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Ischemic stroke
Original research
Rescue intracranial permanent stenting for refractory occlusion following thrombectomy: a propensity matched analysis
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  1. Heloise Ifergan1,
  2. Cyril Dargazanli2,
  3. Wagih Ben Hassen3,
  4. Jean-Francois Hak4,
  5. Benjamin Gory5,
  6. Julien Ognard6,
  7. Kevin Premat7,
  8. Gaultier Marnat8,
  9. Basile Kerleroux3,
  10. François Zhu9,
  11. Guillaume Bellanger10,
  12. Peter B Sporns11,
  13. Guillaume Charbonnier12,
  14. Géraud Forestier13,
  15. Jildaz Caroff14,
  16. Cédric Fauché15,
  17. Frédéric Clarençon7,
  18. Kevin Janot1,
  19. Bertrand Lapergue16,
  20. Gregoire Boulouis1
  21. for the ETIS registry collaborators and the JENI research collaborative
    1. 1 Diagnostic and Interventional Neuroradiology, University Hospital of Tours, Tours, Centre, France
    2. 2 Diagnostic and Interventional Neuroradiology, University Hospital Centre Montpellier, Montpellier, Occitanie, France
    3. 3 Diagnostic and Interventional Neuroradiology, Saint Anne Hospital Centre, Paris, France
    4. 4 Diagnostic and Interventional Neuroradiology, Hospital Timone, University Hospital of Marseille, Marseille, France
    5. 5 Department of Diagnostic and Therapeutic Neuroradiology, University of Lorraine, INSERM U1254, IADI, F-54000, University Hospital of Nancy, Nancy, France
    6. 6 Diagnostic and Interventional Neuroradiology, University and Regional Hospital Centre Brest, Brest, France
    7. 7 Diagnostic and Interventional Neuroradiology, University Hospital of Pitié Salpêtrière, APHP, Paris, France
    8. 8 Diagnostic and Interventional Neuroradiology, University Hospital of Bordeaux, Bordeaux, France
    9. 9 Diagnostic and Interventional Neuroradiology, University Hospital of Nancy, Nancy, France
    10. 10 Diagnostic and Interventional Neuroradiology, University Hospital of Toulouse, Toulouse, France
    11. 11 Diagnostic and Interventional Neuroradiology, University Hospital of Basel, Basel, Switzerland
    12. 12 Diagnostic and Interventional Neuroradiology, University Hospital of Besançon, Besancon, France
    13. 13 Diagnostic and Interventional Neuroradiology, University Hospital of Limoges, Limoges, France
    14. 14 Department of Interventional Neuroradiology - NEURI Brain Vascular Center, Bicêtre Hospital, APHP, Le Kremlin Bicêtre, France
    15. 15 Diagnostic and Interventional Neuroradiology, University Hospital of Poitiers, Poitiers, France
    16. 16 Neurology, Stroke Center, University of Versailles and Saint Quentin en Yvelines, Foch Hospital, Suresnes, France
    1. Correspondence to Dr Heloise Ifergan, Diagnostic and Interventional Neuroradiology, CHU Tours, 37000 Tours, Centre, France; ifergan.heloise{at}hotmail.fr

    Abstract

    Background Rescue intracranial stenting (RIS) can be used in refractory large vessel occlusion (LVO) after mechanical thrombectomy (MT). We aimed to assess the safety and efficacy of RIS versus a propensity matched sample of patients with persistent LVO.

    Methods We retrospectively analysed a multicenter retrospective pooled cohort of patients with anterior LVO (2015−2021) treated with MT, and identified patients with at least three passes and a modified Thrombolysis In Cerebral Infarction (mTICI) score of 0 to 2a. Propensity score matching was used to account for determinants of outcome in patients with or without RIS. The study outcomes included 3 months modified Rankin Scale (mRS) and symptomatic hemorrhagic transformation (HT).

    Results 420 patients with a refractory anterior occlusion were included, of which 101 were treated with RIS (mean age 69 years). Favorable outcome (mRS 0–2) was more frequent in patients with a patent stent at day 1 (53% vs 6%, P<0.001), which was independently associated with an early dual antiplatelet regimen (P<0.05). In the propensity matched sample, patients treated with RIS versus without RIS had similar rates of favorable outcomes (36.8% vs 30.3%, P=0.606). Patients with RIS showed a favorable shift in the overall mRS distributions (common adjusted OR 0.74, 95% CI 0.60 to 0.91, P=0.006). Symptomatic HT was marginally more frequent in the RIS group (9% vs 3%, P=0.07), and there was no difference in 3-month mortality.

    Conclusion In selected patients with a refractory intracranial occlusion despite at least three thrombectomy passes, RIS may be associated with an overall shift towards more favorable clinical outcome, and no significant increase in the odds of symptomatic HT or death.

    • Artery
    • Thrombectomy
    • Stroke
    • Stent
    • Stenosis

    Data availability statement

    Data are available upon reasonable request.

    https://doi.org/10.1136/jnis-2022-020012

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      WHAT IS ALREADY KNOWN ON THIS TOPIC

      • Rescue intracranial stenting (RIS) can be used for obtaining or maintaining vessel permeability in refractory large vessel occlusion after thrombectomy for acute ischemic stroke.

      WHAT THIS STUDY ADDS

      • Using a propensity matched sample of patients with persistent occlusion, we showed that RIS was associated with a significantly more favorable functional outcome, and with no increase of symptomatic hemorrhagic transformation. Functional independence was significantly higher in patients with patent stents at day 1, and patients under dual antiplatelet therapy had notably higher rates of stent patency at day 1.

      HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

      • These results call for the consideration of RIS as a possible strategy in selected patients with refractory occlusion after mechanical thrombectomy, and for the conduct of a randomized trial.

      Introduction

      Mechanical thrombectomy (MT) has a compelling efficacy to improve the outcome of patients with acute ischemic stroke (AIS) due to emergent large vessel occlusion (LVO). The efficacy of MT to improve functional outcome is strongly linked to the completeness and swiftness of revascularization. A successful revascularization is commonly defined as a modified Thrombolysis In Cerebral Infarction (mTICI) score of 2b or above, corresponding to a partial filling of at least 50% of the target territory.1

      Yet, 12–34% of patients treated with MT are not adequately revascularized,2 frequently due to the failure to reach the clot, and in 3–9% no modification of the occlusion configuration is obtained after clot retrieving maneuvers. These ‘refractory’ occlusions can result from inadequate device selection or technical considerations, clot composition, or underlying vessel wall conditions, most notably intracranial atherosclerosis.

      Patients with refractory occlusions harbor a very severe prognosis, in terms of functional outcome and mortality. Intracranial stenting is increasingly reported in acute conditions as a rescue technique for maintaining vessel permeability.3–6 Rescue intracranial stenting (RIS) poses several challenges in the context of AIS, most notably for the management of antithrombotic regimens. Indeed, the risk of hemorrhagic transformation (HT) is likely increased by the initiation of acute antithrombotics and may offset the benefits of sustained adequate revascularization following stent placement.

      Among patients with refractory LVO, defined as mTICI 0 to 2a, despite at least three passes of clot retrieving maneuvers, we aimed to assess the safety and efficacy of RIS versus no RIS in propensity matched samples.

      Patients and methods

      Study design, inclusion, and exclusion criteria

      Sample identification

      We used data from a multicenter retrospective pooled cohort of patients with proximal vessel occlusion of the anterior circulation treated between 2015 and 2021 with MT. Patients were identified in two ways. Patients who received RIS were retrospectively identified in the prospective MT stroke databases at 14 university hospitals in France, using the trainee-led research network Jeunes en Neuroradiologie Interventionnelle (JENI).7 The control population was constituted by retrospectively querying the Endovascular Treatment of Ischemic Stroke (ETIS) registry for patients with TICI 0 to 2a following MT. ETIS, described in detail previously,8 is a nationally representative, prospective registry of patients treated with MT.

      Inclusion and exclusion criteria

      We included consecutive adult patients with AIS, a proximal vessel occlusion of the anterior circulation, defined as an internal carotid or an M1 segment of the middle cerebral artery (MCA) occlusion, that met the following criteria: (1) at least three passes of clot retrieving maneuvers, using a stent retriever, an aspiration catheter or combined; and (2) an mTICI score of 2a, 1 or 0 following these passes in the RIS population, or an mTICI score of 2a, 1 or 0 at the end of the procedure in the control population. Tandem occlusions, isolated internal carotid artery (ICA) occlusions, and posterior circulation LVO were excluded.

      Endpoints

      Primary and secondary outcomes were assessed in the propensity matched samples. The primary endpoint was the proportion of patients with a favorable functional outcome at 3 months using the modified Rankin Scale (mRS), a favorable outcome being defined as an mRS of 0–2.

