Showing papers by "Mikael Mazighi published in 2021"

Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial.

Abstract: Summary Background High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target. Methods We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100–129 mm Hg) or a standard care systolic blood pressure target group (130–185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24–36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov , number NCT03160677 , and the trial is closed at all participating sites. Findings Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24–36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60–1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group. Interpretation An intensive systolic blood pressure target of 100–129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24–36 h as compared with a standard care systolic blood pressure target of 130–185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion. Funding French Health Ministry.

Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER2 Randomized Clinical Trial

Abstract: Importance Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation large vessel occlusion, but the additional benefit of combining contact aspiration with stent retriever is uncertain. Objective To determine whether mechanical thrombectomy for treatment of anterior circulation large vessel occlusion stroke with initial contact aspiration and stent retriever combined results in better final angiographic outcome than with standard stent retriever alone. Design, setting, and participants This trial was a multicenter randomized, open-label, blinded end point evaluation that enrolled 408 patients from October 16, 2017, to May 29, 2018, in 11 French comprehensive stroke centers, with a 12-month outcome follow-up. Patients with a large vessel occlusion in the anterior circulation were included up to 8 hours after symptom onset. The final date of follow-up was June, 19, 2019. Interventions Patients were randomly assigned (1:1 allocation) to receive initial thrombectomy with contact aspiration and stent retriever combined (205) or stent retriever alone (203). Main outcomes and measures The primary outcome was the rate of expanded Thrombolysis In Cerebral Infarction score of 2c or 3 (eTICI 2c/3; ie, scores indicate near-total and total reperfusion grades) at the end of the procedure. Results Among the 408 patients who were randomized, 3 were excluded, and 405 (99.3%) patients (mean age, 73 years; 220 [54%] women and 185 [46%] men) were included in the primary analysis. The rate of eTICI 2c/3 at the end of the endovascular procedure was not significantly different between the 2 thrombectomy groups (64.5% [131 of 203 patients] for contact aspiration and stent retriever combined vs 57.9% [117 of 202 patients] for stent retriever alone; risk difference, 6.6% [95% CI, -3.0% to 16.2%]; adjusted odds ratio [OR], 1.33 [95% CI, 0.88 to 1.99]; P = .17). Of 14 prespecified secondary efficacy end points, 12 showed no significant difference. A higher rate of successful reperfusion was achieved in the contact aspiration combined with stent retriever group vs the stent retriever alone group (eTICI 2b50/2c/3, 86.2% vs 72.3%; adjusted OR, 2.54 [95% CI, 1.51 to 4.28]; P Conclusions and relevance Among patients with acute ischemic stroke due to large vessel occlusion, an initial thrombectomy technique consisting of contact aspiration and stent retriever combined, compared with stent retriever alone, did not significantly improve the rate of near-total or total reperfusion (eTICI 2c/3) at the end of the endovascular procedure, although the trial may have been underpowered to detect smaller differences between groups. Trial registration ClinicalTrials.gov Identifier: NCT03290885.

Mismatch Profile Influences Outcome After Mechanical Thrombectomy

Abstract: 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 re...

ESO guideline for the management of extracranial and intracranial artery dissection.

