Perfusion Imaging and Clinical Outcome in Acute Ischemic Stroke with Large Core.

OBJECTIVE: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue ("core"). Perfusion imaging may identify a subset of patients with large core who benefit from MT. METHODS: We compared two cohorts of LVO-related patients with large core (>50 ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6 hours from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale ≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume). RESULTS: Overall, 107 patients were included (56 MT + BMM and 51 BMM): Mean age was 68 ± 15 years, median core volume 99 ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the two groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95% CI] = 6.8 [1.7-27.0] vs 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio ≥1.8 in the subgroup with core ≥70 ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT + BMM group regardless of the MMRatio. INTERPRETATION: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. ANN NEUROL 2021;90:417-427.

Mismatch Profile Influences Outcome After Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is the recommended treatment for acute ischemic stroke caused by anterior circulation large vessel occlusion. However, despite a high rate of reperfusion, the clinical response to successful MT remains highly variable in the early time window where optimal imaging selection criteria have not been established. We hypothesize that the baseline perfusion imaging profile may help forecast the clinical response to MT in this setting. METHODS: We conducted a prospective multicenter cohort study of patients with large vessel occlusion-related acute ischemic stroke treated by MT within 6 hours. Treatment decisions and the modified Rankin Scale evaluation at 3 months were performed blinded to the results of baseline perfusion imaging. Study groups were defined a posteriori based on predefined imaging profiles: target mismatch (TMM; core volume <70 mL/mismatch ratio >1.2 and mismatch volume >10 mL) versus no TMM or mismatch (MM; mismatch ratio >1.2 and volume >10 mL) versus no MM. Functional recovery (modified Rankin Scale, 0-2) at 3 months was compared based on imaging profile at baseline and whether reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved. RESULTS: Two hundred eighteen patients (mean age, 71±15 years; median National Institutes of Health Stroke Scale score, 17 [interquartile range, 12-21]) were enrolled. Perfusion imaging profiles were 71% TMM and 82% MM. The rate of functional recovery was 54% overall. Both TMM and MM profiles were independently associated with a higher rate on functional recovery at 3 months Adjusted odds ratios were 3.3 (95% CI, 1.4-7.9) for TMM and 5.9 (95% CI, 1.8-19.6) for MM. Reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved in 86% and was more frequent in TMM and MM patients. Reperfusion was associated with a higher rate of functional recovery in MM and TMM patients but not among those with no MM. CONCLUSIONS: In this cohort study, about 80% of the patients with a large vessel occlusion-related acute ischemic stroke had evidence of penumbra, regardless of infarction volume. Perfusion imaging profiles predict the clinical response to MT.

ASCOD Phenotyping of Stroke With Anterior Large Vessel Occlusion Treated by Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Determining the mechanism of large vessel occlusion related acute ischemic stroke is of major importance to initiate a tailored secondary prevention strategy. We investigated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection (ASCOD) classification the distribution of the causes of large vessel occlusion related acute ischemic stroke treated by mechanical thrombectomy. METHODS: This was a predefined substudy of the FRAME (French Acute Multimodal Imaging to Select Patient for Mechanical Thrombectomy). Each patient underwent a systematic etiological workup including brain and vascular imaging, electrocardiogram monitoring lasting at least 24 hours and routine blood tests. Stroke mechanisms were systematically evaluated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection grading system at 3 months. We defined single potential cause by one cause graded 1 in a single domain, possible cause as a cause graded 1 or 2 regardless of overlap, and no identified cause without grade 1 nor 2 causes. RESULTS: A total of 215 patients (mean age 70±14; 50% male) were included. A single potential cause was identified in 148 (69%). Cardio-embolism (53%) was the most frequent, followed by atherosclerosis (9%), dissection (5%) and other causes (1%). Atrial fibrillation accounted for 88% of C1. Overlap between grade 1 causes was uncommon (3%). Possible causes were identified in 168 patients (83%) and 16 (7%) had no cause identified after the initial evaluation. CONCLUSIONS: Cardio-embolism, especially atrial fibrillation, was the major cause of large vessel occlusion related acute ischemic stroke. This finding emphasizes the yield of paroxysmal atrial fibrillation detection in those patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03045146.

Intraoperative Complications of Endovascular Treatment of Intracranial Aneurysms with Coiling or Balloon-assisted Coiling in a Prospective Multicenter Cohort of 1088 Participants: Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm (ARETA) Study.

