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ItemSelection criteria for endovascular therapy for acute ischaemic stroke: Are patients missing out?Maingard, J ; Churilov, L ; Mitchell, P ; Dowling, R ; Yan, B (WILEY, 2018-06-01)INTRODUCTION: Endovascular clot retrieval (ECR) following intravenous thrombolysis is superior to intravenous thrombolysis alone for acute stroke with large vessel occlusion. However, trial selection criteria may exclude potentially salvageable patients. We investigated the impact of published selection criteria on the different proportions of patients excluded and clinical outcome. METHODS: We included patients with anterior circulation stroke treated with ECR from a single centre. Selection criteria from five trials (REVASCAT, EXTEND IA, MR CLEAN, SWIFT PRIME, ESCAPE) and American Stroke Association (ASA) guidelines were applied. We calculated the proportion of patient's ineligible for ECR according to different selection criteria. Clinical benefit and harm were quantified as the number of patients benefiting per 1 patient harmed (NB1H) for each of the 6 applied selection criteria. RESULTS: One hundred and seventy-eight patients were included. Mean age was 74 (SD 14) years, 60.1% were male, median baseline NIHSS was 17 (IQR 13-21). Patients were hypothetically excluded from ECR: REVASCAT 35.4%, EXTENDA IA 86%, SWIFT PRIME 86%, MR CLEAN 2.3%, ESCAPE 93.3% and ASA 29.2%. The NB1H for included and excluded patients respectively in decreasing order of magnitude: EXTEND IA >100 vs 3, ESCAPE >100 vs 3.4, SWIFT PRIME 10 vs 3.3, REVASCAT 4.4 vs 2.9, MR CLEAN 3.7 vs >100, and ASA 3.7 vs 3.9. CONCLUSION: We found that criteria from MR CLEAN, ASA and REVASCAT excluded the lowest proportion of patients with comparable NB1H. We believe that these criteria would be reasonable to be utilised for ECR selection.
ItemSocial Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of AutismBurrows, EL ; Eastwood, AF ; May, C ; Kolbe, SC ; Hill, T ; McLachlan, NM ; Churilov, L ; Hannan, AJ (HINDAWI LTD, 2017-01-01)Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male NL3R451C and WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior in NL3R451C mice. NL3R451C mice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones in NL3R451C mice. This study is the first to show altered mating behavior in the NL3R451C mouse and has provided new insights into the aggressive phenotype in this model.
ItemIs there association between hyperdense middle cerebral artery sign on CT scan and time from stroke onset within the first 24-hours?Haridy, J ; Churilov, L ; Mitchell, P ; Dowling, R ; Yan, B (BMC, 2015-07-03)BACKGROUND: The hyperdense artery sign (HAS) on CT brain scan is an assumed radiological marker of acute intra-arterial thrombotic occlusion. However, the relationship between HAS between time of stroke onset has not been adequately investigated, leading to uncertainty regarding its validity as a marker of acute ischaemia. We attempted to determine if the presence of the hyperdense artery sign is associated with time from stroke onset. METHODS: Retrospective cross-sectional study conducted in a tertiary referral centre. Consecutive patients with acute ischaemic stroke and confirmed middle cerebral arterial occlusion on initial CT angiogram from 2007-2011 were included. Visual estimation and manual measurement of Hounsfield units of affected and corresponding non-affected artery on non-contrast CT was completed and mean density was calculated from four separate readings. Primary outcome measures were Time from stroke onset and HAS on both visual estimation and the ratio of mean value in Hounsfield Units (HU) of affected to non-affected artery. RESULTS: One hundred and fifty-four subjects with confirmed arterial occlusion on CT Angiogram were included in the study. There were no significant differences in age distribution or vascular risk factor presence between subjects with or without HAS. Subjects with HAS were less likely to be male (50.9% vs 70.8%, p = 0.02).) HAS was found in 106 (68.8%) of all subjects. Median NIHSS score at presentation was significantly higher in the HAS group (17 vs 12, p = 0.02). No statistically significant association between HAS and stroke onset time or density ratio between affected and non-affected artery was detected overall within either the first 24-h or on subgroup analysis of those in the first 4.5-h. A small subgroup of three patients with stroke onset greater than 24-h all had absent HAS. CONCLUSIONS: No evidence of a correlation between time of stroke onset and presence of a HAS within the first 24-h post acute ischaemic stroke was identified. The HAS was associated with a higher NIHSS score at presentation.
ItemSuccessful recanalization post endovascular therapy is associated with a decreased risk of intracranial haemorrhage: a retrospective studyWang, DT ; Churilov, L ; Dowling, R ; Mitchell, P ; Yan, B (BMC, 2015-10-07)BACKGROUND: The risks of intracranial haemorrhage (ICH) post intra-arterial therapy (IAT) for stroke are not well understood. We aimed to study the influence of recanalization status post IAT for anterior circulation stroke and posterior circulation stroke on ICH development. METHODS: Retrospective analysis of 193 patients in a prospectively collected database of IAT stroke patients was performed. Successful recanalization was defined as a Thrombolysis in Cerebral Infarction Score of 2b or 3 and symptomatic ICH (SICH) as parenchymal hematoma type 2 (PH2) with neurological deterioration. The association between the recanalization status and ICH/SICH was investigated using logistic regression models adjusted for baseline characteristics selected by univariate analyses. RESULTS: One hundred and thirty-six patients had successful recanalization post procedure, 41 patients developed ICH and 10 patients SICH. There was a statistically significant baseline imbalance between the groups with and without successful recanalization on gender, baseline National Institute of Health Stroke Scale (NIHSS) score, the use of intravenous tPA and intra-arterial urokinase (p < 0.05). Logistic regression analysis adjusted for the above variables and the time to digital subtraction angiography demonstrated a statistically significant association between successful recanalization and ICH (odds ratio 0.42; 95% CI 0.19, 0.95; p = 0.04). CONCLUSION: Successful recanalization post endovascular therapy is statistically significantly and negatively associated with ICH.