of stay, length of follow-up, and functional outcome at discharge, there was no significant difference between the two cohorts. At the midterm follow-up, the rate of in-stent stenosis (PED/PED Flex: 14.2% vs PED Shield: 14.6%, p = 0.927), aneurysm occlusion (complete occlusion: 79.5% vs 80.5%, respectively; neck remnant: 4.7% vs 12.2%; dome remnant: 15.7% vs 7.3%; p = 0.119), and the need for retreatment (5.3% vs 0%, p = 0.097) were comparable between the two cohorts., Conclusions: This study suggests that, as compared to first- and second-generation PED and PED Flex, the third-generation PED Shield offers similar rates of complications, aneurysm occlusion, and in-stent stenosis at the midterm follow-up.

Intracranial aneurysm treatment has been revolutionized over the last decade with the development of flow diversion technology. The use of this technology has evolved rapidly and has proven that cerebrovascular disease treatment remains one of the forefront innovation areas in neurosurgery. The good results on the treatment of internal carotid artery aneurysms up to the communicating segment have motivated the use of flow diversion beyond the circle of Willis and in the posterior circulation. Further advances and innovations of flow-diverting devices are underway and intended to improve the safety and efficacy of this therapy. This review article provides a detailed discussion about the origin, mechanism of action, initial experience, complications, types of devices, and future perspectives of flow diversion technology.

Objective: The authors undertook an evaluation of periprocedural cerebrovascular complications and 30-day outcomes of endovascular treatment for intracranial vertebral artery dissecting aneurysms (IVADAs) and assessed the relevant risk factors., Methods: The authors included a series of 195 patients who had undergone endovascular treatment for 198 IVADAs. Clinical data, morphological characteristics, treatment details, and periprocedural cerebrovascular complications including intraprocedural rupture, intraprocedural thrombosis, intracranial hemorrhage (ICH), transient ischemic attack (TIA), and ischemic stroke (IS) were recorded. After evaluation of the 30-day modified Rankin Scale (mRS) scores, the authors applied univariate and multivariate logistic regression analyses to identify the risk factors for complications and 30-day unfavorable clinical outcomes., Results: There were no intraprocedural ruptures, but the authors recorded intraprocedural thrombosis (n = 5), ICH (n = 3), TIA (n = 1), and IS (n = 13), comprising an 11.1% (22/198) complication rate. Multivariate logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 3.17, 95% confidence interval [CI] 1.20-8.41, p = 0.020), IS history (OR 5.55, 95% CI 1.46-21.01, p = 0.012), and subarachnoid hemorrhage (SAH) (OR 4.48, 95% CI 1.52-13.20, p = 0.007) were risk factors for overall complications, whereas aneurysmal height (OR 0.77, 95% CI 0.61-0.98, p = 0.032) was a protective factor. SAH (OR 6.44, 95% CI 1.54-26.89, p = 0.011) and preprocedural mRS score > 2 (OR 5.07, 95% CI 1.01-25.59, p = 0.049) were independent risk factors for perforator occlusion stroke. Periprocedural cerebrovascular complications (OR 32.09, 95% CI 3.00-343.94, p = 0.004) and preprocedural mRS score > 2 (OR 319.92, 95% CI 30.28-3379.98, p < 0.001) were independent risk factors for 30-day unfavorable clinical outcomes., Conclusions: Hyperlipidemia, IS history, and SAH were independent predictors for overall periprocedural cerebrovascular complications of endovascular treatment for IVADAs, but aneurysmal height was an independent protective factor. SAH and preprocedural mRS score > 2 were independent risk factors for perforator occlusion stroke. Preprocedural mRS score > 2 and periprocedural complications were independent risk factors for 30-day unfavorable clinical outcomes.

