Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

Day 1 Extracranial Internal Carotid Artery Patency Is Associated With Good Outcome After Mechanical Thrombectomy for Tandem Occlusion.

Background and Purpose- Optimal management of the extracranial occlusive component remains controversial in patients with acute ischemic stroke by tandem occlusion treated with mechanical thrombectomy. We investigated the association between extracranial internal carotid artery (ICA) patency at day 1 and the clinical outcome after mechanical thrombectomy. Methods- Consecutive patients with acute ischemic stroke with tandem occlusion were identified from a hospital-based prospective registry from 2011 to 2017. Baseline characteristics, angiographic outcomes, and day 1 ICA patency assessed by MR angiography were analyzed with regard to their associations with 3-month modified Rankin Scale scores. Favorable outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. Results- Of 594 patients with acute ischemic stroke treated with mechanical thrombectomy during the study period, 83 met inclusion criteria. Successful recanalization (modified Thrombolysis in Cerebral Infarction, 2b/3) was achieved in 61.5%. Extracranial ICA was patent in 37 of 83 patients (44.6%) at day 1, more frequently in those with prior intravenous thrombolysis ( P=0.035) or with cervical revascularization procedure (balloon angioplasty or stenting, P=0.034). Favorable 3-month functional outcome was more frequent in patients with patent extracranial ICA at day 1 (adjusted odds ratio, 4.72; 95% CI, 1.76-13.34; P=0.003) independent of intracranial recanalization success. Conclusions- Day 1 stable extracranial ICA patency is associated with better clinical outcome in patients with acute ischemic stroke with tandem occlusions. Randomized studies are needed.

Intravenous Recombinant Tissue-Type Plasminogen Activator: Influence on Outcome in Anterior Circulation Ischemic Stroke Treated by Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) followed by mechanical thrombectomy (MT) improves functional outcome in patients with ischemic stroke related to proximal-vessel occlusion in the anterior circulation. Whether MT alone is as effective as IVT/MT remains controversial. We aimed at evaluating the influence of IVT in patients with large anterior circulation artery occlusion treated with MT. METHODS: We did a prospective observational cohort study in patients with stroke related to large anterior circulation artery occlusion treated by MT who were admitted to Lille University Hospital, Lille, France. We evaluated the influence of IVT on favorable functional outcome (defined as a modified Rankin Scale score 0-2 or similar to the prestroke modified Rankin Scale) and on mortality at month 3. Between-group comparisons in outcomes were adjusted for prespecified confoundors by using a propensity score-adjusted approach. RESULTS: From January 2012 to January 2017, we included 485 patients (median age, 68 years; 46% men; 348 [72%] in the IVT/MT group; 137 [28%] in the MT group). In MT group, 22% of patients had a favorable outcome versus 35% in IVT/MT group (adjusted relative risk, 1.76; 95% confidence interval, 1.23-2.55). Mortality within 3 months occurred less frequently in IVT/MT group (14% versus 32%; adjusted relative risk, 0.46; 95% confidence interval, 0.31-0.70). Successful reperfusion (Thrombolysis in Cerebral Infarction scale 2b-3) was more frequent in IVT/MT group (75% versus 60%; adjusted relative risk, 1.30; 95% confidence interval, 1.11-1.53). There was no difference between groups on hemorrhagic complications. CONCLUSIONS: In this population, previous IVT improved functional outcome and survival at 3 months in patients treated by MT. While waiting for randomized controlled trials, this result encourages not to avoid IVT before MT.

Pre-treatment lesional volume in older stroke patients treated with endovascular treatment.

