Combined Technique for Internal Carotid Artery Terminus or Middle Cerebral Artery Occlusions in the ASTER2 Trial.

BACKGROUND: The aim of this study was to report the results of a subgroup analysis of the ASTER2 trial (Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion) comparing the safety and efficacy of the combined technique (CoT) and stent retriever as a first-line approach in internal carotid artery (ICA) terminus±M1-middle cerebral artery (M1-MCA) and isolated M1-MCA occlusions. METHODS: Patients enrolled in the ASTER2 trial with ICA terminus±M1-MCA and isolated M1-MCA occlusions were included in this subgroup analysis. The effect of first-line CoT versus stent retriever according to the occlusion site was assessed on angiographic (first-pass effect, expanded Treatment in Cerebral Infarction score ≥2b50, and expanded Treatment in Cerebral Infarction score ≥2c grades at the end of the first-line strategy and at the end of the procedure) and clinicoradiological outcomes (24-hour National Institutes of Health Stroke Scale, ECASS-III [European Cooperative Acute Stroke Study] grades, and 3-month modified Rankin Scale). RESULTS: Three hundred sixty-two patients were included in the postsubgroup analysis according to the occlusion site: 299 were treated for isolated M1-MCA occlusion (150 with first-line CoT) and 63 were treated for ICA terminus±M1-MCA occlusion (30 with first-line CoT). Expanded Treatment in Cerebral Infarction score ≥2b50 (odds ratio, 11.83 [95% CI, 2.32-60.12]) and expanded Treatment in Cerebral Infarction score ≥2c (odds ratio, 4.09 [95% CI, 1.39-11.94]) were significantly higher in first-line CoT compared with first-line stent retriever in patients with ICA terminus±M1-MCA occlusion but not in patients with isolated M1-MCA. CONCLUSIONS: First-line CoT was associated with higher reperfusion grades in patients with ICA terminus±M1-MCA at the end of the procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03290885.

Impact of Day 1 carotid patency on outcome in dissection-related tandem occlusions treated with mechanical thrombectomy.

BACKGROUND: The clinical benefit of mechanical thrombectomy(MT) for stroke patients with tandem occlusion is similar to that of isolated intracranial occlusions. However, the management of cervical internal carotid artery(ICA) occlusion during the MT, particularly in the setting of carotid dissection, remains controversial. We aimed to investigate the clinical impact of cervical ICA patency at day 1 on 3-month functional outcome. METHODS: We collected data from the Endovascular Treatment in Ischemic Stroke, a prospective national registry in 30 French centers performing MT between January 2015 and January 2022. Inclusion criteria were consecutive tandem occlusions related to cervical ICA dissection treated with MT. Tandem occlusions of other etiology, isolated cervical ICA occlusions without intracranial thrombus and patients without day-1 ICA imaging were excluded. Primary endpoint was the 3-month functional outcome. Secondary endpoints included intracranial hemorrhage(ICH), excellent outcome, mortality and early neurological improvement. A sensitivity analysis was performed in patients with intracranial favorable recanalization after MT. RESULTS: During the study period, 137 patients were included of which 89(65%) presented ICA patency at day 1. The odds of favorable outcome did not significantly differ between patients with patent and occluded ICA at day 1(68.7 vs 59.1%;aOR=1.30;95%CI 0.56-3.00,p=0.54). Excellent outcome, early neurological improvement, mortality and ICH were also comparable between groups. Sensitivity analysis showed similar results. CONCLUSION: ICA patency at day 1 in patients with tandem occlusions related to dissection did not seem to influence functional outcome. Endovascular recanalization of the cervical ICA including stenting might not be systematically required in this setting.

Effect of small vessel disease severity on blood pressure management after endovascular therapy in the BP TARGET trial.

