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...

Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 × 10−8) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 × 10−4; discovery and replication combined OR = 1.21, P = 4.7 × 10−8). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.

Factors influencing eligibility for ET were extracted from medical records and neuroimaging. Two algorithms were prospectively created to discriminate patients potentially eligible for ET-a restrictive algorithm incorporating the most stringent inclusion and exclusion criteria and a permissive algorithm reflecting the greater lenience that may occur in clinical practice (Figure 1 and Table). Ethics ApprovalEthical approval was obtained from all Adelaide hospitals and from the University of Adelaide (H 155 2008). Informed consent was obtained from patients (or next-of-kin when the patient was unable to consent). No patients (or proxies) declined participation.Background and Purpose-Endovascular thrombectomy (ET) is standard-of-care for ischemic stroke patients with large vessel occlusion, but estimates of potentially eligible patients from population-based studies have not been published. Such data are urgently needed to rationally plan hyperacute services. Retrospective analysis determined the incidence of ET-eligible ischemic strokes in a comprehensive population-based stroke study (Adelaide, Australia 2009-2010. Methods-Stroke patients were stratified via a prespecified eligibility algorithm derived from recent ET trials comprising stroke subtype, pathogenesis, severity, premorbid modified Rankin Score, presentation delay, large vessel occlusion, and target mismatch penumbra. Recognizing centers may interpret recent ET trials either loosely or rigidly; 2 eligibility algorithms were applied: restrictive (key criteria modified Rankin Scale score 0-1, presentation delay <3.5 hours, and target mismatch penumbra) and permissive (modified Rankin Scale score 0-3 and presentation delay <5 hours). Results-In a population of 148 027 people, 318 strokes occurred in the 1-year study period (crude attack rate 215 per 100 000 person-years). The number of ischemic strokes eligible by restrictive criteria was 17/258 (7%; 95% confidence intervals 4%-10%) and by permissive criteria, an additional 16 were identified, total 33/258 (13%; 95% confidence intervals 9%-18%). Two of 17 patients (and 6/33 permissive patients) had thrombolysis contraindications. Using the restrictive algorithm, there were 11 (95% confidence intervals 4-18) potential ET cases per 100 000 person-years or 22 (95% confidence intervals 13-31) using the permissive algorithm. Conclusions-In this cohort, ≈7% of ischemic strokes were potentially eligible for ET (13% with permissive criteria).In similar populations, the permissive criteria predict that ≤22 strokes per 100 000 person-years may be eligible for ET.