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Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion.Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes.Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048).In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

BACKGROUND Monitoring stroke patients in critical-care units for 24 hours after thrombolysis or endovascular thrombectomy is considered standard of care but is not evidence-based. Due to the Covid-19 pandemic, our center modified its protocol in April 2021 with 24-hour critical-care monitoring no longer being guaranteed for stroke patients. We aim to compare the incidence and timing of complications over the first 24 hours post-reperfusion therapies and their association to hospital unit in 2019, 2020 and 2021. METHODS We conducted a single-center retrospective cohort study. We analyzed data from stroke patients treated with thrombolysis and/or endovascular thrombectomy at our center in 2019 (pre-Covid-19, standard of care), 2020 (during Covid-19, standard of care) and 2021 (during Covid-19, new protocol). Data extracted included demographics, the nature and timing of complications within the first 24 hours, and the unit at the time of any complication. Major complications included neurologic deterioration, symptomatic intracranial hemorrhage, recurrent stroke, myocardial infarction, systemic bleeding, rapid assessment of critical events call, and death. RESULTS Three hundred forty-nine patients were included in our study: 78 patients in 2019, 115 patients in 2020, and 156 patients in 2021. In 2021, 32% of patients experienced at least one complication within the first 24 hours compared to 34% in 2020 and 27% in 2019. In 2021, 33% of patients admitted to critical-care units had a complication compared to 31% in 2020 and 26% in 2019. In 2021, 70% of complications had occurred by hour eight compared to 49% in 2020 and 29% in 2019. CONCLUSIONS Despite the change of protocol in April 2021, the incidence and timing of complications did not significantly worsen compared to prior years and were not associated with hospital location. Further research is required to evaluate the necessity of critical care monitoring for 24 hours in this population.

We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion.From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter- and intra-rater agreement were measured using Gwet's ACAlmost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters' experience, hematoma location, volume, or anticoagulation status. Intra-rater agreement was substantial to almost perfect for all but the black hole marker.In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement.• In a sample of 15 raters and 60 patients, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement (Gwet's AC

Background and Purpose: In the settings of thrombectomy, the first-pass effect (FPE), defined by a complete recanalization after one pass with no rescue therapy, has been shown to be associated with an improved outcome. As this phenomenon has been predominantly described in anterior circulation strokes, we aimed to study the prevalence, outcomes, and predictors of FPE in patients with a basilar artery occlusion. Methods: From a prospective multicentric registry, we collected the data of all consecutive basilar artery occlusion patients who underwent thrombectomy and compared the outcomes of patients who achieved FPE and those who did not. We also compared FPE patients with those who achieved a complete recanalization with >1 pass. Finally, a multivariate analysis was performed to determine the predictors of FPE. Results: Data from 280 patients were analyzed in our study, including 84 of 280 patients (30%) with an atheromatous etiology. An FPE was achieved in 93 patients (33.2%), with a significantly higher proportion of good outcomes (modified Rankin Scale score 0-2 at 3 months) and lower mortality than non-FPE patients. An FPE was also associated with improved outcomes compared with patients who went on to have full recanalization with >1 pass. Contact aspiration as first-line strategy was a strong predictor of FPE, whereas baseline antiplatelets and atheromatous etiology were negative predictors. Conclusions: In our study, an FPE was achieved in approximately one-third of patients with a basilar artery occlusion and was associated with improved outcomes. More research is needed to improve devices and techniques to increase the incidence of FPE. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03776877.

Background and purpose Recent clinical trials demonstrated the benefit of thrombectomy beyond 6 h based on the automated measurement of infarct volume exclusively with the RAPID software. We aimed to compare eight tools commonly used for the measurement of infarct volume and see whether they would lead to similar thrombectomy decisions based on the Diffusion-weighted-imaging or computerized-tomography-perfusion Assessment with clinical mismatch in the triage of Wake-up and late-presenting strokes undergoing Neurointervention with Trevo (DAWN) trial imaging inclusion criteria. Materials and Methods The diffusion-weighted-imaging (DWI) infarct volume of 36 patients was measured with 3 automated tools (including RAPID) and 5 non-automated tools. The agreement for the measurements of DWI infarct volume and the resulting thrombectomy decisions were assessed with intraclass correlation coefficient (ICC) and Fleiss’ Kappa (K) statistics. Results The correlation for the measurement of DWI infarct volume between all 9 tools was excellent (ICC > 0.8). After dichotomization, agreement was substantial for any of the cut-points used in DAWN trial. Discrepancies involving at least one of the tools for thrombectomy decisions based on DAWN criteria occurred in one third of cases. Compared with RAPID, the use of any other tool for treatment decision based on DAWN criteria would have led to contradictory decisions in 6% to 19% of cases. Conclusion There are several currently available tools for the measurement of DWI infarct volume with excellent correlation. Despite the high agreement demonstrated in our study, frequent discrepancies between measurements in some dichotomized configurations led to frequent diverging thrombectomy decisions when applying DAWN criteria.

Acute ischemic stroke (AIS) secondary to a basilar artery occlusion (BAO) carries a poor prognosis, especially in cases of severe symptoms, such as coma at presentation. Despite a lack of evidence, mechanical thrombectomy (MT) is often performed as the procedural risks are felt to be minimal compared to the natural history. We sought to evaluate MT efficacy and safety in comatose BAO patients. We performed a retrospective analysis of a multicenter prospective cohort of consecutive AIS patients with BAO who underwent MT. We compared baseline characteristics between comatose and noncomatose BAO patients, as well as clinical outcomes (modified Rankin scale, mRS 0–3 at 3 months). Using a multivariate logistic regression, we examined the population of comatose patients for baseline predictive factors of mortality. We included 269 patients, 72 (27%) comatose and 197 (73%) non-comatose. Despite similar recanalization rates between comatose and non-comatose patients (83% vs. 90% p = 0.221), comatose patient long-term outcomes were dramatically worse (11% mRS 0–3 vs. 54%, p

BACKGROUND AND PURPOSE Mechanical thrombectomy (MT) is the standard of care for patients with anterior circulation large vessel occlusion. Early neurological improvement (ENI), defined as a reduction of ≥ 8 on the National Institutes of Health Stroke Scale (NIHSS) compared with baseline score, or an NIHSS score of 0 or 1 at 24 h after MT, is a strong predictor of 3-month favorable outcome in such patients. The impact of ENI after MT in stroke patients with basilar artery occlusion (BAO) on 3-month outcome is not clear. We aimed to study the effects of ENI in patients with BAO. METHODS We performed a retrospective analysis of a multicenter prospective cohort of all consecutive stroke patients with BAO who underwent MT. We compared clinical outcomes between BAO patient groups according to ENI status. Multivariate analyses were performed to determine the impact of ENI on favorable 90-day outcome (modified Rankin scale score 0-3) and to report factors contributing to ENI. RESULTS A total of 237 patients were included. ENI was observed in 70 patients (30%). Outcomes were significantly better in ENI-positive patients, with 84% achieving favorable outcome (mRS score 0-3) at 3 months versus 30% for ENI-negative patients (P

This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019. During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy. Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer. Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.

To evaluate outcomes of thrombectomy in patients with a basilar artery occlusion (BAO) and mild symptoms, defined by an initial National Institutes of Health Stroke Scale (NIHSS) score ≤6.We performed a retrospective analysis of a multicenter prospective cohort of consecutive patients with acute ischemic stroke with BAO who underwent thrombectomy. We compared baseline and procedural characteristics, as well as outcomes between patients with BAO with an NIHSS score ≤6 and6. Multivariate analyses were performed to determine baseline and procedural predictors of good outcome (modified Rankin Scale score 0-2) among patients with an NIHSS score ≤6.A total of 269 patients were included: 50 (19%) had an initial NIHSS score ≤6 and 219 (81%) had an NIHSS score6. Patients with mild strokes (NIHSS score ≤6) had better outcomes (68% of modified Rankin Scale score 0-2 vs. 27% for NIHSS score6; P0.0001), lower mortality (14% vs. 48; P0.0001) and fewer parenchymal hematomas at day 1 (0% vs. 10%; P = 0.016). A multivariate analysis identified the following predictors for good outcome among patients with BAO with an NIHSS score ≤6: younger age, fewer passes, a cardioembolic cause, and the absence of need for angioplasty/stenting.Thrombectomy seems to be safer and more effective for mild BAO strokes with NIHSS score ≤6 than for more severe patients. Even although thrombectomy showed high rates of recanalization, a substantial proportion (32%) nevertheless had a poor long-term clinical outcome. The number of passes, patient's age, and stroke cause seem to be predictors of clinical outcome.

BackgroundThe COVID-19 pandemic has disrupted acute stroke care logistics, including delays in hyperacute management and decreased monitoring following endovascular therapy (EVT). We aimed to assess the impact of the pandemic on 90-day functional outcome among patients treated with EVT.MethodsThis is an observational cohort study including all patients evaluated for an acute stroke between March 30, 2020 and September 30, 2020 (pandemic cohort) and 2019 (reference cohort) in a high-volume Canadian academic stroke center. We collected baseline characteristics, acute reperfusion treatment and management metrics. For EVT-treated patients, we assessed the modified Rankin score (mRS) at 90 days. We evaluated the impact of the pandemic on a 90-day favourable functional status (defined as mRS 0–2) and death using multivariable logistic regressions.ResultsAmong 383 and 339 patients included in the pandemic and reference cohorts, baseline characteristics were similar. Delays from symptom onset to evaluation and in-house treatment were longer during the early first wave, but returned to reference values in the subsequent months. Among the 127 and 136 EVT-treated patients in each respective cohort, favourable 90-day outcome occurred in 53/99 (53%) vs 52/109 (48%, p=0.40), whereas 22/99 (22%) and 28/109 (26%, p=0.56) patients died. In multivariable regressions, the pandemic period was not associated with 90-day favourable functional status (aOR 1.27, 95% CI 0.60 to 2.56) or death (aOR 0.74, 95% CI 0.33 to 1.63).ConclusionIn this single-center cohort study conducted in a Canadian pandemic epicenter, the first 6 months of the COVID-19 pandemic did not impact 90-day functional outcomes or death among EVT-treated patients.

