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Background and Purpose: Mechanical thrombectomy (MT) is the recommended treatment for acute ischemic stroke caused by anterior circulation large vessel occlusion. However, despite a high rate of reperfusion, the clinical response to successful MT remains highly variable in the early time window where optimal imaging selection criteria have not been established. We hypothesize that the baseline perfusion imaging profile may help forecast the clinical response to MT in this setting. Methods: We conducted a prospective multicenter cohort study of patients with large vessel occlusion–related acute ischemic stroke treated by MT within 6 hours. Treatment decisions and the modified Rankin Scale evaluation at 3 months were performed blinded to the results of baseline perfusion imaging. Study groups were defined a posteriori based on predefined imaging profiles: target mismatch (TMM; core volume 1.2 and mismatch volume >10 mL) versus no TMM or mismatch (MM; mismatch ratio >1.2 and volume >10 mL) versus no MM. Functional recovery (modified Rankin Scale, 0–2) at 3 months was compared based on imaging profile at baseline and whether reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved. Results: Two hundred eighteen patients (mean age, 71±15 years; median National Institutes of Health Stroke Scale score, 17 [interquartile range, 12–21]) were enrolled. Perfusion imaging profiles were 71% TMM and 82% MM. The rate of functional recovery was 54% overall. Both TMM and MM profiles were independently associated with a higher rate on functional recovery at 3 months Adjusted odds ratios were 3.3 (95% CI, 1.4–7.9) for TMM and 5.9 (95% CI, 1.8–19.6) for MM. Reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved in 86% and was more frequent in TMM and MM patients. Reperfusion was associated with a higher rate of functional recovery in MM and TMM patients but not among those with no MM. Conclusions: In this cohort study, about 80% of the patients with a large vessel occlusion–related acute ischemic stroke had evidence of penumbra, regardless of infarction volume. Perfusion imaging profiles predict the clinical response to MT.

Background and objectivePredictors of symptomatic haemorrhagic transformation (s-HT) of cerebral ischaemia after intravenous recombinant tissue-plasminogen activator (rt-PA) were identified in studies using CT scans. We evaluated whether MRI can identify other predictors.MethodWe analysed predictors of s-HT in a cohort of consecutive patients who received intravenous rt-PA for cerebral ischaemia after MRI at baseline. We used receiver operating characteristic curves considering an area under the curve (AUC) of 0.70 or higher as indicating acceptable discrimination.ResultsOf 944 patients, 49 patients (5.2%) developed s-HT. Clinical factors independently associated with s-HT were age (adjusted OR (adjOR) 1.03 for 1 year increase; 95% CI 1.01 to 1.05), excessive alcohol consumption (adjOR 3.13; 95% CI 1.32 to 7.42), recent transient ischaemic attack (adjOR 2.88; 95% CI 1.04 to 7.95) and baseline national institutes of health stroke scale score (adjOR 1.06 for 1 point increase; 95% CI 1.02 to 1.10). MRI predictors were vascular hyperintensities (adjOR 3.89; 95% CI 1.50 to 10.08), old infarcts (adjOR 2.01; 95% CI 1.11 to 3.66) and volume of diffusion-weighted imaging (DWI) abnormality (adjOR 1.02 for 1 cm3 increase; 95% CI 1.01 to 1.03). The only variable with an acceptable discrimination was volume of DWI abnormality (AUC 0.72; 95% CI 0.64 to 0.79), a value of 4 cm3 predicting s-HT with a 78% sensitivity and 58% specificity. Variables that can be assessed only with MRI did not predict s-HT.ConclusionAlthough the volume of DWI abnormality predicts s-HT, other imaging characteristics that can only be assessed with MRI were not significantly associated with s-HT.Trial registration numberNCT01614080

Background and Purpose: Determining the mechanism of large vessel occlusion related acute ischemic stroke is of major importance to initiate a tailored secondary prevention strategy. We investigated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection (ASCOD) classification the distribution of the causes of large vessel occlusion related acute ischemic stroke treated by mechanical thrombectomy. Methods: This was a predefined substudy of the FRAME (French Acute Multimodal Imaging to Select Patient for Mechanical Thrombectomy). Each patient underwent a systematic etiological workup including brain and vascular imaging, electrocardiogram monitoring lasting at least 24 hours and routine blood tests. Stroke mechanisms were systematically evaluated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection grading system at 3 months. We defined single potential cause by one cause graded 1 in a single domain, possible cause as a cause graded 1 or 2 regardless of overlap, and no identified cause without grade 1 nor 2 causes. Results: A total of 215 patients (mean age 70±14; 50% male) were included. A single potential cause was identified in 148 (69%). Cardio-embolism (53%) was the most frequent, followed by atherosclerosis (9%), dissection (5%) and other causes (1%). Atrial fibrillation accounted for 88% of C1. Overlap between grade 1 causes was uncommon (3%). Possible causes were identified in 168 patients (83%) and 16 (7%) had no cause identified after the initial evaluation. Conclusions: Cardio-embolism, especially atrial fibrillation, was the major cause of large vessel occlusion related acute ischemic stroke. This finding emphasizes the yield of paroxysmal atrial fibrillation detection in those patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03045146.

