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In this randomized trial involving patients who had moderate-to-severe acute ischemic stroke with proximal vessel occlusion and a small infarct core, endovascular treatment improved functional outcomes. Ischemic stroke is a devastating condition with a high burden of neurologic disability and death. As a systemic treatment, intravenous alteplase has been shown to be better than conservative care. 1 , 2 Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. 3 , 4 The major reason for the limited efficacy of alteplase is the modest rate of early reperfusion among patients with a large-vessel occlusion. 5 , 6 Local treatment of large-vessel occlusion began with intraarterial delivery of thrombolytic drugs. 7 The . . .

In a trial involving patients with ischemic stroke due to medium-vessel occlusion, thrombectomy within 12 hours did not lead to a better functional outcome and lower mortality at 90 days than usual care.

Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0–2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0–1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0–2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96–1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

BackgroundOptimal technical approaches of large-vessel anterior circulation acute ischemic strokes with concomitant extracranial internal carotid artery tandem occlusions is controversial.PurposeThis systematic review and meta-analysis evaluates: the overall outcomes of patients with tandem occlusions treated with second-generation mechanical thrombectomy devices; differences in outcomes of extracranial versus intracranial first approaches; and differences in outcomes of extracranial stenting at time of procedure versus angioplasty alone.MethodsMEDLINE, EMBASE, and the Web of Science was searched through September 2017 for studies evaluating patients presenting with acute tandem occlusions of the extracranial ICA and intracranial ICA, and/or proximal MCA treated with second-generation mechanical thrombectomy devices. Outcomes were pooled across studies using the random-effects model and expressed as cumulative incidence (event rate) and 95% CI.ResultsThirty-three studies were included in analysis. Overall mRS≤0–2 at 90 days was 47% (95% CI 42% to 51%). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial versus intracranial first approaches, 53% (95% CI 44% to 61%) vs 49% (95% CI 44% to 57%) (P=0.58). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial stenting versus angioplasty alone, 49% (95% CI 42% to 56%) vs 49% (95% CI 33% to 65%) (P=0.39). No other statistical differences in outcome or safety were identified.ConclusionsNearly half of all tandem occlusion patients treated with mechanical thrombectomy have good neurological outcomes. No statistical differences in outcome are identified between extracranial first versus intracranial first approaches, nor extracranial stenting versus angioplasty alone.

BackgroundTandem occlusions of the extracranial carotid and intracranial carotid or middle cerebral artery have a particularly poor prognosis without treatment. Several management strategies have been used with no clear consensus recommendations. We examined subjects with tandem occlusions enrolled in the ESCAPE trial and their outcomes.MethodsData are from the ESCAPE trial. Additional data were sought on interventions for each subject.ResultsThere were 54 (17%) subjects with tandem extracranial and intracranial occlusions. Patients in the endovascular treatment arm (n=30) were more likely to be younger (median age 66 years, p<0.01), male (66.7%, p=0.03), diabetic, and without atrial fibrillation. Subjects with tandem occlusions were more likely to have intracranial internal carotid artery occlusions than M1 occlusions (p<0.01). Of the 30 intervention-arm subjects, 17 (57%) underwent emergency endovascular treatment of the extracranial disease, 10 subjects before and seven subjects after intracranial thrombectomy. Of the remaining 13 subjects, only four required staged carotid revascularization due to persistent severe carotid stenosis; four had cervical pseudo-occlusions with no residual stenosis after large distal carotid thrombus burden aspiration/retrieval. Outcomes were similar between subjects with and without tandem lesions. The use of antithrombotic agents after acute carotid artery stenting was variable but no symptomatic intracerebral hemorrhage was seen in subjects who underwent emergency endovascular treatment of extracranial carotid artery.ConclusionsTandem occlusions occurred in one-sixth of patients and were treated highly variably within the ESCAPE trial. While outcomes were similar, the best method to treat the carotid artery in patients with tandem occlusion awaits further randomized data.Trial registration numberNCT01778335.

