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Tissue no-reflow despite full recanalization following thrombectomy for anterior circulation stroke with proximal occlusion: A clinical study.

ABSTRACT: Despite early thrombectomy, a sizeable fraction of acute stroke patients with large vessel occlusion have poor outcome. The no-reflow phenomenon, i.e. impaired microvascular reperfusion despite complete recanalization, may contribute to such "futile recanalizations". Although well reported in animal models, no-reflow is still poorly characterized in man. From a large prospective thrombectomy database, we included all patients with intracranial proximal occlusion, complete recanalization (modified thrombolysis in cerebral infarction score 2c-3), and availability of both baseline and 24 h follow-up MRI including arterial spin labeling perfusion mapping. No-reflow was operationally defined as i) hypoperfusion ≥40% relative to contralateral homologous region, assessed with both visual (two independent investigators) and automatic image analysis, and ii) infarction on follow-up MRI. Thirty-three patients were eligible (median age: 70 years, NIHSS: 18, and stroke onset-to-recanalization delay: 208 min). The operational criteria were met in one patient only, consistently with the visual and automatic analyses. This patient recanalized 160 min after stroke onset and had excellent functional outcome. In our cohort of patients with complete and stable recanalization following thrombectomy for intracranial proximal occlusion, severe ipsilateral hypoperfusion on follow-up imaging associated with newly developed infarction was a rare occurrence. Thus, no-reflow may be infrequent in human stroke and may not substantially contribute to futile recanalizations.

SUBMITTER: Ter Schiphorst A

PROVIDER: S-EPMC8370008 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Tissue no-reflow despite full recanalization following thrombectomy for anterior circulation stroke with proximal occlusion: A clinical study.

Ter Schiphorst Adrien A Charron Sylvain S Hassen Wagih Ben WB Provost Corentin C Naggara Olivier O Benzakoun Joseph J Seners Pierre P Turc Guillaume G Baron Jean-Claude JC Oppenheim Catherine C

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20200922 2

Despite early thrombectomy, a sizeable fraction of acute stroke patients with large vessel occlusion have poor outcome. The no-reflow phenomenon, i.e. impaired microvascular reperfusion despite complete recanalization, may contribute to such "futile recanalizations". Although well reported in animal models, no-reflow is still poorly characterized in man. From a large prospective thrombectomy database, we included all patients with intracranial proximal occlusion, complete recanaliz ...[more]

PMID: 32960688

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Project description:ImportanceAchieving complete reperfusion is a key determinant of good outcome in patients treated with mechanical thrombectomy (MT). However, data on treatments geared toward improving reperfusion after incomplete MT are sparse.ObjectiveTo determine whether administration of intra-arterial urokinase is safe and improves reperfusion after failed or incomplete MT.Design, setting, and participantsThis observational cohort study included a consecutive sample of patients treated with second-generation MT from January 1, 2010, through August 4, 2017. Data were collected from the prospective registry of a tertiary care stroke center. Of 1274 patients screened, 69 refused to participate, and 993 met the observational studies inclusion criteria of a large vessel occlusion in the anterior circulation. Data were analyzed from September 1, 2017, through September 20, 2019.InterventionOne hundred patients received intra-arterial urokinase after failed or incomplete MT using manual microcatheter injections.Main outcomes and measuresPrimary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the Prolyse in Acute Cerebral Thromboembolism II criteria. Secondary end points included 90-day mortality and 90-day functional independence (defined as modified Rankin Scale score of ≤2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale.ResultsAfter exclusion of patients with posterior circulation strokes and those treated with intra-arterial thrombolytics only, 993 patients were included in the final analyses (median age, 74.6 [interquartile range, 62.6-82.2] years; 505 [50.9%] women). Additional intra-arterial urokinase was administered in 100 patients (10.1%). The most common reason for administering intra-arterial urokinase was incomplete reperfusion (TICI<3) after MT (53 [53.0%]). After adjusting for baseline characteristics underlying case selection, intra-arterial urokinase was not associated with an increased risk of sICH (adjusted odds ratio [aOR], 0.81; 95% CI, 0.31-2.13) or 90-day mortality (aOR, 0.78; 95% CI, 0.43-1.40). Among 53 cases of partial or near-complete reperfusion and treated with intra-arterial urokinase, 32 (60.4%) had early reperfusion improvement, and 18 of 53 (34.0%) had an improvement in TICI grade. Correspondingly, patients treated with intra-arterial urokinase had higher rates of functional independence after adjusting for the selection bias favoring a priori poor TICI grades in the intra-arterial urokinase group (aOR, 1.93; 95% CI, 1.11-3.37).Conclusions and relevanceIn selected patients, adjunctive treatment with intra-arterial urokinase during or after MT was safe and improved angiographic reperfusion. Systemic evaluation of this approach in a multicenter prospective registry or a randomized clinical trial seems warranted.

Project description:BackgroundA large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke.AimTo investigate the association of reperfusion with development of early CED after stroke thrombectomy.MethodsFrom the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ⩾ 2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ⩾1/3 of the hemisphere on imaging scans at 24 h. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 h, were explored.ResultsIn total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p < 0.05, crude risk ratio (RR) 0.42 (95% confidence interval (CI): 0.37-0.49), and adjusted RR 0.50 (95% CI: 0.44-0.57). Analysis of effect modification indicated that severe neurological deficits weakened the association between reperfusion and lower risk of CED. The RR reduction was less favorable in patients with severe neurological deficits, defined as NIHSS score 15 or more at baseline and at 24 h, used as an indicator for larger infarction.ConclusionIn patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy.