Abstract: The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of extracranial artery dissection (EAD) and intracranial artery dissection (IAD). EAD and IAD represent leading causes of stroke in the young, but are uncommon in the general population, thus making it challenging to conduct clinical trials and large observational studies. The guidelines were prepared following the Standard Operational Procedure for European Stroke Organisation guidelines and according to GRADE methodology. Our four recommendations result from a thorough analysis of the literature comprising two randomized controlled trials (RCTs) comparing anticoagulants to antiplatelets in the acute phase of ischemic stroke and twenty-six comparative observational studies. In EAD patients with acute ischemic stroke, we recommend using intravenous thrombolysis (IVT) with alteplase within 4.5 hours of onset if standard inclusion/exclusion criteria are met, and mechanical thrombectomy in patients with large vessel occlusion of the anterior circulation. We further recommend early endovascular or surgical intervention for IAD patients with subarachnoid hemorrhage (SAH). Based on evidence from two phase 2 RCTs that have shown no difference between the benefits and risks of anticoagulants versus antiplatelets in the acute phase of symptomatic EAD, we strongly recommend that clinicians can prescribe either option. In post-acute EAD patients with residual stenosis or dissecting aneurysms and in symptomatic IAD patients with an intracranial dissecting aneurysm and isolated headache, there is insufficient data to provide a recommendation on the benefits and risks of endovascular/surgical treatment. Finally, nine expert consensus statements, adopted by 8 to 11 of the 11 experts involved, propose guidance for clinicians when the quality of evidence was too low to provide recommendations. Some of these pertain to the management of IAD (use of IVT, endovascular treatment, and antiplatelets versus anticoagulation in IAD with ischemic stroke and use of endovascular or surgical interventions for IAD with headache only). Other expert consensus statements address the use of direct anticoagulants and dual antiplatelet therapy in EAD-related cerebral ischemia, endovascular treatment of the EAD/IAD lesion, and multidisciplinary assessment of the best therapeutic approaches in specific situations.

Endovascular Therapy of Anterior Circulation Tandem Occlusions: Pooled Analysis From the TITAN and ETIS Registries.

Abstract: Background and purpose Endovascular therapy for tandem occlusion strokes of the anterior circulation is an effective and safe treatment. The best treatment approach for the cervical internal carotid artery (ICA) lesion is still unknown. In this study, we aimed to compare the functional and safety outcomes between different treatment approaches for the cervical ICA lesion during endovascular therapy for acute ischemic strokes due to tandem occlusion in current clinical practice. Methods Individual patients' data were pooled from the French prospective multicenter observational ETIS (Endovascular Treatment in Ischemic Stroke) and the international TITAN (Thrombectomy in Tandem Lesions) registries. TITAN enrolled patients from January 2012 to September 2016, and ETIS from January 2013 to July 2019. Patients with acute ischemic stroke due to anterior circulation tandem occlusion who were treated with endovascular therapy were included. Patients were divided based on the cervical ICA lesion treatment into stent and no-stent groups. Outcomes were compared between the two treatment groups using propensity score methods. Results A total of 603 patients were included, of whom 341 were treated with acute cervical ICA stenting. In unadjusted analysis, the stent group had higher rate of favorable outcome (90-day modified Rankin Scale score, 0-2; 57% versus 45%) and excellent outcome (90-day modified Rankin Scale score, 0-1; 40% versus 27%) compared with the no-stent group. In inverse probability of treatment weighting propensity score-adjusted analyses, stent group had higher odds of favorable outcome (adjusted odds ratio, 1.09 [95% CI, 1.01-1.19]; P=0.036) and successful reperfusion (modified Thrombolysis in Cerebral Ischemia score, 2b-3; adjusted odds ratio, 1.19 [95% CI, 1.11-1.27]; P Conclusions Patients treated with acute cervical ICA stenting for tandem occlusion strokes had higher odds of 90-day favorable outcome, despite higher odds of intracerebral hemorrhage; however, most of the intracerebral hemorrhages were asymptomatic.

Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: A multicenter, randomized, clinical trial (TITAN) protocol.

Abstract: Background and hypothesisThere is no consensus on the optimal endovascular management of the extracranial internal carotid artery steno-occlusive lesion in patients with acute ischemic stroke due t...

Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study.

Abstract: Background and purpose Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3-month functional outcome and to identify risk factors for aICH after EVT. Methods Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22-36 h post-EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3-month modified Rankin Scale (mRS) score 4-6 and overall 3-month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model. Results Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval [CI] 1.44-2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47-2.18). Hemorrhagic infarction (OR 1.63 [95% CI 1.22-2.18]) and parenchymal hematoma (OR 2.99 [95% CI 1.77-5.02]) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH. Conclusions Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH.

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

Abstract: 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 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.

Clinical Outcome of Acute Ischemic Strokes in Patients with COVID-19.