Objective: Flow diverters have revolutionized the endovascular treatment of intracranial aneurysms. Here, the authors present the first large-scale North American multicenter experience using the Flow Redirection Endoluminal Device (FRED) in the treatment of cerebral aneurysms., Methods: Consecutive cerebral aneurysms treated with FRED at 7 North American centers between June 2020 and November 2021 were included. Data collected included patient demographic characteristics, aneurysm characteristics, periprocedural and long-term complications, modified Rankin Scale (mRS) scores, and radiological follow-up., Results: In total, 133 aneurysms in 116 patients were treated with 123 FRED deployment procedures and included in this study. One hundred twenty-six aneurysms (94.7%) were unruptured, 117 (88.0%) saccular, and 123 (92.5%) located in anterior circulation. The mean (range) aneurysm maximal width and neck width sizes were 7.2 (1.5-42.5) mm and 4.1 (1.0-15.1) mm, respectively. Successful FRED deployment was achieved in 122 procedures (99.2%). Adjunctive coiling was used in 4 procedures (3.3%). Radiological follow-up was available for 101 aneurysms at a median duration of 7.0 months. At last follow-up, complete occlusion was observed in 55.4% of patients, residual neck in 8.9%, and filling aneurysm in 35.6%; among cases with radiological follow-up duration > 10 months, these values were 21/43 (48.8%), 3/43 (7.0%), and 19/43 (44.2%), respectively. On multivariate regression analysis, age (OR 0.93, p = 0.001) and aneurysm neck size (OR 0.83, p = 0.048) were negatively correlated with odds of complete occlusion at latest follow-up. The retreatment rate was 6/124 (4.8%). The overall complication rate was 31/116 (26.7%). Parent vessel occlusion, covered branch occlusion, and in-stent stenosis were detected in 9/99 (9.1%), 6/63 (9.5%), and 15/99 (15.2%) cases, respectively. The FRED-related, symptomatic, thromboembolic, and hemorrhagic complication rates were 22.4%, 12.9%, 6.9%, and 0.9% respectively. The morbidity rate was 10/116 patients (8.6%). There was 1 death due to massive periprocedural internal carotid artery stroke, and 3.6% of the patients had an mRS score > 2 at the last follow-up (vs 0.9% at baseline)., Conclusions: As the first large-scale North American multicenter FRED experience, this study confirmed the ease of successful FRED deployment but suggested lower efficacy and a higher rate of complications than reported by previous European and South American studies on FRED and other flow-diverting devices. The authors recommend judicious use of this device until future studies can better elucidate the long-term outcomes of FRED treatment.

Objective: Flow-diverting stents with a resorbable component have significant theoretical benefits over full metal stents, although currently there are none in clinical use. In this study, the authors sought to determine the immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent., Methods: Bioresorbable stents were deployed into glass tube models to determine porosity and pore density. In vitro flow diversion behavior was evaluated using high frame rate angiography under pulsatile flow conditions in a patient-specific silicone aneurysm model treated with the resorbable stent as well as the Surpass Evolve stent. In vivo flow diversion was characterized by deployment into 20 rabbit saccular aneurysm models, and grading was based on the O'Kelly-Marotta scale and the 4F-flow diversion predictive score., Results: Porosities and pore densities of the bioresorbable stent were in the flow-diverting range for all target vessel diameters. Quantified results of immediate angiography after placement of the bioresorbable stent into a silicone aneurysm model demonstrated greater flow diversion compared to the Evolve stent. Bioresorbable stent placement in saccular aneurysm models resulted in an immediate O'Kelly-Marotta grade of A3 or better and a 4F-flow diversion predictive score of 4 or better in all cases., Conclusions: The bioresorbable stent has immediate flow-diversion characteristics that are comparable to commercially available metal stents. Longer-term studies are underway to determine the ability of the resorbable fibers to act as a neointimal scaffold and result in long-term aneurysm occlusion.

Objective: The Pipeline embolization device (PED) is widely used for the treatment of intracranial aneurysms, including in off-label applications. In this work, the authors compared the real-world efficacy and safety of PED use in on-label and off-label aneurysm treatments., Methods: Clinical and angiographic data of patients who underwent PED placement at a high-volume academic medical center were retrospectively obtained. Treatments were classified as on-label if they fell within the applications approved by the United States Food and Drug Administration as of 2021. Recorded outcomes included aneurysm occlusion, procedural complications, ischemic events, in-stent stenosis, intracranial hemorrhage, postprocedural functional status, and death., Results: In total, 416 aneurysms in 330 patients were treated with PED, comprising 256 aneurysms that received on-label treatments and 160 that received off-label treatments. The overall rate of complete aneurysm occlusion was 76.4% for on-label aneurysms and 75.6% for off-label aneurysms (p = 0.898). The risk of ischemic stroke in patients who underwent off-label treatments was 15.2%, which was higher than the 4.2% rate in patients who underwent on-label treatment (p = 0.003). All other clinical complications, procedural complications, and long-term functional status were comparable between the on-label and off-label groups., Conclusions: In real-world practice, off-label use of PED is common and can achieve similar efficacy as on-label use. However, in aggregate, off-label use was found to carry an increased rate of ischemic complications. With judicious attention to safety and individual patient characteristics, these results highlight the scale and general feasibility of off-label PED use by experts.