Background: Hematoma expansion (HE) is an important therapeutic target in intracerebral hemorrhage. Recently proposed HE definitions have not been validated, and no previous definition has accounted for withdrawal of care (WOC). Objective: To compare conventional and revised definitions of hematoma expansion (HE), while accounting for WOC. Methods: We analyzed data from the ATACH-2 trial, comparing revised definitions of HE incorporating intraventricular hemorrhage (IVH) expansion to the conventional definition of “≥6 mL or ≥33%”. The primary outcome was modified Rankin Scale of 4-6 at 90-days. We calculated the incidence, sensitivity, specificity, positive and negative predictive values, and c- statistic for all definitions of HE. Definitions were compared using non-parametric methods. Secondary analyses were performed after removing patients who experienced WOC. Results: Primary analysis included 948 patients. Using the conventional definition, the sensitivity was 37.1% and specificity was 83.2% for the primary outcome. Sensitivity improved with all three revised definitions (53.3%, 48.7%, and 45.3%, respectively), with minimal change to specificity (78.4%, 80.5%, and 81.0%, respectively). The greatest improvement was seen with the definition “≥6 mL or ≥33% or any IVH”, with increased c -statistic from 60.2% to 65.9% (p < 0.001). Secondary analysis excluded 46 participants who experienced WOC. The revised definitions outperformed the conventional definition in this population as well, with the greatest improvement in c -statistic using “≥6 mL or ≥33% or any IVH” (58.1% vs 64.1%, p < 0.001). Conclusions: HE definitions incorporating intraventricular expansion outperformed conventional definitions for predicting poor outcome, even after accounting for care limitations.

Introduction: Several comprehensive stroke centers (CSC) have reported increased delays to reperfusion in acute stroke during the COVID-19 pandemic, but it is unknown whether the pandemic is associated with worse functional outcomes in EVT-treated patients. Methods: We performed an observational cohort study of consecutive adult patients evaluated for suspected stroke at our CSC (located in Montreal, a Canadian pandemic epicenter) between March 30 and May 15 2020 (prospective pandemic cohort) and 2019 (retrospective non-pandemic cohort). We excluded in-hospital strokes. We compared short-term (in-house door-to-puncture and door-to-recanalization delays, TICI 2b/3, complications during EVT) and long-term (90-day mRS ≤2 and death) outcomes with univariate analyses. We assessed the effect of the pandemic on 90-day mRS while controlling for clinical confounders. Results: Overall, 111 and 106 patients were included in the pandemic and non-pandemic cohorts, respectively. The prevalence of COVID-19 in the pandemic cohort was 3% (3/104). Among ischemic stroke patients, 31/77 (40%) and 41/71 (58%) underwent EVT in each respective cohort (p=0.03). Among EVT-treated patients, baseline characteristics and NIHSS scores were similar (median [interquartile range]: 20 [12-25] vs 18 [14-20], p=0.18), but pre-stroke mRS was lower in the exposed cohort (0 [0-1] vs 1 [0-2], p=0.04). Door-to-puncture (87 [65-102] vs 56 [47-74] min, p=0.07) metrics were similar, but door-to-recanalization (122 [99-126] vs 89 [67-97] min, p Conclusion: The COVID-19 pandemic does not appear to have a negative impact on 90-day functional status among EVT-treated patients despite increased delays to recanalization. However, patient selection may have been stricter during the pandemic, as a smaller proportion of evaluated patients underwent EVT and those treated had lower pre-stroke mRS.

BackgroundThe Embolus Retriever with Interlinked Cages (ERIC) is one of the latest devices for thrombectomies. It has several architectural features that are supposed to enhance its ability to remove clots and prevent distal emboli. We aimed to compare ERIC with standard stent retrievers (SRs) using propensity score (PS) matching.MethodsThe clinical and radiological data of all consecutive patients treated with ERIC or standard FDA-approved stent retrievers were collected from a prospective multicenter registry. We compared procedural outcomes (recanalization rates according to the modified Thrombolysis In Cerebral Infarction (mTICI) score and procedural complications) and clinical outcomes (modified Rankin Scale (mRS) and mortality at 3 months). Matching of the populations with PS was performed to account for differences in baseline characteristics.ResultsA total of 1230 patients were included. In both the PS-matched cohort (195 ERIC patients, 630 SR patients) and the inverse probability of treatment weighting PS-adjusted cohort (206 ERIC patients, 1024 SR patients) there was no difference in terms of successful recanalization (modified TICI score ≥2b), good clinical outcome (mRS=0–2 or equal to pre-stroke mRS), or mortality at 3 months. Patients treated with first-line ERIC had a higher rate of complete recanalization (mTICI 3); however, they also required more passes and more frequent rescue therapy than the SR patient group.ConclusionIn a large multicenter registry with PS matching, the ERIC device provided equivalent angiographic and clinical results to conventional SRs.Clinical trial registrationURL: http://www.clinicaltrials.gov Unique identifier: NCT03776877.

