The amyloid cascade hypothesis suggests that the aggregation and deposition of amyloid-␤ protein is an initiating event in Alzheimer's disease (AD). Using amyloid imaging technology, such as the positron emission tomography (PET) agent Pittsburgh compound-B (PiB), it is possible to explore the natural history of preclinical amyloid deposition in people at high risk for AD. With this goal in mind, asymptomatic (n ϭ 5) and symptomatic (n ϭ 5) carriers of presenilin-1 (PS1) mutations (C410Y or A426P) that lead to early-onset AD and noncarrier controls from both kindreds (n ϭ 2) were studied with PiB-PET imaging and compared with sporadic AD subjects (n ϭ 12) and controls from the general population (n ϭ 18). We found intense and focal PiB retention in the striatum of all 10 PS1 mutation carriers studied (ages 35-49 years). In most PS1 mutation carriers, there also were increases in PiB retention compared with controls in cortical brain areas, but these increases were not as great as those observed in sporadic AD subjects. The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not show the typical regional pattern of PiB retention observed in sporadic AD. Postmortem evaluation of tissue from two parents of PS1C410Y subjects in this study confirmed extensive striatal amyloid deposition, along with typical cortical deposition. The early, focal striatal amyloid deposition observed in these PS1 mutation carriers is often is not associated with clinical symptoms.

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...

Background: To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. Methods: We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007–2010) at a single academic institution. The final study cohort included 87 patients with acute ILAO subjected to multimodal CT imaging within 24 h of symptom onset. LA severity was assessed using the van Swieten scale on non-contrast CT. Leptomeningeal collaterals were graded using CT angiogram source images. Hemorrhagic transformation (HT) was determined on follow-up CT. Multivariate logistic regression controlling for HT, treatment modality, demographic, as well as baseline clinical and imaging characteristics was used to identify independent predictors of a poor outcome (90-day mRS >2). Results: The median National Institutes of Health Stroke Scale (NIHSS) at baseline was 15 (interquartile range 9–21). Twenty-four percent of the studied patients had severe LA. They were more likely to have hypertension (p = 0.028), coronary artery disease (p = 0.015), poor collaterals (p < 0.001), higher baseline NIHSS (p = 0.003), higher mRS at 90 days (p < 0.001), and were older (p = 0.002). Patients with severe LA had a uniformly poor outcome (p < 0.001) irrespective of treatment modality. Poor outcome was independently associated with higher baseline NIHSS (p < 0.001), worse LA (graded and dichotomized, p < 0.001), reduced leptomeningeal collaterals (graded and dichotomized, p < 0.001), presence of HT (p < 0.001), presence of parenchymal hemorrhages (p = 0.01), baseline mRS (p = 0.002), and older age (p = 0.043). The association between severe LA (p = 0.0056; OR 13.86; 95% CI 1.94–∞) and baseline NIHSS (p = 0.0001; OR 5.11; 95% CI 2.07–14.49 for each 10-point increase) with poor outcome maintained after adjustment for confounders in the final regression model. In this model, there was no significant association between presence of HT and poor outcome (p = 0.0572). Conclusion: Coexisting LA may predict poor functional outcome in patients with acute anterior circulation ILAO independent of other known important outcome predictors such as comorbid state, admission functional deficit, collateral status, hemorrhagic conversion, and treatment modality.

Background and Purpose-Statins reduce the risk of stroke recurrence, but the benefits of statins in improving outcome of acute stroke patients have not been well explored. Methods-We assessed potential effects of statins initiated before or within 4 weeks of stroke on 90-day outcome.Favorable outcomes were National Institutes of Health Stroke Scale (NIHSS) score Յ2 at 12 weeks and modified Rankin Scale (mRS) Յ2.