      The secondary outcomes were: (1) ordinal shift in mRS in RIS versus no RIS patients; (2) symptomatic HT, defined as the association of any type of intracerebral hemorrhage (ICH) on brain imaging with a National Institutes of Health Stroke Scale (NIHSS) score >4 points from the value at baseline or the lowest value in the first 7 days, or that led to death or was identified as the predominant cause of the neurological deterioration according to the European Cooperative Acute Stroke Study II (ECASS II) criteria9; and (3) target vessel patency at day 1.

      This report was prepared according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.10

      Baseline and procedural data

      Baseline, demographics, procedural and follow-up data were retrieved from electronic health records at each site by co-investigators.

      The type of MT or thromboaspiration device, and utilization of a balloon catheter, as the first tools were at the operator’s discretion in each center. Similarly, due to the retrospective nature of data acquisition, the decision to proceed to RIS as well as the acute initiation of antithrombotics, and their postoperative management, was done on a case-by-case basis at the treating team’s decision.

      The following data were collected in each participating center: mTICI before MT, anesthetic management, number of passes before stenting, angiographic evaluation of the vessel patency when and if a stentriever was deployed, mTICI before stent implantation, type (name and size) of implanted stent used, stent location, intraoperative antithrombotic regimen, follow-up antithrombotic regimen, acute stent thrombosis (intraoperative) and delay until this event, and stent patency at day 1.

      Post-procedure follow-up outcomes

      For safety assessment, HT and symptomatic intracranial hemorrhage according to ECASS-II,9 delay between stenting and control imaging, modality for control imaging, stent patency at control imaging, delayed (postoperative) stent thrombosis, neurological deterioration due to delayed stent thrombosis, delay until deterioration, 24-hour NIHSS, NIHSS at discharge, and mRS at 3 months were recorded. The stroke etiology was determine according to the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) criteria,11 at each contributing center.

      Standard protocol approvals, registrations, and patient consent

      As for all non-interventional retrospective studies of de-identified data, written informed consent was waived and a commitment to compliance (Reference Methodology CPMR-4) was filed to the French data protection authority (CNIL) before data centralization, in respect of the General Data Protection Regulation. Patients and proxies were informed they could oppose the use of their data for research purposes.

      Statistical analysis

      Continuous variables were summarized using means (SDs) or medians (IQRs) where appropriate, and discrete variables were summarized using counts (percentages). The χ2 test, Fisher’s exact test, t-test, and Mann-Whitney test were used as appropriate for the univariate analysis, with a P value <0.05 (two-tailed) as the threshold for statistical significance.

      In the entire sample of patients treated with RIS, multivariable regression models were used to determine factors that were independently associated with study endpoints. Variables associated with the outcome in univariate analysis (P≤0.1) were entered into nominal and ordinal models and backward elimination was then used to remove non-significant variables (P>0.05).

      To control all potential bias introduced by confounding factors between patients treated by RIS and the controls, a propensity score matching generated by logistic regression was conducted. Patients were matched by using a ratio of 1:1 with a nearest neighbor-matching algorithm without replacement. A caliper of width equal to 0.2 of the SD of the propensity score logit was used. Clinical variables included as contributors to the propensity score were pre-stroke mRS, age, baseline NIHSS, baseline Alberta Stroke Program Early CT Score (ASPECTS), and the delay between onset or last seen well (LSW) and groin puncture.

      In the matched subset we analyzed variables associated with symptomatic HT and a favorable functional outcome (dichotomous), and mRS by an ordinal shift analysis using the same framework as in the unmatched RIS sample (uni- then multivariable models).

      A sensitivity analysis was performed using the same approach, after excluding patients with a TICI 2a reperfusion to assess only those with a TICI 0 or a TICI 1.

      Analyses were done using JMP Pro 14 (SAS Institute Inc, Cary, NC) software.

      Results

      Study population and subgroups

      During the study period, through the trainee-led research network JENI, 101 patients treated with RIS at 14 centers for a refractory anterior LVO despite at least three intracranial passes were retrospectively identified.

      Among the 10 738 screened patients in the ETIS registry, 10 419 were excluded, mostly (7189, 69%) due to adequate revascularization, leaving 319 patients with a persistent occlusion at the end of the thrombectomy procedure, despite at least three passes.

      A total of 420 patients were therefore included in the unmatched study samples, including 101 with RIS. See the flowchart for patient selection details in figure 1.

      Figure 1
      Figure 1

      Flow chart of patient selection. TICI, Thrombolysis In Cerebral Infarction.

      Analysis of patients in the unmatched RIS subgroup

      The characteristics of all 101 patients with RIS analyzed are described in online supplemental table A.

      Supplemental material

      Patients were median 69 years old (IQR 57.5–76) and 44% were females. The median NIHSS at baseline was 12 (IQR 8–17) and 72% had an occlusion of the M1 segment of the MCA. There was a median of 3 passes before permanent stenting (IQR 3–4), which was performed under general anesthesia in 57 patients (56.4%).

      The median number of individual technique passes before RIS was 1 (IQR 1–2) with a stent, 2 (IQR 1–2) with contact aspiration alone, and 2 (IQR 2–4) with a combined (stent+distal aspiration) technique.

      Vessel patency during stent retriever deployment was assessed in 77 patients, of which 74/77 (96.1%) showed antegrade flow. Dual antiplatelet therapy (DAPT) was acutely initiated in 34.7% of patients, and 4% of patients received heparin. The list of implanted stents is provided in online supplemental table B.

      Nineteen patients showed perioperative intra-stent thrombosis (18.8%), an event that was similarly frequent in patients with or without acute DAPT (19% vs 19%, P=1.00). At the end of the procedure, 62% of patients with RIS had a modified TICI score of 2b–2c or 3 online supplemental file 1.

      Outcomes in the unmatched RIS group

      Day 1 vessel patency, and hemorrhagic transformation

      Vessel patency was assessed at day 1 in the entire sample, and 68 stents (67.3 %) were patent. Delayed stent thrombosis had occurred in 22 of 95 patients with a patent stent at the end of the procedure, and five occluded stents at the end of the procedure were patent at day 1. Variables associated with day 1 stent patency are detailed in table 1.

      View this table:
      Table 1

      Day 1 vessel patency in the RIS group, and univariate associations

      Female sex, absence of intravenous thrombolysis, and immediate postoperative or perioperative initiation of a DAPT regimen were more frequent in patients with a patent stent at day 1 (all P<0.05). There were similar rates of HT, whether symptomatic (P=0.304) or not (P=0.437), in patients with an occluded or patent stent at day 1. Although non-significantly different from the single antiplatelet regimen, all symptomatic HTs occurred in patients receiving DAPT (100% vs 0%; P=0.451). There was major heterogeneity in the antiplatelet regimen used at the acute phase of RIS (see online supplemental figure 1), and we identified 29 different strategies for antiplatelet agent (APA) management, including 17 different APA combinations at the acute phase and seven differing strategies for follow-up antithrombotic regimens (single to double APA, single P2Y12 inhibitor to double non-P2Y12, etc).

      Functional outcome

      In the unmatched samples, the overall proportion of favorable outcome was 24.7%, and favorable outcome was more frequent in patients with RIS (38% vs 20%, P<0.001).

      In the RIS group, patients had significantly higher rates of favorable outcome with a patent stent at day 1 (53% vs 6%, P<0.001). Favorable outcome was associated with less frequent acute or delayed stent thrombosis (5% vs 36% in patients with unfavorable outcome, P<0.001), younger age (59±15 vs 70±14, P<0.001), lower baseline NIHSS (P=0.009), shorter onset or LSW to imaging, and acute initiation of DAPT (50% vs 27%, P=0.029). After multivariable adjustment, age, baseline NIHSS, delay until imaging as well as delayed thrombosis (adjusted odds ratio (aOR) 9.7, 95% confidence interval (95% CI) 1.9 to 50.2, P<0.001) remained significantly associated with clinical outcome. The antiplatelet regimen did not.

      The stroke etiology was dominated by large artery atherosclerosis (44%), followed by intracranial atherosclerotic disease (24%) and undetermined etiology (12%), not associated with outcome or stent patency (see details in online supplemental figure 4).

      Propensity score matching and outcome comparisons

      After propensity score matching using pre-stroke mRS status, age at ictus, baseline NIHSS and ASPECTS, and delay since onset or last known well for unwitnessed strokes as score contributors, the matched sample comprised 152 patients, with 76 patients in the RIS arm and 76 in the persistent occlusion arm. Detailed patient characteristics in each arm are presented in table 2. There were no baseline differences between each propensity arm, except for a more frequent history of diabetes (26.3% vs 11.8%, P=0.003), as well as a history of stroke or transient ischemic attack (33% vs 17%, P=0.035), in the RIS arm.

      View this table:
      Table 2

      Univariate comparison of propensity matched arms

      Hemorrhagic transformation

      An HT occurred in 45% of patients and was more frequent in patients with no RIS (37% vs 22%, P=0.049). Symptomatic HT occurred in nine patients and was marginally more frequent in patients with no RIS (9% vs 3%, P=0.07). Due to the low number of occurrences of symptomatic HT, we did not perform a multivariable adjustment to assess determinants. Neither HT nor symptomatic HT were significantly associated with clinical outcome.

      Clinical outcome

      A total of 51 (33.6%) patients achieved a favorable functional outcome, with no differences across matched groups (P=0.606) using this dichotomous outcome.

      In univariable analysis, favorable outcome was associated with younger age (P<0.001) and a smaller baseline NIHSS (P=0.006). Other variables did not influence the outcome, including RIS (32.4% favorable outcome vs 36.8% in the no RIS group, P=0.606). In a multivariable nominal model, with forced adjustment for RIS, there was no independent association between RIS and favorable outcome (aOR 1.26, 95% CI 0.60 to 2.62, P=0.534).

      Using an ordinal shift analysis in the entire matched sample, RIS had a favorable shift in the overall mRS distributions (common aOR 0.74, 95% CI 0.60 to 0.91, P=0.006) along with lower NIHSS (P<0.001) and lower age (P=0.0071).

      When comparing the subgroup of RIS patients with a patent stent at day 1 (49/76, 64%) to those with no RIS, patients in the RIS group had a significantly higher rate of favorable outcome (55.1% vs 32.4%, P=0.01). The association between RIS and a favorable functional outcome remained significant after adjustment for age and NIHSS (aOR 1.42, 95% CI 1.17 to 3.68, P=0.004).

      There were no differences in 3-month mortality in matched RIS and no RIS groups (27% vs 23%, P=1.000). The mRS of matched and unmatched groups are presented in figure 2. A post-hoc subgroup analysis was performed by stratifying per baseline occlusion (MCA or ICA), and is presented in details in online supplemental figure 2. There was a significantly better outcome in patients treated with RIS in both matched and unmatched samples in patients with ICA occlusions, and a similar association was also found in the unmatched sample of patients with MCA occlusions (all P<0.05). In the matched sample of patients with MCA occlusions, there was no association between RIS and a better outcome (P=0.75), but mortality was significantly higher in the no RIS group (24% vs 16%, P=0.03).

      Figure 2
      Figure 2

      Modified Rankin Scale (mRS) distributions at 3 months in unmatched and matched groups. RIS, rescue intracranial stenting.

      All results were similar (effect, significance) after excluding patients with TICI 2a from the RIS sample.

      Discussion

      In this large propensity matched sample of patients treated with RIS for a refractory anterior LVO following failed MT despite at least three passes, we found (1) that a notable proportion of patients treated with RIS achieved a favorable functional outcome, (2) that RIS was associated with better functional outcomes in shift analyses when compared with matched controls, and (3) that RIS was associated with fewer symptomatic ICHs (despite a large proportion of patients being treated with an acute DAPT regimen). These findings shed light on the safety and relevance of RIS for refractory mechanical occlusion.

      Among plausible issues to improve the outcome of patients treated for an AIS due to LVO, RIS has been increasingly used and reported to increase the rates of recanalization after standard MT failure or early reocclusions,3–6 12 and several dedicated trials are underway 13.

      Recent works have reported RIS safety and efficacy in approaching settings. Yet, the main difference between previous publications and the present analysis was that we aimed to match our large group of patients with RIS with the most relevant group of patients that were treated with MT, and with a true refractory occlusion (that is, not the failure to reach the clot). For this purpose, we chose a minimum of three clot retrieving maneuvers in the control group, using the definition of refractory thrombectomy already employed14 15; in practice, rescue maneuvers are rarely performed before two or three attempts to remove the clot. l.16–18 That led to the exclusion of 436 patients for which the main reason for failure was not a refractory occlusion but failure to reach the clot (eg, 0 number of passes). Indeed, we believe that in patients for which the clot is not reached, the question of RIS is irrelevant. Further, stenting for refractory occlusion may not yield similar results to that of stenting for a presumed underlying stenosis. Although there is likely a strong interplay between both entities, we chose to restrict our analyses to true refractory cases.

      This pragmatic choice may explain the main differences between our work and previous studies. Indeed, in an aggregate level meta-analysis, Premat et al found RIS to be associated with improved clinical outcome at 90 days and lower mortality compared with no recanalization,3 which was not the case in our matched sample using mRS 0–2 as a dichotomous outcome measure. Similarly, in a more recent work by Mohammaden et al,6 that used propensity matching, the authors found RIS to be significantly associated with higher rates of functional independence and lower rates of mortality at 3 months. It is likely that in these works, the comparator group (failed revascularization) was slightly biased towards worse outcomes, in that patients for which the clot was not reached or for which fewer than three passes of MT were attempted may have had less favorable baseline or anatomical characteristics that impeached or discouraged the operator to pursue the procedure further. This bias is inherent to retrospective works investigating procedures with yet unconfirmed nefarious or beneficial effects, for which the operator’s decision to proceed is likely influenced by confounders that are poorly evaluated a posteriori.

      Importantly, we found that patients with a patent stent at day 1 had significantly higher rates of functional independence, when compared with both patients with occluded stents, and patients for which RIS was not attempted. This result is among the most stable findings in previous studies,3 6 19–21 highlighting the critical importance of antithrombotic management when an RIS is attempted to maintain stent patency, and the necessary trade-off with hemorrhagic risk in patients with a particularly high risk of HT. This endpoint does not appear in other recent studies on the subject,18 and appears to be a determining factor in the patient’s clinical evolution.

      In that regard, our results do provide additional insight on the association between antithrombotic management and the risks of acute or delayed stent occlusion following RIS and the risk of symptomatic HT. First, among the 95 patients with a patent stent at the end of the procedure, a delayed thrombosis occurred in 22 patients (23.2%) and was almost three times more frequent in patients with a single antiplatelet follow-up regimen, intuitively pleading for the acute initiation of DAPT. Further, while all symptomatic HT occurred in patients with a DAPT regimen, this finding was not statistically more frequent than in patients with a single antiplatelet. Premat et al found that an aggressive antiplatelet regimen did not seem to result in increased rates of symptomatic ICH with low heterogeneity (OR 0.68, 95% CI 0.37 to 1.27, I2=0%).3 Of note, the rates of symptomatic ICH in previous works investigating RIS were of similar magnitude, though slightly higher than that found in our analysis (6%). Wareham et al found22 symptomatic ICH to be 12% (95% CI 8% to 17%), while Stracke and colleagues19 and Forbrig et al 23 found rates of 11% and 12%, respectively. These works have not linked DAPT with higher rates of symptomatic ICH in the context of RIS. In a recent work by Baek et al,21 in which almost 80% of patients were treated with tirofiban infusion (a glycoprotein IIb/IIIa inhibitor), and above 95% with follow-up DAPT, authors reported only 5% of symptomatic HT, in line with the low rates of clinically relevant hemorrhage despite the aggressive antithrombotic regimen.

      An important consideration when analyzing these rates of symptomatic HT, and the counterintuitive absence of higher symptomatic HT in the group of patients for which no RIS was attempted, is that the core ischemic volume is a very strong determinant of the risk of HT. In turn, failure to revascularize being associated with larger final ischemic volumes, it is expected that patients with refractory occlusions will have high risks of HT, and that in patients with RIS, the additional risk bore by DAPT initiation may be partly counterbalanced by an ischemic core reduction volume.

      Expectedly, there was an important variability in the use of antiplatelet drugs in our series (online supplemental figure 1). There was an equal use (44%) of single and dual antiplatelet acute treatment, and acetylsalicylic acid (ASA) alone or abciximab alone were the most frequent treatment regimens at the acute phase (21% both). This heterogeneity in antithrombotic management has recently been reported on a national scale in France by Caroff and colleagues,24 and is a major lead for improvement in such complex neurointerventional procedures. Interestingly, four patients received cangrelor,25 26 a promising agent in RIS due to its immediate action, and reversibility.

      Of note, the results of Gao et al 27 in a recent randomized clinical trial may not be transposable to the acute setting described therein. The authors indeed showed in a sample of patients with symptomatic severe intracranial atherosclerotic stenosis that the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death. Indeed, their results only included patients with atheromatous stenoses, low volumes of ischemia since transient ischemic attack or non-disabling, non-perforator (defined as non-brainstem or non-basal ganglia end artery) territory ischemic stroke, and in elective patients with ideal APA medication.

      These patients differ in many ways from those included in our sample, with emergent symptomatic LVO, and likely differing etiologies for the refractory nature of their occlusions.