Acute ischemic stroke (AIS) secondary to a basilar artery occlusion (BAO) carries a poor prognosis, especially in cases of severe symptoms, such as coma at presentation. Despite a lack of evidence, mechanical thrombectomy (MT) is often performed as the procedural risks are felt to be minimal compared to the natural history. We sought to evaluate MT efficacy and safety in comatose BAO patients.We performed a retrospective analysis of a multicenter prospective cohort of consecutive AIS patients with BAO who underwent MT. We compared baseline characteristics between comatose and noncomatose BAO patients, as well as clinical outcomes (modified Rankin scale, mRS 0-3 at 3 months). Using a multivariate logistic regression, we examined the population of comatose patients for baseline predictive factors of mortality.We included 269 patients, 72 (27%) comatose and 197 (73%) non-comatose. Despite similar recanalization rates between comatose and non-comatose patients (83% vs. 90% p = 0.221), comatose patient long-term outcomes were dramatically worse (11% mRS 0-3 vs. 54%, p 0.0001) and mortality was higher (64% vs. 34%, p 0.0001). Baseline predictors of mortality at 3 months among comatose BAO patients after multivariate analysis were the following: male sex (odds ratio, OR 31.20, 2.57-378.52, p = 0.007), older age (OR 1.13, 1.04-1.24, p = 0.007) and higher serum glucose levels (OR 1.54, 1.07-2.21, p = 0.019).Thrombectomy is technically effective for BAO patients presenting with coma; however, the long-term favorable outcome remains poor. Male sex, old age and hyperglycemia were predictors of mortality in these patients.

Background and Purpose— Previous experimental studies found that the infusion of human purified nascent HDL (high-density lipoprotein) significantly reduced infarct volume and hemorrhagic transformation rate by decreasing neutrophil recruitment. ApoA1-M (apolipoprotein A1-Milano) is a natural variant of human ApoA1 that confers protection against atherosclerosis. Recombinant ApoA1-M has been formulated as a complex with phospholipids to mimic the properties of nascent HDL. The aim of this study was to assess the impact of intravenous ApoA1-M in a transient middle cerebral artery occlusion stroke model in rats. Methods— In a first experiment, rats were subjected to 120-minute transient middle cerebral artery occlusion and intravenous ApoA1-M was infused immediately or 4 hours after occlusion. In a second experiment, rats were subjected to 240-minute transient middle cerebral artery occlusion and intravenous ApoA1-M was infused with or without recombinant tPA (tissue-type plasminogen activator) immediately after recanalization. Primary outcome criteria were the infarct volume and hemorrhagic transformation rate measured at 24 hours. Platelets, coagulation, and neutrophil activation biomarkers were measured in brain homogenates and plasma. Additional in vitro experiments studied the effects of ApoA1-M on platelet aggregation and platelet-neutrophil interactions. Results— The infusion of ApoA1-M immediately or 4 hours after 120-minute transient middle cerebral artery occlusion significantly reduced the infarct volume compared with saline ( P =0.034 and P =0.036, respectively). Compared with tPA alone, co-administration of ApoA1-M and tPA showed similar rates of hemorrhagic transformation. ApoA1-M had no significant inhibition effect on neutrophil activation biomarkers. Platelet activation was slightly decreased in rats treated with ApoA1-M compared with saline. In vitro, the incubation of human and rat platelet-rich plasma with ApoA1-M significantly reduced ADP-induced platelet aggregation ( P =0.001 and P =0.02, respectively). Conclusions— ApoA1-Milano significantly decreased the infarct volume through an inhibition of platelet aggregation but did not reduce hemorrhagic transformation and neutrophils activation as expected after previous experimental studies with nascent HDL. Visual Overview— An online visual overview is available for this article.

ObjectiveTo determine whether the ABC/2 method could accurately and reliably measure infarct volume and guide thrombectomy decision in acute stroke cases presenting with late or unknown onset.MethodsFour physicians who routinely use MRI for acute stroke imaging, blinded to the RAPID results, measured the diffusion-weighted imaging (DWI) infarct volume using the ABC/2 method. Measurements with ABC/2 (the index test) were compared with RAPID (the reference standard) to calculate sensitivity, specificity, and accuracy measures for various volume cutpoints. Thrombectomy decisions based on RAPID and raters' measurements using the criteria from the Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late-Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial criteria were compared. Interrater and intrarater agreement was measured using kappa statistics.ResultsAccuracy with the ABC/2 method was greater than 80% for each rater and each volume cut point. Interrater and intrarater agreement was substantial to excellent for each volume cut point. Treatment decisions with ABC/2 volume estimations showed strong interrater and intrarater agreement, and led to similar thrombectomy decisions compared with RAPID in more than 85% of cases.ConclusionDWI infarct volume measurement using ABC/2 method shows strong accuracy and reliability and may be an acceptable alternative to RAPID software for the application of DAWN criteria for thrombectomy decision-making.

