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...

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A single exposure to a severe stressor (either cold swim or inescapable shock) impairs subsequent performance in a shuttle avoidance-escape task (1), a deficit attributed to reduction in brain noradrenergic activity produced by these stressors. In the present paper, two experiments are described which examine how repeated exposure to such stressors affects (a) shuttle avoidance-escape performance (Experiment 1), and (b) aspects of brain norepinephrine metabolism (Experiment 2). Experiment 1 showed that, whereas subjects receiving the single exposure to cold swim or shock showed a large avoidance-escape deficit, subjects that received repeated exposure to these stressors for 14 days performed similarly to the control group that received no stressor. Experiment 2 showed that, whereas subjects that received one session of the inescapable shock stressor showed a lower level of norepinephrine in hypothalamus and cortex than did subjects that received no shock, subjects that received repeated exposure to inescapable shock or cold swim showed neurochemical "habituation." Subjects that received repeated shock showed elevated tyrosine hydroxylase activity and no depletion of norepinephrine level, and both repeated shock and cold swim caused a decrease in uptake of 3H-norepinephrine by slices of cortex in vitro. Thus, it is concluded that the behavioral and neurochemical changes that were observed after the stressful conditions studied are consistent with the hypothesis that changes in avoidance-escape responding following exposure to these stressful events are due to changes in brain noradrenergic activity.

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Chronic haloperidol treatment during prenatal and postnatal development was found to induce long-term behavioral and psychopharmacological effects. Rats tested shortly after termination of the chronic treatment at weaning or as young adults were hyperactive in the open field and exhibited an attenuated behavioral response to amphetamine and an accentuated cataleptic response to later doses of haloperidol, when compared with control offspring of the same age. Tests at an intermediate interval (adolescence period) showed no significant difference from control offspring on any of these behavioral measures. Adult rats administered haloperidol chronically for the same duration were also hyperactive after termination of treatment. In contrast to the effects of haloperidol during development, these adults exhibited an accentuated behavioral response to amphetamine and an attenuated cataleptic response to a later dose of haloperidol. Compensatory mechanisms in response to chronic haloperidol treatment during development thus appear to be different from those in adulthood.