BACKGROUND: Recent studies in the general stroke population treated with endovascular treatment (EVT) reported that higher pre-treatment lesional volumes were independently associated with poor neurological outcome and functional dependence after stroke. However, it has been not evaluated in older patients. AIM: We test the association between the pre-treatment lesional volume on diffusion-weighted magnetic resonance imaging and relevant outcome measures in older adults with stroke treated with EVT. METHODS: We included consecutive older adults with stroke (⩾80 years old) treated with EVT in two academic comprehensive stroke centers. The association between pre-treatment lesional volume and relevant outcome measures (poor outcome (modified Rankin scale 4-6), 3-month mortality and symptomatic intracerebral hemorrhage (sICH)) was evaluated using univariate and multivariable models. RESULTS: Five hundred seventy-nine patients were included (mean age: 85.6 ± 4.1, median lesional volume was 10 ml; interquartile range: 3-30 ml). Pre-treatment lesional volume was associated with poor functional outcome (adjusted odds ratio (aOR): 1.87, 95% confidence interval (CI): 1.60-2.20, for +1 logarithmic increase of lesional volume), 3-month mortality (aOR: 1.50, CI: 1.28-1.76), and sICH (aOR: 1.67, CI: 1.27-2.20). A threshold lesional volume >35 ml predicted 90% of patients with poor functional outcome and a cut-off >51 ml predicted 90% of patients dead at 3 months. CONCLUSIONS: Pre-treatment lesional volume might contribute, in association with other relevant clinical features, to the selection of older stroke patients who will benefit from EVT.

Thrombectomy Using the EmboTrap II Device in Late Treatment Patients in the Real-World Setting.

OBJECTIVE: We aimed to evaluate the safety and efficacy of endovascular thrombectomy (EVT) using the EmboTrap Revascularization Device (EmboTrap) in patients with ischemic stroke treated >6-24 hours after stroke onset. METHODS: We performed a retrospective analysis of data from a prospective registry of consecutive patients with stroke with anterior circulation large vessel occlusion treated by stent-retriever thrombectomy with EmboTrap II in a single stroke center in France from 2016 to 2017. Patients were divided into late treatment window (>6-24 hours after stroke onset) or early treatment window (≤6 hours) groups. Baseline clinical and imaging characteristics, rates of successful recanalization (modified Thrombolysis in Cerebral Infarction score ≥2b), complications, 3 months good functional outcome (modified Rankin Scale score 0-2), and mortality were analyzed. RESULTS: Of the 225 patients (mean age, 71.5 ± 14.5 years; 55.6% [125/225] female) included in the study, 54 were treated in the late treatment window, with a mean time from last known well to treatment of 651 ± 223 minutes. Compared with the early treatment window group, there were no significant differences in baseline characteristics, successful recanalization (83.3% [45/54] vs. 81.3% [139/171]; P = 0.734), 3 months good functional outcome (37.0% [20/54] vs. 37.4% [64/171]; P = 0.959), or mortality (24.1% [13/54] vs. 27.5% [47/171]; P = 0.621). CONCLUSIONS: This real-world study provides evidence that EVT using EmboTrap is safe and effective in the late treatment window in patients with large vessel occlusion.

MT-DRAGON score for outcome prediction in acute ischemic stroke treated by mechanical thrombectomy within 8 hours.

OBJECTIVES: The MRI-DRAGON score includes clinical and MRI parameters and demonstrates a high specificity in predicting 3 month outcome in patients with acute ischemic stroke (AIS) treated with intravenous tissue plasminogen activator (IV tPA). The aim of this study was to adapt this score to mechanical thrombectomy (MT) in a large multicenter cohort. METHODS: Consecutive cases of AIS treated by MT between January 2015 and December 2017 from three stroke centers were reviewed (n=1077). We derived the MT-DRAGON score by keeping all variables of the MRI-DRAGON score (age, initial National Institutes of Health Stroke Scale score, glucose level, pre-stroke modified Rankin Scale (mRS) score, diffusion weighted imaging-Alberta Stroke Program Early CT score ≤5) and considering the following variables: time to groin puncture instead of onset to IV tPA time and occlusion site. Unfavorable 3 month outcome was defined as a mRS score >2. Score performance was evaluated by c statistics and an external validation was performed. RESULTS: Among 679 included patients (derivation and validation cohorts, n=431 and 248, respectively), an unfavorable outcome was similar between the derivation (51.5%) and validation (58.1%, P=0.7) cohorts, and was significantly associated with all MT-DRAGON parameters in the multivariable analysis. The c statistics for unfavorable outcome prediction was 0.83 (95%CI 0.79 to 0.88) in the derivation and 0.8 (95%CI 0.75 to 0.86) in the validation cohort. All patients (n=55) with an MT-DRAGONscore ≥11 had an unfavorable outcome and 60/63 (95%) patients with an MT-DRAGON score ≤2 points had a favorable outcome. CONCLUSION: The MT-DRAGON score is a simple tool, combining admission clinical and radiological parameters that can reliably predict 3 month outcome after MT.

