CLinical EValuation of WEB 17 device in intracranial aneuRysms (CLEVER): 1-year effectiveness results for ruptured and unruptured aneurysms.

BACKGROUND: The Woven EndoBridge (WEB) device is designed to treat wide-necked bifurcation aneurysms. The WEB 17 is the latest iteration and can be delivered through a 0.017″ microcatheter. The CLEVER study demonstrated that WEB 17 is safe and effective for providing protection against bleeding or rebleeding at 1 month and 1 year. OBJECTIVE: To evaluate angiographic stability at 1 year. METHODS: The CLEVER study was a prospective multicenter study conducted in 17 European centers, involved 163 subjects, comprising 60 ruptured and 103 unruptured aneurysms. Independent assessment of 1-year follow-up imaging was incorporated into the study design. RESULTS: Aneurysm diameters ranged from 2.0 to 9.2 mm, with 95.7% being broad-based (dome-to-neck ratio <2). Follow-up imaging at 1 year was completed for 146 out of 163 subjects (89.6%) and evaluated by an independent core laboratory. The primary efficacy endpoint of adequate occlusion without re-treatment at 1 year was achieved for 120 (82.2%) of all subjects. At 1 year, the adequate occlusion rate was 86.5% for ruptured aneurysms (73.1% complete occlusion) and 82.4% for unruptured aneurysms (57.1% complete occlusion). The overall re-treatment rate at 1 year was 2.6% (4/152), with 3.1% (3/97) for unruptured aneurysms and 1.8% (1/55) for ruptured aneurysms CONCLUSION: Delivery of the WEB 17 via 0.017 inch catheters represents a significant evolution of the WEB design. The results of CLEVER presented here demonstrate that it maintains the same efficacy as previous generations of WEB.

The reversed umbrella: displacement of a Contour device into an MCA aneurysm 18 months after treatment.

SummaryThe Contour is a promising new device designed to treat large-neck intra-cranial aneurysms. We describe a first case of Contour device displacement 18 months after initial treatment.A patient with a 10 mm unruptured right middle cerebral artery bifurcation aneurysm was treated with a 9 mm Contour. The device was correctly positioned at the neck during treatment and at the 6 month angiography follow-up. At 18 months follow-up we noticed a full displacement of the device into the aneurysm dome. The Contour had a reversed shape and the aneurysm was still fully opacified. No neurological event occurred during the whole follow-up. Contour may be a promising tool but needs to be assessed over a long-term period.

CLinical EValuation of WEB 17 device in intracranial aneuRysms (CLEVER): procedural, 30-day and 1-year safety results for ruptured and unruptured aneurysms.

BACKGROUND: Intrasaccular flow disruption is an endovascular approach for the treatment of wide-neck aneurysms and, more specifically, wide-neck bifurcation aneurysms, which are challenging to treat with previously developed technologies. The Woven EndoBridge (WEB) device has demonstrated its efficacy and safety, for both unruptured and ruptured aneurysms. METHODS: The CLEVER study was an observational, multicenter, prospective study conducted in 17 European investigational sites using the WEB 17 device, for the treatment of ruptured and unruptured aneurysms. The study objective was to provide safety and efficacy data on the WEB 17 device in the treatment of wide-neck bifurcation aneurysms. Imaging results were assessed independently by a Corelab and adverse events adjudicated by a Clinical Event Adjudicator. This analysis reports procedural results and safety at 30 days and 12 months. RESULTS: A total of 163 patients (mean age 58.1 years; 68.1% women) with 103 unruptured aneurysms and 60 ruptured aneurysms were enrolled. Most aneurysms were located on the anterior communicating artery (ACom) (37.4%) or the middle cerebral artery (MCA) bifurcation (30.1%). Aneurysm widths ranged from 2.0-9.2 mm, and the mean sac width was 5.0 mm. The WEB procedure was successfully completed in 163 patients (100%). At the 12-month follow-up, major stroke events occurred in 3 of 163 patients (1.8%), and no device-related mortality was observed. CONCLUSION: Endovascular treatment of ruptured and unruptured wide-neck bifurcation aneurysms using WEB 17 is safe, with a low complication rate and no device-related mortality. In particular, none of the ruptured aneurysms bled again up to 1 year of follow-up. TRIAL REGISTRATION NUMBER: NCT03844334.

Endovascular treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial.