BACKGROUND AND PURPOSE: Acute ischaemic stroke patients with cerebral small vessel disease (CSVD), including cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs), have worse outcomes. The effect was investigated of two blood pressure strategies (intensive vs. standard) and blood pressure variability (BPV) after reperfusion according to CSVD burden in the BP TARGET trial. METHODS: Patients with available magnetic resonance imaging at baseline were included. CMBs were described as absent or present and WMH severity was described according to the Fazekas classification (0-1, absent-mild; 2-3, moderate to severe). Outcomes consisted of any intracerebral hemorrhage (ICH) at 24 h and favorable outcome at 90 days (modified Rankin Scale score between 0 and 2). RESULTS: In all, 246 patients were included. The intensive systolic blood pressure target was not associated with lower rates of ICH or favorable outcome according to CSVD subgroups (all p values >0.35). Several BPV parameters were associated with increased odds of ICH in patients with CMBs but not in patients without CMBs (diastolic blood pressure coefficient of variation, odds ratio 2.06, 95% confidence interval [CI] 1.13-3.77, in patients with ≥1 CMB vs. 0.94, 95% CI 0.68-1.31, in patients without CMBs, phet  = 0.026). Several diastolic BPV parameters were associated with worse outcomes in patients with severe WMHs but not in patients without WMHs (diastolic blood pressure coefficient of variation, odds ratio 0.32, 95% CI 0.17-0.61, in patients with severe WMHs vs. 1.09, 95% CI 0.67-1.79, in patients without WMHs; phet  = 0.003). CONCLUSION: No effect of the intensive systolic blood pressure management strategy was found on ICH occurrence or functional outcome according to CSVD burden. BPV was associated with higher odds of ICH in patients with CMBs and worse outcome in patients with moderate-to-severe WMHs.

Effects of weather conditions on endovascular treatment case volume for patients with ischemic stroke.

BACKGROUND: Weather conditions have been shown to influence the occurrence of cardiovascular events. We tested the hypothesis that weather parameters may be associated with variations of case volume of endovascular treatment (EVT) for acute ischemic stroke. METHODS: Individual data from the ETIS (Endovascular Treatment in Ischemic Stroke) French national registry were matched to local weather stations. Meteorological parameters (rainfall, humidity, atmospheric pressure, air temperature) were gathered from national online resources. Weather readings and EVT case volumes were annually standardized per weather station and EVT center, and their associations tested with non-parametric univariable and generalized linear statistical models. RESULTS: Between 2015 and 2021, 9913 EVT procedures addressed by 135 primary stroke units were matched to weather conditions. The mean daily case volume per center was 0.41 [StDev 0.33], and there was a median of 0.84 procedures daily linked to a weather station [StDev 0.47]. We found lower atmospheric pressure (ß estimate -0.04; 95%CI[-0.07;-0.03], p<0.001), higher humidity (ß estimate 0.07; 95%CI [0.05;0.09], p<0.001) and lower temperatures (ß estimate -0.08; 95%CI[-0.10;-0.06], p<0.001) to be associated with higher standardized EVT daily case volumes. These associations were stable when testing them across strata of binned EVT standardized case volumes. CONCLUSIONS: Our study suggests that lower ambient temperature, lower atmospheric pressure, and higher air humidity are associated with significantly more daily EVT cases in a European temperate country. These results may provide insight into both system of care optimization at times of climate change and intracranial LVO pathophysiology. REGISTRATION-URL: https://clinicaltrials.gov/ct2/show/NCT03776877.

Dual-layer carotid stenting for symptomatic carotid web: Results from the Caroweb study.

BACKGROUND & PURPOSE: Carotid Web (CaW) is a growingly recognized cause of ischemic stroke, associated with a high recurrence risk. Several therapeutic strategies have been proposed as a tertiary prevention including carotid stenting, endarterectomy and antithrombotic medications. Among these, carotid stenting with dual-layer stent may be promising to adequately cover the focal arterial dysplasia. Our aim was to investigate the safety and efficacy of the Casper stent in the treatment of symptomatic CaW. METHODS: We conducted a retrospective analysis of consecutive patients presenting with a symptomatic CaW and included in the ongoing prospective observational multicenter CAROWEB registry. The study period was January 2015 to December 2021. Inclusion criteria were CaW treated with dual-layer Casper stent. Patients treated with other types of carotid stent, endarterectomy or antithrombotic medication were excluded. Clinical and radiological initial data and outcomes were recorded. RESULTS: twenty-seven patients (with 28 caw) were included. median age was 52 (iqr: 46-68). median delay between index cerebrovascular event and cervical stenting was 9 days (IQR: 6-101). In all cases, the cervical carotid stenting was successfully performed. No major perioperative complication was recorded. No recurrent stroke or transient ischemic attack was observed during a median follow-up time of 272 days (IQR: 114-635). Long-term imaging follow-up was available in 25/28 (89.3%) stented CaW with a median imaging follow-up of 183 days (IQR: 107-676; range: 90-1542). No in-stent occlusion or stenosis was detected. CONCLUSION: In this study, carotid stenting with dual-layer Casper stent in the treatment of symptomatic CaW was effective regarding stroke recurrence prevention and safe, without procedural nor delayed detected adverse event. However, the optimal therapeutic approach of symptomatic CaW still needs to be explored through randomized trials.