      Similarly, our work differs from that of Al Kasab and colleagues,18 by the fact that the authors investigated the role of RIS in LVO for patients with underlying intracranial atherosclerosis, while our sample comprised less than a quarter of patients with confirmed intracranial atherosclerosis. In that sense, our results are complementary to that of Al Kasab et al, that showed the benefit of RIS for patients with reocclusion or residual stenosis following successful thrombectomy, while we showed similar results in a population of patients with refractory occlusion.

      Importantly, the etiology is most often unknown during thrombectomy and, except for cases of identified stenosis, the exact physiopathology of refractory occlusion is commonly unknown.14 The underlying causes are likely probably diverse, including vessel condition (dissection, atherosclerosis),21 clot characteristics of varying compositions,28 and technical strategy or operative.

      The understanding of the underlying cause for the failure to revascularize was not our objective and the study was in turn not designed to address this question. Yet it is likely that these varying mechanisms may also explain the varying outcomes following stenting than that found in a more homogenous sample of mostly Asian patients with almost exclusively intracranial atherosclerosis.21

      Finally, as the field evolves, it can also be assumed that other therapeutic alternatives may become widely available in the future, such as devices for fibrin-rich tough clots recently evaluated in the Post Marketing Study of Patients to Evaluate NIMBUS Revascularization Effectiveness With Challenging Occlusions (SPERO) Study.29

      Our study has several limitations. First, as a retrospective analysis of prospectively collected, cross-sectional hospital-based cohorts it is subject to the important limitations inherent in such a design. Most importantly, the risk of selection bias for the group of patients that underwent RIS is hard to assess and may have biased the sample towards more favorable patient profiles, that were deemed more likely to benefit from a more aggressive therapeutic approach. We aimed at limiting this bias by using a propensity matched analysis based on strong determinants of poorer outcome (age, NIHSS, treatment delays, etc). Second, this analysis was restricted to patients who had benefited from at least three intracranial passes, leading to uncontrolled confounders. There is not an agreed number of passes before stenting, and some interventionalists may stent after a failed first pass, but we choose to follow a more accepted definition of refractory occlusion. Third, patients with posterior circulation occlusions were excluded to prevent confounding our endpoint (functional outcome) with basilar occlusions that have distinctly worse outcomes, and for which the pathophysiology for refractory occlusion may differ due to varying anatomy and etiological considerations.30 Fourth, the constitution of the RIS group was based on the retrospective query of local databases, with a risk of memorization bias and lack of exhaustivity. We also were unable to read all imaging centrally, and relied on local interpretation, likely introducing heterogeneity in the outcome assessment, despite the experience of all co-investigators. Similarly, we were not able to collect precise procedural information regarding the method for stenting, and the need for presenting angioplasty.

      Among important strengths is the number of RIS cases reported in our analysis, and the use of carefully conducted propensity matching to compare RIS cases against a relevant subgroup of controls. To our knowledge this is indeed the first study to conduct this comparison against patients for which the clot was reached, and in which attempts at retrieving the clot were performed.

      Conclusion

      In selected patients with a refractory intracranial occlusion despite at least three MT passes, rescue intracranial stenting may be associated with an overall shift towards more favorable outcome, and no significant increase in the odds of symptomatic HT. The optimal antithrombotic regimen in this situation remains undetermined, but patients receiving DAPT had notably higher rates of stent patency at day 1, and functional independence rates were significantly higher in patients with patent stents. A pragmatically designed randomized trial, investigating RIS after failed MT, is in order.

      Data availability statement

      Data are available upon reasonable request.

      Ethics statements

      Patient consent for publication

      References

      1. ↵
        2. Goyal M ,
        3. Fargen KM ,
        4. Turk AS , et al
        . 2C or not 2C: defining an improved revascularization grading scale and the need for standardization of angiography outcomes in stroke trials. J Neurointerv Surg 2014;6:83–6. doi:10.1136/neurintsurg-2013-010665
        OpenUrlFREE Full Text
      2. ↵
        2. Campbell BCV ,
        3. Hill MD ,
        4. Rubiera M , et al
        . Safety and efficacy of Solitaire stent thrombectomy: individual patient data meta-analysis of randomized trials. Stroke 2016;47:798–806. doi:10.1161/STROKEAHA.115.012360
        OpenUrlAbstract/FREE Full Text
      3. ↵
        2. Premat K ,
        3. Dechartres A ,
        4. Lenck S , et al
        . Rescue stenting versus medical care alone in refractory large vessel occlusions: a systematic review and meta-analysis. Neuroradiology 2020;62:629–37. doi:10.1007/s00234-020-02360-9
        OpenUrlCrossRefPubMed
      4. ↵
        2. Sajja KC ,
        3. Huded V ,
        4. Prajapati C , et al
        . Rescue stenting for refractory large vessel occlusions in the thrombectomy era: intracranial use of coronary stents in low-mid economic settings. Cureus 2022;14:e23847. doi:10.7759/cureus.23847
      5. ↵
        2. Imam YZ ,
        3. Akhtar N ,
        4. Kamran S , et al
        . Rescue stenting in mechanical thrombectomy refractory occlusions: a single center multiethnic cohort [internet]. 2022. Available: https://www.medrxiv.org/content/10.1101/2022.07.30.22278139v1
      6. ↵
        2. Mohammaden MH ,
        3. Haussen DC ,
        4. Al-Bayati AR , et al
        . Stenting and angioplasty in neurothrombectomy: matched analysis of rescue intracranial stenting versus failed thrombectomy. Stroke 2022;53:2779–88. doi:10.1161/STROKEAHA.121.038248
        OpenUrlCrossRefPubMed
      7. ↵
        2. Kerleroux B ,
        3. Bourcier R ,
        4. Rouchaud A , et al
        . Interventional neuroradiology trainee-led research collaborative JENI, moving forward. J Neuroradiol 2021;48:137–8. doi:10.1016/j.neurad.2021.01.007
        OpenUrl
      8. ↵
        2. Desilles J-P ,
        3. Consoli A ,
        4. Redjem H , et al