OBJECTIVE: The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries. METHODS: Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2. RESULTS: From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%-22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%-28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%-25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%-21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%-37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%-20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%-40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%-21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%-35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%-29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%-33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%-34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%-26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%-34%). CONCLUSIONS: Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial.

Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations.

BACKGROUND: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients. METHODS: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients. RESULTS: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%). CONCLUSIONS: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs.

Aneurysm treatment with the Woven EndoBridge (WEB) device in the combined population of two prospective, multicenter series: 5-year follow-up.

BACKGROUND: Evaluating a new endovascular treatment for intracranial aneurysms must not only demonstrate short-term safety and efficacy, but also evaluate longer-term outcomes (eg, delayed complications, anatomical results, retreatment). The current analysis reports the 5-year clinical and anatomical results of Woven EndoBridge (WEB) treatment in two European combined trial populations (WEBCAST (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy) and WEBCAST-2). METHODS: All adverse events occurring between the procedure and 5-year follow-up were independently evaluated by an expert. Aneurysm occlusion was evaluated by an independent core laboratory using a three-grade scale: complete occlusion, neck remnant, and aneurysm remnant. In cases where data were not available at 5-year follow-up, the last observation carry forward (LOCF) method was used. RESULTS: The safety and efficacy populations comprised 100 patients and 95 aneurysms, respectively. No adverse event related to the device occurred after the procedure during the 5-year follow-up period. Mortality at 5 years was 7.0% (7/100 patients) including mortality related to the WEB (0/100, 0.0%), the procedure (1/100, 1.0%), and another condition (6/100, 6.0%). At 5 years, complete aneurysm occlusion was observed in 49/95 (51.6%) aneurysms, neck remnant in 25/95 (26.3%), and aneurysm remnant in 21/95 (22.1%). Retreatment rate at 5 years was 11.6% (11/95 aneurysms). CONCLUSIONS: This analysis conducted in a population of patients with wide-neck bifurcation aneurysms confirms WEB's safety profile. Additional evidence demonstrates good stability of aneurysm occlusion with adequate occlusion (complete occlusion or neck remnant) at 5 years in 77.9% of aneurysms with a low retreatment rate (11.6%). CLINICAL TRIAL REGISTRATION: WEBCAST and WEBCAST-2: Unique identifier: NCT01778322.

Coating (Coating to Optimize Aneurysm Treatment in the New Flow Diverter Generation) study. The first randomized controlled trial evaluating a coated flow diverter (p64 MW HPC): study design.

BACKGROUND: Due to its high efficacy, flow diversion is increasingly used in the management of unruptured and recanalized aneurysms. Because of the need for perioperative dual antiplatelet treatment (DAPT), flow diversion is not indicated for the treatment of ruptured aneurysms. To overcome this major limitation, surface modification-'coating'-of flow diverters has been developed to reduce platelet aggregation on the implanted device, reduce thromboembolic complications, and facilitate the use of coated flow diverter treatment in patients with single antiplatelet treatment (SAPT). COATING (Coating to Optimize Aneurysm Treatment in the New Flow Diverter Generation) is a prospective, randomized, multicenter trial that aims to determine whether the use of the coated flow diverter p64 MW HPC under SAPT is non-inferior (or even superior) to the use of the bare flow diverter p64 MW under DAPT in relation to thromboembolic and hemorrhagic complications. METHODS: Patients with unruptured or recanalized aneurysms for which endovascular treatment with a flow diverter is indicated will be enrolled and randomly assigned on a 1:1 ratio to one of two treatment groups: p64 MW HPC with SAPT or p64 MW with DAPT. RESULTS: The primary endpoint is the number of diffusion-weighted imaging lesions visualized via MRI assessed within 48 hours (±24 hours) of the index procedure. Secondary primary endpoints are comparing safety and efficacy in both arms. CONCLUSIONS: This randomized controlled trial is the first to directly compare safety and efficacy of coated flow diverters under SAPT with bare flow diverters under DAPT. TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov/ - NCT04870047.

Surgical treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial.

OBJECTIVE: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. METHODS: TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. RESULTS: From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I-II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%-93%) and 105/110 low-grade (95%, 95% CI 90%-98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%-18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%-28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%-9%), 5 (83%) of whom had complications due to preoperative embolization. CONCLUSIONS: The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov).

CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS): 12-month angiographic results of a multicenter study.

BACKGROUND: The CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS) study has shown that the endovascular treatment of ruptured bifurcation aneurysms with the Woven EndoBridge (WEB) is safe and effective and provides protection against rebleeding at 1 month and 1 year. The 12-month angiographic follow-up is an important endpoint of the study. METHODS: The CLARYS study is a prospective multicenter study conducted in 13 European centers. The study enrolled 60 patients with 60 ruptured aneurysms of the anterior and posterior circulation. The study was conducted with an independent assessment of safety outcomes and imaging. RESULTS: Sixty patients with 60 ruptured bifurcation aneurysms to be treated with the WEB were included. Fifty-three aneurysms (88.3%) had a broad base with a dome to neck ratio <2 (mean 1.6). Of these, 46 patients were evaluated by an independent core laboratory with follow-up imaging performed at 12 months or before eventual retreatment. At 1 year, 19/46 aneurysms (41.3%) were completely occluded (Raymond-Roy grade I), 21/46 (45.7%) had a residual neck and 6/46 (13.0%) had residual aneurysm filling. Adequate occlusion was reported in 40/46 (87%) aneurysms. Six patients underwent target aneurysm retreatment. CONCLUSIONS: The CLARYS study has previously shown that the use of the WEB in the endovascular treatment of ruptured bifurcation aneurysms provides effective protection against rebleeding with a good safety profile. The angiographic occlusion rates at 1 year reported here are comparable to those already seen in previous multicenter studies which primarily included unruptured aneurysms.

Effect of intravenous thrombolysis before endovascular therapy on outcome according to collateral status: insight from the ETIS Registry.

BACKGROUND: It is unknown whether collateral status modifies the effect of pretreatment intravenous thrombolysis (IVT) on the outcomes of patients with large vessel occlusions treated with endovascular therapy (EVT). We aimed to assess whether collateral status modifies the effect of IVT on the outcomes of EVT in clinical practice. METHODS: We used data from the ongoing prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France. Patients with anterior circulation proximal large vessel occlusions treated with EVT within 6 hours of symptom onset were enrolled. Patients were divided into two groups based on pretreatment with IVT. The two groups were matched based on baseline characteristics. We tested the interaction between collateral status and IVT in unadjusted and adjusted models. RESULTS: A total of 1589 patients were enrolled in the study, of whom 55% received IVT. Using a propensity score matching method, 724 no IVT patients were matched to 549 IVT patients. In propensity score weighted analysis, IVT was associated with higher odds of early neurological improvement (OR 1.74; 95% CI 1.33 to 2.26), favorable functional outcome (OR 1.66; 95% CI 1.23 to 2.24), excellent functional outcome (OR 2.04; 95% CI 1.47 to 2.83), and successful reperfusion (OR 2.18; 95% CI 1.51 to 3.16). IVT was not associated with mortality or hemorrhagic complications. There was no interaction between collateral status and IVT association with any of the outcomes. CONCLUSIONS: Collateral status does not modify the effect of pretreatment IVT on the efficacy and safety outcomes of EVT.

Long-term follow-up of an overexposure radiation incident in a cohort treated with linear accelerator-based stereotactic radiosurgery for intracranial arteriovenous malformations.

OBJECTIVE: Dosimetric radiosurgery incidents are rare and probably insufficiently reported in scientific publications. After a long follow-up (FU), the authors studied the outcomes of patients treated with overexposure radiation for arteriovenous malformation (AVM) administered via stereotactic radiosurgery (SRS) at their department. METHODS: Between May 2006 and June 2007, 22 patients were treated for AVM with SRS. The mean (range) patient age was 43.5 (11.8-78) years. Previous treatments were embolization (n = 10), SRS (1), and surgery (1). The average (range) volume was 2.1 (0.2-6.4) cm3. The median prescribed minimal dose was 18.0 Gy. An initial error in the estimation of scatter factors led to overexposure to radiation. Due to this incident, the median delivered minimum dose was 25.0 Gy. All patients were prospectively followed with clinical examination and imaging. RESULTS: The mean (range) clinical FU was 14.5 (12.0-15.2) years. AVM obliteration after SRS was completed in 90.9% of patients at a mean (range) of 39.4 (24.4-70.4) months. No patient had post-SRS AVM bleeding. Three patients (13.6%) had new permanent deficits due to radiation-induced changes (RICs). Obliteration without new deficits was achieved in 18 patients (81.8%). Two patients had new epilepsy that was probably due to RIC but well controlled. The median (range) MRI FU was 13.8 (2.5-14.9) years. During MRI FU, two RIC periods were observed: one classic period during the first 3 years showed T1-weighted annular irregular enhancement (13%), and the other period between 5 and 15 years after SRS showed the occurrence of cystic and hemorrhagic lesions (22.7%). There were no cases of radiation-induced tumor. CONCLUSIONS: The present long-term report showed that this overexposure incident probably increased the AVM obliteration rate. This overexposure seems to have induced RIC and in particular a higher rate of cystic and hemorrhagic late lesions with nevertheless moderate clinical consequences. Long-term FU for AVM is mandatory due to the risk of late RIC.