Objective: The long-term safety and efficacy of intrasaccular flow disruption (IFD) for the treatment of brain aneurysms remain unclear. With accumulating experience and increasing use of IFD devices, recent studies have provided additional data regarding their outcomes. This review summarizes the long-term outcomes of IFD-treated brain aneurysms., Methods: A systematic literature review was performed on May 23, 2021, in PubMed, Web of Science, and Ovid MEDLINE for aneurysm treatment outcomes with IFD devices. Procedural details, including use of adjunctive devices and complications, were collected. The quality of studies was assessed using the Downs and Black checklist. Angiographic outcomes were classified as complete occlusion, residual neck, and residual aneurysm. Other outcomes included need for retreatment, permanent neurological deficit, and mortality. Pooled analyses were performed., Results: The final analysis comprised 1217 patients with 1249 aneurysms from 22 studies. The mean aneurysm diameter and neck width were 6.9 and 4.5 mm, respectively, and 27.6% of aneurysms were ruptured. The complete occlusion rates at 12 months and final follow-up (pooled mean duration 15.7 months) were 50.1% and 58.2%, respectively. Adjunctive devices were used in 6.4% of cases. The rates of hemorrhage, symptomatic infarction, permanent neurological deficit, and mortality were 1.2%, 2.8%, 1.0%, and 2.6%, respectively., Conclusions: IFD is a very safe treatment for appropriately selected brain aneurysms with low complication and neurological deterioration rates. However, complete occlusion is achieved in only half of IFD-treated aneurysms at 1 year with a modest increase beyond this time point. As the majority of the studies were single arm, the pooled data are subject to selection and reporting biases. Future device developments, increased operator experience, and direct comparisons with alternative endovascular strategies and surgical clipping may clarify the role of IFD in aneurysm management.

Objective: Ophthalmic artery (OA) aneurysms are surgically challenging lesions that are now mostly treated using endovascular procedures. However, in specialized tertiary care centers with experienced neurosurgeons, controversy remains regarding the optimal treatment of these lesions. This study used propensity adjustment to compare microsurgical and endovascular treatment of unruptured OA aneurysms in experienced tertiary and quaternary settings., Methods: The authors retrospectively reviewed the medical records of all patients who underwent microsurgical treatment of an unruptured OA aneurysm at the University of California, San Francisco, from 1997 to 2017 and either microsurgical or endovascular treatment at Barrow Neurological Institute from 2011 to 2019. Patients were categorized into two cohorts for comparison: those who underwent open microsurgical clipping, and those who underwent endovascular flow diversion or coil embolization. Outcomes included neurological or visual outcomes, residual or recurrent aneurysms, retreatment, and severe complications., Results: A total of 345 procedures were analyzed: 247 open microsurgical clipping procedures (72%) and 98 endovascular procedures (28%). Of the 98 endovascular procedures, 16 (16%) were treated with primary coil embolization and 82 (84%) with flow diversion. After propensity adjustment, microsurgical treatment was associated with higher odds of a visual deficit (OR 8.5, 95% CI 1.1-64.9, p = 0.04) but lower odds of residual aneurysm (OR 0.06, 95% CI 0.01-0.28, p < 0.001) or retreatment (OR 0.12, 95% CI 0.02-0.58, p = 0.008) than endovascular therapy. No difference was found between the two cohorts with regard to worse modified Rankin Scale score, modified Rankin Scale score greater than 2, or severe complications., Conclusions: Compared with endovascular therapy, microsurgical clipping of unruptured OA aneurysms is associated with a higher rate of visual deficits but a lower rate of residual and recurrent aneurysms. In centers experienced with both open microsurgical and endovascular treatment of these lesions, the treatment choice should be based on patient preference and aneurysm morphology.

Objective: Flow-diverter stents (FDSs) are not generally used for the management of acutely ruptured aneurysms with associated subarachnoid hemorrhage (SAH). Herein, the authors present their experience with FDSs in this scenario, focusing on the antiplatelet regimen, perioperative management, and outcome., Methods: The authors retrospectively reviewed their institutional database for the treatment and outcomes of all patients with acutely ruptured aneurysms and associated SAH from July 2010 to September 2018 who had received an FDS implant as stand-alone treatment within 4 days after diagnosis. The protocol with the use of flow diversion in these patients includes a low threshold for placement of external ventricular drains before stenting, followed by the administration of aspirin and clopidogrel with platelet testing before stent implantation. With this approach, the risk of hemorrhage and stent-related thrombus formation is limited. Demographic, clinical, technical, and imaging data were analyzed., Results: Overall, 76 patients (61% females, mean age 42.8 ± 11.3 years) met the inclusion criteria. FDS implantation was performed a median of 2 days after diagnosis. On average, 1.05 devices were used per procedure. There was no procedural mortality directly attributed to the endovascular intervention. Procedural device-related clinical complications were recorded in a total of 6 cases (7.9%) and resulted in permanent neurological morbidity in 2 cases (2.6%). There was complete immediate aneurysm occlusion in 11 patients (14.5%), and persistent aneurysm filling was seen in 65 patients (85.5%). Despite this, no patient presented with rebleeding from the target aneurysm. There was an excellent clinical outcome in 62 patients (81.6%), who had a 90-day modified Rankin Scale score of 0-2. Among the 71 survivors, total or near-total occlusion was observed in 64/67 patients (95.5%) with a 3- to 6-month angiographic follow-up and in all cases evaluated at 12 months. Five patients (6.6%) died during follow-up for reasons unrelated to the procedure or new hemorrhage., Conclusions: Flow diversion is an effective therapeutic strategy for the management of select acutely ruptured aneurysms. Despite low rates of immediate aneurysm occlusion after FDS implantation, the device exerts an important protective effect. The authors' experience confirmed no aneurysm rerupture, high rates of delayed complete occlusion, and complication rates that compare favorably with the rates obtained using other techniques.