Magnitude of Blood Pressure Change After Endovascular Therapy and Outcomes: Insight From the BP-TARGET Trial.

BACKGROUND AND PURPOSE: To assess the association between systolic blood pressure change (ΔSBP) at different time intervals after successful reperfusion with radiographic and clinical outcomes. METHODS: This is a post hoc analysis of the BP-TARGET multicenter trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy). ΔSBP was defined as end of procedure SBP minus mean SBP at different time intervals (15-60 minutes, 1-6 hours, and 6-24 hours postprocedure). The primary outcome was the poor functional outcome (90-day modified Rankin Scale score 3-6). RESULTS: We included a total of 267 patients (130 in the intensive treatment group). Compared with patients with favorable outcome, patients with poor outcome had lower ΔSBP (less SBP reduction) at all times intervals. After adjusting for potential confounders including baseline SBP, both ΔSBP15-60M and ΔSBP6-24H were associated with lower odds of poor outcome (adjusted odds ratio per 5 mm Hg SBP reduction, 0.89 [95% CI, 0.81-0.99], and adjusted odds ratio 0.82 [95% CI, 0.73-0.92], respectively). Concerning safety outcomes, patients with intraparenchymal hemorrhage had lower ΔSBP at all time intervals. ΔSBP15-60M was associated with lower odds of any intraparenchymal hemorrhage (adjusted odds ratio per 5 mm Hg SBP reduction 0.91 [95% CI, 0.83-0.99]). Conversely, ΔSBP was not associated with mortality or neurological deterioration at any time interval. CONCLUSIONS: After successful reperfusion, ΔSBP had a linear relationship with poor outcome and the risk of poor outcome was higher with less reduction from the baseline SBP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03160677.

Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial.

BACKGROUND: Acute ischemic stroke (AIS) patients with a history of hypertension experience worse outcomes, which may be explained by a deleterious impact of the renin-angiotensin system (RAS) overactivation. We sought to investigate whether prestroke antihypertensive treatments (AHT) influenced baseline stroke severity and neurological outcomes, in patients with AIS successfully treated by endovascular therapy. METHODS: We performed a post hoc analysis of the BP TARGET trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) and included hypertensive patients with available data regarding AHT at admission, categorized as RAS inhibitors (ACE [angiotensin-converting enzyme] inhibitors, ARBs [angiotensin 2 receptor blockers], and ß-blockers) and non-RAS inhibitors (calcium channel blockers and diuretics). Associations of each AHT with National Institutes of Health Stroke Scale (NIHSS) score at baseline were investigated in linear mixed model adjusted for the number of treatments and center. Associations of each AHT with 24-hour NIHSS change, intracranial hemorrhage were performed using linear mixed model adjusted for baseline NIHSS, the number of treatments, center, age, and sex and adjusted for age, sex, diabetes, and current smoking for favorable outcome. All analyses were performed on cases-available data regarding the low number of missing data. RESULTS: Overall, 203 patients with at least one AHT were included. Patients under non-RAS inhibitor treatments had a higher NIHSS score at baseline (adjusted mean difference=3.28 [95% CI, 1.33-5.22]; P=0.001). Conversely, patients under RAS inhibitor treatments had a lower baseline NIHSS score (adjusted mean difference=-2.81 [95% CI, -5.37 to -0.25]; P=0.031). Intracranial hemorrhage occurrence was significantly more frequent in patients under non-RAS inhibitor treatments (adjusted odds ratio of 2.48 [95% CI, 1.12-5.47]; P=0.025). Conversely, the use of RAS inhibitor treatments before AIS was not associated with higher odds of radiographic intracranial hemorrhage. Patients with non-RAS inhibitor treatments had less improvement of NIHSS at 24 hours compared with patients without (adjusted mean difference, 2.83 [95% CI, -0.16 to 5.81]; P=0.063). Baseline RAS inhibitor or noninhibitor treatments were not associated with favorable outcome. CONCLUSIONS: We showed an opposite effect of baseline AHT, based on their effect on the RAS. Patients treated with RAS inhibitor agents before AIS exhibited less severe AIS compared with patients under non-RAS inhibitor treatments, developed less intracranial hemorrhage at 24 hours and had a trend toward better NIHSS score at 24 hours. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03160677.

Effect of blood pressure variability in the randomized controlled BP TARGET trial.

BACKGROUND AND PURPOSE: The Blood Pressure Target in Acute Ischemic Stroke to Reduce Hemorrhage After Endovascular Therapy (BP TARGET) trial evaluated whether an intensive systolic blood pressure (SBP) target resulted in reduced rates of intracranial hemorrhage (ICH) after successful endovascular therapy (EVT) but did not assess the effect of blood pressure variability (BPV) on functional outcomes and ICH occurrence. We sought to evaluate this question in the BP TARGET trial. METHODS: We performed a post hoc analysis of the BP TARGET trial and included patients with at least 50% of blood pressure (BP) recordings during the first 24 h after EVT. BPV parameters were SBP and diastolic BP (DBP) coefficient of variation (CV), standard deviation (SD), maximum-minimum (max-min), successive variation (SV), and time rate. The primary outcome was favorable functional outcome (3-month modified Rankin Scale between 0 and 2); the secondary outcome was the rate of ICH at 24 h. RESULTS: We included 290 patients (mean number of BP measures = 30.4, SD = 8.0). BPV parameters (SBPSD , SBPmax-min , SBPCV ) were higher in the intensive SBP target group. Only DBP BPV parameters were associated with worse functional outcomes in the unadjusted model (DBPSD , DBPmax-min , DBPCV , and DBPSV ), but not after adjustment. Higher SBPmax-min was associated with worse functional outcomes in Thrombolysis in Cerebral Infarction 2B patients (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.38-1.02), but not in patients with complete reperfusion (OR = 1.27, 95% CI = 0.80-2.02, p for heterogeneity (phet =0.037). None of the BPV parameters was associated with ICH, regardless of the randomization group or the reperfusion grade. CONCLUSIONS: BPV was significantly higher in the intensive SBP target group but was not associated with functional outcome or ICH.

Intravenous abciximab as a rescue therapy for immediate reocclusion after successful mechanical thrombectomy in acute ischemic stroke patients.

Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome. The aim of this study was to gain insights into the mechanisms underlying immediate reocclusion, and to evaluate the efficacy and safety of the glycoprotein IIb/IIIa antagonist abciximab, for its treatment. Clinical data were collected from April 2015 to April 2019 in a monocentric prospective registry of AIS patients treated by MT. All patients with immediate reocclusion were retrospectively selected and subdivided into 2 groups according to abciximab treatment status. In vitro, the separate and combined effects of abciximab and alteplase on clot formation in whole blood under flow conditions were further investigated in microfluidic chambers. From 929 MT-treated patients, 21 had post-MT immediate reocclusion. Abciximab treatment in reocclusion patients (n = 10) led to higher rate of final recanalization (p < .001) while it did not increase bleeding complications. Flow chamber experiments revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. Our results underscore a key role for platelet aggregation and the potential of Glycoprotein IIb/IIIa antagonists as a rescue therapy in post-MT immediate reocclusion.

Association of Hypotension During Thrombectomy and Outcomes Differs With the Posterior Communicating Artery Patency.

BACKGROUND AND PURPOSE: Hypotension during endovascular therapy for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, we investigated whether hypotension during endovascular therapy had the same effect on FO according to the posterior communicating artery (PComA) patency. METHODS: We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). Patients were included if they had middle cerebral artery occlusions. Primary outcome was favorable FO, defined by a modified Rankin Scale scores between 0 and 2 at 3 months. RESULTS: One hundred forty-eight patients with middle cerebral artery occlusion were included. In patients with no PComA, an increase in minimum mean arterial pressure was positively associated with favorable FO (odds ratio per 10 mm Hg increase, 1.59 [95%CI, 1.11-2.25]; P=0.010), whereas no association was found in patients with a PComA (odds ratio, 0.77 [95% CI, 0.54-1.08]; P=0.12). Patients with no PComA and longer cumulative time with mean arterial pressure <90 mm Hg or systolic blood pressure <140 mm Hg had significantly lower rates of favorable FO, with an odds ratio per 10-minute increase of 0.75 (95% CI, 0.59-0.94; P=0.010) and 0.74 (95% CI, 0.60-0.91; P=0.003), but not in patients with a PComA. CONCLUSIONS: Hypotension during endovascular therapy for middle cerebral artery occlusion is consistently associated with worse FO in patients with no PComA but not in those with a PComA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02523261.

Effect of Operator's Experience on Proficiency in Mechanical Thrombectomy: A Multicenter Study.

BACKGROUND AND PURPOSE: We aimed to evaluate among trained interventional neuroradiologist, whether increasing individual experience was associated with an improvement in mechanical thrombectomy (MT) procedural performance metrics. METHODS: Individual MT procedural data from 5 centers of the Endovascular Treatment in Ischemic Stroke registry and 2 additional high-volume stroke centers were pooled. Operator experience was defined for each operator as a continuous variable, cumulating the number of MT procedures performed since January 2015, as MT became standard of care or, if later than this date, since the operator started performing mechanical thrombectomies in autonomy. We tested the associations between operator's experience and procedural metrics. RESULTS: A total of 4516 procedures were included, performed by 36 operators at 7 distinct centers, with a median of 97.5 endovascular treatment procedures per operator (interquartile range, 57-170.2) over the study period. Higher operator's experience, analyzed as a continuous variable, was associated with a significantly shorter procedural duration (ß estimate, -3.98 [95% CI, -5.1 to -2.8]; P<0.001), along with local anesthesia and M1 occlusion location in multivariable models. Increasing experience was associated with better Thrombolysis in Cerebral Infarction scores (estimate, 1.02 [1-1.04]; P=0.013). CONCLUSIONS: In trained interventional neuroradiologists, increasing experience in MT is associated with significantly shorter procedural duration and better reperfusion rates, with a theoretical ceiling effect observed after around 100 procedures. These results may inform future training and practice guidelines to set minimal experience standards before autonomization, and to set-up operators' recertification processes tailored to individual case volume and prior experience.

Glenzocimab does not impact glycoprotein VI-dependent inflammatory haemostasis.

Not available.

Location of intracranial aneurysms is the main factor associated with rupture in the ICAN population.

BACKGROUND AND PURPOSE: The ever-growing availability of imaging led to increasing incidentally discovered unruptured intracranial aneurysms (UIAs). We leveraged machine-learning techniques and advanced statistical methods to provide new insights into rupture intracranial aneurysm (RIA) risks. METHODS: We analysed the characteristics of 2505 patients with intracranial aneurysms (IA) discovered between 2016 and 2019. Baseline characteristics, familial history of IA, tobacco and alcohol consumption, pharmacological treatments before the IA diagnosis, cardiovascular risk factors and comorbidities, headaches, allergy and atopy, IA location, absolute IA size and adjusted size ratio (aSR) were analysed with a multivariable logistic regression (MLR) model. A random forest (RF) method globally assessed the risk factors and evaluated the predictive capacity of a multivariate model. RESULTS: Among 994 patients with RIA (39.7%) and 1511 patients with UIA (60.3 %), the MLR showed that IA location appeared to be the most significant factor associated with RIA (OR, 95% CI: internal carotid artery, reference; middle cerebral artery, 2.72, 2.02-3.58; anterior cerebral artery, 4.99, 3.61-6.92; posterior circulation arteries, 6.05, 4.41-8.33). Size and aSR were not significant factors associated with RIA in the MLR model and antiplatelet-treatment intake patients were less likely to have RIA (OR: 0.74; 95% CI: 0.55-0.98). IA location, age, following by aSR were the best predictors of RIA using the RF model. CONCLUSIONS: The location of IA is the most consistent parameter associated with RIA. The use of 'artificial intelligence' RF helps to re-evaluate the contribution and selection of each risk factor in the multivariate model.