Abstract: INTRODUCTION: Acute ischemic stroke (AIS) and thrombotic events (TEs) were reported in patients with COVID-19. Clinical outcome of AIS in the course of COVID-19 remains unknown. We compared early clinical outcome and mortality of COVID-positive (+) patients admitted for AIS with COVID-negative (-) ones. We hypothesized that COVID+ patients would have poorer clinical outcomes and present a higher rate of TEs and mortality compared with COVID- ones. METHODS: In this multicentric observational retrospective study, we enrolled patients over 18 years old admitted for AIS in 3 stroke units of the Parisian region during lockdown from March 17, 2020, to May 2, 2020. COVID-19 status as well as demographic, clinical, biological, and imaging data was collected retrospectively from medical records. Poor outcome was defined as modified Rankin score (mRS) 3-6 (3-6) at discharge. We also compared TE frequency and mortality rate through a composite criterion in both groups. RESULTS: Two hundred and sixteen patients were enrolled; mean age was 68 years old, and 63% were male. Forty patients were CO-VID+ (18.5%) and 176 were COVID-. Obesity was statistically more frequent in the COVID+ group (36 vs. 13% p < 0.01). The percentage of patients with mRS (3-6) at discharge was higher in the COVID+ group compared with the COVID- group (60 vs. 41%, p = 0.034). The main predictor of presenting a mRS (3-6) at discharge was high NIHSS score at admission (OR, CI 95%: 1.325, 1.22-1.43). Mortality rate was higher in the COVID+ group (12 vs. 3.4%, p = 0.033) as well as TE frequency (15 vs. 2.8%, p < 0.01). CONCLUSION: In this study, patients with AIS infected by SARS-CoV-2 showed a poorer early outcome than COVID- ones. However, when compared to other factors, COVID-19 was not a significant predictor of poor outcome. Vascular morbidity and mortality rates were significantly higher in the COVID+ group compared with the COVID- group.

Antiplatelet Therapy During Emergent Extracranial Internal Carotid Artery Stenting: Comparison of Three Intravenous Antiplatelet Perioperative Strategies

Abstract: Introduction Guidelines for antiplatelet therapy administration, during emergent stenting for extra-cranial internal carotid artery (EC-ICA) occlusion in the setting of acute ischemic stroke (AIS) are lacking. Different antiplatelet regimen are used in association to endovascular therapy (EVT) for the treatment of EC-ICA lesions. We aimed to compare the clinical and radiological effects of three intravenous antiplatelet agents used during emergent EC-ICA stenting. Material and Methods Clinical data were collected from January 2015 to December 2019 in a monocentric prospective registry of AIS patients treated by EVT. All patients who underwent emergent EC-ICA stenting were sorted regarding the intravenous antiplatelet agent used during the procedure. Results Among 218 patients treated by EVT for an EC-ICA occlusion of the anterior circulation during the study period, 70 underwent an emergent stenting of the EC-ICA. 60 were included in the present study, 9 received intravenous (IV) Cangrelor, 8 IV abciximab and 43 Aspirin. The rate of favorable neurological outcome, defined as modified Rankin Scale (mRS) ≤ 2 at three months were better in the Cangrelor and Aspirin groups (66,7% and 58,1%, respectively) than in the Abciximab group (37,5%), as well as, the rate of any intracranial ICH (22,2% and 37,2% vs 62,5%). The rate of acute stent reocclusion was similar between groups. Conclusion When used as a rescue treatment during emergent stenting of EC-ICA, Cangrelor and Aspirin present a better safety profile than Abciximab, with less intracranial hemorrhages and a higher rate of good clinical outcome. Additional studies are needed to confirm these findings.

Endovascular therapy with or without intravenous thrombolysis in acute stroke with tandem occlusion.

