Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Diagnostic Performance of Carotid Ring Sign on CT-Angiography in Internal Carotid True Occlusion.

BACKGROUND: To differentiate between pseudo occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for patients with acute ischemic stroke. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography. In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO. METHODS: One thousand four hundred and twenty patients with anterior circulation stroke receiving endovascular therapy were consecutively recruited through a hospital- and web-based registry. Two hundred patients with nonvisualization of the proximal ICA were included in the analysis after a retrospective screening. Diagnosis of PO or TO of the cervical segment of ICA was made based on digital subtraction angiography. Diagnostic performances of carotid ring sign on arterial-phasic CTA and delayed contrast filling on multiphasic computed tomography angiography were evaluated and compared. RESULTS: One-hundred twelve patients had ICA PO and 88 had TO. Carotid ring sign was more common in patients with TO (70.5% versus 6.3%; P<0.001), whereas delayed contrast filling was more common in PO (94.9% versus 7.7%; P<0.001). The sensitivity and specificity of carotid ring sign in diagnosing carotid TO were 0.70 and 0.94, respectively, whereas sensitivity and specificity of delayed contrast filling was 0.95 and 0.92 in judging carotid PO. CONCLUSIONS: Carotid ring sign is a potent imaging marker in diagnosing ICA TO. Carotid ring sign could be complementary to delayed contrast filling sign in differentiating TO from PO, in particular in centers with only single-phasic CTA.

CTP-Defined Large Core Is a Better Predictor of Poor Outcome for Endovascular Treatment Than ASPECTS-Defined Large Core.

BACKGROUND: Recent trials confirmed the effectiveness of endovascular therapy in patients with large ischemic cores. Yet the optimal neuroimaging modalities to define large core remains unclear. We tried to address this question by comparing the functional outcomes in patients receiving thrombectomy selected by either noncontrast computed tomography Alberta Stroke Program Early Computed Tomography Score (ASPECTS) or computed tomography perfusion (CTP). METHODS: This study retrospectively selected patients enrolled in the International Stroke Perfusion Registry between August 2011 and April 2022. Patients with acute stroke with large vessel occlusion in anterior circulation treated with endovascular therapy were included. All received both CTP and noncontrast computed tomography. The primary outcome was defined as poor functional outcome represented by a modified Rankin Scale score of 5 to 6 at 3 months. Large cores were defined in terms of either (1) noncontrast computed tomography ASPECTS ≤5 or (2) core volume ≥70 mL on CTP. RESULTS: A total of 1115 patients were included in the analysis, of which 90 patients had ASPECTS ≤5 (8.1%) and 97 patients CTP core ≥70 mL (8.7%). A fair agreement between ASPECTS and CTP with a κ value of 0.31 (0.21-0.40) was found. Compared with patients with neither CTP nor ASPECTS large cores, those with only ASPECTS-defined large cores (ie, ASPECTS ≤5; n=56) did not have a higher adjusted odds of poor outcome (29%; odds ratio, 1.84 [0.91-3.73]; P=0.089). However, patients with CTP large core but not ASPECTS-defined large core (n=63) had a higher adjusted odds of poor outcome (60%; odds ratio, 3.91 [2.01-7.60]; P<0.001). In time-stratified subgroup analysis (>6 versus ≤6 hours), ASPECTS showed no discriminative difference between ≤5 and >5 in poor outcome for patients receiving endovascular therapy within 6 hours. CONCLUSIONS: CTP core ≥70 mL-defined large cores are more predictive of poor outcome than ASPECTS ≤5-defined core in endovascular therapy patients, particularly within 6 hours after stroke onset.

Effects of admission hyperglycemia and intravenous thrombolysis allocation in acute basilar artery occlusion after endovascular treatment: Analysis of the ATTENTION registry.