What predicts poor outcome after successful thrombectomy in early time window?

BACKGROUND: Half of the patients with large vessel occlusion (LVO)-related acute ischemic stroke (AIS) who undergo endovascular reperfusion are dead or dependent at 3 months. We hypothesize that in addition to established prognostic factors, baseline imaging profile predicts outcome among reperfusers. METHODS: Consecutive patients receiving endovascular treatment (EVT) within 6 hours after onset with Thrombolysis In Cerebral Infarction (TICI) 2b, 2c and 3 revascularization were included. Poor outcome was defined by a modified Rankin scale (mRS) 3-6 at 90 days. No mismatch (NoMM) profile was defined as a mismatch (MM) ratio ≤1.2 and/or a volume <10 mL on pretreatment imaging. RESULTS: 187 patients were included, and 81 (43%) had a poor outcome. Median delay from stroke onset to the end of EVT was 259 min (IQR 209-340). After multivariable logistic regression analysis, older age (OR 1.26, 95% CI 1.06 to 1.5; p=0.01), higher National Institutes of Health Stroke Scale (NIHSS) (OR 1.15, 95% CI 1.06 to 1.25; p<0.0001), internal carotid artery (ICA) occlusion (OR 3.02, 95% CI 1.2 to 8.0; p=0.021), and NoMM (OR 4.87, 95% CI 1.09 to 22.8; p=0.004) were associated with poor outcome. In addition, post-EVT hemorrhage (OR 3.64, 95% CI 1.5 to 9.1; p=0.04) was also associated with poor outcome. CONCLUSIONS: The absence of a penumbra defined by a NoMM profile on baseline imaging appears to be an independent predictor of poor outcome after reperfusion. Strategies aiming to preserve the penumbra may be encouraged to improve these patients' outcomes.

CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS): results of 1-month and 1-year assessment of rebleeding protection and clinical safety in a multicenter study.

BACKGROUND: The primary goal of the CLARYS study is to assess the protection against rebleeding when treating ruptured bifurcation aneurysms with the Woven EndoBridge (WEB) device. METHODS: The CLARYS study is a prospective, multicenter study conducted in 13 European centers. Patients with ruptured bifurcation aneurysms were consecutively included between February 2016 and September 2017. The primary endpoint was defined as the rebleeding rate of the target aneurysm treated with the WEB within 30 days postprocedure. Secondary endpoints included periprocedural and postprocedural adverse events, total procedure and fluoroscopy times, and modified Rankin Scale score at 1 month and 1 year. RESULTS: Sixty patients with 60 ruptured bifurcation aneurysms to be treated with the WEB were included. A WEB device was successfully implanted in 93.3%. The rebleeding rate at 1 month and 1 year was 0%. The mean fluoroscopy time was 27.0 min. Twenty-three periprocedural complications were observed in 18 patients and resolved without sequelae in 16 patients. Two of these complications were attributed to the procedure and/or the use of the WEB, leading to a procedure/device-related intraoperative complication rate of 3.3%. Overall mortality at 1 month and 1 year was 1.7% and 3.8%, respectively and overall morbidity at 1 month and 1 year was 15% and 9.6%, respectively. WEB-related 1-month and 1-year morbidity and mortality was 0%. CONCLUSIONS: The interim results of CLARYS show that the endovascular treatment of ruptured bifurcation aneurysms with the WEB is safe and effective and, in particular, provides effective protection against rebleeding. It may induce profound change in the endovascular management of ruptured bifurcation aneurysms.

