Acute Endovascular Treatment of Patients With Ischemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection.
ABSTRACT: Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO. Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24-48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO. Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (resp. mean -5 vs. mean -1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (-4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00). Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD.
Project description:BACKGROUND:Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT. METHODS:MR CLEAN-MED is a multicenter phase III trial with a prospective, 2?×?3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300?mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS ??2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6?h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90?days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24?h and at 5-7?days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality. DISCUSSION:Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA. TRIAL REGISTRATION:ISRCT, ISRCTN76741621 . Dec 6, 2017.
Project description:Background and Purpose: Endovascular treatment (EVT) for acute vertebrobasilar intracranial atherosclerosis-related large vessel occlusion (ICAS-LVO) and its outcomes are not well known. We aimed to evaluate endovascular and clinical outcomes of vertebrobasilar ICAS-LVO patients who underwent EVT. Methods: Consecutive acute stroke patients who underwent EVT for vertebrobasilar LVO were retrospectively reviewed. Patients were assigned to the ICAS (+) or the ICAS (-) group based on angiographical findings. Procedural details and clinical outcomes were compared between the ICAS (+) and ICAS (-) groups. Results: This study included 77 patients with acute vertebrobasilar LVO who underwent EVT. Among the study subjects, 24 (31.2%) had an ICAS-LVO. Recanalization was achieved in 19 patients in the ICAS (+) group (79.2%), which was comparable with the ICAS (-) group (84.9%; p = 0.529). However, recanalization using conventional endovascular modalities (stent retriever thrombectomy, contact aspiration thrombectomy, or intra-arterial urokinase infusion) was less successful in the ICAS (+) group (36.8%) than the ICAS (-) group (100.0%; p < 0.001). All the remaining patients in the ICAS (+) group required specific rescue treatments appropriate for ICAS, including balloon angioplasty, stenting, or intra-arterial glycoprotein IIb/IIIa inhibitor infusion to obtain a successful recanalization. Procedural time was not significantly longer in the ICAS (+) group. The rates of favorable outcomes (37.5% vs. 41.5%; p = 0.740), death, and symptomatic intracerebral hemorrhage were not significantly different between the groups. Conclusion: ICAS-LVO was common in patients who underwent EVT for acute vertebrobasilar LVO. Although conventional modalities were often ineffective for vertebrobasilar ICAS-LVO, a comparable recanalization rate could be obtained with ICAS-specific modalities. Recanalization rate and procedural time were comparable, and clinical outcomes did not differ between patients with or without ICAS-LVO.
Project description:Background and purpose: Tirofiban and oral antiplatelet drugs can be used to inhibit reocclusion and restore microvascular reperfusion during endovascular treatment (EVT). This study compared recanalization rates, symptomatic intracranial hemorrhage (SICH), 90 day mortality, and functional outcomes between periprocedural tirofiban and antiplatelet therapy in patients with acute intracranial atherosclerosis-related vertebrobasilar artery occlusion. Methods: A total of 105 consecutive patients with acute intracranial atherosclerosis-related vertebrobasilar artery occlusion who underwent EVT + tirofiban + oral antiplatelet or EVT + oral antiplatelet therapy at the Beijing Tiantan Hospital between January 2012 and July 2018 were included. Baseline characteristics, procedural parameters, and functional outcomes were assessed. Results: Among the 105 patients, 74 underwent EVT + tirofiban + oral antiplatelet therapy, while 31 underwent EVT + oral antiplatelet drug therapy. EVT + tirofiban + oral antiplatelet therapy resulted in higher recanalization rates compared to EVT + oral antiplatelet drug therapy (93.24% vs. 77.42%; p = 0.038), whereas the risk for SICH, 90 day mortality, and functional independence outcomes did not differ between the groups. Logistic regression analysis revealed that EVT + tirofiban + oral antiplatelet therapy had an increased probability of higher recanalization rates (OR 0.18 [95% confidence interval (CI) 1.24-24.39]; p = 0.025). There were no differences in SICH (OR 0.00 [95% CI 0.00-Inf]; p = 0.998), 90 day mortality (OR 1.19 [95% CI 0.17-4.05]; p = 0.826), or functional independence (modified Rankin score 0 to ? 2) (OR 1.43 [95% CI 0.23-2.17]; p = 0.538) between the groups. Conclusions: Ninety day functional outcomes of EVT + tirofiban + oral antiplatelet therapy were not superior to those of EVT + oral antiplatelet drug therapy; however, the recanalization rate was higher and the risks for SICH and 90 day mortality were lower.