Project description:BackgroundEndovascular thrombectomy (EVT) has been proven effective in anterior circulation stroke due to large vessel occlusion (LVO). However, translation from randomized clinical trials (RCTs) with highly selected patients to real-world requires confirmation, particularly to identify associations outside of strict selection criteria.AimsThis study aims to compare functional outcomes after EVT in real-world with those reported in RCTs, and to identify associations with functional outcome after EVT outside RCT-criteria.MethodsThis study analyzed longitudinal German real-world data from the Stroke Research Consortium in Northern Bavaria (STAMINA) cohort from January, 2015 to June, 2019. We conducted a trial emulation, comparing patients with anterior circulation stroke and LVO meeting selection criteria for RCTs investigating EVT (1) predominantly within 6 hours with those from HERMES meta-analysis, and (2) within 6-24 hours with those from AURORA meta-analysis. We (3) analyzed treatment effects of EVT and association with functional outcome in patients treated outside RCT criteria.ResultsOf 598 patients, 281 (47.0%) met RCT-criteria for treatment within 6 hours (hereinafter STAMINA-HERMES), 74 (12.4%) met RCT-criteria for treatment within 6-24 hours (STAMINA-AURORA), and 277 (46.3%) patients received EVT outside RCT-criteria. We observed no difference in rates of functional independence or mortality, comparing STAMINA-HERMES with HERMES meta-analysis (mRS 0-1: n=120/281 [43%] vs. 291/633 [46%], p=0.36; mortality: n=34/281 [12%] vs. 97/633 [15%], p=0.20), and STAMINA-AURORA with AURORA meta-analysis (mRS 0-1: n=26/74 [35%] vs. 122/266 [46%], p=0.10, mortality: n=10/74 [14%] vs. 45/266 [17%], p=0.48). Patients treated outside RCT-criteria had worse outcome (mRS 0-1: n=38/277 [14%], mortality: n=90/277 [32%], both p<0.001); possibly driven by pre-existing functional dependence (n=172/277 [62%]). Compared to matched controls, EVT outside of RCT-criteria was associated with lower mortality (absolute treatment effect: -14%, 95% Confidence Interval [CI] -23 to -5, p<0.01), but not with recovery to functional independence or premorbid functional status (treatment effect: 4%, CI -4 to 11, p=0.34), which was associated with lower NIHSS (Odds ratio [OR] 0.86, CI 0.80-0.92, p<0.001) and age (OR 0.95, CI 0.93-0.98, p=0.002).ConclusionsTranslation of EVT outcomes reported in RCTs into real-world is possible, however, almost half of patients did not meet trial criteria. Identification of patients who functionally benefit from frequently performed EVT outside RCT-criteria requires further investigation.Trial registrationClinicaltrials.gov, NCT04357899.

Project description:BackgroundEndovascular thrombectomy (EVT) has emerged as the established standard of care for the treatment of anterior circulation large-vessel occlusion (LVO). However, its benefits remain unclear in specific patient populations. Herein, we present an updated systematic review and meta-analysis aimed at thoroughly assessing the effectiveness and safety of combining EVT with medical treatment (MT) compared with MT alone.MethodsThis systematic review was performed in accordance with the PRISMA guideline. The MEDLINE, Embase, and Cochrane databases were systematically searched to identify relevant articles published until December 30, 2023. The inclusion criteria restricted articles to randomized clinical trials (RCTs). We pooled odds ratios (OR) and their respective 95% confidence intervals (CIs).ResultsFifteen RCTs involving 3897 patients were included in the study. EVT plus MT was associated with a significant reduction in disability at 90 days (OR = 1.91, [1.61-2.26]), improved functional independence (modified Rankin Scale [mRS] 0-2) (OR = 2.19 [1.81-2.64]), excellent functional outcomes (mRS 0-1) (OR = 2.37, [1.45-3.87]), improved independent ambulation (mRS 0-3) (OR = 2.17, [1.75-2.69]), and higher rates of partial/complete recanalization (OR = 2.18, [1.66-2.87] compared with EVT. Efficacy outcomes for both large and small infarct cores were statistically favorable following EVT. Safety outcomes showed comparable rates, except for intracerebral and subarachnoid hemorrhage, which favored MT alone.ConclusionThis meta-analysis supports the use of EVT plus MT as the standard of care for acute ischemic stroke patients with LVO of any infarct core size, as it offers substantial improvements in functional outcomes and recanalization. Safety considerations, particularly the risk of hemorrhage, warrant careful patient selection. These findings provide valuable insights for optimizing stroke management protocols and enhancing patient outcomes.

Dataset Information

Tissue no-reflow despite full recanalization following thrombectomy for anterior circulation stroke with proximal occlusion: A clinical study.

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Tissue <i>no-reflow</i> despite full recanalization following thrombectomy for anterior circulation stroke with proximal occlusion: A clinical study.

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