Objective: Flow diversion is increasingly used to treat a variety of intracranial aneurysms with good safety and efficacy; however, there is some evidence that this treatment is associated with a larger postoperative ischemic burden on imaging than that with other traditional endovascular modalities. These findings typically do not manifest as neurological deficits, but any subtle effects on cognition remain unknown. In this study, the authors describe the neurocognitive performance of a cohort of patients with unruptured intracranial aneurysms (UIAs) before and after treatment with flow diversion. This is the first report of cognitive outcomes following aneurysm treatment with flow diversion., Methods: The authors prospectively collected data on cognitive function using the Montreal Cognitive Assessment (MoCA) tool in patients with UIAs who were undergoing endovascular aneurysm treatment with flow diversion between June 2017 and July 2019. Patients completed the MoCA prior to intervention, at the 1-month follow-up after treatment, and again at 6 months after the procedure. All patients with UIAs treated with flow diversion were included regardless of age, aneurysm location, or morphology, unless their functional status precluded completion of the MoCA instrument. A repeated-measures linear mixed-effects model was used to compare preintervention and postintervention cognitive status at the time intervals outlined., Results: Fifty-one patients with 61 aneurysms underwent endovascular aneurysm treatment with flow diversion (mean age 52.5 years, 90.2% females). There was no difference between baseline and postprocedure MoCA scores at any time interval (p > 0.05). The MoCA scores at baseline, 1 month postprocedure, and 6 months postprocedure were 26.1, 26.2, and 26.6, respectively. There was also no difference between pre- and postprocedure scores on any individual domain of the instrument (visuospatial, naming, attention, language, abstraction, delayed recall, and orientation) at any time interval (p > 0.05). Thirty-four patients had follow-up MRI or CT imaging, 5 of whom showed radiographic changes or ischemia. All patients with follow-up clinical evaluation had a 6-month modified Rankin Scale score ≤ 2., Conclusions: Flow diversion is increasingly used in the treatment of intracranial aneurysms. This study suggests that this treatment may not alter neurocognitive function. Larger patient samples and longer follow-ups with other tests of cognitive functions are needed to confirm these findings.

Objective: There is currently no standardized follow-up imaging strategy for intracranial aneurysms treated with the Pipeline embolization device (PED). Here, the authors use follow-up imaging data for aneurysms treated with the PED to propose a standardizable follow-up imaging strategy., Methods: A retrospective review of all patients who underwent treatment for ruptured or unruptured intracranial aneurysms with the PED between March 2013 and March 2017 at 2 major academic institutions in the US was performed., Results: A total of 218 patients underwent treatment for 259 aneurysms with the PED and had undergone at least 1 follow-up imaging session to assess aneurysm occlusion status. There were 235 (90.7%) anterior and 24 posterior (9.3%) circulation aneurysms. On Kaplan-Meier analysis, the cumulative incidences of aneurysm occlusion at 6, 12, 18, and 24 months were 38.2%, 77.8%, 84.2%, and 85.1%, respectively. No differences in the cumulative incidence of aneurysm occlusion according to aneurysm location (p = 0.39) or aneurysm size (p = 0.81) were observed. A trend toward a decreased cumulative incidence of aneurysm occlusion in patients 70 years or older was observed (p = 0.088). No instances of aneurysm rupture after PED treatment or aneurysm recurrence after occlusion were noted. Sixteen (6.2%) aneurysms were re-treated with the PED; 11 of these had imaging follow-up data available, demonstrating occlusion in 3 (27.3%)., Conclusions: The authors propose a follow-up imaging strategy that incorporates 12-month digital subtraction angiography and 24-month MRA for patients younger than 70 years and single-session digital subtraction angiography at 12 months in patients 70 years or older. For recurrent or persistent aneurysms, re-treatment with the PED or use of an alternative treatment modality may be considered.