Immediate post-operative aneurysm occlusion after endovascular treatment of intracranial aneurysms with coiling or balloon-assisted coiling in a prospective multicenter cohort of 1189 patients: Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm (ARETA) Study.

BACKGROUND: Coiling, including balloon-assisted coiling (BAC), is the first-line therapy for ruptured and unruptured aneurysms. Its efficacy can be clinically evaluated by bleeding/rebleeding rate after coiling, and anatomically evaluated by aneurysm occlusion post-procedure and during follow-up. We aimed to analyze immediate post-coiling aneurysm occlusion and associated factors within the Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm (ARETA) population. METHODS: Between December 2013 and May 2015, 16 neurointerventional departments prospectively enrolled participants treated for ruptured and unruptured aneurysms (ClinicalTrials.gov: NCT01942512). Participant demographics, aneurysm characteristics, and endovascular techniques were recorded. In patients with aneurysms treated by coiling or BAC, immediate post-operative aneurysm occlusion was independently evaluated by a core lab using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. RESULTS: Of 1135 participants (age 53.8±12.8 years, 754 women (66.4%)), 1189 aneurysms were analyzed. Treatment modality was standard coiling in 645/1189 aneurysms (54.2%) and BAC in 544/1189 (45.8%). Immediate post-operative aneurysm occlusion was complete occlusion in 57.8%, neck remnant in 34.4%, and aneurysm remnant in 7.8%. Adequate occlusion (complete occlusion or neck remnant) was significantly more frequent in aneurysms with size <10 mm (93.1% vs 86.3%; OR 1.8, 95% CI 1.1 to 3.2; p=0.02) and in aneurysms with a narrow neck (95.8% vs 89.6%; OR 2.5, 95% CI 1.5 to 4.1; p=0.0004). Patients aged <70 years had significantly more adequate occlusion (92.7% vs 87.2%; OR 1.9, 95% CI 1.1 to 3.4; p=0.04). CONCLUSIONS: Immediately after aneurysm coiling, including BAC, adequate aneurysm occlusion was obtained in 92.2%. Age <70 years, aneurysm size <10 mm, and narrow neck were factors associated with adequate occlusion. TRIAL REGISTRATION NUMBER: NCT01942512, http://www.clinicaltrials.gov.

Aneurysm treatment with WEB in the cumulative population of two prospective, multicenter series: 3-year follow-up.

BACKGROUND: WEB treatment is an endovascular approach for wide-neck bifurcation aneurysms that has demonstrated high safety and good efficacy in mid-term follow-up. While evaluating safety in the long term is important to determine if delayed adverse events occur affecting late morbidity and mortality, the most important point to evaluate is the long-term stability of aneurysm occlusion. The current analysis reports the 3-year clinical and anatomical results of WEB treatment in the combined population of two European trials (WEBCAST (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy) and WEBCAST-2). METHODS: Aneurysm occlusion was evaluated using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. RESULTS: The safety population comprised 79 patients. The efficacy population comprised 61 aneurysms. Aneurysm locations were middle cerebral artery in 32/61 aneurysms (52.5%), anterior communicating artery in 13/61 (21.3%), basilar artery in 9/61 (14.8%), and internal carotid artery terminus in 7/61 (11.5%). No adverse events related to the device or procedure occurred between 2 and 3 years. At 3 years, complete occlusion was observed in 31/61 (50.8%) aneurysms, neck remnant in 20/61 (32.8%), and aneurysm remnant in 10/61 (16.4%). Between 1 year and 3 years, aneurysm occlusion was improved or stable in 53/61 (86.9%) aneurysms and worsened in 8/61 (13.1%). Worsening was mostly from complete occlusion to neck remnant in 6/61 (9.8%) aneurysms. The retreatment rate at 3 years was 11.4%. CONCLUSIONS: This analysis confirms the high safety profile of WEB. Moreover, evidence demonstrates the great stability of aneurysm occlusion with adequate occlusion (complete occlusion or neck remnant) in 83.6% of aneurysms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. WEBCAST and WEBCAST-2: Unique identifier: NCT01778322.

Delayed thromboembolic events after coiling of unruptured intracranial aneurysms in a prospective cohort of 335 patients.