Background Thromboembolic events and intraoperative rupture are the most frequent neurologic complications of intracranial aneurysm coiling. Their frequency has not been evaluated in recent series. Purpose To provide an analysis of complications, clinical outcome, and participant and aneurysm risk factors after aneurysm coiling or balloon-assisted coiling within the Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm, or ARETA, cohort. Materials and Methods Sixteen neurointerventional departments prospectively enrolled participants 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 within the overall cohort treated with coiling or balloon-assisted coiling for a single aneurysm. Rates of neurologic complications were analyzed, and associated factors were studied by using univariable analyses (Student t test, χ2 test, or Fisher exact test, as appropriate) and multivariable analyses (logistic regressions). Results A total of 1088 participants (mean age ± standard deviation, 54 years ± 13; 715 women [65.7%]) were analyzed. Thromboembolic events and intraoperative rupture were reported in 113 of 1088 participants (10.4%) and 34 of 1088 participants (3.1%), respectively. Poor clinical outcome (defined as modified Rankin Scale score of 3-6) was reported in 29 of 113 participants (25.7%) with thromboembolic events and in 11 of 34 participants (32.4%) with intraoperative rupture (P = .44). Factors associated with thromboembolic events were female sex (odds ratio [OR], 1.7; 95% confidence interval [CI]: 1.1, 2.8; P = .02) and middle cerebral artery location (OR, 1.9; 95% CI: 1.2, 3.0; P = .008). Factors associated with intraoperative rupture were anterior communicating artery location (OR, 2.2; 95% CI: 1.1, 4.7; P = .03) and small aneurysm size (OR, 3.0; 95% CI: 1.5, 6.3; P = .003). Conclusion During aneurysm coiling or balloon-assisted coiling, thromboembolic events were more frequent than were intraoperative rupture. Both complications were associated with poor clinical outcome in a similar percentage of participants. Risk factors for thromboembolic events were female sex and middle cerebral artery location. Risk factors for intraoperative rupture were small aneurysm size and anterior cerebral or communicating artery location. © RSNA, 2020.

Concordance in Aneurysm Size at Time of Rupture in Familial Intracranial Aneurysms.

Background and Purpose- Intracranial aneurysm (IA) size and location are important determinants of aneurysm rupture risk. In familial IAs there is concordance of location; however, if such concordance exists for size is unknown. We analyzed the concordance of aneurysm size at time of rupture in familial IAs. Methods- In pairs of affected relatives with aneurysmal subarachnoid hemorrhage, the ratio between the largest and the smallest aneurysm size at time of rupture was calculated. We also compared the proportion of families in which both IAs ruptured at a size < or ≥7 mm with the proportion of families in which one IA ruptured at <7 mm and another ≥7 mm. We calculated the repeatability with corresponding 95% CI for aneurysm size at time of rupture. Results- About 130 patients from 64 families were included. Of the 68 affected pairs 18 (26%) had a ratio ≤1.2, 38 (57%) had a ratio >1.2, and 12 (17%) had a ratio ≥3. We found no difference between the proportion of families (n=31; 49%) who both had IA at time of rupture <7 mm (n=20; 31%) or both ≥7 mm (n=11; 18%) and the proportion of those families with one patient with an IA <7 mm and another with an IA ≥7 mm (n=33; 51%; P=0.86). Overall, the repeatability in aneurysm size at rupture within familial IAs was 0.10 (95% CI, 0-0.35). Conclusions- There is no good concordance in aneurysm size at rupture within familial IAs. These data suggest that size of a ruptured IA in a family member should not significantly impact on the management of a familial unruptured IA in a relative.

Predictive Value of Susceptibility Vessel Sign for Arterial Recanalization and Clinical Improvement in Ischemic Stroke.