Antiplatelet Therapy During Emergent Extracranial Internal Carotid Artery Stenting: Comparison of Three Intravenous Antiplatelet Perioperative Strategies.

INTRODUCTION: Guidelines for antiplatelet therapy administration, during emergent stenting for extra-cranial internal carotid artery (EC-ICA) occlusion in the setting of acute ischemic stroke (AIS) are lacking. Different antiplatelet regimen are used in association to endovascular therapy (EVT) for the treatment of EC-ICA lesions. We aimed to compare the clinical and radiological effects of three intravenous antiplatelet agents used during emergent EC-ICA stenting. MATERIAL AND METHODS: Clinical data were collected from January 2015 to December 2019 in a monocentric prospective registry of AIS patients treated by EVT. All patients who underwent emergent EC-ICA stenting were sorted regarding the intravenous antiplatelet agent used during the procedure. RESULTS: Among 218 patients treated by EVT for an EC-ICA occlusion of the anterior circulation during the study period, 70 underwent an emergent stenting of the EC-ICA. 60 were included in the present study, 9 received intravenous (IV) Cangrelor, 8 IV abciximab and 43 Aspirin. The rate of favorable neurological outcome, defined as modified Rankin Scale (mRS) ≤ 2 at three months were better in the Cangrelor and Aspirin groups (66,7% and 58,1%, respectively) than in the Abciximab group (37,5%), as well as, the rate of any intracranial ICH (22,2% and 37,2% vs 62,5%). The rate of acute stent reocclusion was similar between groups. CONCLUSION: When used as a rescue treatment during emergent stenting of EC-ICA, Cangrelor and Aspirin present a better safety profile than Abciximab, with less intracranial hemorrhages and a higher rate of good clinical outcome. Additional studies are needed to confirm these findings.

Early Brain Imaging Shows Increased Severity of Acute Ischemic Strokes With Large Vessel Occlusion in COVID-19 Patients.

BACKGROUND AND PURPOSE: Reports are emerging regarding the association of acute ischemic strokes with large vessel occlusion and coronavirus disease 2019 (COVID-19). While a higher severity of these patients could be expected from the addition of both respiratory and neurological injury, COVID-19 patients with strokes can present with mild or none respiratory symptoms. We aimed to compare anterior circulation large vessel occlusion strokes severity between patients with and without COVID-19. METHODS: We performed a comparative cohort study between patients with COVID-19 who had anterior circulation large vessel occlusion and early brain imaging within 3 hours from onset, in our institution during the 6 first weeks of the COVID-19 outbreak and a control group admitted during the same calendar period in 2019. RESULTS: Twelve COVID-19 patients with anterior circulation large vessel occlusion and early brain imaging were included during the study period and compared with 34 control patients with anterior circulation large vessel occlusion and early brain imaging in 2019. Patients in the COVID-19 group were younger (P=0.032) and had a history of diabetes mellitus more frequently (P=0.039). Patients did not significantly differ on initial National Institutes of Health Stroke Scale nor time from onset to imaging (P=0.18 and P=0.6, respectively). Patients with COVID-19 had more severe strokes than patients without COVID-19, with a significantly lower clot burden score (median: 6.5 versus 8, P=0.016), higher rate of multivessel occlusion (50% versus 8.8%, P=0.005), lower DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Scores; median: 5 versus 8, P=0.006), and higher infarct core volume (median: 58 versus 6 mL, P=0.004). Successful recanalization rate was similar in both groups (P=0.767). In-hospital mortality was higher in the COVID-19 patients' group (41.7% versus 11.8%, P=0.025). CONCLUSIONS: Early brain imaging showed higher severity large vessel occlusion strokes in patients with COVID-19. Given the massive number of infected patients, concerns should be raised about the coming neurovascular impact of the pandemic worldwide.