Effect of In-Hospital Remote Ischemic Perconditioning on Brain Infarction Growth and Clinical Outcomes in Patients With Acute Ischemic Stroke: The RESCUE BRAIN Randomized Clinical Trial.

Importance: Treatment with remote ischemic perconditioning has been reported to reduce brain infarction volume in animal models of stroke. Whether this neuroprotective effect was observed in patients with acute ischemic stroke remains unknown. Objective: To determine whether treatment with remote ischemic perconditioning administered to the leg of patients with acute ischemic stroke can reduce brain infarction volume growth. Design, Setting, and Participants: This proof-of-concept multicenter prospective randomized open-label with blinded end point clinical trial was performed from January 12, 2015, to May 2, 2018. Patients were recruited from 11 stroke centers in France. Of the 188 patients who received magnetic resonance imaging within 6 hours of symptom onset and were confirmed to have carotid ischemic stroke, 93 were randomized to receive treatment with lower-limb remote ischemic perconditioning in addition to standard care (the intervention group), and 95 were randomized to receive standard care alone (the control group). Interventions: Randomization on a 1:1 ratio to receive treatment with remote ischemic perconditioning (4 cycles of 5-minute inflations and 5-minute deflations to the thigh to 110 mm Hg above systolic blood pressure) in addition to standard care or standard care alone. Main Outcomes and Measures: The change in brain infarction volume growth between baseline and 24 hours, measured by a diffusion-weighted sequence of magnetic resonance imaging scans of the brain. Results: A total of 188 patients (mean [SD] age, 67.2 [15.7] years; 98 men [52.1%]) were included in this intention-to-treat analysis. At hospital admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range [IQR], 6-16) and the median brain infarction volume was 11.4 cm3 (IQR, 3.6-35.8 cm3); 164 patients (87.2%) received intravenous thrombolysis, and 64 patients (34.0%) underwent mechanical thrombectomy. The median increase in brain infarction growth was 0.30 cm3 (IQR, 0.11-0.48 cm3) in the intervention group and 0.37 cm3 (IQR, 0.19-0.55 cm3) in the control group (mean between-group difference on loge-transformed change, -0.07; 95% CI, -0.33 to 0.18; P = .57). An excellent outcome (defined as a score of 0-1 on the 90-day modified Rankin Scale or a score equal to the prestroke modified Rankin Scale score) was observed in 46 of 90 patients (51.1%) in the intervention group and 37 of 91 patients (40.7%) in the control group (P = .12). No significant differences in 90-day mortality were observed between the intervention and control groups (14 of 90 patients; Kaplan-Meier estimate, 15.8% vs 10 of 91 patients; Kaplan-Meier estimate, 10.4%, respectively; P = .45) or with symptomatic intracerebral hemorrhage (4 of 88 patients [4.5%] in both groups; P = .97). Conclusions and Relevance: In this study, treatment with remote ischemic perconditioning, during or after reperfusion therapies, had no significant effect on brain infarction volume growth at 24 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT02189928.

Real-World Thrombectomy Using the Sofia Catheter.

OBJECTIVE: To study the safety and performance of real-world thrombectomy using the SOFIA Catheter in our comprehensive stroke center. METHODS: We conducted a cohort study from a prospective clinical registry of consecutive stroke patients treated by mechanical thrombectomy between March 2016 and September 2017. Baseline clinical and imaging characteristics, recanalization rates, complications, and clinical outcomes were analyzed. RESULTS: Among the 140 patients included, 54 were treated using aspiration first, 64 were treated using aspiration and stent-retriever straightaway, and 22 were treated with SOFIA as a rescue device. Successful recanalization (Modified Thrombolysis In Cerebral Infarction score 2b/3) was achieved in 82.1% patients and good outcomes in 34.3%. Symptomatic intracranial hemorrhage occurred in 7.1% and mortality in 25%. CONCLUSIONS: In our single-center experience, thrombectomy using the SOFIA as an intermediate or aspiration catheter provided high recanalization rates under everyday conditions.

