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Local Anesthesia Without Sedation During Thrombectomy for Anterior Circulation Stroke Is Associated With Worse Outcome

and the ETIS Registry Investigators
Originally publishedhttps://doi.org/10.1161/STROKEAHA.120.029194Stroke. 2020;51:2951–2959

Abstract

Background and Purpose:

The best anesthetic management for mechanical thrombectomy of large vessel occlusion strokes is still uncertain and could impact the quality of reperfusion and clinical outcome. We aimed to compare the efficacy and safety outcomes between local anesthesia (LA) and conscious sedation in a large cohort of acute ischemic stroke patients with anterior circulation large vessel occlusion strokes treated with mechanical thrombectomy in current, everyday clinical practice.

Methods:

Patients undergoing mechanical thrombectomy for anterior large vessel occlusion strokes at 4 comprehensive stroke centers in France between January 1, 2018, and December 31, 2018, were pooled from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France. Intention-to-treat and per-protocol analyses were used.

Results:

Among the included 1034 patients, 762 were included in the conscious sedation group and 272 were included in the LA group. In the propensity score matched cohort, the rate of favorable outcome (90-day modified Rankin Scale score 0–2) was significantly lower in the LA group than in the conscious sedation group (40.0% versus 52.0%, matched relative risk=0.76 [95% CI, 0.60–0.97]), as well as the rate of successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b–3; 76.6% versus 87.1%; matched relative risk=0.88 [95% CI, 0.79–0.98]). There was no difference in procedure time between the 2 groups. In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar significant differences were found for favorable outcomes and successful reperfusion. In inverse probability of treatment weighting-propensity score-adjusted cohort, a higher rate of 90-day mortality and a lower parenchymal hematoma were observed after LA. The sensitivity analysis restricted to our per-protocol sample provided similar results in the matched- and inverse probability of treatment weighting-propensity cohorts.

Conclusions:

In the Endovascular Treatment in Ischemic Stroke registry mainly included patients in early time window (<6 hours), LA was associated with lower odds of favorable outcome, successful reperfusion, and higher odds of mortality compared with conscious sedation for mechanical thrombectomy of large vessel occlusion.

Introduction

Despite the remarkable advances in the endovascular treatment of large vessel occlusion (LVO) strokes, the best anesthetic management approach is still unknown.1,2 Previous studies comparing general anesthesia (GA) to conscious sedation (CS) reported conflicting results.3–7 In the single-center, randomized SIESTA trial (Sedation Versus Intubation for Endovascular Stroke Treatment), there was no significant difference in the outcome between CS and GA.3 Similar results were reported in the GOLIATH (General or Local Anesthesia in Intra Arterial Therapy) and ANSTROKE (Anesthesia During Stroke) trials.4,5 A recent meta-analysis found that the use of protocol-based GA, compared with procedural CS, was significantly associated with less disability at 3 months.6 On the contrary, analysis of the HERMES group (Highly Effective Reperfusion Using Multiple Endovascular Devices) demonstrated an association between poor outcome and GA,7 a finding that was also demonstrated in a post hoc analysis of the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke).8 However, CS provides better pain management and anesthetic support which can theoretically reduce patient motion and preserve patient cooperation. Studies comparing local anesthesia (LA) to other anesthesia techniques, such as GA and CS, are scarce. A previous single-center retrospective study compared CS to LA found an association between CS and poor outcome without reduction in procedure time or complications.9 However, the study was limited by the small sample size and monocentric design.

The objective of this study was to compare the functional and safety outcomes between LA and CS during mechanical thrombectomy (MT) for anterior circulation LVO strokes using data from the prospective multicenter Endovascular Treatment in Ischemic Stroke (ETIS) registry.

Methods

Data of this study are available from the corresponding author on a reasonable request.

Patient Population

Patients undergoing MT for LVO stroke of the anterior circulation at 4 comprehensive stroke centers between January 1, 2018, and December 31, 2018, were included. Nine centers participate to date in the prospective multicenter ETIS registry in France, but data from 4 centers were used due to the participation of the other 5 centers after December 31, 2018. Data of the ETIS registry were collected and stored in electronic Case Report Forms (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03776877) and informed consent was obtained. Previously published work described ETIS methodology in details.10 Briefly, the ETIS registry included consecutive patients with acute ischemic stroke with LVO treated with MT in high-volume (annual MT >250/y) comprehensive stroke centers in France. All patients 18 years of age or older were included in this study. No patients were excluded based on National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early CT Score scores on presentation, administration of intravenous thrombolysis, or time from onset to puncture.