Background: Carboxypeptidase U (CPU, CPB2, TAFIa) is a potent attenuator of fibrinolysis. The inhibition of CPU is thus an interesting strategy for improving thrombolysis. Objectives: The time course of CPU generation and proCPU consumption were assessed in an experimental rat model of acute ischemic stroke (AIS). In addition, the effects of the selective CPU inhibitor AZD9684 on CPU kinetics, microvascular thrombosis (MT), and AIS outcome were evaluated. Methods: Rats were subjected to transient middle cerebral artery occlusion (tMCAO) and received recombinant tissue-type plasminogen activator (tPA), a specific CPU inhibitor (AZD9684), combination therapy of tPA and AZD9684, or saline for 1 hour using a randomized treatment regime. CPU and proCPU levels were determined at five time points and assessed in light of outcome parameters (a.o.: infarct volume and fibrin[ogen] deposition as a measure for MT). Results: Clear activation of the CPU system was observed after AIS induction, in both saline- and tPA-treated rats. Maximal CPU activities were observed at treatment cessation and were higher in tPA-treated animals compared to the saline group. Concomitant proCPU consumption was more pronounced in tPA-treated rats. AZD9684 suppressed the CPU activity and reduced fibrin(ogen) deposition, suggesting a reduction of MT. Nonetheless, a significant decrease in infarct volume was not observed. Conclusions: A pronounced activation of the CPU system was observed during tMCAO in rats. Selective inhibition of CPU with AZD9684 was able to reduce fibrin(ogen) deposition and brain edema, suggesting a reduction of MT but without a significant effect on final infarct volume.

The best management of brain arteriovenous malformation (bAVM) patients remains unknown. Randomized allocation may be more readily accepted when there is uncertainty and disagreement regarding the management of potential participants. In planning for a trial, we aimed to assess variability and agreement among physicians managing bAVM patients.A portfolio composed of 35 patients was sent to 47 clinicians of various specialties managing bAVM patients. For each patient, physicians were asked their best management decision (surgery/embolization/radiosurgery/conservative), their confidence level, and whether they would include the patient in a randomized trial comparing conservative and curative management. Seven physicians, who had access to all images of each patient, independently responded twice, to assess inter and intra-rater agreement using kappa statistics.The inter-rater agreement (30 raters, including 16 neuroradiologists) for best management decision was only "fair" (κ [95%CI]=0.210[0.157; 0.295]). Agreement remained below 'substantial' (κ.6) between physicians of the same specialty, and when no distinctions were made between various treatments (when responses were dichotomized as conservative versus curative). With access to all images the inter-rater agreement remained fair. The intra-rater agreement reached "substantial" only for the dichotomized decisions. Responding clinicians were willing to include 54.4% of patients (mainly unruptured bAVMs) in a randomized trial.There is a lack of agreement among clinicians involved in the management of bAVM patients. In this study a substantial proportion of clinicians were willing to offer randomized allocation of management options to a substantial number of patients.

BackgroundThe ‘first pass effect’ (FPE), which was originally described with stent retrievers, designates a (near-)complete revascularization obtained after a single device pass with no rescue therapy, and is associated with improved clinical outcome and decreased mortality.ObjectiveWe report the rate and benefits of FPE in the Aspiration versus Stent Retriever (ASTER) trial.Materials and methodsASTER is a randomized trial comparing angiographic revascularization with the stent retriever (SR) and contact aspiration (CA) thrombectomy techniques, assessed by an external core laboratory using the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Rates of FPE (defined by mTICI 2c/3 after a single pass with no rescue therapy) were compared between patients treated with SR and CA techniques. Outcomes were compared between FPE-SR and FPE-CA patients, and between FPE and non-FPE patients.ResultsFPE was achieved in 97/336 patients (28.9%), with no significant difference between SR and CA (respectively 53/169 patients (31.3%) vs 44/167 patients (26.3%), adjusted RR for CA versus SR 0.84, 95% CI 0.54 to 1.31; p=0.44). After prespecified adjustment for allocated arm and randomization stratification factors, FPE in patients was associated with a significantly improved clinical outcome and a decreased mortality, and a significantly lower rate of hemorrhagic transformation and procedural complications than in non-FPE patients.ConclusionIn the ASTER trial, similar rates of FPE were achieved with SR and CA, and FPE was associated with a significantly improved outcome. New techniques and devices to improve the rate of FPE are warranted.Trial registration numberUnique identifier: NCT02523261.