Objective: Flow diversion for posterior circulation aneurysms performed using the Pipeline embolization device (PED) constitutes an increasingly common off-label use for otherwise untreatable aneurysms. The safety and efficacy of this treatment modality has not been assessed in a multicenter study., Methods: A retrospective review of prospectively maintained databases at 8 academic institutions was performed for the years 2009 to 2016 to identify patients with posterior circulation aneurysms treated with PED placement., Results: A total of 129 consecutive patients underwent 129 procedures to treat 131 aneurysms; 29 dissecting, 53 fusiform, and 49 saccular lesions were included. At a median follow-up of 11 months, complete and near-complete occlusion was recorded in 78.1%. Dissecting aneurysms had the highest occlusion rate and fusiform the lowest. Major complications were most frequent in fusiform aneurysms, whereas minor complications occurred most commonly in saccular aneurysms. In patients with saccular aneurysms, clopidogrel responders had a lower complication rate than did clopidogrel nonresponders. The majority of dissecting aneurysms were treated in the immediate or acute phase following subarachnoid hemorrhage, a circumstance that contributed to the highest mortality rate in those aneurysms., Conclusions: In the largest series to date, fusiform aneurysms were found to have the lowest occlusion rate and the highest frequency of major complications. Dissecting aneurysms, frequently treated in the setting of subarachnoid hemorrhage, occluded most often and had a low complication rate. Saccular aneurysms were associated with predominantly minor complications, particularly in clopidogrel nonresponders.

OBJECTIVE Flow diversion requires neointimal stent overgrowth to deliver aneurysm occlusion. The existing literature on aneurysm occlusion is limited by heterogeneous follow-up, variable antiplatelet regimens, noninvasive imaging modalities, and nonstandard occlusion assessment. Using a large, single-center cohort with low attrition and standardized antiplatelet tapering, the authors evaluated outcomes after flow diversion of anterior circulation aneurysms to identify predictors of occlusion and aneurysm persistence. METHODS Data from a prospective, IRB-approved database was analyzed for all patients with anterior circulation aneurysms treated by flow diversion with the Pipeline embolization device (PED) at the authors' institution. Follow-up consisted of catheter cerebral angiography at 6 and 12 months postembolization. Clopidogrel was discontinued at 6 months and aspirin was reduced to 81 mg daily at 12 months. Occlusion was graded as complete, trace filling, entry remnant, or aneurysm filling. Multivariate logistic regression was performed to identify predictors of aneurysm persistence. RESULTS Follow-up catheter angiography studies were available for 445 (91%) of 491 PED procedures performed for anterior circulation aneurysms between August 2011 and August 2016. Three hundred eighty-seven patients accounted for these 445 lesions with follow-up angiography. The population was 84% female; mean age was 56 years and mean aneurysm size was 6.6 mm. Aneurysms arose from the internal carotid artery (83%), anterior cerebral artery (13%), and middle cerebral artery (4%). Morphology was saccular in 90% of the lesions, and 18% of the aneurysms has been previously treated. Overall, complete occlusion was achieved in 82% of cases at a mean follow-up of 14 months. Complete occlusion was achieved in 72%, 78%, and 87% at 6, 12, and 24 months, respectively. At 12 months, adjunctive coiling predicted occlusion (OR 0.260, p = 0.036), while male sex (OR 2.923, p = 0.032), aneurysm size (OR 3.584, p = 0.011), and incorporation of a branch vessel (OR 2.206, p = 0.035) predicted persistence. Notable variables that did not predict aneurysm occlusion were prior treatments, vessel of origin, fusiform morphology, and number of devices used. CONCLUSIONS This is the largest single-institution study showing high rates of anterior circulation aneurysm occlusion after Pipeline embolization. Predictors of persistence after flow diversion included increasing aneurysm size and incorporated branch vessel, whereas adjunctive coiling predicted occlusion.

OBJECTIVEThe second-generation Pipeline embolization device (PED), Flex, has several design upgrades, including improved opening and the ability to be resheathed, in comparison with the original device (PED classic). The authors hypothesized that Flex is associated with a lower rate of major complications.METHODSA prospective, IRB-approved, single-institution database was analyzed for all patients with anterior circulation aneurysms treated by flow diversion. The PED classic was used from August 2011 to January 2015, and the Pipeline Flex has been used since February 2015.RESULTSA total of 568 PED procedures (252 classic and 316 Flex) were performed for anterior circulation aneurysms. The average aneurysm size was 6.8 mm. Patients undergoing treatment with the Flex device had smaller aneurysms (p = 0.006) and were more likely to have undergone previous treatments (p = 0.001). Most aneurysms originated along the internal carotid artery (89% classic and 75% Flex) but there were more anterior cerebral artery (18%) and middle cerebral artery (7%) deployments with Flex (p = 0.001). Procedural success was achieved in 96% of classic and 98% of Flex cases (p = 0.078). Major morbidity or death occurred in 3.5% of cases overall: 5.6% of classic cases, and 1.9% of Flex cases (p = 0.019). On multivariate logistic regression, predictors of major complications were in situ thrombosis (OR 4.3, p = 0.006), classic as opposed to Flex device (OR 3.7, p = 0.008), and device deployment in the anterior cerebral artery or middle cerebral artery as opposed to the internal carotid artery (OR 3.5, p = 0.034).CONCLUSIONSFlow diversion of anterior circulation cerebral aneurysms is associated with an overall low rate of major complications. The complication rate is significantly lower since the introduction of the second-generation PED (Flex).