Background and Purpose- Our goal was to evaluate whether the presence of a low signal intensity known as susceptibility vessel sign (SVS) on T2*-gradient echo imaging sequence was predictive of arterial recanalization and the early clinical improvement after mechanical thrombectomy. Methods- This observational study was based on a prospective database of acute ischemic strokes treated by mechanical thrombectomy. Inclusion criteria were patients with acute anterior ischemic stroke, diagnosed by magnetic resonance imaging, including a T2*-gradient echo imaging sequence, and treated by mechanical thrombectomy. Two independent readers assessed the presence of an SVS. Successful recanalization was defined as a Thrombolysis in Cerebral Infarction score of 2b-3 after mechanical thrombectomy. Early clinical improvement was estimated by the difference between the baseline National Institutes of Health Stroke Scale and the National Institutes of Health Stroke Scale on day 1 after treatment Results- The SVS was detected in 137 (76%) out of 180 patients. The kappa interrater agreement was 0.71 with a 95% CI of 0.59 to 0.82. Successful recanalization was associated with an SVS+ with odds ratio, 2.48; 95% CI, 1.05-5.74; P=0.03. The early clinical improvement was better in patients with an SVS+ (median, -6; interquartile range, -11 to 0) compared with SVS- patients (median, -1; interquartile range, -10 to 3) with P=0.01. Conclusions- The visualization of SVS is a reliable and easily accessible predictive factor of recanalization success and early clinical improvement.

"Real life" impact of anesthesia strategy for mechanical thrombectomy on the delay, recanalization and outcome in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: Choice of anesthesia type on outcome for mechanical thrombectomy (MT) in acute ischemic stroke remains controversial. The goal of our research was to study the impact of anesthesia strategy on the delay, angiographic and neurological outcome of MT performed under general anesthesia (GA) vs. conscious sedation (CS). METHODS: This prospective, single-center observational study included patients with anterior circulation large vessel occlusion (ACLVO) strokes treated with MT within 6 hours of symptom onset. All time metrics were evaluated. Angiographic and clinical outcomes were assessed by recanalization rate (mTICI) and 3-month functional independence (mRs). Complications and mortality rate were recorded as safety outcomes. RESULTS: In total, 303 consecutive thrombectomies were performed, 86.8% under GA. NIHSS was higher in GA, with median of 19.0 for GA and 16.5 for CS (P = 0.049). Median time from arrival in hospital (door) to groin puncture was 83 min (IQR = 45.0-109.5) for GA compared to 72 min (IQR = 35.0-85.3) for CS, P = 0.170). Median time from arrival in the angiosuite to groin puncture was 20 min (IQR = 15.0-29.0) for GA compared to 15 min (IQR = 10.0-20.0) for CS, P = 0.017). There were no significant differences in recanalization time metrics, successful revascularization rate, functional independence and mortality rate at three months. CONCLUSIONS: GA induced a 5 to 10 minutes delay for groin puncture, without impact on recanalization time metrics, or neurological outcome at 3 months. Our results demonstrate that a well-organized workflow is associated with reasonable delay in performing GA for MT, without effect on outcome compared to sedation.

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.

Electrical impedance measurements can identify red blood cell-rich content in acute ischemic stroke clots ex vivo associated with first-pass successful recanalization.

Background: Electrochemical impedance spectroscopy can determine characteristics such as cell density, size, and shape. The development of an electrical impedance-based medical device to estimate acute ischemic stroke (AIS) clot characteristics could improve stroke patient outcomes by informing clinical decision making. Objectives: To assess how well electrical impedance combined with machine learning identified red blood cell (RBC)-rich composition of AIS clots ex vivo, which is associated with a successfully modified first-pass effect. Methods: A total of 253 clots from 231 patients who underwent thrombectomy in 5 hospitals in France, Japan, Serbia, and Spain between February 2021 and October 2023 were analyzed in the Clotbase International Registry. Electrical impedance measurements were taken following clot retrieval by thrombectomy, followed by Martius Scarlet Blue staining. The clot components were quantified via Orbit Image Analysis, and RBC percentages were correlated with the RBC estimations made by the electrical impedance machine learning model. Results: Quantification by Martius Scarlet Blue staining identified RBCs as the major component in clots (RBCs, 37.6%; white blood cells, 5.7%; fibrin, 25.5%; platelets/other, 30.3%; and collagen, 1%). The impedance-based RBC estimation correlated well with the RBC content determined by histology, with a slope of 0.9 and Spearman's correlation of r = 0.7. Clots removed in 1 pass were significantly richer in RBCs and clots with successful recanalization in 1 pass (modified first-pass effect) were richer in RBCs as assessed using histology and impedance signature. Conclusion: Electrical impedance estimations of RBC content in AIS clots are consistent with histologic findings and may have potential for clinically relevant parameters.

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.

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.

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.

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.

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.

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.

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.