The variable rate of infarct progression in acute ischemic stroke as assessed by various thresholds excludes a substantial proportion of patients due to time or core constraints. We evaluated 106 patients with any-type occlusion to compare these thresholds and assessed performance of hypoperfusion index (HI) for fast and slow rate of infarct progression. Seven (12.5%) were classified fast progressors and 23 (46%), 25 (50%), 12 (24%), and 33 (66%) slow progressors using different core and time criteria. In comparison, HI categorized 100% (n = 106) of cohort with optimal cutoff 0.5 for any-type occlusion (slow progressors: HI ≤ 0.5), sensitivity/specificity 100%/91%, AUC 0.94, and indicative of eligibility for reperfusion and clinical outcomes (median 90-day modified Rankin Scale; 2 for HI ≤ 0.5 versus 5). Estimation of progressors by HI seems comprehensive but needs external validation.

BackgroundThe endovascular clip system (eCLIPs) is a novel device with both neck bridging and flow-diversion properties that make it suitable for the treatment of wide-necked bifurcation aneurysms.ObjectiveTo describe the clinical and radiologic outcomes of the eCLIPs device, including the first-in-man use of the latest version of the device.MethodsThis is a retrospective case series on all the wide-necked bifurcation aneurysms treated with the eCLIPs device in our center. The immediate and latest radiologic and clinical outcomes were assessed.ResultsThe device was successfully implanted in 12 of 13 patients. After a median follow-up period of 19 months (range 3–64 months), all patients with available data (11/12) had a good radiologic outcome (modified Raymond-Roy classification scores of 1 or 2). Two patients (18.2%) underwent re-treatment with simple coiling through the device. One of these had a subarachnoid hemorrhage prior to re-treatment. There were no major complications (death or permanent neurologic deficits) associated with use of the device.ConclusionOur series demonstrates occlusion rates that are similar to those of standard stent-assisted coiling and intrasaccular flow diversion for wide-necked bifurcation aneurysms. Larger registry-based studies are necessary to support our findings.

BackgroundThe optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.MethodsESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling.ResultsAmong 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0–2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0–2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1).ConclusionsTandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

BackgroundBetter reperfusion status results in smaller infarct volumes and better outcomes after thrombectomy. However, if large tissue volumes are already infarcted at baseline, reperfusion might also increase the risk of intracranial hemorrhage. This study aims to investigate the interaction between reperfusion status, baseline ischemic changes, and intracranial hemorrhage following thrombectomy.MethodsRetrospective analysis of the ESCAPE-NA1 randomized trial. Unadjusted and adjusted logistic regression models were used to estimate the associations of Alberta Stroke Program Early CT Score (ASPECTS) and expanded Treatment In Cerebral Infarction (eTICI) score on post-treatment hemorrhage. Treatment effect modification was assessed by including multiplicative interaction terms (ASPECTS*eTICI) in these models.ResultsA total of 1077 patients were included. Median age was 70.8 (IQR 60.7–79.7) and 543 (50.4%) were female. Any intracranial hemorrhage on 24-hour follow-up imaging occurred in 368/1077 (34.2%) patients. There was evidence of modification of the effect of final angiogram eTICI score on any intracranial hemorrhage by baseline ASPECTS (P=0.008). Marginal probabilities showed increased hemorrhage risk for patients with low ASPECTS with increasing final eTICI scores. This association was reversed in patients with small baseline ischemic changes and successful reperfusion. There was no association with symptomatic intracranial hemorrhage or parenchymal hematoma.ConclusionThe association of post-thrombectomy reperfusion status and post-treatment hemorrhage may be modified by the extent of baseline ischemia. Reperfusion is associated with reduced risk of hemorrhage in patients with small baseline infarcts, but increased hemorrhage risk in patients with extensive ischemic changes at baseline. However, no significant association was found with symptomatic intracranial hemorrhage or parenchymal hematoma.Trial registration numberNCT02930018.