Objective: Paraclinoid aneurysms represent approximately 5% of intracranial aneurysms (Drake et al. [1968]). Visual impairment, which occurs in 16%-40% of patients, is among the most common presentations of these aneurysms (Day [1990], Lai and Morgan [2013], Sahlein et al. [2015], and Silva et al. [2017]). Flow-diverting stents, such as the Pipeline Embolization Device (PED), are increasingly used to treat these aneurysms, in part because of their theoretical reduction of mass effect (Fiorella et al. [2009]). Limited data on paraclinoid aneurysms treated with a PED exist, and few studies have compared outcomes of patients after PED placement with those of patients after clipping or coiling., Methods: The authors performed a retrospective analysis of 115 patients with an aneurysm of the cavernous to ophthalmic segments of the internal carotid artery treated with clipping, coiling, or PED deployment between January 2011 and March 2017. Postoperative complications were defined as new neurological deficit, aneurysm rupture, recanalization, or other any operative complication that required reintervention., Results: A total of 125 paraclinoid aneurysms in 115 patients were treated, including 70 with PED placement, 23 with coiling, and 32 with clipping. Eighteen (14%) aneurysms were ruptured. The mean aneurysm size was 8.2 mm, and the mean follow-up duration was 18.4 months. Most aneurysms were discovered incidentally, but visual impairment, which occurred in 21 (18%) patients, was the most common presenting symptom. Among these patients, 15 (71%) experienced improvement in their visual symptoms after treatment, including 14 (93%) of these 15 patients who were treated with PED deployment. Complete angiographic occlusion was achieved in 89% of the patients. Complications were seen in 17 (15%) patients, including 10 (16%) after PED placement, 2 (9%) after coiling, and 5 (17%) after clipping. Patients with incomplete aneurysm occlusion had a higher rate of procedural complications than those with complete occlusion (p = 0.02). The rate of postoperative visual improvement was significantly higher among patients treated with PED deployment than in those treated with coiling (p = 0.01). The significant predictors of procedural complications were incomplete occlusion (p = 0.03), hypertension, (p = 0.04), and diabetes (p = 0.03)., Conclusions: In a large series in which patient outcomes after treatment of paraclinoid aneurysms were compared, the authors found a high rate of aneurysm occlusion and a comparable rate of procedural complications among patients treated with PED placement compared with the rates among those who underwent clipping or coiling. For patients who presented with visual symptoms, those treated with PED placement had the highest rate of visual improvement. The results of this study suggest that the PED is an effective and safe modality for treating paraclinoid aneurysms, especially for patients who present with visual symptoms.

Objective: The Pipeline embolization device (PED) has become a valuable tool in the treatment of cerebral aneurysms. Although failures with PED treatment have been reported, the characteristics and course of these aneurysms remain a topic of uncertainty., Methods: Electronic medical records and imaging studies were reviewed for all patients treated with the PED between July 2010 and March 2015 to identify characteristics of patients and aneurysms with residual filling after PED treatment., Results: Of 316 cases treated at a single institution, 281 patients had a long-term follow-up. A total of 52 (16.4%) aneurysms with residual filling were identified and constituted the study population. The mean patient age in this population was 58.8 years. The mean aneurysm size was 10.1 mm ± 7.15 mm. Twelve aneurysms were fusiform (23%). Of the aneurysms with residual filling, there were 20 carotid ophthalmic (CO) aneurysms (20% of all CO aneurysms treated), 10 other paraclinoid aneurysms (16.4% of all paraclinoid aneurysms), 7 posterior communicating artery (PCoA) aneurysms (21.9% of all PCoA aneurysms), 7 cavernous internal carotid artery (ICA) aneurysms (14.9% of all cavernous ICA aneurysms), 4 vertebrobasilar (VB) junction aneurysms (14.8% of all VB junction aneurysms), and 3 middle cerebral artery (MCA) aneurysms (25% of all MCA aneurysms). Eleven patients underwent placement of more than one PED (21.2%), with a mean number of devices of 1.28 per case. Eight of 12 aneurysms were previously treated with a stent (15.4%). Nineteen patients underwent re-treatment (36.5%); the 33 patients who did not undergo re-treatment (63.5%) were monitored by angiography or noninvasive imaging. In multivariate analysis, age older than 65 years (OR 2.65, 95% CI 1.33-5.28; p = 0.05), prior stent placement across the target aneurysm (OR 2.94, 95% CI 1.15-7.51; p = 0.02), aneurysm location in the distal anterior circulation (MCA, PCoA, and anterior choroidal artery: OR 2.72, 95% CI 1.19-6.18; p = 0.017), and longer follow-up duration (OR 1.06, 95% CI 1.03-1.09; p < 0.001) were associated with incomplete aneurysm occlusion., Conclusions: While the PED can allow for treatment of large, broad-necked aneurysms with high efficacy, treatment failures do occur (16.4%). Aneurysm size, shape, and previous treatment may influence treatment outcome.