Background and purpose Hemorrhagic transformation (HT) is a complication of stroke that can occur spontaneously or after treatment. We aimed to assess the inter- and intrarater reliability of HT diagnosis. Methods Studies assessing the reliability of the European Cooperative Acute Stroke Study (ECASS) classification of HT or of the presence (yes/no) of HT were systematically reviewed. A total of 18 raters independently examined 30 post-thrombectomy computed tomography scans selected from the Aspiration versus STEnt-Retriever (ASTER) trial. They were asked whether there was HT (yes/no), what the ECASS classification of the particular scan (0/HI1/HI2/PH1/PH2) (HI indicates hemorrhagic infarctions and PH indicates parenchymal hematomas) was and whether they would prescribe an antiplatelet agent if it was otherwise indicated. Agreement was measured with Fleiss' and Cohen's κ statistics. Results The systematic review yielded four studies involving few (≤3) raters with heterogeneous results. In our 18-rater study, agreement for the presence of HT was moderate [κ = 0.55; 95% confidence interval (CI), 0.41-0.68]. Agreement for ECASS classification was only fair for all five categories, but agreement improved to substantial (κ = 0.72; 95% CI, 0.69-0.75) after dichotomizing the ECASS classification into 0/HI1/HI2/PH1 versus PH2. The inter-rater agreement for the decision to reintroduce antiplatelet therapy was moderate for all raters, but substantial among vascular neurologists (κ = 0.70; 95% CI, 0.57-0.84). Conclusion The ECASS classification may involve too many categories and the diagnosis of HT may not be easily replicable, except in the presence of a large parenchymal hematoma.

Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5 %, (95 %CI [61.9–82.6 %]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100 % [65.5–100 %]). FD resulted in modest occlusion rates (15.4 % [8.9–25.1 %]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1 %]) or a control group (13/42 articles [30.9 %]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

PurposeThe DAWN trial (Diffusion weighted imaging or CT perfusion Assessment with clinical mismatch in the triage of Wake-up and late presenting strokes undergoing Neurointervention with Trevo) has demonstrated the benefits of thrombectomy in patients with unknown or late onset strokes, using automated software (RAPID) for measurement of infarct volume. Because RAPID is not available in all centers, we aimed to assess the accuracy and repeatability of visual infarct volume estimation by clinicians and the consequences for thrombectomy decisions based on the DAWN criteria.Materials and methods18 physicians, who routinely depend on MRI for acute stroke imaging, assessed 32 MR scans selected from a prospective databaseover two independent sessions. Raters were asked to visually estimate the diffusion weighted imaging (DWI) infarct volume for each case. Sensitivity, specificity, and accuracy of the estimated volumes were compared with the available RAPID measurements for various volume cut-off points. Thrombectomy decisions based on DAWN criteria with RAPID measurements and raters’ visual estimates were compared. Inter-rater and intra-rater agreement was measured using kappa statistics.ResultsThe mean accuracy of raters was ConclusionThe visual assessment of DWI infarct volume lacks accuracy and repeatability, and could lead to a significant number of erroneous decisions when applying the DAWN criteria.

Purpose We aimed to conduct an external validation of the selection criteria of the diffusion-weighted-imaging or computerized-tomography-perfusion assessment with clinical mismatch in the triage of wake-up and late-presenting strokes undergoing Neurointervention with Trevo (DAWN) trial1,2 in a cohort of unknown onset stroke (UOS) patients treated with thrombectomy. Materials and methods A study cohort of UOS patients was selected from a prospectively collected thrombectomy database to match the inclusion criteria of DAWN. Patients were stratified according to DAWN Groups A/B/C. Group A criteria identified patients≥80 years old with a NIHSS ≥10 + DWI volume Results Out of 102 patients, 60 (59%) were defined as DAWN-eligible. Among these, 26 patients (43%) reached a mRS ≤2 at 3 months follow-up (vs. 52/107 patients [49%] in the DAWN trial thrombectomy group; p=0.52) (figure 1). The proportion of DAWN-ineligible patients for Groups A/B/C with a mRS ≤2 were 2/13 patients (15%), 12/22 patients (55%), and 2/7 patients (29%), respectively. Conclusion The results of the DAWN trial were externally validated in a UOS cohort where the trial’s selection criteria identified a similar proportion of responders to thrombectomy. Additional trials are needed to address benefit in patients with larger infarct volumes who were not eligible for DAWN. References Jovin TG, Saver JL, Ribo M, et al. Diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake up and late presenting strokes undergoing neurointervention with Trevo (DAWN) trial methods. Int J Stroke 2017:1747493017710341. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. New England Journal of Medicine 2017. Disclosures R. Blanc: None. C. Ducroux: None. N. Khoury: None. A. Lecler: None. M. Piotin: None. R. Fahed: None.

We thank Van de Graaf et al for their thoughtful comments. In fact, the principal finding of our latter study was that targeting neutrophil extracellular traps (NETs) in acute ischemic stroke (AIS) thrombi with human recombinant DNAse 1 (deoxyribonuclease 1) led to an increased thrombolytic effect of tPA (tissue-type plasminogen activator).1 NETs may, therefore, constitute a valuable target for future therapies aimed at improving AIS outcomes. Although we were able to demonstrate the presence of NETs in large AIS thrombi retrieved during endovascular therapy, we did not assess the presence of NETs in downstream microvascular thrombosis in patients with AIS. However, evidence supports that NETs likely …