        . Successful reperfusion with mechanical thrombectomy is associated with reduced disability and mortality in patients with pretreatment diffusion-weighted imaging-Alberta stroke program early computed tomography score ≤6. Stroke 2017;48:963–9. doi:10.1161/STROKEAHA.116.015202
        OpenUrlAbstract/FREE Full Text
      9. ↵
        2. Hacke W ,
        3. Kaste M ,
        4. Fieschi C , et al
        . Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998;352:1245–51. doi:10.1016/s0140-6736(98)08020-9
        OpenUrlCrossRefPubMedWeb of Science
      10. ↵
        2. von Elm E ,
        3. Altman DG ,
        4. Egger M , et al
        . The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg 2014;12:1495–9. doi:10.1016/j.ijsu.2014.07.013
        OpenUrlCrossRefPubMed
      11. ↵
        2. Adams HP ,
        3. Bendixen BH ,
        4. Kappelle LJ , et al
        . Classification of subtype of acute ischemic stroke. definitions for use in a multicenter clinical trial. TOAST. trial of org 10172 in acute stroke treatment. Stroke 1993;24:35–41. doi:10.1161/01.str.24.1.35
        OpenUrlAbstract/FREE Full Text
      12. ↵
        2. Cornelissen SA ,
        3. Andersson T ,
        4. Holmberg A , et al
        . Intracranial stenting after failure of thrombectomy with the Embotrap® device. Clin Neuroradiol 2019;29:677–83. doi:10.1007/s00062-018-0697-x
        OpenUrlPubMed
      13. ↵
        2. Chi DCT
        . Rescue intracranial stenting in acute ischemic stroke [internet]. 2021. Available: https://clinicaltrials.gov/ct2/show/NCT04986774
      14. ↵
        2. Abdalla RN ,
        3. Cantrell DR ,
        4. Shaibani A , et al
        . Refractory stroke thrombectomy: prevalence, etiology, and adjunctive treatment in a North American cohort. AJNR Am J Neuroradiol 2021;42:1258–63. doi:10.3174/ajnr.A7124
        OpenUrlAbstract/FREE Full Text
      15. ↵
        2. Sweid A ,
        3. Sajja KC ,
        4. Mouchtouris N , et al
        . Rescue stenting for acute ischemic stroke with refractory emergent large vessel occlusion in the modern thrombectomy era. Clin Neurol Neurosurg 2022;215:107183. doi:10.1016/j.clineuro.2022.107183
        OpenUrl
      16. ↵
        2. Meyer L ,
        3. Fiehler J ,
        4. Thomalla G , et al
        . Intracranial stenting after failed thrombectomy in patients with moderately severe stroke: a multicenter cohort study. Front Neurol 2020;11:97. doi:10.3389/fneur.2020.00097
        OpenUrlPubMed
      17. ↵
        2. Cabral LS ,
        3. Mont’Alverne F ,
        4. Silva HC , et al
        . Device size selection can enhance Y-stentrieving efficacy and safety as a rescue strategy in stroke thrombectomy. J Neurointerv Surg 2022;14:558–63.
        OpenUrlAbstract/FREE Full Text
      18. ↵
        2. Al Kasab S ,
        3. Almallouhi E ,
        4. Alawieh A , et al
        . Outcomes of rescue endovascular treatment of emergent large vessel occlusion in patients with underlying intracranial atherosclerosis: insights from STAR. J Am Heart Assoc 2021;10:e020195. doi:10.1161/JAHA.120.020195
      19. ↵
        2. Stracke CP ,
        3. Fiehler J ,
        4. Meyer L , et al
        . Emergency intracranial stenting in acute stroke: predictors for poor outcome and for complications. J Am Heart Assoc 2020;9:e012795. doi:10.1161/JAHA.119.012795
      20. ↵
        2. Pérez-García C ,
        3. Gómez-Escalonilla C ,
        4. Rosati S , et al
        . Use of intracranial stent as rescue therapy after mechanical thrombectomy failure-9-year experience in a comprehensive stroke centre. Neuroradiology 2020;62:1475–83. doi:10.1007/s00234-020-02487-9
        OpenUrl
      21. ↵
        2. Baek J-H ,
        3. Kim BM ,
        4. Ihm EH , et al
        . Clinical outcomes of rescue stenting for failed endovascular thrombectomy: a multicenter prospective registry. J Neurointerv Surg 2022;14:1166–72. doi:10.1136/neurintsurg-2021-018308
        OpenUrlAbstract/FREE Full Text
      22. ↵
        2. Wareham J ,
        3. Flood R ,
        4. Phan K , et al
        . A systematic review and meta-analysis of observational evidence for the use of bailout self-expandable stents following failed anterior circulation stroke thrombectomy. J Neurointerv Surg 2019;11:675–82. doi:10.1136/neurintsurg-2018-014459
        OpenUrlAbstract/FREE Full Text
      23. ↵
        2. Forbrig R ,
        3. Lockau H ,
        4. Flottmann F , et al
        . Intracranial rescue stent angioplasty after stent-retriever thrombectomy: multicenter experience. Clin Neuroradiol 2019;29:445–57. doi:10.1007/s00062-018-0690-4
        OpenUrlPubMed
      24. ↵
        2. Caroff J ,
        3. Aubert L ,
        4. Lavenu-Bombled C , et al
        . Antithrombotic therapies for neurointerventional surgery: a 2021 French comprehensive national survey. J Neurointerv Surg 2023;15:402–7. doi:10.1136/neurintsurg-2021-018601
        OpenUrlAbstract/FREE Full Text
      25. ↵
        2. Marnat G ,
        3. Delvoye F ,
        4. Finitsis S , et al
        . A multicenter preliminary study of cangrelor following thrombectomy failure for refractory proximal intracranial occlusions. AJNR Am J Neuroradiol 2021;42:1452–7. doi:10.3174/ajnr.A7180
        OpenUrlAbstract/FREE Full Text
      26. ↵
        2. Marnat G ,
        3. Finistis S ,
        4. Delvoye F , et al
        . Safety and efficacy of cangrelor in acute stroke treated with mechanical thrombectomy: endovascular treatment of ischemic stroke registry and meta-analysis. AJNR Am J Neuroradiol 2022;43:410–5. doi:10.3174/ajnr.A7430
        OpenUrlAbstract/FREE Full Text
      27. ↵
        2. Gao P ,
        3. Wang T ,
        4. Wang D , et al
        . Effect of stenting plus medical therapy vs medical therapy alone on risk of stroke and death in patients with symptomatic intracranial stenosis: the CASSISS randomized clinical trial. JAMA 2022;328:534–42. doi:10.1001/jama.2022.12000
        OpenUrlCrossRefPubMed
      28. ↵
        2. Gunning GM ,
        3. McArdle K ,
        4. Mirza M , et al
        . Clot friction variation with fibrin content; implications for resistance to thrombectomy. J Neurointerv Surg 2018;10:34–8. doi:10.1136/neurintsurg-2016-012721
        OpenUrlAbstract/FREE Full Text
      29. ↵
        2. van den Berg R ,
        3. Ribó M ,
        4. Arnberg F , et al
        . P64 NIMBUS geometric clot extractor for tough clots: SPERO study results and clot composition. Internet. ESMINT Abstracts; BMA House, Tavistock Square, London, WC1H 9JR: BMJ Publishing Group Ltd, September 2022 doi:10.1136/neurintsurg-2022-ESMINT.85
      30. ↵
        2. Pirson FAVA ,
        3. Boodt N ,
        4. Brouwer J , et al
        . Etiology of large vessel occlusion posterior circulation stroke: results of the MR CLEAN registry. Stroke 2022;53:2468–77. doi:10.1161/STROKEAHA.121.038054
        OpenUrlCrossRefPubMed