This study was to investigate the admission hyperglycemia and modified effect of intravenous thrombolysis (IVT) on clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT). We prospectively recruited acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Hyperglycemia on admission was defined as glucose ≥7.8 â€‹mmol/L. We performed multivariable logistic regression analysis to evaluate the correlation of hyperglycemia on admission with the primary outcome defined as a modified Rankin scale (mRS) score of <4 â€‹at 90 days, and the secondary outcomes defined as successful recanalization, mRS 0-1 and 0-2 â€‹at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. There were 1195 patients with acute BAO treated with EVT of whom 519 had hyperglycemia on admission. Hyperglycemia on admission was inversely associated with favorable neurological outcomes (mRS 0-3: adjusted odd ratio [aOR] 0.69, 95 â€‹% confidence intervals [CI] 0.54-0.89, P â€‹= â€‹0.004; mRS 0-1: aOR 0.67, 95 â€‹% CI 0.50-0.90, P â€‹= â€‹0.008; mRS 0-2: aOR 0.73, 95 â€‹% CI 0.56-0.95; P â€‹= â€‹0.02). Hyperglycemia on admission was not correlated to sICH nor successful recanalization. In the subgroup of BAO patients treated with direct EVT, those with hyperglycemia on admission had a higher mortality rate, and overall worse clinical outcomes at 90 days than patients without hyperglycemia. A significant interaction was observed between IVT and hyperglycemia on admission (Pinteraction â€‹= â€‹0.017). In patients with acute BAO treated with EVT, hyperglycemia on admission was associated with worse functional outcomes at 90 days but was not correlated with sICH nor successful recanalization. The effect of admission hyperglycemia appears to be modified by IVT allocation. Unique identifier: ChiCTR2000041117.

Predictive factors of poor outcome and mortality among anterior ischaemic stroke patients despite successful recanalisation in China: a secondary analysis of the CAPTURE trial.

OBJECTIVES: This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation. SETTING AND PARTICIPANTS: This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18-80 years with LVO in anterior circulation. INTERVENTIONS: Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher's exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach. RESULTS: Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass. CONCLUSIONS: Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy. TRIAL REGISTRATION NUMBER: NCT04995757.

A nomogram predicts early neurological deterioration after mechanical thrombectomy in patients with ischemic stroke.

Introduction: Early neurological deterioration (END) is common in acute ischemic stroke and is directly associated with poor outcome after stroke. Our aim is to develop and validate a nomogram to predict the risk of END after mechanical thrombectomy (MT) in acute ischemic stroke patients with anterior circulation large-vessel occlusion. Methods: We conducted a real-world, multi-center study in patients with stroke treated with mechanical thrombectomy. END was defined as a worsening by 2 or more NIHSS points within 72-hour after stroke onset compared to admission. Multivariable logistic regression was used to determine the independent predictors of END, and the discrimination of the scale was assessed using the C-index. Calibration curves were constructed to evaluate the calibration of the nomogram, and decision curves were used to describe the benefits of using the nomogram. Results: A total of 1007 patients were included in our study. Multivariate logistic regression analysis found age, admission systolic blood pressure, initial NIHSS scores, history of hyperlipemia, and location of occlusion were independent predictors of END. We developed a nomogram that included these 6 factors, and it revealed a prognostic accuracy with a C-index of 0.678 in the derivation group and 0.650 in the validation group. The calibration curves showed that the nomogram provided a good fit to the data, and the decision curves demonstrated a large net benefit. Discussion: Our study established and validated a nomogram to stratify the risk of END before mechanical embolectomy and identify high-risk patients, who should be more cautious when making clinical decisions.

Endovascular Treatment for Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of acute ischemic stroke worldwide. Patients with acute large vessel occlusion due to underlying ICAD (ICAD-LVO) often do not achieve successful recanalization when undergoing mechanical thrombectomy (MT) alone, requiring rescue treatment, including intra-arterial thrombolysis, balloon angioplasty, and stenting. Therefore, early detection of ICAD-LVO before the procedure is important to enable physicians to select the optimal treatment strategy for ICAD-LVO to improve clinical outcomes. Early diagnosis of ICAD-LVO is challenging in the absence of consensus diagnostic criteria on noninvasive imaging and early digital subtraction angiography. In this review, we summarize the clinical and diagnostic criteria, prediction of ICAD-LVO prior to the procedure, and EVT strategy of ICAD-LVO and provide recommendations according to the current literature.

Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials.

BACKGROUND: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. METHODS: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986. FINDINGS: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly. INTERPRETATION: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment. FUNDING: Stryker and Amsterdam University Medical Centers, University of Amsterdam.

Impact of anesthesia modalities on functional outcome of mechanical thrombectomy in patients with acute ischemic stroke: a subgroup analysis of DIRECT-MT trial.