CS as first-line sedation management before MT was defined as CS group, while the patients enrolled at one center, which used no sedation management before MT, was defined as no sedation group. No protocol was present in the no sedation group and protocol exists in every CS center. No anesthesiologist was present in the angiosuite during MT in the setting of LA, whereas anesthesiologist was systematically present for CS. Subcutaneous injection of ≈10 mL of Xylocaine was done for LA and was also applied in the setting of CS. CS was performed with intravenous injection of Remifentanil. Blood pressure was monitored noninvasively in both groups without specific objectives, except that mean blood pressure should be around >100 mm Hg in patients treated under CS. In both groups, the systolic blood pressure was maintained <185 mm Hg in case of prior intravenous thrombolysis in compliance with the American Heart Association/American Stroke Association guidelines.11 Hypotension was treated with intravenous injection of Ephedrine during MT only in the CS group. The institutional review board at each site approved this study.

Outcomes

Our primary outcome was the favorable outcome, defined as a modified Rankin Scale (mRS) score 0–2 at 90 days or a mRS equal to prestroke situation. Ninety days after the acute event, functional outcome was assessed by board-certified vascular neurologists during a routinely scheduled clinical visit or by a study nurse certified in administering the mRS during a standardized telephone interview if the patient was unable to attend. Secondary outcomes included excellent outcome (90-day mRS score 0–1 or equal to prestroke mRS), early neurological improvement (24-hour NIHSS decrease ≥4 or NIHSS at 24-hour 0–1), 24-hour NIHSS shift (defined as baseline NIHSS- 24-hour NIHSS), final reperfusion status which was assessed by the modified Thrombolysis in Cerebral Ischemia grade, and the workflow metrics. Successful and complete reperfusion was defined as an modified Thrombolysis in Cerebral Ischemia grade 2b–3 and modified Thrombolysis in Cerebral Ischemia grade 3 at the end of MT, respectively. Safety outcomes included the all-causes mortality at 90 days, the occurrence of any procedural complication (dissection, perforation, and embolus in a new territory) and the occurrence of cerebral hemorrhage according to the ECASS II (European Collaborative Acute Stroke Study) classification.12 Imaging criteria were evaluated by a local investigator of each center.

Statistical Analysis

Quantitative variables are expressed as means (SD) in the case of normal distribution or medians (interquartile range) otherwise. Categorical variables are expressed as numbers (percentage). Normality of distributions was assessed using histograms and the Shapiro-Wilk test. Patients were divided in 2 groups according to center’s anesthetic protocol (LA versus CS). Baseline characteristics were described according to the 2 study groups, and the magnitude of the between-group differences was assessed by calculating the absolute standardized difference; an absolute standardized difference >10% was interpreted as a meaningful difference.13 We compared the outcomes between the 2 study groups after taking into account the potential confounding factors by using prespecified propensity score methods.14

The effects of the anesthetic approach were estimated by using propensity score matching method (propensity score was used to assemble well-balanced groups) as primary analysis and by using inverse probability of treatment weighting (IPTW) propensity score method (using stabilized inverse propensity score as weighty in regression models). The propensity score was estimated using a nonparsimonious multivariable logistic regression model, with anesthetic protocol as dependent variable and all the characteristics listed in the Table as covariates. Patients included in LA group were matched 1:1 to patients in CS group according to propensity score using the greedy nearest neighbor matching algorithm with a caliper width of 0.2 SD of logit for propensity score.15,16 To evaluate bias reduction after using the propensity score matching method, absolute standardized differences were calculated after propensity score matching. Because of missing baseline data (range from 0% to 12.2%), we estimated the effect sizes in matched- and IPTW-propensity score cohorts after handling missing covariate values by multiple imputation,17 using a regression switching approach (chained equations with m=10 imputations obtained).18 Imputation procedure was performed under the missing at random assumption using all variables listed in the Table (including anesthesia groups) with a predictive mean matching method for continuous variables and multinomial or binary logistic regression model for categorical variables. In each imputed data set, we calculated the propensity score and assembled a matched cohort to provide both matched and IPTW-propensity score-adjusted effect sizes, which were later combined by using Rubin’s rules.19