      Supplementary materials

      • Supplementary Data

        This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

      Footnotes

      • Twitter @gcharbonnier, @jildazz, @gboulouis

      • Collaborators 1/ ETIS registry collaborators:Sarah Adam (Hospital Center of Vannes, Vannes, France); Amira Al Raaisi (Rothschild Foundation, Paris, France); Sonia Alamowitch (University Hospital of La Pitié Salpétrière, Paris, France); Lionel Alb (University Hospital of Nancy, Nancy, France); Jean-François Albucher (University Hospital of Toulouse, Toulouse, France); Pierre Louis Alexandre (University Hospital of Nantes, Nantes, France); Quentin Alias (University Hospital of Rennes, Rennes, Francemariam Annan University Hospital of Tours, Tours) Francerené Anxionnat (University Hospital Of Nancy, Nancy, France); Caroline Arquizan (University Hospital of Montpellier, Bordeaux, France); Gérard Audibert (University Hospital of Nancy, Nancy, France); Guillaume Ballan (Hospital Center of Bayonne, Bayonne, France); Alexandre Bani-Sadr (University Hospital of Lyon, Lyon, France); Stephanie Bannier (Hospital Center of Bayonne, Bayonne, France); Laura Baptiste (University Hospital of Dijon, Dijon, France); Charlotte Barbier (University Hospital of Caen, Caen, France); Flore Baronnet (University Hospital of La Pitié Salpétrière, Paris, France); Xavier Barreau (University Hospital of Bordeaux, Bordeaux, France); Bruno Thierry Barroso (Hospital Center of Pau, Pau, France); Grégoire Barthel (University Hospital of Nancy, Nancy, France); Edouard Beaufreton (University Hospital of Rennes, Rennes, France); Marine Beaumont (University Hospital of Nancy, Nancy, France); Yannick Bejot (University Hospital of Dijon, Dijon, France); Guillaume Bellanger (University Hospital of Toulouse, Toulouse, France); Wagih Ben Hassen (Psychiatry And Neurosciences University Hospital, Paris, France); Charline Benoit (Foch Hospital, Suresnes, France); Jérome Berge (University Hospital of Bordeaux, Bordeaux, France); Patricia Bernady (Hospital Center of Bayonne, Bayonne, France); Corentin Berthet (University Hospital Of Grenoble, Grenoble, France); Yves Berthezene (University Hospital of Lyon, Lyon, France); Mehdi Beyragued (University Hospital of Lyon, Lyon, France); Richard Bibi (University Hospital of Tours, Tours, France); Alessandra Biondi (University Hospital of Besançon, Besançon, France); Raphaël Blanc (Rothschild Foundation, Paris, France); William Boisseau (Rothschild Foundation, Paris, France); Clémentine Bonaz (University Hospital of Grenoble, Grenoble, France); Louise Bonnet (University Hospital of Besançon, Besançon, France); Fabrice Bonneville (University Hospital of Toulouse, Toulouse, France); Laure Bottin (University Hospital of La Pitié Salpétrière, Paris, France); Benjamin Bouamra (University Hospital of Besançon, Besançon, France); Kamel Boubagra (University Hospital of Grenoble, Grenoble, France); Jean Bouchart (University Hospital of Caen, Caen, France); Marion Boulanger (University Hospital of Caen, Caen, France); Grégoire Boulouis (University Hospital of Tours, Tours, France); Romain Bourcier (University Hospital of Nantes, Nantes, France); Frédéric Bourdain (Hospital Center Of Bayonne, Bayonne, France); Nathalie Bourgois (University Hospital of Clermont Ferrand, Clermont Ferrand, France); Abdelghani Fakhreddine Boustia (University Hospital of Rennes, Rennes, France); Arnaud Bretonniere (University Hospital of Tours, Tours, France); Madalina Brezeanu (University Hospital of Nancy, Nancy, France); Pierre Briau (University Hospital Of Bordeaux, Bordeaux, France); Marie Bruguet (University Hospital of Brest, Brest, France); Julien Burel (University Hospital of Rouen, Rouen, France); Federico Cagnazzo (University Hospital of Montpellier, Bordeaux, France); Hélène Cailliez (Hospital Center of Bayonne, Bayonne, France); Lionel Calviere (University Hospital of Toulouse, Toulouse, France); Matteo Cappucci (University Hospital of Lyon, Lyon, France); Jildaz Caroff (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Hélène Castagnet (Hospital Center of Pau, Pau, France); Nathalie Caucheteux (University Hospital of Reims, Reims, France); Emmanuel Chabert (University Hospital of Clermont Ferrand, Clermont Ferrand, France); Vanessa Chalumeau (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Stéphane Charara (University Hospital of Grenoble, Grenoble, France); Guillaume Charbonnier (University Hospital of Besançon, Besançon, France); Olivier Chassin (University Hospital Of Kremlin Bicêtre, Kremlin Bicêtre, France); François Chedeville (Hospital Center of Vannes, Vannes, France); Bailiang Chen (University Hospital of Nancy, Nancy, France); Cyril Chivot (University Hospital of Amiens, Amiens, France); Tae-Hee Cho (University Hospital of Lyon, Lyon, France); Frédéric Clarencon (University Hospital of La Pitié Salpétrière, Paris, France); Julien Cogez (University Hospital of Caen, Caen, France); Christophe Cognard (University Hospital of Toulouse, Toulouse, France); Pierre Olivier Comby (University Hospital of Dijon, Dijon, France); Arturo Consoli (Foch Hospital, Suresnes, France); Jordan Coris (University Hospital of Brest, Brest, France); Jonathan Cortese (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Lucas Corti (University Hospital of Montpellier, Bordeaux, France); Oguzhan Coskun (Foch Hospital, Suresnes, France); Vincent Costalat (University Hospital of Montpellier, Bordeaux, France); Thomas Courret (University Hospital of Bordeaux, Bordeaux, France); Audrey Courselle (University Hospital of Amiens, Amiens, France); Sophie Crozier (University Hospital of La Pitié Salpétrière, Paris, France); Pauline Cuisenier (University Hospital of Grenoble, Grenoble, France); Camille Dahan (Hospital Center of Pau, Pau, France); Jean Darcourt (University Hospital of Toulouse, Toulouse, France); Cyril Dargazanli (University Hospital of Montpellier, Bordeaux, France); Benjamin Daumas Duport (University Hospital of Nantes, Nantes, France); Solene De Gaalon (University Hospital of Nantes, Nantes, France); Séverine Debiais (University Hospital of Tours, Tours, France); Sabrina Debruxelles (University Hospital Of Bordeaux, Bordeaux, France); Kevin Delaforge (University Hospital of Amiens, Amiens, France); Stephen Delorme (University Hospital of La Pitié Salpétrière, Paris, France); François Delvoye (Rothschild Foundation, Paris, France); Stéphanie Demasles (Hospital Center of Pau, Pau, France); Christian Denier (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Anne-Laure Derelle (University Hospital of Nancy, Nancy, France); Laurent Derex (University Hospital of Lyon, Lyon, France); Imad Derraz (University Hospital of Montpellier, Bordeaux, France); Hubert Desal (University Hospital of Nantes, Nantes, France); Xavier Desdoit (University Hospital of Amiens, Amiens, France); Jean-Philippe Desilles (Rothschild Foundation, Paris, France); Olivier Detante (University Hospital of Grenoble, Grenoble, France); Federico Di Maria (Foch Hospital, Suresnes, France); Marian Douarinou (University Hospital of Nancy, Nancy, France); Alexandre Doucet (University Hospital of Reims, Reims, France); Gaulthier Duloquin (University Hospital of Dijon, Dijon, France); Shotar Eimad (University Hospital of La Pitié Salpétrière, Paris, France); Omer Eker (University Hospital of Lyon, Lyon, France); Emmanuel Ellie (Hospital Center of Bayonne, Bayonne, France); Simon Escalard (Rothschild Foundation, Paris, France); François Eugene (University Hospital of Rennes, Rennes, France); Serge Evrard (Foch Hospital, Suresnes, France); Isabelle Favre Wiki (University Hospital of Grenoble, Grenoble, France); Manuel Fernandez (University Hospital of Amiens, Amiens, France); Jean-Christophe Ferre (University Hospital of Rennes, Rennes, France); Anna Ferrier (University Hospital of Clermont Ferrand, Clermont Ferrand, France); Andrea Filip (University Hospital of Lyon, Lyon, France); Olivier Flabeau (Hospital Center of Bayonne, Bayonne, France); Julia Fontaine (University Hospital of Lyon, Lyon, France); Louis Fontaine (University Hospital of Toulouse, Toulouse, France); Géraud Forestier (University Hospital of Limoges, Limoges, France); Sophie Gallas (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Grégory Gascou (University Hospital of Montpellier, Bordeaux, France); Marie Gaudron (University Hospital of Tours, Tours, France); Jean-Yves Gauvrit (University Hospital of Rennes, Rennes, France); Christophe Gelmini (University Hospital of Reims, Reims, France); Jean-Christophe Gentric (University Hospital of Brest, Brest, France); Sam Ghazanfari (University Hospital of La Pitié Salpétrière, Paris, France); Roxana Gheoca (University Hospital of Strasbourg, Strasbourg, France); Jean Baptiste Girot (University Hospital of Angers, Angers, France); Philippe Goas (University Hospital of Brest, Brest, France); Sophie Godard (University Hospital of Angers, Angers, France); Alexis Gonnet (Hospital Center of Pau, Pau, France); Benjamin Gory (University Hospital of Nancy, Nancy, France); Lucas Gorza (Foch Hospital, Suresnes, France); Sophie Guettier (University Hospital of Caen, Caen, France); Maud Guillen (University Hospital of Rennes, Rennes, France); Benoît Guillon (University Hospital of Nantes, Nantes, France); Olivier Heck (University Hospital of Grenoble, Grenoble, France); Marc Hermier (University Hospital of Lyon, Lyon, France); David Higue (Hospital Center of Bayonne, Bayonne, France); Julien