Key Points Question In patients with proximal anterior circulation occlusion stroke presenting in the extended window, are rates of favorable outcomes at 90 days comparable in the patients selected for thrombectomy with noncontrast computed tomography vs patients selected with computed tomography perfusion or magnetic resonance imaging? Findings In a multicenter cohort of 1604 patients in the extended window with large-vessel occlusion, patients selected by noncontrast computed tomography had comparable clinical and safety outcomes with patients selected by computed tomography perfusion or magnetic resonance imaging. Meaning These findings suggest noncontrast computed tomography alone may be used as an alternative to advanced imaging in selecting patients with late-presenting large-vessel occlusion for mechanical thrombectomy., This cohort study compares the clinical outcomes of patients with stroke who presented 6 to 24 hours after symptom onset and were selected for mechanical thrombectomy by noncontrast computed tomography vs those selected by computed tomography perfusion or magnetic resonance imaging., Importance Advanced imaging for patient selection in mechanical thrombectomy is not widely available. Objective To compare the clinical outcomes of patients selected for mechanical thrombectomy by noncontrast computed tomography (CT) vs those selected by computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) in the extended time window. Design, Setting, and Participants This multinational cohort study included consecutive patients with proximal anterior circulation occlusion stroke presenting within 6 to 24 hours of time last seen well from January 2014 to December 2020. This study was conducted at 15 sites across 5 countries in Europe and North America. The duration of follow-up was 90 days from stroke onset. Exposures Computed tomography with Alberta Stroke Program Early CT Score, CTP, or MRI. Main Outcomes and Measures The primary end point was the distribution of modified Rankin Scale (mRS) scores at 90 days (ordinal shift). Secondary outcomes included the rates of 90-day functional independence (mRS scores of 0-2), symptomatic intracranial hemorrhage, and 90-day mortality. Results Of 2304 patients screened for eligibility, 1604 patients were included, with a median (IQR) age of 70 (59-80) years; 848 (52.9%) were women. A total of 534 patients were selected to undergo mechanical thrombectomy by CT, 752 by CTP, and 318 by MRI. After adjustment of confounders, there was no difference in 90-day ordinal mRS shift between patients selected by CT vs CTP (adjusted odds ratio [aOR], 0.95 [95% CI, 0.77-1.17]; P = .64) or CT vs MRI (aOR, 0.95 [95% CI, 0.8-1.13]; P = .55). The rates of 90-day functional independence (mRS scores 0-2 vs 3-6) were similar between patients selected by CT vs CTP (aOR, 0.90 [95% CI, 0.7-1.16]; P = .42) but lower in patients selected by MRI than CT (aOR, 0.79 [95% CI, 0.64-0.98]; P = .03). Successful reperfusion was more common in the CT and CTP groups compared with the MRI group (474 [88.9%] and 670 [89.5%] vs 250 [78.9%]; P

ObjectiveTo test the hypothesis that remote intracerebral hemorrhages (r-ICHs) after IV thrombolysis occur in preexisting brain lesions.MethodWe prospectively collected baseline data from consecutive patients treated with IV thrombolysis for cerebral ischemia and reviewed their baseline MRI scans to identify preexisting lesions in those who developed r-ICH. We evaluated outcomes with the modified Rankin Scale (mRS) and defined good outcomes as scores of 0 to 2 or similar to the preexisting mRS score.ResultsOf 944 patients, 24 (2.5%) had r-ICH: lobar in 14, deep in 7, and both in 3. Sixteen of them (1.7% of all patients, 66.7% of those with r-ICH) were asymptomatic. Of the 41 r-ICHs found in these patients, 17 (41%) occurred within a lesion present before thrombolysis: 6 cerebral microbleeds (CMBs), 6 old and 1 recent infarct, and 4 areas of white matter hyperintensity. Patients with r-ICH were more likely to have strictly lobar CMBs (p = 0.049). They were 10 years older (p = 0.007), had a 16–mm Hg higher systolic blood pressure (p = 0.035) at baseline, and had more CMBs (p = 0.007). r-ICHs were better predicted by clinical (age, baseline systolic blood pressure) than imaging (purely lobar CMBs and having >5 CMBs) variables. r-ICHs tended to be associated with worse outcomes.ConclusionWe identified preexisting brain lesions in nearly half of the patients with r-ICH. All were of vascular origin, supporting the hypothesis that r-ICHs occur in preexisting brain lesions. Higher-field machines could help identifying preexisting lesions in those who developed r-ICH in an apparently normal area.

