The role of infarct location in patients with DWI-ASPECTS 0–5 acute stroke treated with thrombectomy

International audienceObjective To determine whether hemisphere involvement and infarct location on the Alberta Stroke Program CT Score (ASPECTS) template should serve as predictors of 90-day clinical outcome in patients with acute ischemic stroke with pretreatment diffusion-weighted imaging (DWI)–ASPECTS 0–5 treated with mechanical thrombectomy (MT). Methods We analyzed data of all consecutive patients included in the Endovascular Treatment in Ischemic Stroke registry between January 1, 2012, and August 31, 2018, who presented with a pretreatment DWI-ASPECTS 0–5 and underwent MT. Multivariable analyses were performed in order to identify the role of infarct location and hemisphere involvement on good outcome defined by a modified Rankin Scale (mRS) score 0–2 at 90 days and on the whole distribution of mRS (shift analysis). Results A total of 344 patients with a DWI-ASPECTS 0–5 (median 4, IQR 3–5) were included. Neither infarct location nor hemisphere involvement was found to be an independent predictor of good outcome. Involvement of the M6 region in right-sided strokes (adjusted odds ratio [aOR] 2.6, 99% confidence interval [CI] 1.14–5.8; p = 0.003) and the internal capsule in left-sided strokes (aOR 2.6, 99% CI 0.8–7.9; p < 0.020) independently predicted increased disability on the mRS distribution in the affected subpopulations. Conclusion Our study suggests that neither hemisphere nor infarct location should be considered as an exclusion criterion for MT in patients with stroke with pretreatment DWI-ASPECTS 0–5. The involvement of specific regions of interest was associated with increased disability. These may provide valuable information regarding stroke management options and neurologic recovery for use of caregivers in the postacute phase

Mothership versus drip and ship for thrombectomy in patients who had an acute stroke: a systematic review and meta-analysis

International audienceBackground The effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke due to large vessel occlusion is time-dependent. While only stroke centers with endovascular capabilities perform MT, many patients who had a stroke initially present to the closest primary stroke centers capable of administering earlier intravenous thrombolysis, and then require to be transferred to a comprehensive stroke center for MT. Purpose To compare the outcomes of this care pathway (drip and ship (DS)) with that whereby patients are directly transferred to a comprehensive stroke center (mothership (MS)). Methods We performed a systematic review and meta-analysis of published studies using several electronic databases to determine whether successful reperfusion (modified Thrombolysis In Cerebral Infarction ≥2b), functional independence at 90 days (modified Rankin Scale score ≤2), symptomatic intracranial hemorrhage, and 90-day mortality differed between those who underwent MT with the DS or the MS treatment pathway. Outcomes were meta-analyzed and the results expressed as adjusted relative risk (aRR) for the primary analysis and unadjusted relative risk (uRR) for secondary analysis. Results Eight studies including 2068 patients were selected, including one study reporting results fully adjusted for baseline characteristics. Patients undergoing MS had better functional independence than those undergoing DS (uRR=0.87, 95% CI 0.81 to 0.93; aRR=0.87, 95% CI 0.77 to 0.98). No difference was found between the treatment pathways in successful reperfusion (uRR=1.05, 95% CI 0.95 to 1.15; aRR=1.00, 95% CI 0.92 to 1.10), symptomatic intracranial hemorrhage (uRR=1.37, 95% CI 0.91 to 2.06; aRR, 1.53, 95% CI 0.79 to 2.98), and 90-day mortality (uRR=1.00, 95% CI 0.84 to 1.19; aRR=1.21, 95% CI 0.89 to 1.64). Conclusions Patients who had an acute ischemic stroke admitted directly to a comprehensive stroke center (MS patients) with endovascular capacities may have better 90-day outcomes than those receiving DS treatment. However, major limitations of current evidence (ie, retrospective studies and selection bias) suggest a need for adequately powered studies. Multicenter randomized controlled trials are expected to answer this question

Acute Stroke With Large Ischemic Core Treated by Thrombectomy Predictors of Good Outcome and Mortality