BACKGROUND: This subgroup analysis of Direct Intraarterial Thrombectomy in Order to Revascularize Acute Ischemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals Multicenter Randomized Clinical Trial (DIRECT-MT) aimed to investigate the influence of anesthesia modalities on the outcomes of endovascular treatment. METHODS: Patients were divided into two groups by receiving general anesthesia (GA) or non-general anesthesia (non-GA). The primary outcome was assessed by the between-group difference in the distribution of the modified Rankin Scale (mRS) at 90 days, estimated using the adjusted common odds ratio (acOR) by multivariable ordinal regression. Differences in workflow efficiency, procedural complication, and safety outcomes were analyzed. RESULTS: Totally 636 patients were enrolled (207 for GA and 429 for non-GA groups). There was no significant shift in the mRS distribution at 90 days between the two groups (acOR, 1.093). The median time from randomization to reperfusion was significantly longer in GA group (116 vs. 93 min, P < 0.0001). Patients in non-GA group were associated with a significantly lower NIHSS score at early stages (24 h, 11 vs 15; 5-7 days or discharge, 6.5 vs 10). The rate of severe manipulation-related complication did not differ significantly between GA and non-GA groups (0.97% vs 3.26%; P = 0.08). There are no differences in the rate of mortality and intracranial hemorrhage. CONCLUSIONS: In the subgroup analysis of DIRECT-MT, we found no significant difference in the functional outcome at 90 days between general anesthesia and non-general anesthesia, despite the workflow time being significantly delayed for patients with general anesthesia. Clinical trail registration clinicaltrials.gov Identifier: NCT03469206.

Thrombus migration in patients with acute ischaemic stroke undergoing endovascular thrombectomy.

OBJECTIVE: The impact of thrombus migration (TM) prior to endovascular thrombectomy (EVT) on clinical outcomes and revascularisation rates remains unknown. We aimed to examine whether preinterventional TM modifies the treatment effects of direct EVT versus bridging EVT in acute large vessel occlusion patients. METHODS: All patients undergoing catheter angiography in the Direct Intra-arterial thrombectomy in order to Revascularise acute ischaemic stroke patients with large vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicentre randomised clinical Trial were included. TM was determined by radiologists unaware of the study by analysing discrepancies between computed tomographic angiography at baseline and first-run digital subtraction angiography before EVT. The primary outcome was the score on the modified Rankin scale (mRS) assessed at 90 days. RESULTS: Of 627 included patients, the TM rate was 11.3% (71/627). In the multivariable logistic regression model, baseline National Institutes of Health Stroke Scale score (adjusted OR 0.956, 95% CI 0.916 to 0.999; p=0.043) and intravenous thrombolysis (adjusted OR 2.614, 95% CI 1.514 to 4.514; p<0.001) were independently associated with TM. The patients with TM were less likely to be completely recanalised than those without TM (21.27% vs 36.23%, p=0.040). The interaction of TM and the EVT treatment effect did not significantly affect mRS shift analysis (p=0.687) or mRS scores of 0 to 1 (p=0.436). CONCLUSION: Preinterventional TM does not modify the treatment effects of direct versus bridging EVT on functional outcomes in patients with acute ischaemic stroke with anterior large vessel occlusion. TM leads to a lower complete recanalisation rate.

Comparing a novel Catfish flow restoration device and the Solitaire stent retriever for thrombectomy revascularisation in emergent largevessel occlusion stroke: a prospective randomised controlled study.

BACKGROUND: The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion (ELVO) stroke. The current trial aimed to assess whether the Catfish stent retriever is non-inferior to the Solitaire stent retriever in terms of outcomes in ELVO stroke. METHODS: This was a randomised, prospective, parallel-group, multicentre, open-label, non-inferiority study conducted at 18 sites in China. The primary outcome was the proportion of cases with successful recanalisation (modified thrombolysis in cerebral infarction score of 2b or 3) following the procedure. Secondary efficacy outcomes included the National Institutes of Health Stroke Scale scores at 24 hours and 7 days or discharge if earlier, time from artery puncture to successful recanalisation and good clinical outcome (modified Rankin scale score ≤2) at 90 days. Safety outcomes included symptomatic intracranial haemorrhage, all cause-death and severe adverse events at 90 days. RESULTS: Between 3 March 2019 and 5 June 2021, 118 and 120 patients were randomly allocated to the Catfish and Solitaire groups, respectively. The primary endpoint after all endovascular procedures was non-inferior in the Catfish group (88.5%, 100/113) than in the Solitaire group (87.7%, 100/114), with a rate difference (RD) of 0.78% (95% CI -7.64 to -9.20; p=0.001). Sensitivity analysis only considering the per-protocol set also yielded similar results, with an RD of 0.83% (95% CI -7.03 to -8.70; p<0.001). Additionally, the proportions of cases with good clinical outcomes (47.8% vs 50.0%, p=0.739) and all-cause death rates (17.7% vs 18.8%, p=0.700) were similar in both groups at 90 days. CONCLUSIONS: The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke. TRIAL REGISTRATION NUMBER: NCT03820882.

Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

Association of Perfusion Lesion Variables With Functional Outcome in Patients With Mild Stroke and Large Vessel Occlusion Managed Medically.

BACKGROUND AND OBJECTIVES: The best management of patients with mild stroke and large vessel occlusion (LVO) remains unclear. This study aimed to identify perfusion imaging predictors of poor functional outcome in such patients. METHODS: This cohort study retrospectively selected patients enrolled in the International Stroke Perfusion Imaging Registry between August 2011 and April 2022. The registry enrolled patients with acute ischemic stroke and with baseline CT perfusion scanned within 24 hours of stroke onset. This study identified patients with mild symptoms, defined by an NIH Stroke Scale score of ≤5. Patients with LVO of anterior circulation were selected. This study further selected patients who received medical management and excluded patients who received endovascular treatment. The primary outcome was poor functional outcome defined as a modified Rankin Scale of 3-6 at 3 months. Perfusion lesion was defined by delay time > 3 seconds on CTP. Regression analyses were used to identify clinical and imaging variables that predicted poor functional outcome. RESULTS: A total of 139 patients with mild stroke were included, of whom 27 (19%) had poor functional outcome. Patients with poor outcome, compared with those with good outcome, had much larger perfusion lesion volume (median 80 mL vs 41 mL, p < 0.001). Perfusion lesion was a significant predictor of poor outcome in either univariable regression (crude OR = 1.02, 95% CI = [1.01-1.03]) or multivariable regression model (adjusted OR = 1.01, 95% CI = [1.01-1.02]), adjusting for occlusion site, good collaterals, baseline stroke severity, age, IV thrombolysis (IVT), and onset to scan time. A perfusion lesion of 65 mL was the optimal cutpoint to identify poor functional outcome (sensitivity = 59%, specificity = 77%). Patients with perfusion lesion ≥65 mL, compared with patients with perfusion lesion <65 mL, showed a much higher rate of poor functional outcome (38% vs 11%, p < 0.001). Of the 139 patients in this study, 95 received IVT. Patients treated with or without IVT did not influence their outcomes (crude OR = 0.74, 95% CI = [0.31-1.78]). DISCUSSION: A perfusion lesion of ≥65 mL predicted poor functional outcome in mild stroke patients with LVO.

Impact of leukoaraiosis in patients with acute ischemic stroke treated with thrombectomy: a post hoc analysis of the DIRECT-MT trial.

BACKGROUND: The influence of leukoaraiosis in patients with acute ischemic stroke (AIS) given intra-arterial treatment (IAT) with or without preceding intravenous thrombolysis (IVT) remains unknown. OBJECTIVE: To assess the clinical and radiological outcomes of IAT in patients with or without leukoaraiosis. METHODS: Patients of the direct mechanical thrombectomy trial (DIRECT-MT) whose leukoaraiosis grade could be assessed were included. DIRECT-MT was a randomized clinical trial performed in China to assess the effect of direct IAT compared with intravenous thrombolysis plus IAT. We employed the Age-Related White Matter Changes Scale for grading leukoaraiosis (ARWMC, 0 indicates no leukoaraiosis, 1-2 indicates mild-to-moderate leukoaraiosis, and 3 indicates severe leukoaraiosis) based on brain CT. The primary outcome was the score on the modified Rankin Scale (mRS) assessed at 90 days. RESULTS: There were 656 patients in the trial, 649 patients who were included, with 432 patients without leukoaraiosis, and 217 (33.4%) patients with leukoaraiosis divided into mild-to-moderate (n=139) and severe groups (n=78). Leukoaraiosis was a predictor of a worse mRS score (adjusted OR (aOR)=0.7 (95% CI 0.5 to 0.8)) and higher mortality (aOR=1.4 (1.1 to 1.9)), but it was not associated with symptomatic intracranial hemorrhage (sICH) (aOR=0.9 (0.5 to 1.5)). IVT preceding IAT did not increase sICH risk for patients with no (aOR=1.4 (0.6 to 3.4)), mild-to-moderate (aOR=1.5 (0.3 to 7.8)), or severe (aOR=1.5 (0.1 to 21.3)) leukoaraiosis. CONCLUSION: Patients with leukoaraiosis with AIS due to large vessel occlusion are at increased risk of a poor functional outcome after IAT but demonstrate similar sICH rates, and IVT preceding IAT does not increase the risk of sICH in Chinese patients with leukoaraiosis.