Table. Baseline Characteristics According to First-Line Anesthetic Approach in Acute Ischemic Stroke Patients Admitted for Thrombectomy Before and After Propensity Score Matching

CharacteristicsBefore MatchingAfter Matching
CS (n=636)LA (n=238)ASD, %CS (n=222)LA (n=222)ASD, %
Age, y median (IQR)73 (61–81)71 (61–81)2.2*74 (61–83)71 (61–81)5.1*
Men331 (52.1)122 (51.4)1.4116 (52.4)114 (51.4)1.5
Medical history
 Hypertension398 (62.6)154 (64.8)4.5144 (64.9)144 (65.0)0.3
 Diabetes mellitus136 (21.4)41 (17.3)10.438 (17.0)39 (17.6)2.0
 Hypercholesterolemia213 (33.4)79 (33.3)0.576 (34.0)74 (33.4)1.3
 Current smoking130 (20.5)45 (18.9)3.741 (18.6)41 (18.6)0.3
 Prior coronary disease110 (17.2)44 (18.5)3.244 (19.7)42 (18.7)2.0
 Prior stroke or TIA92 (14.4)40 (17.0)7.034 (15.4)36 (16.0)1.2
Clinical status
 Antithrombotic therapy286 (44.9)127 (53.3)16.9115 (51.9)116 (52.2)0.5
 Prestroke mRS score ≥1129 (20.3)47 (19.7)1.642 (18.8)43 (19.4)1.4
 Admission SBP, mm Hg, mean±SD147±29150±2810.4149±29150±281.5
 Cardioembolic cause242 (38.1)131 (55.0)34.3119 (53.7)118 (52.9)1.1
 NIHSS score, median (IQR)16 (10–20)16 (11–19)0.4*16 (11–20)16 (11–19)6.5*
Imaging
 ASPECTS, median (IQR)7 (6–9)8 (6–9)14.9*7 (6–9)8 (6–9)1.1*
 Initial imaging modality, MRI vs CT523 (82.2)200 (84.0)4.9186 (83.6)186 (83.6)1.4
Site of occlusion
 MCA-M1323 (50.8)147 (61.8)31.9133 (60.1)133 (59.8)7.6
 MCA-M295 (14.9)16 (6.7)18 (8.0)16 (7.1)
 Carotid T116 (18.2)31 (13.0)28 (12.5)31 (13.8)
 Cervical ICA35 (5.5)12 (5.0)29 (13.1)31 (13.9)
 Tandem67 (10.5)32 (13.4)14 (6.2)12 (5.4)
Treatment
 Prior use of IV thrombolysis320 (50.4)155 (65.1)30.2141 (63.5)140 (63.1)1.2
 Mechanical thrombectomy548 (86.1)196 (82.4)10.3186 (83.9)186 (83.7)0.4
Workflow, median (IQR), min
 Onset to groin puncture249 (191–321)266 (194–322)7.4240 (184–310)263 (188–321)12.9
 Onset to angiosuite room229 (170–300)246 (175–295)34.5218 (163–288)245 (172–295)13.9
 Angiosuite room to groin puncture16 (11–24)19 (14–27)11.218 (12–26)19 (14–26)11.4

Values expressed as numbers (%) unless otherwise indicated. Values were calculated after handling missing data using multiple imputation procedure. ASD indicates absolute standardized difference; ASPECTS, Alberta Stroke Program Early CT Score; CS, conscious sedation; ICA, internal carotid artery; IQR, interquartile range; IV, intravenous; LA, local anesthesia; MCA, middle cerebral artery; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; SBP, systolic blood pressure; and TIA, transient ischemic attack.

* Estimated using the rank-transformed data.

† Not included in propensity score calculation.

In propensity score matched cohort, between-group comparisons were done using a generalized estimating equations model (binomial distribution, log function with a compound symmetry working correlation structure) for binary outcomes, or using a linear mixed model with a matched blocks as random effect for continuous outcomes (admission NIHSS was included as covariate fixed effect for comparison in NIHSS change from baseline to 24 hours). In IPTW-propensity score-adjusted cohort, comparisons were done using weighted log-binomial regression models for binary outcomes or linear regression models for continuous outcomes (admission NIHSS was including as covariate fixed effect for comparison in NIHSS change from baseline to 24 hours). Using patients in CS group as reference, we derived from these regression models, relative risks and mean difference, as treatment effect size measures, with their 95% CIs.