Protective Effect of ApoA1 (Apolipoprotein A1)-Milano in a Rat Model of Large Vessel Occlusion Stroke.

Background and Purpose- Previous experimental studies found that the infusion of human purified nascent HDL (high-density lipoprotein) significantly reduced infarct volume and hemorrhagic transformation rate by decreasing neutrophil recruitment. ApoA1-M (apolipoprotein A1-Milano) is a natural variant of human ApoA1 that confers protection against atherosclerosis. Recombinant ApoA1-M has been formulated as a complex with phospholipids to mimic the properties of nascent HDL. The aim of this study was to assess the impact of intravenous ApoA1-M in a transient middle cerebral artery occlusion stroke model in rats. Methods- In a first experiment, rats were subjected to 120-minute transient middle cerebral artery occlusion and intravenous ApoA1-M was infused immediately or 4 hours after occlusion. In a second experiment, rats were subjected to 240-minute transient middle cerebral artery occlusion and intravenous ApoA1-M was infused with or without recombinant tPA (tissue-type plasminogen activator) immediately after recanalization. Primary outcome criteria were the infarct volume and hemorrhagic transformation rate measured at 24 hours. Platelets, coagulation, and neutrophil activation biomarkers were measured in brain homogenates and plasma. Additional in vitro experiments studied the effects of ApoA1-M on platelet aggregation and platelet-neutrophil interactions. Results- The infusion of ApoA1-M immediately or 4 hours after 120-minute transient middle cerebral artery occlusion significantly reduced the infarct volume compared with saline (P=0.034 and P=0.036, respectively). Compared with tPA alone, co-administration of ApoA1-M and tPA showed similar rates of hemorrhagic transformation. ApoA1-M had no significant inhibition effect on neutrophil activation biomarkers. Platelet activation was slightly decreased in rats treated with ApoA1-M compared with saline. In vitro, the incubation of human and rat platelet-rich plasma with ApoA1-M significantly reduced ADP-induced platelet aggregation (P=0.001 and P=0.02, respectively). Conclusions- ApoA1-Milano significantly decreased the infarct volume through an inhibition of platelet aggregation but did not reduce hemorrhagic transformation and neutrophils activation as expected after previous experimental studies with nascent HDL. Visual Overview- An online visual overview is available for this article.

Treatment of Acute Ischemic Stroke due to Large Vessel Occlusion With COVID-19: Experience From Paris.

BACKGROUND AND PURPOSE: Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking. We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19. METHODS: All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included. Baseline clinical and radiological findings, treatment, and short-term outcomes are reported. RESULTS: We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO. Eight were men, with a median age of 59.5 years. Seven had none or mild symptoms of COVID-19 at stroke onset. Median time from COVID-19 symptoms to stroke onset was 6 days. All patients had brain imaging within 3 hours from symptoms onset. Five patients had multi-territory LVO. Five received intravenous alteplase. All patients had mechanical thrombectomy. Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital. CONCLUSIONS: Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19. Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.

DNA Content in Ischemic Stroke Thrombi Can Help Identify Cardioembolic Strokes Among Strokes of Undetermined Cause.

BACKGROUND AND PURPOSE: Identification of acute ischemic stroke (AIS) cause is crucial for guidance of secondary prevention. Previous studies have yielded inconsistent results regarding possible correlations between AIS cause and thrombus composition, as assessed by semiquantitative histological analysis. Here, we performed a correlation analysis between AIS cause and AIS thrombus cellular composition and content, as assessed using quantitative biochemical assays. METHODS: Homogenates of 250 patients with AIS thrombi were prepared by mechanical grinding. Platelet, red blood cell, and leukocyte content of AIS thrombi were estimated by quantification of GP (glycoprotein) VI, heme, and DNA in thrombus homogenates. AIS cause was defined as cardioembolic, noncardioembolic, or embolic stroke of undetermined source, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment). RESULTS: Cardioembolic thrombi were richer in DNA (35.8 versus 13.8 ng/mg, P<0.001) and poorer in GPVI (0.104 versus 0.117 ng/mg, P=0.045) than noncardioembolic ones. The area under the receiver operating characteristic curve of DNA content to discriminate cardioembolic thrombi from noncardioembolic was 0.72 (95% CI, 0.63-0.81). With a threshold of 44.7 ng DNA/mg thrombus, 47% of thrombi from undetermined cause would be classified as cardioembolic with a specificity of 90%. CONCLUSIONS: Thrombus DNA content may provide an accurate biomarker for identification of cardioembolic thrombi in patients with AIS with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03268668.