BACKGROUND: Coiling is the first-line treatment for the management of unruptured intracranial aneurysms (UIAs), but delayed thromboembolic events (TEEs) can occur after such treatment. ARETA (Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm) is a prospective multicenter study conducted to analyze aneurysm recanalization. We analyzed delayed TEEs in the UIA subgroup. METHODS: Sixteen neurointerventional departments prospectively enrolled patients treated for ruptured and unruptured aneurysms between December 2013 and May 2015. Participant demographics, aneurysm characteristics, and endovascular techniques were recorded. Data were analyzed from participants with UIA treated by coiling or balloon-assisted coiling. We assessed the rates, timing, management, clinical outcomes, and risk factors for delayed TEEs using univariable and multivariable analyses. RESULTS: The rate of delayed TEEs was 2.4% (95% CI 1.0% to 4.6%) in patients with unruptured aneurysms, with all events occurring in the week following the procedure. In multivariate analysis, two factors were associated with delayed TEEs: autosomal dominant polycystic kidney disease (ADPKD): 20.0% in patients with ADPKD vs 1.9% in patients without ADPKD (OR 27.3 (95% CI 3.9 to 190.2), p=0.0008) and post-procedure aneurysm remnant: 9.4% in patients with post-procedure aneurysm remnant vs 1.6% in patients with adequate occlusion (OR 9.9 (95% CI 1.0 to 51.3), p=0.006). We describe modalities of management as well as clinical outcomes. CONCLUSIONS: Delayed TEE is a relatively rare complication after coiling of UIAs. In this series, all occurred in the week following the initial procedure. Two factors were associated with delayed TEE: ADPKD and aneurysm remnant at procedure completion. CLINICAL TRIAL REGISTRATION: NCT01942512.

Rebleeding and bleeding in the year following intracranial aneurysm coiling: analysis of a large prospective multicenter cohort of 1140 patients-Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm (ARETA) Study.

BACKGROUND: Endovascular treatment is the first line therapy for the management of ruptured and unruptured intracranial aneurysms, but delayed aneurysm rupture leading to bleeding/rebleeding can occur subsequently. ARETA (Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm) is a prospective, multicenter study conducted to analyze aneurysm recanalization. We analyzed delayed bleeding and rebleeding in this large cohort. METHODS: 16 neurointerventional departments prospectively enrolled patients treated for ruptured and unruptured aneurysms between December 2013 and May 2015 (ClinicalTrials.gov: NCT01942512). Participant demographics, aneurysm characteristics and endovascular techniques were recorded. Data were analyzed from participants with ruptured or unruptured aneurysms treated by coiling or balloon-assisted coiling. Rates of bleeding and rebleeding were analyzed and associated factors were studied using univariable and multivariable analyses. RESULTS: The bleeding rate was 0.0% in patients with unruptured aneurysms and 1.0% (95% CI 0.3% to 1.7%) in patients with ruptured aneurysms. In multivariate analysis, two factors were associated with rebleeding occurrence: incomplete aneurysm occlusion after initial treatment (2.0% in incomplete aneurysm occlusion vs 0.2% in complete aneurysm occlusion, OR 10.2, 95% CI 1.2 to 83.3; p=0.03) and dome-to-neck ratio (1.5±0.5 with rebleeding vs 2.2±0.9 without rebleeding, OR 0.2, 95% CI 0.04 to 0.8; p=0.03). Modalities of management of aneurysm rebleeding as well as clinical outcomes are described. CONCLUSIONS: Aneurysm coiling affords good protection against bleeding (for unruptured aneurysms) and rebleeding (for ruptured aneurysms) at 1 year with rates of 0.0% and 1.0%, respectively. Aneurysm occlusion and dome-to-neck ratio are the two factors that appear to play a role in the occurrence of rebleeding.

Role of distal cerebral vasculature in vessel constriction after aneurysm treatment with flow diverter stents.