Our first analyses covered the whole study group according to an intention-to-treat principle. All analyses were repeated after excluding patients who did receive sedation (CS or GA) from the center with LA as first-line anesthetic approach and patients who received LA or GA from the centers with CS as first-line anesthetic approach (defined as a sensitivity per-protocol analysis). Statistical testing was conducted at the 2-tailed α-level of 0.05. Data were analyzed using the SAS software version 9.3 (SAS Institute, Cary, NC).

Results

Patients Population

A total of 1034 acute ischemic stroke patients with LVO were admitted for MT at the participating centers during the study period. Of these, 762 were enrolled at 3 centers using a CS as first-line anesthetic approach, and the remaining 272 patients were enrolled at one center using LA. Of these, 126 patients from CS and 34 from the LA group were excluded from analysis due to absence of LVO or missing information on site of occlusion on noninvasive imaging (Figure 1). Of the patients from CS group, 7 (1.1%) received no sedation and 41 (6.6%) received GA. Of the patients from LA group, 37 (16.3%) received CS and 5 (2.2%) received GA. In patients who did not received MT, sedation management (either CS or GA) was used in 100% of cases (n=78/78) from CS group and 2.4% of cases (n=1/41) from LA group.

Figure 1.

Figure 1. Study flow chart. CS indicates conscious sedation; LVO, large vessel occlusion; MT, mechanical thrombectomy; and PS, propensity score.

Two hundred twenty-two matched pairs were found in main intention-to-treat analysis, and 167 matched pairs were found in the sensitivity per-protocol analysis. The Table shows the baseline characteristics after handling missing values by multiple imputations according to the 2 study groups before and after propensity score matching (see Table I in the Data Supplement for baseline characteristics before matching and handling missing values, and Table II in the Data Supplement for baseline characteristics before and after matching in per-protocol analysis). Before matching, several meaningful differences were found; the stronger differences (absolute standardized difference >30%) were observed for cardioembolism cause, site of occlusion in noninvasive imaging, use of intravenous thrombolysis prior MT and time from onset to angiosuite admission. These differences were reduced after propensity score matching with a maximum absolute standardized difference of 13.9% for time from onset to angiosuite admission (Table; Figure I in the Data Supplement).

Outcomes and First-Line Anesthetic Management

In the propensity score matched cohort, favorable outcome (primary outcome) was achieved significantly less often in the LA group (40.0%) than in the CS group (52.0%, matched relative risk=0.76 [95% CI, 0.60–0.97], Figure 2). Similarly, the rate of successful reperfusion was significantly lower in the no sedation group than in the CS group (76.6% versus 87.1%; matched relative risk=0.88 [95% CI, 0.79–0.98]). In IPTW-propensity score-adjusted cohort, similar significant differences were found both for favorable outcome and successful reperfusion. The difference in favorable outcome in favor of CS is mainly observed for carotid T and tandem occlusion, although the between-group difference did reach the significance level only in IPTW-adjusted analysis for Carotid T occlusion (Figure 3). Regarding other study efficacy outcomes (excellent outcome, early neurological improvement, 24-hour NIHSS shift, or complete reperfusion), the effectiveness criteria of the no sedation group were worse than those of the CS group, with only a significant difference for complete reperfusion in IPTW-propensity score-adjusted cohort (relative risk, 0.73 [95% CI, 0.57–0.93]). The mean NIHSS improvement from baseline to 24 hours was not different between the 2 groups in both matched (mean log difference, −0.80 [95% CI, −2.76 to 1.16]; P=0.42) and IPTW (−1.4 [95% CI, −2.9 to 0.06]; P=0.059) propensity score cohorts. In patients with successful reperfusion, there was no significant difference in the time from angiosuite arrival to reperfusion in both matched (mean loge difference, −0.04 [95% CI, −13.2 to 0.06]; P=0.44) and IPTW (−0.02 [95% CI, −10.1 to 0.06]; P=0.055) propensity score cohorts.

Figure 2.