White matter hyperintensity burden in patients with ischemic stroke treated with thrombectomy.

INTRODUCTION: To determine the influence of white matter hyperintensity (WMH) burden on functional outcome, rate of symptomatic intracerebral hemorrhage (sICH), and procedural success in patients with acute ischemic stroke (AIS) treated by mechanical thrombectomy (MT) with current stentriever/aspiration devices. METHODS: Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. WMH volumes were obtained by semiautomated planimetric segmentation and tested in association with the rate of favorable outcome (90-day functional independence), substantial recanalization after MT, and sICH. RESULTS: A total of 496 participants were included between 2015 and 2018 (50% female, mean age 68.1 ± 15.0 years). Overall, 434 (88%) patients presented with detectable WMH (mean ± SD 4.93 ± 7.7). Patients demonstrated increasingly worse outcomes with increasing WMH volumes (odds ratio [aOR]1.05 per 1-cm3 increase for unfavorable outcome, 95% confidence interval [CI] 1.01-1.06, p = 0.014). Fifty-seven percent of patients in the first quartile of WMH volume vs 28% in the fourth quartile demonstrated favorable outcome (p < 0.001). WMH severity was not associated with sICH rate (aOR 0.99, 95% CI 0.93-1.04, p = 0.66), nor did it influence recanalization success (aOR 0.99, 95% CI 0.96-1.02, p = 0.84). CONCLUSION: Our study provides evidence that in patients with AIS due to LVO and high burden of WMH as assessed by pretreatment MRI, the safety and efficacy profiles of MT are similar to those in patients with lower WMH burden and confirms that they are at higher risk of unfavorable outcome. Because more than a quarter of patients in the highest WMH quartile experienced favorable 3 months outcome, WMH burden may not be a good argument to deny MT. CLINICALTRIALSGOV IDENTIFIER: NCT01062698.

In-hospital ischaemic stroke treated with intravenous thrombolysis or mechanical thrombectomy.

Patients with in-hospital strokes (IHS) may be eligible for recanalization therapies. The objective of this study is to compare outcomes in patients with IHS and community-onset strokes (COS) treated by recanalization therapy. We analysed data prospectively collected in consecutive patients treated by thrombolysis, thrombectomy, or both for cerebral ischemia at the Lille University Hospital. We compared four outcomes measures at 3 months in patients with IHS and COS: (1) modified Rankin scale (mRS) 0-1, (2) mRS 0-2, (3) death, and (4) symptomatic intracranial haemorrhage (ECASS 2 definition). Of 1209 patients, 64 (5.3%) had IHS, with an increasing proportion over time (p = 0.001). Their median onset-to-needle time was 128 min vs. 145 in COS (p < 0.001). They were more likely to have had a recent TIA [odds ratio (OR) 30.1; 95% confidence interval (CI) 11.5-78.7], to have been treated by vitamin K antagonist before (OR 4.2; 95% CI 1.4-12.0) and to undergo mechanical thrombectomy (45 vs. 10%, p < 0.001). They were less likely to have a pre-stroke mRS 0-1 (OR 0.22; 95% CI 0.09-0.50). After adjustment, IHS was not associated with any of the four outcome measures. Patients with IHS are treated 17 min earlier than patients with COS, but, taking into account that they were already in the hospital, delays are still too long. Their outcome does not differ from that of patients with COS, suggesting room for improvement if delays can be reduced. IHS being frequent, pre-specified pathways should be organised.

Outcome of intracerebral hemorrhage associated with different oral anticoagulants.

OBJECTIVE: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH). METHODS: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. RESULTS: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6-38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0-27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52-1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18-1.19 [p = 0.11]). CONCLUSIONS: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.