Project description:INTRODUCTION:The efficacy of both intravenous treatment (IVT) and endovascular treatment (EVT) for patients with acute ischaemic stroke strongly declines over time. Only a subset of patients with ischaemic stroke caused by an intracranial large vessel occlusion (LVO) in the anterior circulation can benefit from EVT. Several prehospital stroke scales were developed to identify patients that are likely to have an LVO, which could allow for direct transportation of EVT eligible patients to an endovascular-capable centre without delaying IVT for the other patients. We aim to prospectively validate these prehospital stroke scales simultaneously to assess their accuracy in predicting LVO in the prehospital setting. METHODS AND ANALYSIS:Prehospital triage of patients with suspected stroke symptoms (PRESTO) is a prospective multicentre observational cohort study in the southwest of the Netherlands including adult patients with suspected stroke in the ambulance. The paramedic will assess a combination of items from five prehospital stroke scales, without changing the normal workflow. Primary outcome is the clinical diagnosis of an acute ischaemic stroke with an intracranial LVO in the anterior circulation. Additional hospital data concerning the diagnosis and provided treatment will be collected by chart review. Logistic regression analysis will be performed, and performance of the prehospital stroke scales will be expressed as sensitivity, specificity and area under the receiver operator curve. ETHICS AND DISSEMINATION:The Institutional Review Board of the Erasmus MC University Medical Centre has reviewed the study protocol and confirmed that the Dutch Medical Research Involving Human Subjects Act (WMO) is not applicable. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. The best performing scale, or the simplest scale in case of clinical equipoise, will be integrated in a decision model with other clinical characteristics and real-life driving times to improve prehospital triage of suspected stroke patients. TRIAL REGISTRATION NUMBER:NTR7595.
Project description:BACKGROUND:endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients remains unclear. The present study aims to investigate whether IVT followed by ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS with LVO. METHODS:we achieved a single center retrospective study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. Functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up brain CT scan infarct volume (EFIV) (for recanalized patients only), symptomatic intracerebral hemorrhage (sICH) and 3-month mortality were the outcomes of interests. Independent predictors of the outcomes were explored with multivariable logistic regression. RESULTS:145 subjects were included in the study, of whom 70 underwent direct ET and 75 were treated with CoT. Functional independence at 3-months was more frequent in CoT subjects compared to patients who received direct ET (mRS score 0-1: 48.5% vs 18.6%; P < 0.001. mRS score 0-2: 67.1% vs 37.3%; P < 0.001); CoT patients had also higher first-pass success rate (62.7% vs 38.6%, P < 0.05), higher recanalization rate (84.3% vs 65.3%; P = 0.009) and, in recanalized subjects, smaller EFIV (16.4 ml vs 62.3 ml; P = 0.003). Mortality and intracranial bleeding did not differ between the two groups. In multivariable regression analysis, low baseline NIHSS score (P < 0.05), vessel recanalization (P = 0.05) and CoT (P = 0.03) were independent predictors of favorable outcome at three months. CONCLUSIONS:CoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.
Project description:BACKGROUND:Mechanical thrombectomy has been proven as a standard care for moderate to severe ischemic stroke with anterior large vessel occlusion (LVO); however, whether it is equally effective in mild ischemic stroke (MIS) is controversial. METHODS:In this retrospective study, a total of 177 Chinese patients presenting with MIS (NIHSS ≤8) and LVO between January 2014 and September 2017 from seven comprehensive stroke centers were identified. Odds of good outcome with endovascular thrombectomy versus medical treatment were obtained by logistic regression analysis and propensity-score matching method, and a meta-analysis pooled results from six studies (n = 733). RESULTS:Good outcome (mRS: 0-1) was 58.2% (46/79) in the thrombectomy and 46.9% (46/98) in the medical group, which showed no statistical significance before adjustment (P = 0.13; OR = 1.57, 95% CI: 0.86 to 2.86). The adjusted ORs of thrombectomy versus medical group were 3.23 (95% CI, 1.35 to 7.73; P = 0.008) by multivariable logistic analysis, 2.78 (1.12 to 6.89; P = 0.02) by propensity score matching analysis, and 3.20 (1.22 to 8.37; P = 0.01) by propensity score matching analysis with additional adjustments, respectively. Thrombectomy treatment did not result in excessive mortality or symptomatic intracranial hemorrhage after adjustments. The meta-analysis did not confirm the associations between good outcome and endovascular treatment. CONCLUSIONS:The current study indicates that endovascular thrombectomy is associated with good functional outcome in MIS patients with LVO, and without additional risk of symptomatic intracranial hemorrhage and mortality. Although the meta-analysis failed to demonstrate its superiority compared to medical treatment, randomized clinical trials are needed.