The objective of this paper was to report a rare complication of basilar artery (BA) tourniquet treatment of a giant basilar tip aneurysm, and to discuss possible causes for the formation of a de novo giant posterior cerebral artery (PCA) aneurysm. A 34-year-old woman underwent satisfactory treatment of a ruptured giant basilar bifurcation aneurysm by BA ligation (Drake tourniquet) in 1985. She presented 25 years later with a new aneurysm in the left PCA, successfully treated by coil embolization. To the authors' knowledge, this is the first case of de novo aneurysm formation on a PCA, and the first de novo aneurysm reported as a complication of BA ligation therapy by Drake tourniquet. Long-term follow-up is necessary in patients with treated cerebral aneurysms, particularly those occurring in young patients, those with multiple aneurysms, those with complex posterior circulation aneurysms, and those undergoing flow diversion or flow-altering therapies.

OBJECTIVE Intracranial bifurcation aneurysms are complex lesions for which current therapy, including simple coiling, balloon- or stent-assisted coiling, coil retention, or intrasaccular devices, is inadequate. Thromboembolic complications due to a large burden of intraluminal metal, impedance of access to side branches, and a high recurrence rate, due largely to the unmitigated high-pressure flow into the aneurysm (water hammer effect), are among the limitations imposed by current therapy. The authors describe herein a novel device, eCLIPs, and its use in a preclinical laboratory study that suggests the device's design and functional features may overcome many of these limitations. METHODS A preclinical model of wide-necked bifurcation aneurysms in rabbits was used to assess functional features and efficacy of aneurysm occlusion by the eCLIPs device. RESULTS The eCLIPs device, in bridging the aneurysm neck, allows coil retention, disrupts flow away from the aneurysm, leaves the main vessel and side branches unencumbered by intraluminal metal, and serves as a platform for endothelial growth across the neck, excluding the aneurysm from the circulation. CONCLUSIONS The eCLIPs device permits physiological remodeling of the bifurcation.

OBJECTIVE Treatment of wide-necked intracranial aneurysms is associated with higher recanalization and complication rates; however, the most commonly used methods are not specifically designed to work in bifurcation lesions. To address these issues, the authors describe the evolution in the design and use of the eCLIPs (Endovascular Clip System) device, a novel hybrid stent-like assist device with flow diverter properties that was first described in 2008. METHODS A registry was established covering 13 international centers at which patients were treated with the second-generation eCLIPs device. Aneurysm morphology and rupture status, device neck coverage, coil retention, and procedural and late morbidity and mortality were recorded. For those patients who had undergone successful implantation more than 6 months earlier, the final imaging and clinical follow-up results and need for re-treatment were recorded. RESULTS Thirty-three patients were treated between June 2013 and September 2015. Twenty-five (76%) patients had successful placement of an eCLIPs device; 23 (92%) of these 25 patients had complete data. Eight cases of nondeployment occurred during the 1st year of use, consistent with a learning curve; no failures of deployment occurred thereafter. Two periprocedural transient ischemic attacks and 2 asymptomatic thrombotic events occurred. Twenty-one (91%) of 23 patients underwent follow-up at an average of 8 months (range 3-18 months); 9 (42.9%) of these 21 patients demonstrated an improvement in Raymond grade at follow-up; no cases of worsening Raymond grade were recorded, and 17 (81.0%) patients sustained a modified Raymond-Roy Classification class of I or II angiographic result at follow-up. Two delayed ruptures were recorded, both in previously coiled, symptomatic giant aneurysms where the device was used as a part of a salvage strategy. CONCLUSIONS The second-generation eCLIPs device is a viable treatment option for bifurcation aneurysms. The aneurysm occlusion rates in this initial clinical series are comparable to the initial experience with other bifurcation support devices.

OBJECTIVE The Pipeline Embolization Device (PED) is now a well-established option for the treatment of giant or complex aneurysms, especially those arising from the anterior circulation. Considering the purpose of such treatment is to maintain patency of the parent vessel, postembolization occlusion of the parent artery can be regarded as an untoward outcome. Antiplatelet therapy in the posttreatment period is therefore required to minimize such events. Here, the authors present a series of patients with anterior circulation aneurysms treated with the PED who subsequently experienced parent vessel occlusion (PVO). METHODS The authors performed a retrospective review of all anterior circulation aneurysms consecutively treated at a single institution with the PED through 2014, identifying those with PVO on follow-up imaging. Aneurysm size and location, number of PEDs used, and follow-up digital subtraction angiography results were recorded. When available, pre- and postembolization platelet function testing results were also recorded. RESULTS Among 256 patients with anterior circulation aneurysms treated with the PED, the authors identified 8 who developed PVO after embolization. The mean aneurysm size in this cohort was 22.3 mm, and the number of PEDs used per case ranged from 2 to 10. Six patients were found to have asymptomatic PVO discovered incidentally on routine follow-up imaging between 6 months and 3 years postembolization, 3 of whom had documented "delayed" PVO with prior postembolization angiograms confirming aneurysm occlusion and a patent parent vessel at an earlier time. Two additional patients experienced symptomatic PVO, one of which was associated with early discontinuation of antiplatelet therapy. CONCLUSIONS In this large series of anterior circulation aneurysms, the authors report a low incidence of symptomatic PVO, complicating premature discontinuation of postembolization antiplatelet or anticoagulation therapy. Beyond the subacute period, asymptomatic PVO was more common, particularly among complex fusiform or very large-necked aneurysms, highlighting an important phenomenon with the use of PED for the treatment of anterior circulation aneurysms, and suggesting that extended periods of antiplatelet coverage may be required in select complex aneurysms.