Hissier (University Hospital of Rennes, Rennes, France); Gabriela Hossu (University Hospital of Nancy, Nancy, France); Vi-Tuan Hua (University Hospital of Reims, Reims, France); Régis Hubrecht (Hospital Center of Pau, Pau, France); Lisa Humbertjean-Selton (University Hospital of Nancy, Nancy, France); Héloïse Ifergan (University Hospital of Tours, Tours, France); Leon Ikka (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Waliyde Jabeur (Foch Hospital, Suresnes, France); Kevin Janot (University Hospital of Tours, Tours, France); Anne Christine Januel (University Hospital of Toulouse, Toulouse, France); Jérémy Jouan (Hospital Center of Vannes, Vannes, France); Aurore Jourdain (University Hospital of Brest, Brest, France); Adrian Kastler (University Hospital of Grenoble, Grenoble, France); Garambois Katia (University Hospital of Grenoble, Grenoble, France); Basile Kerleroux (Psychiatry and Neurosciences University Hospital, Paris, France); Vincent L’allinec (University Hospital of Angers, Angers, France); Estelle La Porte (University Hospital of Caen, Caen, France); Jean-Christophe Lacour (University Hospital of Nancy, Nancy, France); Quentin Laferte (University Hospital of Amiens, Amiens, France); Laurent Lagoarde-Segot (Hospital Center of Bayonne, Bayonne, France); Chantal Lamy (University Hospital of Amiens, Amiens, France); Bertrand Lapergue (Foch Hospital, Suresnes, France); Thibault Lapotre (University Hospital of Rennes, Rennes, France); Maria Veronica Lassalle (University Hospital of Rennes, Rennes, France); Morgane Laubacher (University Hospital of Lyon, Lyon, France); Valérie Lauer (University Hospital of Strasbourg, Strasbourg, France); Karine Lavandier (Hospital Center of Bar le Duc, France); Arnaud Le Guen (Hospital Center of Vannes, Vannes, France); Anthony Lebras (Hospital Center of Vannes, Vannes, France); Alderic Lecluse (University Hospital of Angers, Angers, France); Sara Leder (University Hospital of La Pitié Salpétrière, Paris, France); Margaux Lefebvre (University Hospital of Rouen, Rouen, France); Pierre-Henri Lefevre (University Hospital of Montpellier, Bordeaux, France); Anne Leger (University Hospital of La Pitié Salpétrière, Paris, France); Nicolas Legris (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Loic Legris (University Hospital of Grenoble, Grenoble, France); Brivale Lemogne (University Hospital of Dijon, Dijon, France); Stéphanie Lenck (University Hospital of La Pitié Salpétrière, Paris, France); Cédric Lenoble (University Hospital of Nantes, Nantes, France); Zoé Lepine (Hospital Center of Pau, Pau, France); Liang Liao (University Hospital of Nancy, Nancy, France); Jean-Sébastien Liegey (University Hospital of Bordeaux, Bordeaux, France); Arthur Lionnet (University Hospital of Nantes, Nantes, France); Elie Lteif (University Hospital of Clermont Ferrand, Clermont Ferrand, France); Ludovic Lucas (University Hospital of Bordeaux, Bordeaux, France); Mehdi Mahmoudi (University Hospital of Montpellier, Bordeaux, France); Benjamin Maier (Rothschild Foundation, Paris, France); Cécile Malrain (University Hospital of Rennes, Rennes, France); Pierre-François (Manceau University Hospital of Reims, Reims, France); Raluca Marasescu (Hospital Center of Pau, Pau, France); Denis Marechal (University Hospital of Brest, Brest, France); Gaultier Marnat (University Hospital of Bordeaux, Bordeaux, France); Evelyne Massardier (University Hospital of Rouen, Rouen, France); Agnès Masson (University Hospital of Nancy, Nancy, France); Mikael Mazhigi (Rothschild Foundation, Paris, France); Laura Mechtouff (University Hospital of Lyon, Lyon, France); François-Mathias Merrien (University Hospital of Brest, Brest, France); Cristian Mihalea (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Gioia Mione (University Hospital of Nancy, Nancy, France); Elisabeth Molinier (University Hospital of Tours, Tours, France); Ricardo Moreno (University Hospital of Clermont Ferrand, Clermont Ferrand, France); Solène Moulin (University Hospital of Reims, Reims, France); Thierry Moulin (University Hospital of Besançon, Besançon, France); Charbel Mounayer (University Hospital of Limoges, Limoges, France); Isabelle Mourand (University Hospital of Montpellier, Bordeaux, France); Olivier Naggara (Psychiatry And Neurosciences University Hospital, Paris, France); Thi-Ngoc-Phuong Nguyen (University Hospital of Reims, Reims, France); Norbert Nighoghossian (University Hospital of Lyon, Lyon, France); Julien Ognard (University Hospital of Brest, Brest, France); Stephane Olindo (University Hospital of Bordeaux, Bordeaux, France); Jean-Marc Olivot (University Hospital of Toulouse, Toulouse, France); Elodie Ong (University Hospital of Lyon, Lyon, France); Elisa Ouin (University Hospital of Amiens, Amiens, France); Augustin Ozanne (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Ozlem Ozkul-Wermester (University Hospital of Rouen, Rouen, France); Paolo Pagano (University Hospital of Reims, Reims, France); Laurentiu Paiusan (University Hospital of Reims, Reims, France); Chrysanthi Papagiannaki (University Hospital of Rouen, Rouen, France); Jean Papaxanthos (University Hospital Of Bordeaux, Bordeaux, France); Lisa Papillon University Hospital of Bordeaux, Bordeaux, France); Pauline Paris (University Hospital of Clermont Ferrand, Clermont Ferrand, France); Anne Pasco-Papon (University Hospital of Angers, Angers, France); Marco Pasi (University Hospital of Tours, Tours, France); Benoit Pegat (Hospital Center of Vannes, Vannes, France); Irène Pierre-Paul (University Hospital of Strasbourg, Strasbourg, France); Michel Piotin (Rothschild Foundation, Paris, France); Silvia Pizzuto (Foch Hospital, Suresnes, France); Sophie Planel (University Hospital of Nancy, Nancy, France); Iona Podar (University Hospital of Nancy, Nancy, France); Mathilde Poli (University Hospital of Bordeaux, Bordeaux, France); Raoul Pop (University Hospital of Strasbourg, Strasbourg, France); Julia Potenza (Hospital Center of Bayonne, Bayonne, France); Kevin Premat (University Hospital of La Pitié Salpétrière, Paris, France); Cécile Preterre (University Hospital of Nantes, Nantes, France); Sabine Prud’hon (University Hospital of Brest, Brest, France); Véronique Quenardelle (University Hospital of Strasbourg, Strasbourg, France); Nicolas Raposo (University Hospital Of Toulouse, Toulouse, France); Marie Raquin (University Hospital of Clermont Ferrand, Clermont Ferrand, France); Lucie Rascle (University Hospital of Lyon, Lyon, France); Nicolas Raybaud (University Hospital of Besançon, Besançon, France); Hocine Redjem (Rothschild Foundation, Paris, France); Marie Reitter (University Hospital Of Nancy, Nancy, France); Pauline Renou (University Hospital of Bordeaux, Bordeaux, France); Sébastien Richard (University Hospital of Nancy, Nancy, France); Johann Sebastian Richter (Hospital Center of Pau, Pau, France); Frédéric Ricolfi (University Hospital of Dijon, Dijon, France); Roberto Riva (University Hospital of Lyon, Lyon, France); Georges Rodesch (Foch Hospital, Suresnes, France); Christine Rodriguez-Regent (Psychiatry and Neurosciences University Hospital, Paris, France); Thomas Ronziere (University Hospital of Rennes, Rennes, France); Charlotte Rosso (University Hospital of La Pitié Salpétrière, Paris, France); Aymeric Rouchaud (University Hospital of Limoges, Limoges, France); Pierre Yves Rousseau (University Hospital of Brest, Brest, France); Ameli Roxanna (University Hospital of Lyon, Lyon, France); Valérie Ruche (Hospital Center of Bar le Duc, France); Sharmila Sagnier (University Hospital of Bordeaux, Bordeaux, France); Maher Sahnoun (University Hospital of Reims, Reims, France); Fabrizio Salaris (University Hospital of Caen, Caen, France); Suzana Saleme (University Hospital of Limoges, Limoges, France); Mariana Sarov (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Emmanuelle Schmitt (University Hospital of Nancy, Nancy, France); Romain Schneckenburger (University Hospital of Caen, Caen, France); Isabelle Serre (University Hospital of Reims, Reims, France); Alessandro Sgreccia (Foch Hospital, Suresnes, France); Igor Sibon (University Hospital of Bordeaux, Bordeaux, France); Stanislas Smajda (Rothschild Foundation, Paris, France); Sébastien Soize (University Hospital of Reims, Reims, France); Antoine Soulages (Hospital Center of Bayonne, Bayonne, France); Nader Sourour (University Hospital of La Pitié Salpétrière, Paris, France); Laurent Spelle (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Adriana Tabarna (University Hospital of Nancy, Nancy, France); Philippe Tall (University Hospital of Toulouse, Toulouse, France); Maia Tchikviladze (Foch Hospital, Suresnes, France); Adrien Ter Schiphorst (University Hospital of Montpellier, Bordeaux, France); Guillaume Tessier (University Hospital of Nantes, Nantes, France); Pierre Thouant (University Hospital of Dijon, Dijon, France); Serge Timsit (University Hospital of Brest, Brest, France); Thomas Tourdias (University Hospital of Bordeaux, Bordeaux, France); Emmanuel Touze (University Hospital of Caen, Caen, France); Clément Tracol (University Hospital of Rennes, Rennes, France); Aude Triquenot (University Hospital of Rouen, Rouen, France); Denis Trystram (Psychiatry and Neurosciences University Hospital, Paris, France); Malwina Trzeciak (University Hospital of Strasbourg, Strasbourg, France); Guillaume Turc (Psychiatry And Neurosciences University Hospital, Paris, France); Françis Turjman (University Hospital of