Project description:BACKGROUND:Randomized controlled trials (RCTs) demonstrated efficacy and safety of endovascular treatment (ET) in anterior circulation large vessel occlusions (LVO). We aimed at investigating how stroke patients treated by thrombectomy in clinical practice and their outcome compare to cohorts and results of thrombectomy trials. METHODS:In a prospective study, we consecutively included stroke patients treated by thrombectomy (2015-2017). Baseline characteristics, procedural and outcome data were analyzed. Outcome was assessed by modified Rankin Scale (mRS) at 90?days. Ordinal regression analysis was performed to identify predictors of outcome. RESULTS:Thrombectomy was applied in 264 patients (median 75?years, 49.6% female). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16, 58.0% received concomitant intravenous thrombolysis, 62.1% were referred from external hospitals. Median Alberta Stroke Program Early CT Score (ASPECTS) was 7. Successful recanalization (modified Thrombolysis in Cerebral Infarction Score, mTICI 2b/3) was achieved in 72.0%. Symptomatic intracranial hemorrhage (sICH) occurred in 4.5%. Independent outcome (mRS 0-2) was achieved in 26.2%, poor outcome (mRS 5-6) in 49.2%. Only 33.5% met the stringent enrolment criteria of previous RCTs. Lower age, baseline NIHSS, pre-stroke mRS, higher ASPECTS, and successful recanalization were independent predictors of favourable outcome. CONCLUSIONS:The majority of stroke patients treated by ET in clinical practice would not have qualified for randomization in prior RCTs. Outcome in real-life patient cohorts is worse than in the highly selected cohorts from randomized trials, while rates of successful recanalization, sICH and outcome predictors are the same. Our findings support ET in broader patient populations than in the RCTs and may improve treatment decision in individual stroke patients with LVO in clinical practice.
Project description:Earlier or preprocedural identification of occlusion pathomechanism is crucial for effective endovascular treatment. As leptomeningeal collaterals tend to develop well in chronic ischemic conditions such as intracranial atherosclerosis (ICAS), we investigated whether leptomeningeal collaterals can be a preprocedural marker of ICAS-related large vessel occlusion (ICAS-LVO) in endovascular treatment. A total of 226 patients who underwent endovascular treatment were retrospectively reviewed. We compared the pattern of leptomeningeal collaterals between patients with ICAS-LVO and without. Leptomeningeal collaterals were assessed by preprocedural computed tomography angiography (CTA) and basically categorized by three different collateral assessment methods. Better leptomeningeal collaterals were significantly associated with ICAS-LVO, although they were not independent for ICAS-LVO. When leptomeningeal collaterals were dichotomized to incomplete (<100%) and complete (100%), the latter was significantly more frequent in patients with ICAS-LVO (52.5% versus 20.4%) and remained an independent factor for ICAS-LVO (odds ratio, 3.32; 95% confidence interval, 1.52-7.26; p = 0.003). The area under the curve (AUC) value of complete leptomeningeal collateral supply was 0.660 for discrimination of ICAS-LVO. Incomplete leptomeningeal collateral supply was not likely ICAS-LVO, based on the high negative predictive value (88.6%). Considering its negative predictive value and the independent association between complete leptomeningeal collateral supply and ICAS-LVO, leptomeningeal collaterals could be helpful in the preprocedural determination of occlusion pathomechanism.
Project description:To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT).A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed.Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0-2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (?70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.39; p < 0.00001). No difference was found for mortality at 90 days and sICH between endovascular therapy and medical management in all analyses and subgroup analyses.This meta-analysis provides strong evidence that endovascular intervention combined with medical management, including IV tissue plasminogen activator for eligible patients, improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of LVO.
Project description:BACKGROUND:The potential of neuroprotective agents should be revisited in the era of endovascular thrombectomy (EVT) for acute large-artery occlusion because their preclinical effects have been optimized for ischemia and reperfusion injury. Neu2000, a derivative of sulfasalazine, is a multi-target neuroprotectant. It selectively blocks N-methyl-D-aspartate receptors and scavenges for free radicals. This trial aimed to determine whether neuroprotectant administration before EVT is safe and leads to a more favorable outcome. METHODS:This trial is a phase-II, multicenter, three-arm, randomized, double-blinded, placebo-controlled, blinded-endpoint drug trial that enrolled participants aged ??19 years undergoing an EVT attempt less than 8 h from symptom onset, with baseline National Institutes of Health Stroke Scale (NIHSS) score???8, Alberta Stroke Program Early CT score???6, evidence of large-artery occlusion, and at least moderate collaterals on computed tomography angiography. EVT-attempted patients are randomized into control, low-dose (2.75 g), and high-dose (5.25 g) Neu2000KWL over 5 days. Seventy participants per group are enrolled for 90% power, assuming that the treatment group has a 28.4% higher proportion of participants with functional independence than the placebo group. The primary outcome, based on intention-to-treat criteria is the improvement of modified Rankin Scale (mRS) scores at 3 months using a dichotomized model. Safety outcomes include symptomatic intracranial hemorrhage within 5 days. Secondary outcomes are distributional change of mRS, mean differences in NIHSS score, proportion of NIHSS score 0-2, and Barthel Index >?90 at 1 and 4 weeks, and 3 months. DISCUSSION:The trial results may provide information on new therapeutic options as multi-target neuroprotection might mitigate reperfusion injury in patients with acute ischemic stroke before EVT. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT02831088 . Registered on 13 July 2016.