OBJECTIVE The Flow Diversion in the Treatment of Intracranial Aneurysm Trial (FIAT) was designed to guide the clinical use of flow diversion, an innovative method to treat intracranial aneurysms, within a care trial and to study safety and efficacy. METHODS FIAT, conducted in 3 Canadian hospitals, proposed randomized allocation to flow diversion or standard management options (observation, coil embolization, parent vessel occlusion, or clip placement), and a registry of non-randomized patients treated with flow diversion. The primary safety outcome was death or dependency (modified Rankin Scale score > 2) at 3 months, to be determined for all patients who received flow diversion at any time. The primary efficacy outcome was angiographic occlusion at 3-12 months combined with an independent clinical outcome. RESULTS Of 112 participating patients recruited between May 2, 2011, and February 25, 2015, 78 were randomized (39 in each arm), and 34 received flow diversion within the registry. The study was halted due to safety concerns. Twelve (16%) of 75 patients (95% CI 8.9%-26.7%) who were allocated to or received flow diversion at any time were dead (n = 8) or dependent (n = 4) at 3 months or more, crossing a predefined safety boundary. Death or dependency occurred in 5 (13.2%) of 38 patients randomly allocated and treated by flow diversion (95% CI 5.0%-28.9%) and in 5 (12.8%) of 39 patients allocated to standard treatment (95% CI 4.8%-28.2%). Efficacy was below expectations of the trial hypothesis: 16 (42.1%) of 38 patients (95% CI 26.7%-59.1%) randomly allocated to flow diversion failed to reach the primary outcome, as compared with 14 (35.9%) of 39 patients allocated to standard treatment (95% CI 21.7%-52.9%). CONCLUSIONS Flow diversion was not as safe and effective as hypothesized. More randomized trials are needed to determine the role of flow diversion in the management of aneurysms. Clinical trial registration no.: NCT01349582 (clinicaltrials.gov).

OBJECTIVE The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. METHODS The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data. RESULTS At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0-1 were demonstrated in 80 subjects. CONCLUSIONS Pipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth. Clinical trial registration no.: NCT00777088 (clinicaltrials.gov).

The Pipeline Embolization Device (PED) was approved for the treatment of intracranial aneurysms from the petrous to the superior hypophyseal segment of the internal carotid artery. However, since its approval, its use for treatment of intracranial aneurysms in other locations and non-sidewall aneurysms has grown tremendously. The authors report on a cohort of 15 patients with 16 cerebral aneurysms that incorporated an end vessel with no significant distal collaterals, which were treated with the PED. The cohort includes 7 posterior communicating artery aneurysms, 5 ophthalmic artery aneurysms, 1 superior cerebellar artery aneurysm, 1 anterior inferior cerebellar artery aneurysm, and 2 middle cerebral artery aneurysms. None of the aneurysms achieved significant occlusion at the last follow-up evaluation (mean 24 months). Based on these observations, the authors do not recommend the use of flow diverters for the treatment of this subset of cerebral aneurysms.

Successful application of endovascular neurosurgery depends on high-quality imaging to define the pathology and the devices as they are being deployed. This is especially challenging in the treatment of complex cases, particularly in proximity to the skull base or in patients who have undergone prior endovascular treatment. The authors sought to optimize real-time image guidance using a simple algorithm that can be applied to any existing fluoroscopy system. Exposure management (exposure level, pulse management) and image post-processing parameters (edge enhancement) were modified from traditional fluoroscopy to improve visualization of device position and material density during deployment. Examples include the deployment of coils in small aneurysms, coils in giant aneurysms, the Pipeline embolization device (PED), the Woven EndoBridge (WEB) device, and carotid artery stents. The authors report on the development of the protocol and their experience using representative cases. The stent deployment protocol is an image capture and post-processing algorithm that can be applied to existing fluoroscopy systems to improve real-time visualization of device deployment without hardware modifications. Improved image guidance facilitates aneurysm coil packing and proper positioning and deployment of carotid artery stents, flow diverters, and the WEB device, especially in the context of complex anatomy and an obscured field of view.