Abstract: Background Endovascular therapy (EVT) is effective and safe in patients with tandem occlusion. The benefit of intravenous thrombolysis (IVT) prior to EVT in acute tandem occlusion is debatable. Objective To compare EVT alone with EVT plus IVT in patients with acute ischemic stroke due to anterior circulation tandem occlusions. Methods This is an individual patient pooled analysis of the Thrombectomy In TANdem lesions (TITAN) and Endovascular Treatment in Ischemic Stroke (ETIS) Registries. Patients were divided into two groups based on prior IVT treatment: (1) IVT+ group, which included patients who received IVT prior to EVT, (2) IVT− group, which included patients who did not receive IVT prior to EVT. Propensity score (inverse probability of treatment weighting (IPTW)) was used to reduce baseline between-group differences. The primary outcome was favorable outcome—that is, modified Rankin Scale (mRS) score 0 to 2 at 90 days. Results Overall, 602 consecutive patients with an acute stroke with tandem occlusion were included (380 and 222 in the bridging therapy and EVT alone groups, respectively). Onset to imaging time was shorter in the IVT+ group (median 103 vs 140 min). In contrast, imaging to puncture time was longer in the IVT+ group (median 107 vs 91 min). In IPTW analysis, the IVT+ group had higher odds of favorable outcome, excellent outcome (90-day mRS score 0–1), and successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b/3 at the end of EVT). There was no difference in the risk of significant hemorrhagic complications between groups. In secondary analysis of patients treated with acute cervical internal carotid artery stenting, bridging therapy was associated with higher odds of favorable outcome and lower odds of mortality at 90 days. Conclusions Our results suggest that bridging therapy in patients with acute ischemic stroke due to anterior tandem occlusion is safe and may improve functional outcome, even in the setting of acute cervical internal carotid artery stenting during EVT.

Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline

Abstract: Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes. Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient’s serum, at the acute phase of stroke, to determine if they could predict PSCI 3 months later. We found long-term spatial memory was impaired in diabetic mice 6 weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients. we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients.

Age and Outcome after Endovascular Treatment in Anterior Circulation Large-Vessel Occlusion Stroke: ETIS Registry Results.

Abstract: Background Increasing patient age has been identified in clinical trials as a poor prognostic factor for functional independence after endovascular treatment (EVT) for acute ischemic stroke. These findings may not be fully generalizable to clinical practice due to strict inclusion and exclusion criteria in these trials. We aim to assess and quantify the association of patient age, especially in patients >80 and >90 years old, with functional outcome after EVT in current, everyday clinical practice. Methods The ETIS (Endovascular Treatment in Ischemic Stroke) Registry is an ongoing, prospective, observational study of 6 comprehensive stroke centers in France. We analyzed 1,708 patients treated between January 2017 and December 2018 and assessed the association of patient age with functional outcome adjusting for demographic and procedural predictors of functional outcome. Results The positive effect of mechanical thrombectomy diminished significantly with increasing age: compared to the 18-80 years age group, the odds for achieving a good functional outcome at 90 days after the procedure decreased in the 80-90 and >90 years groups (multilevel OR: 0.38, 95% CI: 0.28-0.51 and OR: 0.2, 95% CI: 0.09-0.45, respectively, p 90 years group). Conclusion Patient age is strongly associated with functional outcome after EVT for acute ischemic stroke. The positive effect of thrombectomy persists in older age groups, even after adjustment for prognostic factors related to poor functional outcome. Stroke physicians should provide EVT irrespective of the patient's age.

Time from I.V. Thrombolysis to Thrombectomy and Outcome in Acute Ischemic Stroke.

Abstract: OBJECTIVE Whether the time from intravenous thrombolysis (IVT) to endovascular treatment (EVT) in patients with acute ischemic stroke has an effect on the functional outcome is unknown. METHODS The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, multicenter, observational study that perform EVT in France. Data were analyzed from patients treated by IVT and EVT between October 2013 and December 2018 in 6 comprehensive stroke centers. In the primary analysis, we assessed the association of time from IVT administration to start of EVT with functional outcome (measured with the modified Rankin Scale [mRS]), by means of ordinal logistic regression. Secondary end points included angiographic and safety outcomes. RESULTS We analyzed 1,986 patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent IVT and EVT. An increased IVT to start of EVT time was associated with a worse functional outcome at 90 days (mRS = 0-2, adjusted odds ratio [OR] per 30 minutes increase in time = 0.91, 95% confidence interval [CI] = 0.86-0.96; mRS = 0-1, adjusted OR per 30 minutes increase in time = 0.89, 95% CI = 0.84-0.94), a lower chance of modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b to 3 reperfusion (adjusted OR per 30 minutes increase in time = 0.93, 95% CI = 0.87-0.98), and an increased probability of symptomatic intracerebral hemorrhage (adjusted OR per 30 minutes increase in time = 1.09, 95% CI = 0.99-1.18). INTERPRETATION These findings provide a basis for further studies to determine if the functional outcome of patients with stroke can be greatly improved by optimizing IVT to EVT times. ANN NEUROL 2021;89:511-519.

Endovascular treatment as the main approach for Spetzler-Martin grade III brain arteriovenous malformations

Abstract: Background Because Spetzler–Martin (SM) grade III brain arteriovenous malformations (bAVMs) constitute a heterogeneous group of lesions with various combination of sizes, eloquence, and venous drainage patterns, their management is usually challenging. The aim of this study is to evaluate the clinical/imaging outcomes and the procedural safety of endovascular approach as the main treatment for the cure of SM grade III bAVMs. Methods In this retrospective study, prospectively collected data of SM grade III bAVMs treated by endovascular techniques between 2010 and 2018 at our hospital were reviewed. Patients older than 16 years with angiographic follow-up of at least 6 months after endovascular treatment were entered in the study. The patients had a mean follow-up of 12 months. The data were assessed for clinical outcome (modified Rankin Scale), permanent neurological deficit, post-operative complications, and optimal imaging outcome, defined by complete exclusion of AVM. The independent predictive variables of poor outcome or hemorrhagic complication were assessed using binary logistic regression. Results Sixty-five patients with 65 AVMs were included in the study. Mean age of the patients was 40.0±14.4. Most common presentation was hemorrhage (61.5%). The patients underwent one to eight endovascular procedures (median=2). Mean nidus diameter was 30.2±13.0. A complete obliteration of AVM was achieved in 57 patients (87.7%). Post-procedure significant hemorrhagic and ischemic complications were seen in 13 (20%) and five (7.7%) patients respectively, leading to five (7.7%) transient and four (6.2%) permanent neurological deficits. Eight patients (12.3%) experienced worsening of mRS after embolization. Ten patients (15.4%) had poor outcome (mRS 3–5) at follow-up and two (3%) died. Conclusions Endovascular treatment can achieve a high rate of complete exclusion of grade III AVM but may be associated (as in other treatment modalities) with significant important complications. Clinical trial registration number NCT02879071.

Changes in Neuroendovascular Procedural Volume During the COVID-19 Pandemic: An International Multicenter Study.

Abstract: BACKGROUND AND PURPOSE: The effect of coronavirus disease 2019 (COVID-19) pandemic on performance of neuroendovascular procedures has not been quantified. METHODS: We performed an audit of performance of neuroendovascular procedures at 18 institutions (seven countries) for two periods; January-April 2019 and 2020, to identify changes in various core procedures. We divided the region where the hospital was located based on the median value of total number of COVID-19 cases per 100,00 population-into high and low prevalent regions. RESULTS: Between 2019 and 2020, there was a reduction in number of cerebral angiograms (30.9% reduction), mechanical thrombectomy (8% reduction), carotid artery stent placement for symptomatic (22.7% reduction) and asymptomatic (43.4% reduction) stenoses, intracranial angioplasty and/or stent placement (45% reduction), and endovascular treatment of unruptured intracranial aneurysms (44.6% reduction) and ruptured (22.9% reduction) and unruptured brain arteriovenous malformations (66.4% reduction). There was an increase in the treatment of ruptured intracranial aneurysms (10% increase) and other neuroendovascular procedures (34.9% increase). There was no relationship between procedural volume change and intuitional location in high or low COVID-19 prevalent regions. The procedural volume reduction was mainly observed in March-April 2020. CONCLUSIONS: We provided an international multicenter view of changes in neuroendovascular practices to better understand the gaps in provision of care and identify individual procedures, which are susceptible to change.

Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol.

Abstract: Introduction Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT. Methods and analysis DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0–2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0–2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment. Ethics and dissemination The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal. Trial registration number NCT03969511.

Rescue carotid puncture for ischemic stroke treated by endovascular therapy: a multicentric analysis and systematic review.

Abstract: Background Endovascular therapy (EVT) for acute ischemic stroke (AIS) can be challenging in older patients with supra-aortic tortuosity. Rescue carotid puncture (RCP) can be an alternative in case of supra-aortic catheterization failure by femoral access, but data regarding RCP are scarce. We sought to investigate the feasibility, effectiveness and safety of RCP for AIS treated by EVT. Methods Patients treated by EVT with RCP were included from January 2012 to December 2019 in the Endovascular Treatment in Ischemic Stroke (ETIS) multicentric registry. Main outcomes included reperfusion rates (≥TICI2B), 3 month functional outcome (modified Rankin Scale) and 3 month mortality. We also performed an additional systematic review of the literature according to the PRISMA checklist to summarize previous studies on RCP. Results 25 patients treated by EVT with RCP were included from the ETIS registry. RCP mainly concerned elderly patients (median age 85 years, range 73–92) with supra-aortic tortuosity (n=16 (64%)). Intravenous thrombolysis (IVT) was used for nine patients (36%). Successful reperfusion was achieved in 64%, 87.5% of patients were dependent at 3 months, and 3 month mortality was 45.8%. The systematic review yielded comparable results. In pooled individual data, there was a shift toward better functional outcome in patients with successful reperfusion (median (IQR) 4 (2–6) vs 6 (4–6), p=0.011). Conclusion RCP mainly concerned elderly patients admitted for AIS with anterior LVO with supra-aortic tortuosity. The procedure seemed feasible, notably for patients treated with IVT, and led to significant reperfusion rates at the end of procedure, but with pronounced unfavorable outcomes at 3 months. RCP should be performed under general anesthesia to avoid life-threatening complications and ensure airways safety. Finally, RCP led to low rates of closure complications, emphasizing that this concern should not withhold RCP, if indicated.

Influence of prior intravenous thrombolysis on outcome after failed mechanical thrombectomy: ETIS registry analysis.

Abstract: Background Despite constant improvements in recent years, sufficient reperfusion after mechanical thrombectomy (MT) is not reached in up to 15% of patients with large vessel occlusion stroke (LVOS). The outcome of patients with unsuccessful reperfusion after MT especially after intravenous thrombolysis (IVT) use is not known. We investigated the influence of initial IVT in this particular group of patients with failed intracranial recanalization. Methods We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry from January 2015 to December 2019. Patients presenting with LVOS of the anterior circulation and final modified Thrombolysis in Cerebral Infarction score (mTICI) of 0, 1 or 2a were included. Posterior circulation, isolated cervical carotid occlusions and successful reperfusions (mTICI 2b, 2c or 3) were excluded. The primary endpoint was favorable outcome (modified Rankin Scale score of 0–2) after 3 months. Secondary endpoints were safety outcomes including mortality, any intracranial hemorrhage (ICH), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) rates. Results Among 5076 patients with LVOS treated with MT, 524 patients with insufficient recanalization met inclusion criteria, of which 242 received IVT and 282 did not. Functional outcome was improved in the MT+IVT group compared with the MT alone group, although the difference did not reach statistical significance (23.0% vs 12.9%; adjusted OR=1.82; 95% CI 0.98 to 3.38; p=0.058). However, 3 month mRS shift analysis showed a significant benefit of IVT (adjusted OR=1.68; 95% CI 1.56 to 6.54). ICH and sICH rates were similar in both groups, although PH rate was higher in the MT+IVT group (adjusted OR=3.20; 95% CI 1.56 to 6.54). Conclusions Among patients with LVOS in the anterior circulation and unsuccessful MT, IVT was associated with improved functional outcome even after unsuccessful MT. Despite recent trials questioning the place of IVT in the LVOS reperfusion strategy, these findings emphasize a subgroup of patients still benefiting from IVT.

A Novel Mouse Model for Cerebral Venous Sinus Thrombosis

Abstract: Cerebral venous sinus thrombosis (CVST) is an uncommon cause of stroke resulting in parenchymal injuries associated with heterogeneous clinical symptoms and prognosis. Therefore, an experimental animal model is required to further study underlying mechanisms involved in CVST. This study is aimed at developing a novel murine model suitable and relevant for evaluating injury patterns during CVST and studying its clinical aspects. CVST was achieved in C57BL/6J mice by autologous clot injection into the superior sagittal sinus (SSS) combined with bilateral ligation of external jugular veins. Clot was prepared ex vivo using thrombin before injection. On days 1 and 7 after CVST, SSS occlusion and associated-parenchymal lesions were monitored using different modalities: in vivo real-time intravital microscopy, magnetic resonance imaging (MRI), and immuno-histology. In addition, mice were subjected to a neurological sensory-motor evaluation. Thrombin-induced clot provided fibrin- and erythrocyte-rich thrombi that lead to reproducible SSS occlusion at day 1 after CVST induction. On day 7 post-CVST, venous occlusion monitoring (MRI, intravital microscopy) showed that initial injected-thrombus size did not significantly change demonstrating no early spontaneous recanalization. Microscopic histological analysis revealed that SSS occlusion resulted in brain edema, extensive fibrin-rich venular thrombotic occlusion, and ischemic and hemorrhagic lesions. Mice with CVST showed a significant lower neurological score on post-operative days 1 and 7, compared to the sham-operated group. We established a novel clinically CVST-relevant model with a persistent and reproducible SSS occlusion responsible for symptomatic ischemic and hemorrhagic lesions. This method provides a reliable model to study CVST physiopathology and evaluation of therapeutic new regimens.

Thrombolysis Improves Reperfusion and the Clinical Outcome in Tandem Occlusion Stroke Related to Cervical Dissection: TITAN and ETIS Pooled Analysis.

Abstract: BACKGROUND AND PURPOSE Despite the widespread adoption of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke (LVOS) in the anterior circulation, the optimal strategy for the treatment tandem occlusion related to cervical internal carotid artery (ICA) dissection is still debated. This individual patient pooled analysis investigated the safety and efficacy of prior intravenous thrombolysis (IVT) in anterior circulation tandem occlusion related to cervical ICA dissection treated with MT. METHODS We performed a retrospective analysis of two merged prospective multicenter international real-world observational registries: Endovascular Treatment in Ischemic Stroke (ETIS) and Thrombectomy In TANdem occlusions (TITAN) registries. Data from MT performed in the treatment of tandem LVOS related to cervical ICA dissection between January 2012 and December 2019 at 24 comprehensive stroke centers were analyzed. The primary endpoint was a favorable outcome defined as 90-day modified Rankin Scale (mRS) score of 0-2. RESULTS The study included 144 patients with tandem occlusion LVOS due to cervical ICA dissection, of whom 94 (65.3%) received IVT before MT. Prior IVT was significantly associated with a better clinical outcome considering the mRS shift analysis (common odds ratio, 2.59; 95% confidence interval [CI], 1.35 to 4.93; P=0.004 for a 1-point improvement) and excellent outcome (90-day mRS 0-1) (adjusted odds ratio [aOR], 4.23; 95% CI, 1.60 to 11.18). IVT was also associated with a higher rate of intracranial successful reperfusion (83.0% vs. 64.0%; aOR, 2.70; 95% CI, 1.21 to 6.03) and a lower rate of symptomatic intracranial hemorrhage (4.3% vs. 14.8%; aOR, 0.21; 95% CI, 0.05 to 0.80). CONCLUSIONS Prior IVT before MT for the treatment of tandem occlusion related to cervical ICA dissection was safe and associated with an improved 90-day functional outcome.

Timing and Spectrum of Neurological Complications After Flow Diverter Implantation for Intracranial Aneurysms.

Abstract: Background and Purpose: The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications. Methods: This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD. Results: Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186-1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month. Conclusions: Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.

First-line thrombectomy strategy for anterior large vessel occlusions: results of the prospective ETIS egistry

Abstract: Background The best recanalization strategy for mechanical thrombectomy (MT) remains unknown as no randomized controlled trial has simultaneously evaluated first-line stent retriever (SR) versus contact aspiration (CA) versus the combined approach (SR+CA). Objective To compare the efficacy and safety profiles of SR, CA, and SR+CA in patients with acute ischemic stroke (AIS) treated by MT. Methods We analyzed data of the Endovascular Treatment in Ischemic Stroke (ETIS) Registry, a prospective, multicenter, observational study of patients with AIS treated by MT. Patients with M1 and intracranial internal carotid artery (ICA) occlusions between January 2015 and March 2020 in 15 comprehensive stroke centers were included. We assessed the association of first-line strategy with favorable outcomes at 3 months (modified Rankin Scale score 0–2), successful recanalization rates (modified Thrombolysis In Cerebral Infarction (mTICI) 2b/3), and safety outcomes. Results We included 2643 patients, 406 treated with SR, 1126 with CA, and 1111 with SR+CA. CA or SR+CA achieved more successful recanalization than SR for M1 occlusions (aOR=2.09, (95% CI 1.39 to 3.13) and aOR=1.69 (95% CI 1.12 to 2.53), respectively). For intracranial ICA, SR+CA achieved more recanalization than SR (aOR=2.52 (95% CI 1.32 to 4.81)), no differences were observed between CA and SR+CA. SR+CA was associated with lower odds of favorable outcomes compared with SR (aOR=0.63 (95% CI 0.44 to 0.90)) and CA (aOR=0.71 (95% CI 0.55 to 0.92)), higher odds of mortality at 3 months (aOR=1.56 (95% CI 1.22 to 2.0)) compared with CA, and higher odds of symptomatic intracranial hemorrhage (aOR=1.59 (95% CI 1.1 to 2.3)) compared with CA. Conclusions Despite high recanalization rates, our results question the safety of the combined approach, which was associated with disability and mortality. Randomized controlled trials are needed to evaluate the efficacy and safety of these techniques.

Association of Hypotension During Thrombectomy and Outcomes Differs With the Posterior Communicating Artery Patency

Abstract: Background and Purpose: Hypotension during endovascular therapy for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, w...

Impact of Prior Antiplatelet Therapy on Outcomes After Endovascular Therapy for Acute Stroke: Endovascular Treatment in Ischemic Stroke Registry Results.

Abstract: Background and Purpose: The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared proce...

Intravenous abciximab as a rescue therapy for immediate reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients.

Abstract: Background – Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome.Objective – The aim...

The ARTISSE intrasaccular device for intracranial aneurysm treatment: short-term, mid-term and long-term clinical and angiographic results.

Abstract: Background The concept of intra-aneurysmal flow disruption has emerged as a new paradigm for the treatment of primarily bifurcation aneurysms. The purpose of this study was to determine the clinical and angiographic outcomes of patients treated with the new ARTISSE intrasaccular device (ISD). Methods Selected patients with bifurcation aneurysms that matched the indications of the ARTISSE ISD defined by the manufacturer were treated in a single center. Clinical and angiographic follow-up was conducted at 6 and 36 months. Aneurysm occlusion was assessed using the Raymond–Roy classification scale. Results Nine subjects with nine unruptured bifurcation aneurysms were enrolled. Mean aneurysm size was 7.2±1.2 mm (range 5.5–9.7 mm). An adequate aneurysm occlusion (defined as a complete occlusion or a neck remnant) was achieved in 6/9 patients (66.7%) at 6 months and 4/7 patients (57.1%) at 36 months follow-up. Two of the nine subjects experienced a major stroke (22.2%), including one on postoperative day 1 due to a procedure-related parent vessel occlusion and subsequent ischemic stroke. The other major stroke occurred within the 36-month follow-up period during treatment of a separate aneurysm with coils, leading to perforation with hemorrhagic stroke causing a permanent neurological deficit. Conclusion The ARTISSE ISD was successfully deployed in all nine cases. There were, however, several procedure-related complications and results in terms of angiographic aneurysm occlusion were modest.