Figure 2. Comparisons in angiographic and clinical outcomes according to first-line anesthetic approach in stroke patients treated with thrombectomy in matched and inverse probability of treatment weighting (IPTW) analyses. 1 Prespecified as primary outcome measure. 2 Calculated using a generalized estimating equation (GEE) model for binary data with a log link function to account the matched design. 3 Calculated using log-binomial regression model weighted by IPTW-propensity score. Number of events (%), and relative risks (RRs) were calculated after handling missing values for variables included in the propensity score and outcomes by multiple imputation (m=10). Favorable outcome was defined as 90-day modified Rankin Scale (mRS) score 0–2 or equal to prestroke mRS, excellent outcome as 90-day mRS score 0–1 or equal to prestroke mRS and early neurological improvement as a 24-h National Institutes of Health Stroke Scale (NIHSS) decrease ≥4 or NIHSS at 24-h 0–1. CS indicates conscious sedation; ICH, intracranial hemorrhage; LA, local anesthesia; mTICI, modified Thrombolysis in Cerebral Infarction; and sICH, symptomatic intracranial hemorrhage.

Figure 3.

Figure 3. Association of first-line anesthetic approach with favorable outcome according to site of occlusion in matched and inverse probability of treatment weighting (IPTW) analyses. Number of favorable outcome (%) and relative risk (RRs) were calculated after handling missing values for variables included in the propensity score and outcomes by multiple imputations (m=10). Favorable outcome was defined as 90-day modified Rankin Scale (mRS) score 0–2 or equal to prestroke mRS. CS indicates conscious sedation; ICA, internal carotid artery; LA, local anesthesia; and MCA, middle cerebral artery.

With respect to the safety outcomes, we found no significant differences in the matched-propensity score cohort (Figure 2). However, in IPTW, a higher mortality rate (odds ratio, 1.66 [95% CI, 1.27–2.15]) and lower parenchymal hematoma rate (OR, 0.59 [95% CI, 0.35–0.97]) were observed in the LA group. The sensitivity analysis restricted to our per-protocol sample provided similar results across all studied outcomes in the matched-as well as in the IPTW-propensity cohorts (Table III in the Data Supplement).

Discussion

In this study, we compared the outcomes of acute ischemic stroke patients with LVO treated by MT according to the type of the first-line anesthetic approach. We found that LA compared to CS was associated with a lower likelihood of favorable outcome and reperfusion and a higher likelihood of mortality without effect on procedure time.

The optimal anesthetic approach during MT is still unknown, and the literature is inconsistent.3–7,20–22 van de Graaf et al compared LA to CS in a single-center study of 140 patients and found a significant association between CS and poor outcome.9 In the present study of 874 patients, we observed a significant higher rate of favorable outcome and successful reperfusion and a lower rate of mortality in the CS group. Results were similar using both intention-to-treat and per-protocol analysis. The better clinical outcome observed in the CS group can be explained, at least in part, by the higher rate of successful reperfusion, compared with the LA group.23,24 Interestingly and in accordance with the previous study,9 we did not find differences in time metrics between the 2 groups.

There are significant differences between our study and the previous study that should be highlighted. First, our study included larger sample size and had the advantage of multicenter design compared with the single-center design of the previous study.9 Moreover, our study period was January 2018 to December 2018, while the previous study included patients from March 2014 to June 2016. It is conceivable that both neurointerventionists and anesthesiologists have become more experienced with periprocedural management, including prevention hypotension. Third, our protocol mandate maintaining mean blood pressure above 100 mm Hg, which possibly reduced the possible detrimental effect of CS that was found in the previous study.25,26 In fact, ETIS group reported recently that pulse pressure variability during MT is an independent predictor of worse clinical outcome,26 supporting the need for a close monitoring of blood pressure variability during MT, which is not the case in our practice of LA. The above-mentioned differences could explain some of the inconsistencies between our findings and the above study’s findings. In a recent letter to editor, Samuels et al22 emphasized the importance of considering LA as a separate entity when comparing GA to non-GA approaches. We strongly agree with Samuels et al’s suggestion and reiterate that future studies should differentiate between LA and CS when comparing GA to non-GA anesthetic techniques.