Contains fulltext : 245661.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). OBJECTIVE: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. EXPOSURES: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES: Clinical characteristics and mortality rate. RESULTS: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Background and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P P P R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution.

The epileptogenicity of recombinant tissue-plasminogen activator (rt-PA) has been suggested, but seizures were not evaluated in randomised controlled trials. To evaluate whether rt-PA was associated with early seizures in a cohort of consecutive patients with cerebral ischaemia. We included consecutive adults with ischaemic stroke due to large-vessel occlusion from the North-of-France stroke network selected for a mechanical thrombectomy (MT). Patients without contraindication received i.v. rt-PA. We evaluated stroke severity with the National Institutes of Health Stroke Scale (NIHSS), and functional status with the modified Rankin scale (mRS), and recorded epileptic seizures occurring between the end of imaging and day 7. We performed statistics using propensity analyses. We included 1638 patients (783 men, 47.8%; median age 71 years; median NIHSS score 16; 1007 treated by rt-PA, 61.5%), in whom 60 (3.7%) developed early epileptic seizures. After adjustment on propensity scores, early seizures were associated with infections [adjusted odds ratio (adjOR) 2.86; 95% confidence interval (CI) 1.37–5.95] and delay between stroke recognition and end of MT (adjOR 1.04 for 10 min more; 95% CI 1.01–1.08), but not with rt-PA (adjOR 1.35; 95% CI 0.55–3.33). The propensity-matched analysis of 343 pairs of patients found no difference in the occurrence of early seizures between those with and without rt-PA (p = 0.386). We found no significant association between rt-PA and early epileptic seizures. If rt-PA has the potential for epileptogenicity, the magnitude of the effect should be modest compared to its favourable effect on functional outcome.

Patients treated at off-hours for acute conditions have increased mortality rates. This effect has been poorly evaluated in patients treated by mechanical thrombectomy (MT). This study aimed at comparing outcomes between patients treated at off-hours and at working hours by MT for acute stroke due to large-vessel occlusion in the anterior circulation, in a well-organised network. We included consecutive adults who underwent MT for large-vessel occlusion in the anterior circulation over a 51-month period, in the network of 16 hospitals from the North-of-France area, sharing similar protocols. Patients underwent magnetic resonance imaging-scans at admission and then 22–36 h later. We compared 3-month outcomes of patients treated at off-hours and at working time, the primary outcome being a modified Rankin scale (mRS) 0 to 2. The study population consisted of 1,179 patients (631 women, 53.5%; mean age 72 years; median baseline National Institutes of Stroke Scale 17; 639 at off-hours, 54.2%; 734 treated with rt-PA, 62.3%; median delay stroke recognition to end of MT 281 min). No patient was lost to follow-up. The outcomes did not differ between the two groups: adjusted odds ratio (adjOR) for mRS 0–2: 0.89; 95% confidence interval (CI) 0.67–1.18; adjOR for mRS 0–1: 0.91; 95% CI 0.68–1.21; adjOR for death 1.12; 95% CI 0.81–1.55). Our study did not show worse outcomes in patients treated at off-hours. This result suggests that the off-hours effect reported in other studies can be minimized by a coordinated organisation of stroke care providing similar levels of care at off-hours.

Cognitive impairment is frequent after stroke, and several studies have suggested that biological and imaging characteristics present before stroke are associated with the development of post-stroke cognitive impairment. The aim of our study was to systematically review biological and imaging predictors of cognitive impairment after stroke. Studies were identified from bibliographic databases and reference lists, and were included if conducted in patients with acute stroke, with at least 30 patients, and a follow-up of at least 3 months. We included articles on potential biomarkers of cognitive impairment that pre-existed to stroke. We identified 22,169 articles, including 20,349 with abstract. After analysis, 66 studies conducted in 42 cohorts met selection criteria. They included 30–9522 patients [median 170; interquartile range (IQR) 104–251] with a median follow-up of 12 months (IQR 3–36). All studies met quality criteria for description of the study population and standardization of biomarkers. Twenty-nine studies met all quality criteria. There was no convincing evidence that any biological marker may predict cognitive impairment. The most consistent predictors of cognitive impairment after stroke were global atrophy and medial temporal lobe atrophy. Pre-existing cerebral atrophy is the most consistent predictor of cognitive impairment that can be identified in patients with an acute stroke.