Thrombosis origin identification of cardioembolism and large artery atherosclerosis by distinct metabolites.

BACKGROUND: The diagnosis of cerebral thrombosis origin is challenging and remains unclear. This study aims to identify thrombosis due to cardioembolism (CE) and large artery atherosclerosis (LAA) from a new perspective of distinct metabolites. METHODS: Distinct metabolites between 26 CE and 22 LAA origin thrombi, which were extracted after successful mechanical thrombectomy in patients with acute ischemic stroke in the anterior circulation, were analyzed with a ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) system. Enriched metabolic pathways related to the metabolites were identified. Least absolute shrinkage selection operator regression analyses and a filtering method were used to select potential predictors. Furthermore, four machine learning classifiers, including decision tree, logistic regression, random forest (RF), and k means unsupervised classification model, were used to evaluate the predictive ability of the selected metabolites. RESULTS: UPLC-QTOF-MS analysis revealed that levels of 88 and 55 metabolites were elevated in LAA and CE thrombi, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference between the pathways enriched in the two types of thrombi. Six metabolites (diglyceride (DG, 18:3/24:0), DG (22:0/24:0), phytosphingosine, galabiosylceramide (18:1/24:1), triglyceride (15:0/16:1/o-18:0), and glucosylceramide (18:1/24:0)) were finally selected to build a predictive model. The predictive RF model was confirmed to be the best, with a satisfactory stability and prediction capacity (area under the curve=0.889). CONCLUSIONS: Six metabolites as potential predictors for distinguishing between cerebral thrombi of CE and LAA origin were identified. The results are useful for understanding the pathogenesis and for secondary stroke prevention.

Predictors of futile recanalization in basilar artery occlusion patients undergoing endovascular treatment: a post hoc analysis of the ATTENTION trial.

Background: Few studies have focused on factors associated with futile recanalization in patients with an acute basilar artery occlusion (BAO) that was treated with modern endovascular therapy (EVT). The aim of this study was to explore the factors associated with futile recanalization in patients with an acute BAO presented within 12 h. Methods: This is a post-hoc analysis of the ATTENTION trial (The Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion, ClinicalTrials.gov, number NCT04751708). Demographics, clinical characteristics, acute stroke workflow interval times, and imaging characteristics were compared between the futile recanalization and favorable recanalization groups. The favorable outcome was defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, successful reperfusion was defined as thrombolysis in cerebral infarction (TICI) 2b and 3 on the final angiogram, and futile recanalization was defined as failure to achieve a favorable outcome despite successful reperfusion. A multivariate analysis was performed to identify the predictors of futile recanalization. Results: In total, 185 patients were included in the final analysis: 89 (48.1%) patients had futile recanalization and 96 (51.9%) patients had favorable recanalization. In the multivariable logistic regression analysis, older age (OR 1.04, 95% CI 1.01 to 1.08, p = 0.01) and diabetes mellitus (OR 3.35, 95% CI 1.40 to 8.01, p = 0.007) were independent predictors of futile recanalization. Conclusion: Futile recanalization occurred in nearly half of patients with acute BAO following endovascular treatment. Old age and diabetes mellitus were identified as independent predictors of futile recanalization after endovascular therapy for acute BAO.

Application of Balloon AngioplaSty with the dIstal protection of Stent Retriever (BASIS) technique for acute intracranial artery atherosclerosis-related occlusion.

Background: Endovascular therapy (EVT) is complex in the context of intracranial atherosclerosis (ICAS)-related large vessel occlusion (LVO) and the re-occlusion rates are high due to residual stenosis, the procedure time is long and the optimal EVT technique is unclear. The Balloon AngioplaSty with the dIstal protection of Stent Retriever (BASIS) technique is a novel thrombectomy technique that allows emergent balloon angioplasty to be performed via the wire of the retrieval stent. Our study presents our initial experience with the BASIS technique in ICAS-related LVO and assesses its feasibility. Method: In patients with ICAS-related LVO treated with BASIS, clinical and angiographic data were retrospectively analyzed. Angiographic data included first-pass reperfusion (PFR), the rate of residual stenosis, distal emboli, and re-occlusion post-procedure. The Extended Thrombolysis in Cerebral Infarction (eTICI) scale was used to assess reperfusion extent, and an eTICI score ≥2b was defined as successful perfusion. Clinical outcome was evaluated at 3 months (modified Rankin score [mRS]), and an mRS ≤ 2 was defined as a good clinical outcome. Results: A total of seven patients with ICAS-related LVO were included, and the median age of the patients was 76 years. All patients achieved eTICI 3 reperfusion and FPR. The residual stenosis rate ranged from 5 to 10%. None of the patients had re-occlusion post-procedure. The median puncture-to-reperfusion time was 51 min. None of the patients had a symptomatic cerebral hemorrhage, re-occlusion, distal embolism, and dissection. Good clinical outcomes were observed in four patients (4/7, 57.1%), and 1 patient (1/7, 14.3%) died. Conclusion: The BASIS technique is feasible and safe for treating acute ICAS-related LVO.