We acknowledge that our study has several limitations mainly related to the nonrandomized design. First, despite that we used propensity score analysis, to minimize the difference in baseline characteristics, our results could be confounded by variables that were not included in the propensity model. Second, we cannot rule out bias that could have been introduced by multiple imputations that were used to handle missing data. Third, we do not have data available for blood pressure during and after MT; therefore, we could not study the effect of anesthetic approach on procedural blood pressure. Fourth, LA was performed in only one out of the four included centers; therefore, it is possible that the difference between the studied groups was center related. Notably, all centers included are higher volume centers; therefore, we do not believe that the difference in outcome can be fully explained by the difference in center experience.

Conclusions

Our data suggest that CS could be superior to LA for neurothrombectomy with respect to the functional and safety outcomes, especially in the early time window (<6 hours). Future randomized controlled trials are needed to determine the best anesthetic technique for LVO MT.

Nonstandard Abbreviations and Acronyms

CS

conscious sedation

ECASS II

European Collaborative Acute Stroke Study II

ETIS

Endovascular Treatment in Ischemic Stroke

GA

general anesthesia

IPTW

inverse probability of treatment weighting

LA

local anesthesia

LVO

large vessel occlusion

mRS

modified Rankin Scale

MT

mechanical thrombectomy

NIHSS

National Institutes of Health Stroke Scale

Supplemental Materials

Tables I–III

Figure I

Appendix

Endovascular Treatment in Ischemic Stroke (ETIS) Investigators

Fondation Adolphe de Rothschild: Michel Piotin, Raphael Blanc, Hocine Redjem, Simon Escalard, Jean-Philippe Desilles, Gabriele Ciccio, Stanislas Smajda, Mikael Mazighi, Mikael Obadia, Candice Sabben, Ovide Corabianu, Thomas de Broucker, Didier Smadja, Sonia Alamowitch, Olivier Ille, Eric Manchon, Pierre-Yves Garcia, Guillaume Taylor, Malek Ben Maacha.

Hôpital Foch: Adrien Wang, Serge Evrard, Maya Tchikviladze, Nadia Ajili, Bertrand Lapergue, David Weisenburger, Lucas Gorza, Oguzhan Coskun, Arturo Consoli, Federico Di Maria, Georges Rodesh, Morgan Leguen, Julie Gratieux, Fernando Pico, Haja Rakotoharinandrasana, Philippe Tassan, Roxanna Poll, Sylvie Marinier.

CHU Bordeaux: Gaultier Marnat, Florent Gariel, Xavier Barreau, Jérôme Berge, Louis Veunac, Patrice Menegon, Igor Sibon, Ludovic Lucas, Stéphane Olindo, Pauline Renou, Sharmila Sagnier, Mathilde Poli, Sabrina Debruxelles, Thomas Tourdias, Jean-Sebastien Liegey.

CHU Nantes: Romain Bourcier, Lili Detraz, Benjamin Daumas-Duport, Pierre-Louis Alexandre, Monica Roy, Cédric Lenoble, Vincent L’allinec, Jean-Baptiste Girot, Hubert Desal.

CHU Nancy: Benjamin Gory, Isabelle Costa, Serge Bracard, René Anxionnat, Marc Braun, Anne-Laure Derelle, Romain Tonnelet, Liang Liao, François Zhu, Emmanuelle Schmitt, Sophie Planel, Sébastien Richard, Lisa Humbertjean, Gioia Mione, Jean-Christophe Lacour, Nolwenn Riou-Comte, Gabriela Hossu, Marine Beaumont, Mitchelle Bailang, Gérard Audibert, Marie Reitter, Agnès Masson, Lionel Alb, Adriana Tabarna, Marcela Voicu, Iona Podar, Madalina Brezeanu.

CHU Montpellier: Vincent Costalat, Caroline Arquizan, Cyril Dargazanli, Grégory Gascou, Pierre-Henri Lefèvre, Imad Derraz, Carlos Riquelme, Nicolas Gaillard, Isabelle Mourand, Lucas Corti.

Footnotes

*A list of all ETIS Investigators is given in the Appendix.

This manuscript was sent to Natan M. Bornstein, Consulting Editor, for review by expert referees, editorial decision, and final disposition.

For Sources of Funding and Disclosures, see page 2958.

The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.120.029194.

Correspondence to: Benjamin Gory, MD, PhD, Department of Diagnostic and Therapeutic Neuroradiology, CHRU Nancy, Hôpital Central, 29 Ave du Maréchal de Lattre de Tassigny, 54035 Nancy, France. Email

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