Lyon, Lyon, France); Stephane Vannier (University Hospital of Rennes, Rennes, France); Christine Vassilev (University Hospital of La Pitié Salpétrière, Paris, France); Laura Venditti (University Hospital of Kremlin Bicêtre, Kremlin Bicêtre, France); Louis Veunac (Hospital Center of Bayonne, Bayonne, France); Irina Viakhireva (University Hospital of Brest, Brest, France); Jérémie Vial (University Hospital of Amiens, Amiens, France); Alain Viguier (University Hospital of Toulouse, Toulouse, France); Denis Vivien (University Hospital of Caen, Caen, France); Marcela Voicu (University Hospital of Nancy, Nancy, France); Adrien Wang (Foch Hospital, Suresnes, France); David Weisenburger-Lile (Foch Hospital, Suresnes, France); Anthony Wietrich (Hospital Center of Bar le Duc, France); Aymeric Wittwer (University Hospital of La Pitié Salpétrière, Paris, France); Valérie Wolff (University Hospital of Strasbourg, Strasbourg, France); Marion Yger (University Hospital of La Pitié Salpétrière, Paris, France); Abderrahim Zerroug (University Hospital of Clermont Ferrand, Clermont Ferrand, France); François Zhu (University Hospital of Nancy, Nancy, France); 2/ the JENI research collaborative: Thibault Agripnidis (University Hospital of Marseille, Marseille, France); Julien Allard (Psychiatry and Neurosciences University Hospital, Paris, France); Mariam Annan (University Hospital of Tours, Tours, France); Xavier Barreau (University Hospital of Bordeaux, Bordeaux, France); Valère Barrot (University Hospital of Tours, Tours, France); Guillaume Bellanger (University Hospital of Toulouse, Toulouse, France); Wagih Ben Hassen (Psychiatry And Neurosciences University Hospital, Paris, France); Amel Benali (University Hospital of Montpellier, Montpellier, France); Jérome Berge (University Hospital of Bordeaux, Bordeaux, France); Richard Bibi (University Hospital of Tours, Tours, France); Marc Bintner (University Hospital of La Réunion, Saint-Denis, France); Alessandra Biondi (University Hospital of Besançon, Besançon, France); Wilson Bizimana (University Hospital of Rabat, Rabat, Maroc); Federico Bolognini (University Hospital of Colmar, Colmar, France); Laure Bottin (University Hospital of La Pitié Salpétrière, Paris, France); Julien Boucherit (University Hospital of Angers, Angers, France); Grégoire Boulouis (University Hospital of Tours, Tours, France); Romain Bourcier (University Hospital of Nantes, Nantes, France); Arnaud Bretonniere (University Hospital of Tours, Tours, France); Martin Bretzner (University Hospital of Lille, Lille, France); Julien Burel (University Hospital of Rouen, Rouen, France); Federico Cagnazzo (University Hospital of Montpellier, Montpellier, France); Guillaume Charbonnier (University Hospital of Besançon, Besançon, France); Vladimir Charron (University Hospital of Tours, Tours, France); Mourad Cheddad El Aouni (University Hospital of Brest, France); Petru Florin Coltea (University Hospital of Strasbourg, Strasbourg, France); Pierre-Olivier Comby (University Hospital of Dijon, Dijon, France); Arturo Consoli (Foch Hospital, Suresnes, France); Jonathan Cortese (University Hospital Kremlin-Bicêtre, Le Kremlin-Bicêtre, France); Vincent Costalat (University Hospital of Montpellier, Montpellier, France); Jean Darcourt (University Hospital of Toulouse, Toulouse, France); Cyril Dargazanli (University Hospital of Montpellier, Montpellier, France); François Delvoye (Rothschild Foundation, Paris, France); François Delvoye (Rothschild Foundation, Paris, France); Imad Derraz (University Hospital of Montpellier, Montpellier, France); Maxime Drai (University Hospital of Marseille, Marseille, France); Victor Dumas (University Hospital of Poitiers, Poitiers, France); Vincent Durous (University Hospital of Lyon, Lyon, France); Ahmed-Ali El Ahmadi (University Hospital of Marseille, Marseille, France); Abderrahim El Houfia (University Hospital of Tours, Tours, France); Mahmoud Elhorany (University Hospital of Le Caire, Le Caire, Egypte); François Eugene (University Hospital of Rennes, Rennes, France); Sérine Ferhat (University Hospital of Besançon, Besançon, France); Géraud Forestier (University Hospital of Limoges, Limoges, France); Florent Gariel (University Hospital of Bordeaux, Bordeaux, France); Grégory Gascou (University Hospital of Montpellier, Montpellier, France); Marie Gaudron (University Hospital of Tours, Tours, France); Sébastien Gazzola (University Hospital of Toulon, Toulon, France); Clara Gilbert (University Hospital of Limoges, Limoges, France); Jean-Baptiste Girot (University Hospital of Angers, Angers, France); Alexis Guedon (University Hospital Lariboisière, France); Jean-François Hak (University Hospital of Marseille, Marseille, France); Riyad Hanafi (University Hospital of Lille, Lille, France); Olivier Heck (University Hospital of Grenoble, Grenoble, France); Denis Herbreteau (University Hospital of Tours, Tours, France); Clémence Hoche (University Hospital of Tours, Tours, France); Quentin Holay (University Hospital of Toulon, Toulon, France); Héloïse Ifergan (University Hospital of Tours, Tours, France); Kevin Janot (University Hospital of Tours, Tours, France); Paul Janvier (Hospital Of Saint-Germain-en-Laye, France); Erwah Kalsoum (University Hospital of La Pitié Salpétrière, Paris, France); Vincent L’allinec (University Hospital of Angers, Angers, France); Morgane Laubacher (University Hospital of Lyon, Lyon, France); Finoana Laza Nomenjanahary (University Hospital of Poitiers, Poitiers, France); Margaux Lefebvre (University Hospital of Marseille, Marseille, France); Pierre-Henri Lefevre (University Hospital of Montpellier, Montpellier, France); Liang Liao (University Hospital of Nancy, Nancy, France); Mehdi Mahmoudi (University Hospital of Montpellier, Montpellier, France); Pierre-François Manceau (University Hospital of Reims, Reims, France); Gaultier Marnat (University Hospital of Bordeaux, Bordeaux, France); Maichael Mekhail (University Hospital of La Pitié Salpétrière, Paris, France); Patrice Menegon (University Hospital of Bordeaux, Bordeaux, France); Dan Sorin Mihoc (University Hospital of Strasbourg, Strasbourg, France); Elisabeth Molinier (University Hospital of Tours, Tours, France); Ricardo Moreno (University Hospital of Clermont-Ferrand, Clermont-Ferrand, France); Charbel Mounayer (University Hospital of Limoges, Limoges, France); Samuel Mouyal (University Hospital of La Pitié Salpétrière, Paris, France); Chama Naciri (University Hospital of Casablanca, Casablanca, Maroc); Soumia Nasri (University Hospital of Oujda, Oujda, Maroc); Julien Ognard (University Hospital of Brest, France); Nezha Ouazzani (University Hospital of Rabat, Rabat, Maroc); Zineb Ouslim (Rothschild Foundation, Paris, France); Marco Pasi (University Hospital of Tours, Tours, France); Raoul Pop (University Hospital of Strasbourg, Strasbourg, France); Panagiotis Primikris (University Hospital of Besançon, Besançon, France); Marios Psychogios (University Hospital of Basel, Basel, Switzerland); Alias Quentin (University Hospital of Rouen, Rouen, France); Nicolas Raynaud (University Hospital of Poitiers, Poitiers, France); Anthony Reyre (University Hospital of Marseille, Marseille, France); Sebastian Richter (University Hospital of Pau, Pau, France); Carlos Riquelme (University Hospital of Montpellier, Montpellier, France); Christine Rodriguez (Psychiatry and Neurosciences University Hospital, Paris, France); Aymeric Rouchaud (University Hospital of Limoges, Limoges, France); Marina Sachet (University Hospital of Saint Etienne, Saint-Etienne, France); Suzana Saleme (University Hospital of Limoges, Limoges, France); Jacques Sedat (University Hospital of Nice, Nice, France); Eimad Shotar (University Hospital of La Pitié Salpétrière, Paris, France); Florence Tahon (Hospital of Clerval, Marseille, France); Benoit Testud (University Hospital of Marseille, Marseille, France); Sergio Vancheri (University Hospital of Besançon, Besançon, France); Stéphane Velasco (University Hospital of Poitiers, Poitiers, France); Sivadji Vingadassalom (University Hospital of Marseille, Marseille, France); Giovanni Vitale (University Hospital of Besançon, Besançon, France); Riccardo Zannoni (University Hospital of Saint Etienne, Saint-Etienne, France); François Zhu (University Hospital of Nancy, Nancy, France).

      • Contributors HI: planning, conduct, acquisition of data, and reporting of the work (drafting and critical revisions). CD, WBH, J-FH, BG, JO, KP, GM, BK, FZ, GB, PBS, GC, GF, JC, CF, FC, KJ: acquisition of data, revisions for important intellectual content. BL: planning, conduct, acquisition of data, and reporting of the work (drafting and critical revisions). GB: guarantor, planning, conduct, acquisition of data, statistical analysis, and reporting of the work (drafting and critical revisions).

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests GM: consulting fees from Stryker, Balt and Microvention, and paid lectures from Medtronic, Johnson & Johnson, and Phenox. JC: consulting fees and paid lectures from Medtronic, Balt and Stryker. He is a member of the editorial board of the JNIS. BL: research grants from Microvention, Balt and Phénox. FC: paid to the Institution for the PHRC national for DISCOUNT and for BLITZ studies. Consulting fees from Balt, Microvention, Stryker, and Medtronic, payment from Penumbra. Paid by Artedrone board member. Stock or stock options in Intradys and Collavidence.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.