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

Background and Purpose— Orolingual angioedema (OLAE) is a life-threatening complication of intravenous thrombolysis. Our objective was to compare outcomes of patients with and without OLAE. Methods— We prospectively included consecutive patients who received intravenous thrombolysis for cerebral ischemia at Lille University Hospital. We examined tongue and lips every 15 minutes during thrombolysis and ≤30 minutes after. We evaluated the 3-month outcome with the modified Rankin scale (mRS) and compared outcomes of patients with and without OLAE. Results— Of 923 consecutive patients, 20 (2.2%) developed OLAE. None of them needed oro-tracheal intubation. They were more likely to be under angiotensin-converting enzyme inhibitors (adjusted odds ratio [adjOR], 3.9; 95% confidence interval [CI], 1.6–9.7; P =0.005) to have total insular infarcts (OR, 5.0; 95% CI, 1.5–16.5; P =0.004) and tended to develop more symptomatic intracerebral hemorrhages. Results concerning angiotensin-converting enzyme inhibitors were not modified after adjustment for propensity scores (OR, 4.4; 95% CI, 1.6–11.9; P =0.004) or matched analysis based on propensity scores (OR, 3.4; 95% CI, 1.3–8.1; P =0.010). Patients with OLAE did not significantly differ at 3 months for the proportion of patients with mRS score of 0 to 1 (adjOR, 0.9; 95% CI, 0.3–2.1), mRS score of 0 to 2 (adjOR, 0.8; 95% CI, 0.1–1.8), and death (adjOR, 1.1; 95% CI, 0.3–3.8). Conclusions— OLAE occurs in 1 of 50 patients who receive intravenous thrombolysis, 1 of 10 in case of total insular infarct, and 1 of 6 if they are under angiotensin-converting enzyme inhibitors. Their long-term outcome does not differ from that of other patients.

Introduction There are limited data on cerebrovascular events in patients with stable coronary artery disease. To study the risk of cerebrovascular event, the relative proportion of ischaemic stroke and intracranial haemorrhage, and their prognostic factors in stable coronary artery disease are investigated. Patients and methods The CORONOR registry prospectively recruited, between February 2010 and April 2011, 4184 unselected stable coronary artery disease outpatients. All events occurring during a five-year follow-up were adjudicated. Results Ninety-six patients had an ischaemic stroke and 34 had an intracranial haemorrhage, reaching a cumulative incidence after five years of 3.2 (2.7–3.8)%. During the same period, 677 deaths and 170 myocardial infarctions (ST-elevation MI, n = 55; non-ST-elevation MI, n = 115) occurred. In elderly individuals, the number of cerebrovascular events was higher than that of myocardial infarctions and largely exceeded that of ST-elevation myocardial infarctions. Predictors of ischaemic stroke were: previous history of stroke (subhazard ratio (SHR)=3.16(1.95–5.14)), absence of statin therapy at inclusion (SHR = 2.45(1.47–4.10), increasing age (SHR = 1.45(1.16–1.82) per 10-year increase) and diabetes mellitus (SHR = 1.65(1.10–2.49)). Predictors of intracranial haemorrhage were: combination of vitamin K antagonists with an antiplatelet agent at inclusion (SHR = 5.41(2.49–11.75), single antiplatelet therapy as reference), and increasing age (SHR = 1.47(1.12–1.93) per 10-year increase). Discussion In stable coronary artery disease patients, the brain deserves attention. In patients at high risk of ischaemic stroke, secondary prevention could be intensified. Our results raise awareness of the hazard of the association of antiplatelet drugs with oral anticoagulants in stable coronary artery disease patients. Conclusion While improving the prevention of future vaso-occlusive events should be our ultimate goal in coronary artery disease patients, the net clinical benefit of our treatments should carefully be studied.

International audience; Objective: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue (“core”). Perfusion imaging may identify a subset of patients with large core who benefit from MT.Methods: We compared two cohorts of LVO-related patients with large core (>50 ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6 hrs from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume).Results: Overall, 107 patients were included (56 MT + BMM + 51 BMM): Mean age was 68 ± 15 yrs, median core volume 99 ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the 2 groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (Pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95%CI] = 6.8 [1.7-27.0] vs. 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio≥1.8 in the subgroup with core≥70 ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT + BMM group regardless of the MMRatio.Interpretation: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. This article is protected by copyright. All rights reserved.