BACKGROUND AND PURPOSE An external validation of the selection criteria of diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake-up and late-presenting strokes undergoing the Neurointervention with Trevo (DAWN) and the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE3) trials was conducted in a cohort of unknown onset stroke (UOS) patients treated with thrombectomy. METHODS A validation cohort of UOS patients was selected from a prospectively collected thrombectomy database to match the inclusion criteria of DAWN and DEFUSE 3. Patients with an initial National Institutes of Health Stroke Scale (NIHSS) ≥10 were stratified according to the DAWN selection criteria. Patients ≤90 years old with an initial NIHSS ≥6 were stratified according to the DEFUSE 3 selection criteria. The proportions of patients with a modified Rankin Scale (mRS) ≤2 at 3 months follow-up were compared between DAWN-eligible patients and the DAWN trial thrombectomy group, and between DEFUSE 3-eligible patients and the DEFUSE 3 trial thrombectomy group. RESULTS Of the 60/102 (59%) DAWN-eligible patients, 26 patients (43%) reached a mRS ≤2 at 3 months follow-up [versus 52/107 patients (49%) in the DAWN trial thrombectomy group; P = 0.52]. Of the 100/117 (85%) DEFUSE 3-eligible patients, 48 patients (48%) reached a mRS ≤2 at 3 months follow-up [versus 41/92 patients (45%) in the DEFUSE 3 trial thrombectomy group; P = 0.67]. Of the DAWN-ineligible and DEFUSE 3-ineligible patients who underwent thrombectomy, 38% (16/42) and 41% (7/17) of patients reached a mRS ≤2, respectively. CONCLUSION The results of the DAWN and DEFUSE 3 trials were externally validated in a UOS cohort where the trials' selection criteria identified a similar proportion of responders to thrombectomy.

Background Hemorrhagic transformation (HT) is a complication of stroke [1] that can occur spontaneously or after treatment. We aimed to assess the interrater and intrarater reliability of HT diagnosis. Methods Studies assessing the reliability of the European Cooperative Acute Stroke Study (ECASS) classification [2] of HT or of the presence (yes/no) of HT were systematically reviewed. Eighteen raters independently examined 30 post-thrombectomy [3] computed tomography scans selected from the Aspiration versus Stentriever (ASTER) trial [4] . They were asked whether there was HT (yes/no), what the ECASS classification of the particular scan (0/HI1/HI2/PH1/PH2) was, and whether they would prescribe an antiplatelet agent if it was otherwise indicated. Agreement [5] was measured with Fleiss’ and Cohen's kappa statistics. Results The systematic review yielded 4 studies involving few (≤ 3) raters with heterogeneous results. In our 18-rater study, agreement for the presence of HT was moderate (κ=0.55, 95%CI [0.41–0.68]). Agreement for ECASS classification was only fair for all 5 categories, but agreement improved to substantial (k = 0.72, 95%CI [0.69-0.75]) after dichotomizing ECASS into 0/HI1/HI2/PH1 versus PH2. The interrater agreement for the decision to reintroduce antiplatelet therapy was moderate for all raters, but substantial among vascular neurologists (κ=0.70 [0.57–0.84]). Conclusion The ECASS classification may involve too many categories and the diagnosis of HT may not be easily replicable, except in the presence of a large parenchymal hematoma. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02523261 .

Background and Purpose— Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones and granular proteins produced by activated neutrophils. NETs have been identified as major triggers and structural factors of thrombosis. A recent study designated extracellular DNA threads from NETs as a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the presence of NETs in thrombi retrieved during endovascular therapy in patients with acute ischemic stroke (AIS) and their impact on tPA-induced thrombolysis. Methods— We analyzed thrombi from 108 AIS patients treated with endovascular therapy. Thrombi were characterized by hematoxylin/eosin staining, immunostaining, and ex vivo enzymatic assay. Additionally, we assessed ex vivo the impact of deoxyribonuclease 1 (DNAse 1) on thrombolysis of AIS thrombi. Results— Histological analysis revealed that NETs contributed to the composition of all AIS thrombi especially in their outer layers. Quantitative measurement of thrombus NETs content was not associated with clinical outcome or AIS pathogenesis but correlated significantly with endovascular therapy procedure length and device number of passes. Ex vivo, recombinant DNAse 1 accelerated tPA-induced thrombolysis, whereas DNAse 1 alone was ineffective. Conclusions— This study suggests that thrombus NETs content may be responsible for reperfusion resistance, including mechanical or pharmacological approaches with intravenous tPA, irrespectively of their etiology. The efficacy of a strategy involving an administration of DNAse 1 in addition to tPA should be explored in the setting of AIS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02907736.

Background and Purpose— We aimed to study the intrarater and interrater agreement of clinicians attributing DWI-ASPECTS (Diffusion-Weighted Imaging–Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging–Fluid Attenuated Inversion Recovery) mismatch in patients with acute ischemic stroke referred for mechanical thrombectomy. Methods— Eighteen raters independently scored anonymized magnetic resonance imaging scans of 30 participants from a multicentre thrombectomy trial, in 2 different reading sessions. Agreement was measured using Fleiss κ and Cohen κ statistics. Results— Interrater agreement for DWI-ASPECTS was slight (κ=0.17 [0.14–0.21]). Four raters (22.2%) had a substantial (or higher) intrarater agreement. Dichotomization of the DWI-ASPECTS (0–5 versus 6–10 or 0–6 versus 7–10) increased the interrater agreement to a substantial level (κ=0.62 [0.48–0.75] and 0.68 [0.55–0.79], respectively) and more raters reached a substantial (or higher) intrarater agreement (17/18 raters [94.4%]). Interrater agreement for DWI-FLAIR mismatch was moderate (κ=0.43 [0.33–0.57]); 11 raters (61.1%) reached a substantial (or higher) intrarater agreement. Conclusions— Agreement between clinicians assessing DWI-ASPECTS and DWI-FLAIR mismatch may not be sufficient to make repeatable clinical decisions in mechanical thrombectomy. The dichotomization of the DWI-ASPECTS (0–5 versus 0–6 or 0–6 versus 7–10) improved interrater and intrarater agreement, however, its relevance for patients selection for mechanical thrombectomy needs to be validated in a randomized trial.

Background and Purpose— Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How hyperglycemia impacts the pathophysiology of acute ischemic stroke remains largely unknown. We investigated how preexisting hyperglycemia increases ischemia/reperfusion cerebral injury. Methods— Normoglycemic and streptozotocin-treated hyperglycemic rats were subjected to transient middle cerebral artery occlusion. Infarct growth and brain perfusion were assessed by magnetic resonance imaging. Markers of platelet, coagulation, and neutrophil activation were measured in brain homogenates and plasma. Downstream microvascular thromboinflammation (DMT) was investigated by intravital microscopy. Results— Hyperglycemic rats had an increased infarct volume with an increased blood–brain barrier disruption and hemorrhagic transformation rate compared with normoglycemic rats. Magnetic resonance imaging scans revealed that hyperglycemia enhanced and accelerated lesion growth and was associated with hemorrhagic transformation originating from territories that were still not completely reperfused at 1 hour after middle cerebral artery recanalization. Intravital microscopy and analysis of brain homogenates showed that DMT began immediately after middle cerebral artery occlusion and was exacerbated by hyperglycemia. Measurement of plasma serotonin and matrix metalloproteinase-9 indicated that platelets and neutrophils were preactivated in hyperglycemic rats. Neutrophils from hyperglycemic diabetic patients showed increased adhesion to endothelial cells as compared with neutrophils from normoglycemic donors in flow chamber experiments. Conclusions— We show that hyperglycemia primes the thromboinflammatory cascade, thus, amplifying middle cerebral artery occlusion–induced DMT. DMT exacerbation in hyperglycemic rats impaired reperfusion and precipitated neurovascular damage, blood–brain barrier disruption, and hemorrhagic transformation. Our results designate DMT as a possible target for reduction of the deleterious impact of hyperglycemia in acute ischemic stroke.

Introduction L’infarctus cerebral est une des causes majeures de handicap. Aucun agent neuroprotecteur n’a prouve son efficacite chez l’homme. Une etude animale a montre une efficacite de l’injection de HDLs a la phase aigue de l’AVC. Objectifs Notre objectif etait de montre une efficacite semblable avec l’injection d’ApoA1-Milano (forme mutee de l’HDL) a la phase aigue de l’infarctus cerebral chez le rat. Patients et methodes Nous avons realise 5 protocoles dans un modele d’ischemie-reperfusion. Le 1er consistait en l’injection d’ApoA1-Milano juste apres l’occlusion arterielle, le 2eme testait l’injection de l’ApoA1-Milano 4 heures apres l’occlusion. Le 3eme et le 4eme ont permis d’evaluer l’ApoA1-Milano en traitement adjuvant du tPA. Enfin nous avons teste l’ApoA1-Milano dans un modele diabetique. Nos criteres d’evaluation etaient le volume d’infarctus, l’œdeme cerebral, le taux de transformation hemorragique et la mortalite. Resultats Chez les rats sains, nous avons trouve une reduction significative du volume de l’infarctus lors de l’injection d’ApoA1-Milano, immediatement (p = 0,0343) et quatre heures apres l’occlusion arterielle (p = 0,0364). Dans le troisieme et le quatrieme protocole nous n’avons pas montre d’efficacite de l’ApoA1-Milano en traitement adjuvant du tPA pour le taux des transformations hemorragiques. Chez les rats diabetiques, l’ApoA1-Milano n’a pas montre d’efficacite. Discussion L’ApoA1-Milano aurait un effet protecteur vis a vis de la barriere hemato-encephalique. Cependant en traitement adjuvant du tPA l’ApoA1-Milano n’a pas montre de benefice sur les transformations hemorragiques a la difference du HDL purifie. Ceci peut s’expliquer par le fait que l’ApoA1-Milano n’est qu’un constituant du HDL. Enfin l’inefficacite de l’ApoA1-Milano dans le modele diabetique peut s’expliquer par la « durete » de celui-ci. Conclusion L’ApoA1-Milano aurait un effet sur le volume de l’infarctus, mais pas sur les transformations hemorragiques. Des explorations complementaires sont necessaires pour comprendre le mecanisme d’action de l’ApoA1-Milano. Informations complementaires Ce projet de recherche a pu etre realiser grâce a la bourse de recherche de la societe francaise de Neurologie 2015/2016.