BACKGROUND: Treatment of intracranial aneurysms with flow diverter stent (FDS) procedures can lead to caliber changes of jailed vessels. The reason some branches remain unchanged and others are affected by narrowing remains unknown. OBJECTIVE: To investigate the influence of resistance to flow from distal vasculature on stent-induced hemodynamic modifications affecting bifurcating vessels. MATERIALS AND METHODS: Radiological images and demographic data were acquired for 142 aneurysms treated with a FDS. Vascular resistance was estimated from patient-specific anatomic data. Correlation analysis was used to identify correspondence between anatomic data and clinical outcome. Computational Fluid Dynamics was performed on a typical patient-specific model to evaluate the influence of FDS on flow. Relevant hemodynamic variables along the bifurcating vessels were quantitatively analyzed and validated with in vitro data obtained using power Doppler ultrasound. RESULTS: Statistical analysis showed a correlation between clinical outcome and FDS resistance to flow considering overall jailed vessel vascular resistance (r=0.5, P<0.001). Computational predictions of blood flow showed that hemodynamics is minimally affected by FDS treatment in the ophthalmic artery. CONCLUSIONS: Jailed vessels are affected by narrowing when resistance to flow from the FDS constitutes a larger proportion of the overall vessel resistance to flow. This knowledge may contribute to better understanding of intracranial hemodynamics after a FDS procedure and reinforce indications for flow diversion in the treatment of intracranial aneurysms.

SAFE study (Safety and efficacy Analysis of FRED Embolic device in aneurysm treatment): 1-year clinical and anatomical results.

BACKGROUND AND PURPOSE: Flow diversion is an innovative and increasingly used endovascular treatment for intracranial aneurysms. Its initial evaluation with the first devices available showed good efficacy of this treatment with variable safety results. The Flow Direction Endoluminal Device (FRED) has a specific design and was evaluated in a single-arm, multicenter, prospective, Good Clinical Practice study: SAFE (Safety and efficacy Analysis of FRED Embolic device in aneurysm treatment). This analysis reports clinical results at 1 year and anatomical results at 6 months and 1 year. METHODS: Patients with unruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. A Clinical Event Committee and a Core Laboratory independently evaluated clinical outcome and anatomical results. RESULTS: Thirteen interventional neuroradiology centers included 103 patients/aneurysms. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral or anterior communicating artery in 9 (8.7%), and middle cerebral artery in 8 (7.8%). Most aneurysms were small (<10 mm) in 71 patients (68.9%). Cumulative 1-year mortality and morbidity rates were 2/103 (1.9%) and 3/103 (2.9%), respectively, one death being related to cancer. At 1 year, anatomical results were: complete occlusion in 66/90 patients (73.3%), neck remnant in 7/90 patients (7.8%), and aneurysm remnant in 17/90 patients (18.9%). CONCLUSIONS: SAFE study analysis at 1 year confirms the excellent safety profile of the FRED device for aneurysm treatment, with low morbidity and mortality rates (2.9% and 1.9%, respectively) and demonstrates its efficacy (adequate occlusion in 73/90 (81.1%)). CLINICAL TRIAL REGISTRATION: Unique identifier: NCT02921698; Results.

Feasibility, complications, morbidity, and mortality results at 6 months for aneurysm treatment with the Flow Re-Direction Endoluminal Device: report of SAFE study.

BACKGROUND AND PURPOSE: Flow diverters are increasingly used for the treatment of intracranial aneurysms. Evaluation of the first devices available for clinical use showed high efficacy of this treatment although safety results were worse compared with coiling or balloon-assisted coiling. The Safety and Efficacy Analysis of FRED Embolic Device in Aneurysm Treatment (SAFE) trial is a single-arm, multicenter, prospective study conducted to precisely analyze the safety and efficacy of the FRED and FRED Jr devices. METHODS: Unruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. Adverse events were independently evaluated by a Clinical Event Committee with a vascular neurosurgeon and an interventional neuroradiologist. Primary safety outcome measures were morbidity and mortality rates at 6 months after treatment. RESULTS: A total of 103 patients/aneurysms were included in 13 interventional neuroradiology (INR) centers. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral artery or anterior communicating artery in nine (8.7%), and middle cerebral artery in eight (7.8%). Aneurysms were small (<10 mm) in 71 patients (68.9%). Treatment was successfully performed in 98/103 patients (95.1%). Thromboembolic (TE) complications occurred in 5/103 patients (4.9%), intraoperative rupture in 2/103 patients (1.9%), delayed aneurysm rupture in 1/103 patient (1.0%), and delayed hematoma occurred in 1/103 patient (1.0%). Six-months' mortality and morbidity rates were 1/102 (1.0%) and 2/102 (2.0%), respectively. CONCLUSIONS: Aneurysm treatment with the FRED device is safe with low mortality (1.0%) and morbidity (2.0%). CLINICAL TRIAL REGISTRATION: NCT02921698.