In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program; WAKE-UP ClinicalTrials.gov number, NCT01525290; and EudraCT number, 2011-005906-32 .).

Background and Purpose— Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Methods— Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion–diffusion mismatch not progressing to infarction after 1 month. Results— Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent ( P =0.006), and National Institutes of Health Stroke Scale score on admission was lower ( P =0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction ( P =0.0003). Conclusions— Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00975962.

IMPORTANCE Endovascular therapy (EVT) is the standard of care for select patients who had a stroke caused by a large vessel occlusion in the anterior circulation, but there is uncertainty regarding the optimal anesthetic approach during EVT. Observational studies suggest that general anesthesia (GA) is associated with worse outcomes compared with conscious sedation (CS). OBJECTIVE To examine the effect of type of anesthesia during EVT on infarct growth and clinical outcome. DESIGN, SETTING, AND PARTICIPANTS The General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center prospective, randomized, open-label, blinded end-point evaluation that enrolled patients from March 12, 2015, to February 2, 2017. Although the trial screened 1501 patients, it included 128 consecutive patients with acute ischemic stroke caused by large vessel occlusions in the anterior circulation within 6 hours of onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not provide consent were excluded. Primary analysis was unadjusted and according to the intention-to-treat principle. INTERVENTIONS Patients were randomized to either the GA group or the CS group (1:1 allocation) before EVT. MAIN OUTCOMES AND MEASURES The primary end point was infarct growth between magnetic resonance imaging scans performed before EVT and 48 to 72 hours after EVT. The hypothesis formulated before data collection was that patients who were under CS would have less infarct growth. RESULTS Of 128 patients included in the trial, 65 were randomized to GA, and 63 were randomized to CS. For the entire cohort, the mean (SD) age was 71.4 (11.4) years, and 62 (48.4%) were women. Baseline demographic and clinical variables were balanced between the GA and CS treatment arms. The median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21). Four patients (6.3%) in the CS group were converted to the GA group. Successful reperfusion was significantly higher in the GA arm than in the CS arm (76.9% vs 60.3%; P = .04). The difference in the volume of infarct growth among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs 19.4 [2.4-79.0] mL; P = .10). There were better clinical outcomes in the GA group, with an odds ratio for a shift to a lower modified Rankin Scale score of 1.91 (95% CI, 1.03-3.56). CONCLUSIONS AND RELEVANCE For patients who underwent thrombectomy for acute ischemic stroke caused by large vessel occlusions in the anterior circulation, GA did not result in worse tissue or clinical outcomes compared with CS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02317237

Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.

Campbell, B. C. V. et al. (2018) Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data. Lancet Neurology, 17(1), pp. 47-53. (doi:10.1016/S1474-4422(17)30407-6) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/149670/ variables. An alternative approach using propensity-score stratification was also used. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Bias was assessed using the Cochrane tool.Findings: Of 1764 patients in 7 trials, 871 were allocated to endovascular thrombectomy. After exclusion of 74 patients (72 who did not undergo the procedure and 2 with missing data on anaesthetic strategy), 236/797 (30%) of endovascular patients were treated under GA. At baseline, GA patients were younger and had shorter time to randomisation but similar pre-treatment clinical severity compared to non-GA. Endovascular thrombectomy improved functional outcome at 3 months versus standard care in both GA (adjusted common odds ratio (cOR) 1·52, 95%CI 1·09-2·11, p=0·014) and non-GA (adjusted cOR 2·33, 95%CI 1·75-3·10, p<0·001) patients. However, outcomes were significantly better for those treated under non-GA versus GA (covariate-adjusted cOR 1·53, 95%CI 1·14-2·04, p=0·004; propensitystratified cOR 1·44 95%CI 1·08-1·92, p=0·012). The risk of bias and variability among studies was assessed to be low.Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. Funding:The HERMES collaboration was funded by an unrestricted grant from Medtronic to the University of Calgary. Research in contextEvidence before this study between abolition of the thrombectomy treatment effect in MR CLEAN and no effect in THRACE. Three single-centre randomised trials of general anaesthesia versus conscious sedation found either no difference in functional outcome between groups or a slight benefit of general anaesthesia. Added value of this studyThese data from contemporary, high quality randomised trials form the largest study to date of the association between general anesthesia and the benefit of endovascular thrombectomy versus standard care. We used two different approaches to adjust for baseline imbalances (multivariable logistic regression and propensity-score stratification). We found that GA for endovascular thrombectomy, as practiced in contemporary clinical care across a wide range of expert centres during the rand...