Effect of Steady and Dynamic Blood Pressure Parameters During Thrombectomy According to the Collateral Status.

Background and Purpose- Guidelines regarding blood pressure (BP) management during endovascular therapy (EVT) for anterior circulation strokes are questionable since the optimal BP target is a matter of debate. To evaluate the importance of hemodynamic control during EVT, we investigated the impact of dynamic and steady BP parameters during EVT on functional outcome (part 1) and according to the collateral status (CS; part 2). Methods- We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Recanalization). BP was measured noninvasively during EVT and CS assessed on the angiographic run before EVT. We studied dynamic BP parameter using BP variability (coefficient of variation) and steady BP parameter (hypotension time defined as systolic BP <140 mm Hg and mean arterial pressure <90 mm Hg). The primary outcome was favorable outcome defined as a 3-month modified Rankin Scale score between 0 and 2. Results- Among the 381 patients of the ASTER study, 172 patients were included in part 1 and 159 in part 2. Systolic BP, diastolic BP, and mean arterial pressure variability were negatively associated with favorable outcome regardless of CS: per 10-unit increase, adjusted odds ratios were 0.45 (95% CI, 0.20-0.98), 0.37 (95% CI, 0.19-0.72), and 0.35 (95% CI, 0.16-0.76), respectively. According to CS, the hypotension time with periprocedural mean arterial pressure <90 mm Hg was negatively associated with favorable outcome in patients with poor CS (adjusted odds ratio, 0.88 [95% CI, 0.72-1.09]) but not in patients with good CS (adjusted odds ratio, 1.24 [95% CI, 0.91-1.67]; Phet=0.047). Conclusions- The CS did not modify the association between dynamic parameters and functional outcomes, but some findings suggest that the CS modifies the association between steady parameter and functional outcomes. Hypotension time according to the CS was not statistically predictive of poor outcomes but displayed a trend toward worse outcomes for patients with poor CS only.

Diagnostic Performances of the Susceptibility Vessel Sign on MRI for the Prediction of Macroscopic Thrombi Features in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The "white" compared to "Red-Black" visual aspect of the thrombus at withdrawal with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) was related to atypical etiologies like infective endocarditis. The susceptibility vessel sign (SVS) and the two-layered SVS (TL-SVS) could help predict outcome and cardio-embolic etiology of AIS. We aim to evaluate the diagnostic performance of the SVS and TLSVS to predict the visual aspect of the thrombus. MATERIALS AND METHODS: We included patients treated by MT and screened with MRI for the SVS and the TL-SVS for whom thrombus photograph was available. Photographs underwent a double-blind evaluation by neuroradiologists who classified the thrombus as "White" or "Red-Black". Logistic regression assessed the association of Red-Black thrombus and age, sex, baseline National Institutes of Health Stroke Scale, occlusion site, the IVr-tPA administration, SVS and TL-SVS. We calculated the diagnostic performances of the SVS to predict a Red-Black type thrombus. RESULTS: Between May 2017 and July 2018, 139 patients were included in the study. On multivariate analysis, only SVS was an independent predictor for Red-Black thrombus (Odd ratio 8.31, 95%CI2.30 to 32, p value<0.001). Concerning SVS diagnostic performances, the specificity was 0.58 (95%CI0.28 to 0.85), the sensitivity was 0.87 (95%CI0.80 to 0.93), the negative predictive value was 0.30 (95% 0.13 to 0.53), the positive predictive value was 0.96 (95%CI0.90 to 0.99) and accuracy was 0.85 (95%CI0.78 to 0.90). CONCLUSION: The SVS on MRI provides a good prediction accuracy to anticipate the macroscopic visual aspect of the thrombus after MT for AIS.