International audienceL arge baseline ischemic core acute stroke patients were excluded by the recent therapeutic trials demonstrating the clinical benefit of mechanical thrombectomy (MT). 1-3 The MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) failed to demonstrate an MT benefit in patients with a baseline Alberta Stroke Program Early CT (ASPECT) score of 0 to 4 (n=28), 4 while EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial), 5 SWIFT-PRIME (Solitaire With the Intention Background and Purpose-Acute stroke patients with a large ischemic core may still benefit from mechanical thrombectomy (MT), but the predictors of clinical outcome are not well known after MT. We investigated the clinical and imaging factors associated with good outcome and mortality at 90 days in acute stroke patients with a large baseline ischemic core treated with MT. Methods-Data from the multicentric prospective ETIS (Endovascular Treatment in Ischemic Stroke) registry of consecutive acute ischemic stroke patients treated with MT from January 1, 2012, to August 31, 2016, were retrospectively analyzed. Baseline large ischemic core was defined as diffusion-weighted imaging (DWI)-Alberta Stroke Program Early CT Score of ≤5. The degree of disability was assessed by the modified Rankin Scale at 90 days. Outcomes included good outcome (modified Rankin Scale score of ≤2), and mortality (modified Rankin Scale score of 6). Results-Among 216 patients with DWI-Alberta Stroke Program Early CT Score of ≤5 (median DWI volume 77 mL, interquartile range 52-120 mL) treated with MT, good outcome was achieved in 55 (25.4%) patients and 75 (34.7%) died at 90 days. Hemorrhagic transformation was detected in 40 (18.5%) patients within 24 hours post-MT. Older age (adjusted odds ratio [OR] for every 10 years, 0.62; 95% CI, 0.48-0.80; P<0.001) and increased DWI lesional volume (adjusted OR, 0.98; 95% CI, 0.97-0.99; P<0.001) were associated with a lower chance of achieving a good outcome, while successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] grades of ≤2b) predicted good outcome (adjusted OR, 4.56; 95% CI, 1.79-11.62; P=0.001). Successful recanalization (OR, 0.46; 95% CI, 0.22-0.97; P=0.042), increased DWI lesional volume (OR, 1.02; 95% CI, 1.01-1.03; P<0.001), age (OR for every 10 years, 1.72; 95% CI, 1.31-2.26; P<0.001), and diabetes mellitus (OR, 3.23; 95% CI, 1.34-7.8; P=0.009) were independent predictors of 90-day mortality. Conclusions-Successful recanalization and baseline DWI lesional volume are the strongest predictors of outcome in stroke patients with a large ischemic core

Admission Blood Pressure and Outcome of Endovascular Therapy: Secondary Analysis of ASTER Trial

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

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

Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

International audienceInborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)–specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines

Safety and Outcome of Carotid Dissection Stenting During the Treatment of Tandem Occlusions: A Pooled Analysis of TITAN and ETIS

International audienceBackground and Purpose: The efficacy of endovascular therapy in patients with acute ischemic stroke due to tandem occlusion is comparable to that for isolated intracranial occlusion in the anterior circulation. However, the optimal management of acute cervical internal carotid artery lesions is unknown, especially in the setting of carotid dissection, but emergency carotid artery stenting (CAS) is frequently considered. We investigated the safety and efficacy of emergency CAS for carotid dissection in patients with acute stroke with tandem occlusion in current clinical practice. Methods: We retrospectively analyzed a prospectively maintained database composed of 2 merged multicenter international observational real-world registries (Endovascular Treatment in Ischemic Stroke and Thrombectomy in Tandem Lesion). Data from endovascular therapy performed in the treatment of tandem occlusions related to acute cervical carotid dissection between January 2012 and January 2019 at 24 comprehensive stroke centers were analyzed. Results: The study assessed 136 patients with tandem occlusion due to dissection, including 65 (47.8%) treated with emergency CAS and 71 (52.2%) without. The overall rates of favorable outcome (90-day modified Rankin Scale score, 0–2) and successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b–3) were 58.0% (n=76 [95% CI, 49.6%–66.5%]) and 77.9% (n=106 [95% CI, 71.0%–85.0%]), respectively. In subgroup analyses, the rate of successful reperfusion (89.2% versus 67.6%; adjusted odds ratio, 2.24 [95% CI, 1.33–3.77]) was higher after CAS, whereas the 90-day favorable outcome (54.3% versus 61.4%; adjusted odds ratio, 0.84 [95% CI, 0.58–1.22]), symptomatic intracerebral hemorrhage (sICH; 10.8% versus 5.6%; adjusted odds ratio, 1.59 [95% CI, 0.79–3.17]), and 90-day mortality (8.0% versus 5.8%; adjusted odds ratio, 1.00 [95% CI, 0.48–2.09]) did not differ. In sensitivity analyses of patients with successful intracranial reperfusion, CAS was not associated with an improved clinical outcome. Conclusions: Emergency stenting of the dissected cervical carotid artery during endovascular therapy for tandem occlusions seems safe, whatever the quality of the intracranial reperfusion

Surgical treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial

International audienceOBJECTIVE The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. METHODS TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I–II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%–93%) and 105/110 low-grade (95%, 95% CI 90%–98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%–18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%–28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%–9%), 5 (83%) of whom had complications due to preoperative embolization. CONCLUSIONS The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 ( ClinicalTrials.gov

Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations

The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons