Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial.

BACKGROUND We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER URL: https://www. CLINICALTRIALS gov ; Unique identifier: NCT03192332

Effect of antiangiogenic administration on arteriovenous malformations

Les Malformations Artérioveineuses sont des lésions vasculaires évolutives. Elles peuvent avoir des conséquences neurologiques lourdes liées au risque hémorragique élevé qui est leur mode de révélation le plus fréquent. Le développement de meilleurs outils d’imagerie a beaucoup amélioré le diagnostic de ces lésions et a permis une meilleure compréhension de leur interaction avec le tissu cérébral. Néanmoins, Leur 4eme dimension et leur évolution restent encore obscures.Par ailleurs, les traitements actuels (embolisation, microchirurgie, chirurgie stéréotaxique) sont associés à des risques de morbidité et mortalité importants.Pour ces raisons, nous avons travaillé sur un traitement potentiel peu invasif: des agents antiangiogéniques. Un modèle porcin simplifié a été élaboré consistant en l’occlusion unilatérale de l’artère carotide primitive et externe par voie endovasculaire. Ce modèle a présenté des preuves d’angiogénèse et des modifications anatomopathologiques proches de celles des MAVc humaines. Le Bevacizumab, un anticorps monoclonal pour le VEGF, a été administré in situ sur ce modèle. Les résultats ont montré que l’agent antiangiogénique altère l’angiogénèse sur les specimens histologiques. L’épaisseur de la paroi des vaissaux a été stabilisée après l’injection de Bevacizumab mais le volume des retia est demeuré identique montrant que le volume dépend de l’angiogénèse mais probablement également du fluxBrain arteriovenous malformations are dynamic, evolving vascular lesions. They present high morbidity rates due to hemorrhagic presentation that is the most frequent symptom at onset and potentially high mortality rates .Up to date imaging techniques has greatly facilitated the diagnosis of these lesions and the better understanding of their relation to adjacent brain tissue. However, it remains still a challenge to define their four dimensional nature and its consequences, a fact that can actually optimize their treatment. Embolization, surgery and stereotactic radiosurgery that are currently used in the treatment of AVMs carry also significant morbi-mortality risks. For this reason, a potential minimally invasive treatment with antiangiogenic agents was tested. A swine model was firstly created using the animal’s rete mirabile and performing an endovascular occlusion of one common and external carotid artery. This simplified model presented evidence of angiogenesis and histologic findings that are also observed in human AVMs compared to a control group. Secondly, Bevacizumab that is a monoclonal antibody to vascular endothelial growth factor, was in situ administered on this model. The results showed that the antiangiogenic agent tampered angiogenesis on histologic samples by stabilizing the wall thickness of the arteries but it did not have any effect on volume that is probably depending on flow and not only on angiogenesis

Intra-arterial in-situ bevacizumab injection effect on angiogenesis. Results on a swine angiogenesis model

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Efficacy and safety of embolization in arteriovenous malformations of the extremities and head and neck: a retrospective study of 32 cases

International audienceBackground: Definitive treatment of arteriovenous malformations (AVMs) consists of complete surgical excision. When not possible, embolization may be performed. Objectives: We aimed to evaluate the efficacy and safety of embolization for AVMs of the extremities and head and neck. Materials and methods: This retrospective study included all patients undergoing embolization for AVMs of skin and soft tissues on the limbs, head and neck, in the University Hospital Center of Tours between January 1996 and December 2009. The main outcome was efficacy, assessed by two independent assessors, as the percentage of AVM devascularized at the end of embolization. Secondary outcomes were patient satisfaction, evolution of symptoms and safety of embolization. Results: We included 32 AVMs in 31 patients, for 66 embolizations evaluated. In 18 AVMs (56.3%), devascularization was greater than 75% of the initial vascularization. Efficacy was lower for AVMs of the upper limbs than other body parts (p = 0.003). For 18 patients who could be contacted by telephone, the mean global satisfaction was 6.0 +/- 2.7 on a scale of 0 to 10, and 13 (72.2%) reported an improvement of the symptoms linked to the AVM. Severe adverse events were reported after 4 embolizations, all located on the head and neck. Conclusion: Embolization can lead to good devascularization and improve symptoms linked to AVMs, especially in lower limbs. Minor complications are frequent, and severe adverse events may occur, especially after procedures on the head and neck

Is there an inherited anatomical conformation favoring aneurysmal formation of the anterior communicating artery?

International audienceOBJECTIVE The pathophysiological mechanisms responsible for the formation of intracranial aneurysms (IAs) remain only partially elucidated. However, current evidence suggests a genetic component. The purpose of this study was to investigate the specific anatomical variations in the arterial complex that are associated with the presence of anterior communicating artery (ACoA) aneurysms in the familial forms of IAs. METHODS This multicenter study investigated bifurcation IAs in patients who had a sporadic ACoA IA without a family history of IA (SACAA group), in patients who had an ACoA IA with a family history of IA (FACAA group), and in their healthy first-degree relatives (HFDRs). Through the use of MR angiography (MRA) reconstructions, the symmetry of the A1 segments and the angle between the A1 and A2 segments were analyzed on 3D models for each group. These measurements were then compared among the 3 groups. RESULTS Twenty-four patients with SACAA, 24 patients with FACAA, and 20 HFDRs were included in the study. Asymmetrical configuration of the A1 segments was more frequent in the FACAA group than in the HFDR group (p = 0.002). The aneurysm-side A1-A2 angle was lower in the FACAA group (p = 0.003) and SACAA group (p = 0.007) than in the HFDR group. On the contralateral side, there was no difference in A1-A2 angles between groups. CONCLUSIONS The anatomical shape of the ACoA complex seems to be similarly associated with the presence of ACoA IAs in both the FACAA and SACAA groups. This highlights the role played by hemodynamic constraints in aneurysm formation and questions the hypothesis of the hereditary character of these anatomical shapes

Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics

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Quantitative evaluation of WEB shape modification: A five-year follow-up study

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Is bridging therapy still required in stroke due to carotid artery terminus occlusions?

International audienceIntroduction - Studies comparing endovascular stroke treatment using mechanical thrombectomy (MT) with or without prior IV tissue plasminogen activator (tPa) have included only 30% of internal carotid artery terminus occlusions (ICA-O), a known predictor of recanalization failure with IV tPa. Objective - To carry out a retrospective multicenter analysis of prospectively collected data of consecutive patients to investigate the impact of intravenous thrombolysis on ICA-O by comparing patients treated with MT alone or bridging therapy (BT). Material and methods - Patients with ICA-O treated with MT alone or BT were retrospectively examined and compared. Demographic data, vascular risk factors, treatment modalities, complications, technical and clinical outcomes were recorded. A propensity score (PS) analysis was used to compare modified Rankin Scale (mRS) score at 3 months and intracerebral hemorrhage (ICH) between groups. Results - 141 consecutive patients (60% BT/40% MT) were included between January 2014 and June 2016. Baseline characteristics did not differ between the groups. There was no significant difference in the rate of Thrombolysis in Cerebral Infarction 2b/3, distal emboli, and median number of passes between the groups. There was a significant difference between BT and MT groups in the median time between imaging and groin puncture (median 97 min vs 75, p=0.007), the rate of ICH (44% vs 27%, p=0.05), but not for symptomatic ICH (18% vs 13%, p=0.49). With PS, there was a trend towards a higher rate of ICH (OR=2.3, 95% CI 0.9 to 5.9, p=0.09) in the BT group compared with the MT alone group, with no difference in mRS score ≤2 at 3 months (OR=1.6, 95% CI 0.7 to 3.7, p=0.29). Conclusion - There was no significant difference in clinical outcomes between patients receiving bridging therapy versus direct thrombectomy. Bridging therapy delayed time to groin puncture and increased ICH rate

Heritability of territory of ruptured and unruptured intracranial aneurysms in families.

BackgroundA previous study suggested that intracranial aneurysms are more likely to occur in the same arterial territory within families. We aimed to replicate this analysis in independent families and in a sample limited to intracranial aneurysms that ruptured.MethodsAmong families with ≥2 first-degree relatives with intracranial aneurysms, we randomly matched index families to comparison families, and compared concordance in intracranial aneurysm territory between index and comparison families using a conditional logistic events/trials model. We analyzed three European cohorts separately, and pooled the results with those of the Familial Intracranial Aneurysm study by performing an inverse variance fixed effects meta-analysis. The main analysis included both unruptured and ruptured intracranial aneurysms, and a secondary analysis only ruptured intracranial aneurysms.ResultsAmong 70 Dutch, 142 Finnish, and 34 French families, concordance regarding intracranial aneurysm territory was higher within families than between families, although not statistically significant. Meta-analysis revealed higher concordance in territory within families overall (odds ratio [OR] 1.7, 95%CI 1.3-2.2) and for each separate territory except the anterior cerebral artery. In the analysis of ruptured intracranial aneurysms, overall territory concordance was higher within families than between families (OR 1.8; 95%CI 1.1-2.7) but the territory-specific analysis showed statistical significance only for the internal carotid artery territory.ConclusionsWe confirmed that familial intracranial aneurysms are more likely to occur in the same arterial territory within families. Moreover, we found that ruptured aneurysms were also more likely to occur in the same arterial territory within families

Video_1_The human placenta as a model for training and research in mechanical thrombectomy: Clarifications and use of the chorionic plate veins.AVI

Indications for mechanical thrombectomy in acute ischemic stroke are increasing, resulting in the continuous development of new devices and techniques. Therefore, there is a need for a realistic testing and training environment that offers the opportunity to practice different procedures and test the latest devices. Some authors have described the use of the human placenta as a model for neurointerventional surgery, with striking similarities to real-life conditions. This model has many advantages, including its relatively low cost and minimal infrastructure requirements, with fewer ethical concerns compared to animal models. So far, some preparation and set-up details were missing, and only arteries from the chorionic plate were used. This article provides the necessary clarifications and a mapping of the chorionic plate veins, so that the use of this model, which is particularly well suited for mechanical thrombectomy, can be as easy and wide as possible. A video explaining how to prepare the model is provided.</p