Mild and moderate cardioembolic stroke patients may benefit more from direct mechanical thrombectomy than bridging therapy: A subgroup analysis of a randomized clinical trial (DIRECT-MT).

Background: The benefit of intravenous alteplase before endovascular thrombectomy is unclear in patients with acute cardioembolic stroke. Methods: We collected cardioembolic (CE) stroke patient data from the multicentre randomized clinical trial of Direct Intra-arterial Thrombectomy to Revascularize Acute Ischaemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals (DIRECT-MT). The primary outcome was the 90-day modified Rankin Scale (mRS) score. Five subgroups of cardioembolic stroke patients were analyzed. A multivariable ordinal logistic regression analysis analyzed the difference in the primary outcome between the direct mechanical thrombectomy (MT) and bridging therapy groups. An interaction term was entered into the model to test for subgroup interaction. The DIRECT-MT trial is registered with clinicaltrials.gov Identifier: NCT03469206. Results: A total of 290 CE stroke patients from the DIRECT-MT trial were enrolled in this study: 146 patients in the direct MT group and 144 patients in the bridging therapy group. No difference between the two treatment groups in the primary outcome was found (adjusted common odds ratio, 1.218; 95% confidence interval, 0.806 to 1.841; P = 0.34). In the subgroup analysis, CE stroke patients with an NIHSS ≤ 15 in the direct MT group were associated with better outcomes (47 vs. 53, acOR, 3.14 [1.497, 6.585]) and lower mortality (47 vs. 53, aOR, 0.16 [0.026, 0.986]) than those in the bridging therapy group, while there were no significant differences between the two treatment groups in the outcome and mortality of CE stroke patients with an NIHSS >15. Conclusion: Mild and moderate cardioembolic stroke patients may benefit more from direct mechanical thrombectomy than bridging therapy. This need to be confirmed by further prospective studies in a larger number of patients.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Influence of pre-stroke dependency on safety and efficacy of endovascular therapy: A systematic review and meta-analysis.

Background and purpose: In the landmark trials studying endovascular thrombectomy (EVT), pre-stroke dependent (PSD) patients were generally excluded. This systematic review and meta-analysis aimed to compare the safety and efficacy of EVT between PSD and pre-stroke independent (PSI) patients. Methods: We searched CENTRAL, Embase, and Ovid MEDLINE up to 11 November 2021 for studies assessing PSD and PSI patients, which were separately defined as pre-stroke mRS score >2 or >1, and ≤2 or ≤1 accordingly. Two authors extracted data and assessed the risk of bias. A meta-analysis was carried out using the random-effects model. Adjusted OR and 95% CI were used to estimate adjusted pool effects. The main outcomes included favorable outcomes, successful recanalization, symptomatic intracranial hemorrhage, and 90-day mortality. Results: A total of 8,004 records met the initial search strategy, and ten studies were included in the final decision. Compared with PSImRS≤2, PSDmRS>2 had a lower favorable outcome (OR 0.51; 95% CI, 0.33-0.79) and higher 90-day mortality (OR 3.32; 95% CI, 2.77-3.98). No significant difference was found in successful recanalization and sICH. After adjustment, only 90-day mortality (aOR 1.99; 95% CI, 1.58-2.49) remained significantly higher in PSDmRS>2. Compared with PSImRS≤1, PSDmRS>1 had lower 90-day mortality (OR, 3.10; 95% CI, 1.84-5.24). No significant difference was found regarding the favorable outcome, successful recanalization, and sICH. After adjustment, no significant difference was found in a favorable outcome, but a higher rate of 90-day mortality (aOR, 2.13; 95% CI, 1.66-2.72) remained in PSDmRS>1. Conclusions: PSD does not innately influence the EVT outcomes regarding sICH and favorable outcomes but may increase the risk of 90-day mortality. Until further evidence is available, it is reasonable to suggest EVT for patients with PSD.