Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack

BACKGROUND AND PURPOSE: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. RESULTS: In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). CONCLUSION: In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment

Stroke Severity and Comorbidity Index for Prediction of Mortality after Ischemic Stroke from the Virtual International Stroke Trials Archive-Acute Collaboration

M. Kaste on työryhmän VISTA-Acute Collaboration jäsen.Background: There is increasing interest in the use of administrative data (incorporating comorbidity index) and stroke severity score to predict ischemic stroke mortality. The aim of this study was to determine the optimal timing for the collection of stroke severity data and the minimum clinical dataset to be included in models of stroke mortality. To address these issues, we chose the Virtual International Stroke Trials Archive (VISTA), which contains National Institutes of Health Stroke Scale (NIHSS) on admission and at 24 hours, as well as outcome at 90 days. Methods: VISTA was searched for patients who had baseline and 24-hour NIHSS. Improvement in regression models was performed by the net reclassification improvement (NRI) method. Results: The clinical data among 5206 patients were mean age, 69 +/- 13; comorbidity index, 3.3 +/- .9; median NIHSS at baseline, 12 (interquartile range [IQR] 8-17); NIHSS at 24 hours, 9 (IQR 8-15); and death at 90 days in 15%. The baseline model consists of age, gender, and comorbidity index. Adding the baseline NIHSS to model 1 improved the NRI by 0.671 (95% confidence interval [CI] 0.595-0.747) [or 67.1% correct reclassification between model 1 and model 2]. Adding the 24 hour NIHSS term to model 1 (model 3) improved the NRI by 0.929 (95% CI 0.857-1.000) for model 3 versus model 1. Adding the variable thrombolysis to model 3 (model 4) improve NRI by 0.1 (95% CI 0.023-0.178) [model 4 versus model 3]. Conclusion: The optimal model for the prediction of mortality was achieved by adding the 24-hour NIHSS and thrombolysis to the baseline model.Peer reviewe

Early in-hospital exposure to statins and outcome after intracerebral haemorrhage - Results from the Virtual International Stroke Trials Archive

Introduction Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome. Patients and methods Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome. Results A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale <= 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3-3.6). Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3-5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors. Discussion It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias. Conclusion Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Localization and Broadband Follow-up of the Gravitational-wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams. </p

Googling Stroke ASPECTS to Determine Disability: Exploratory Analysis from VISTA-Acute Collaboration.

The summed Alberta Stroke Program Early CT Score (ASPECTS) is useful for predicting stroke outcome. The anatomical information in the CT template is rarely used for this purpose because traditional regression methods are not adept at handling collinearity (relatedness) among brain regions. While penalized logistic regression (PLR) can handle collinearity, it does not provide an intuitive understanding of the interaction among network structures in a way that eigenvector method such as PageRank can (used in Google search engine). In this exploratory analysis we applied graph theoretical analysis to explore the relationship among ASPECTS regions with respect to disability outcome. The Virtual International Stroke Trials Archive (VISTA) was searched for patients who had infarct in at least one ASPECTS region (ASPECTS ≤ 9, ASPECTS = 10 were excluded), and disability (modified Rankin score/mRS). A directed graph was created from a cross correlation matrix (thresholded at false discovery rate of 0.01) of the ASPECTS regions and demographic variables and disability (mRS > 2). We estimated the network-based importance of each ASPECTS region by comparing PageRank and node strength measures. These results were compared with those from PLR. There were 185 subjects, average age 67.5 ± 12.8 years (55% Males). Model 1: demographic variables having no direct connection with disability, the highest PageRank was M2 (0.225, bootstrap 95% CI 0.215-0.347). Model 2: demographic variables having direct connection with disability, the highest PageRank were M2 (0.205, bootstrap 95% CI 0.194-0.367) and M5 (0.125, bootstrap 95% CI 0.096-0.204). Both models illustrate the importance of M2 region to disability. The PageRank method reveals complex interaction among ASPECTS regions with respects to disability. This approach may help to understand the infarcted brain network involved in stroke disability

Googling Stroke ASPECTS to Determine Disability: Exploratory Analysis from VISTA-Acute Collaboration

The summed Alberta Stroke Program Early CT Score (ASPECTS) is useful for predicting stroke outcome. The anatomical information in the CT template is rarely used for this purpose because traditional regression methods are not adept at handling collinearity (relatedness) among brain regions. While penalized logistic regression (PLR) can handle collinearity, it does not provide an intuitive understanding of the interaction among network structures in a way that eigenvector method such as PageRank can (used in Google search engine). In this exploratory analysis we applied graph theoretical analysis to explore the relationship among ASPECTS regions with respect to disability outcome. The Virtual International Stroke Trials Archive (VISTA) was searched for patients who had infarct in at least one ASPECTS region (ASPECTS ≤ 9, ASPECTS = 10 were excluded), and disability (modified Rankin score/mRS). A directed graph was created from a cross correlation matrix (thresholded at false discovery rate of 0.01) of the ASPECTS regions and demographic variables and disability (mRS > 2). We estimated the network-based importance of each ASPECTS region by comparing PageRank and node strength measures. These results were compared with those from PLR. There were 185 subjects, average age 67.5 ± 12.8 years (55% Males). Model 1: demographic variables having no direct connection with disability, the highest PageRank was M2 (0.225, bootstrap 95% CI 0.215-0.347). Model 2: demographic variables having direct connection with disability, the highest PageRank were M2 (0.205, bootstrap 95% CI 0.194-0.367) and M5 (0.125, bootstrap 95% CI 0.096-0.204). Both models illustrate the importance of M2 region to disability. The PageRank method reveals complex interaction among ASPECTS regions with respects to disability. This approach may help to understand the infarcted brain network involved in stroke disability

How well do standard stroke outcome measures reflect quality of life? A retrospective analysis of clinical trial data

Background and Purpose—Quality of life (QoL) is important to stroke survivors yet is often recorded as a secondary measure in acute stroke randomized controlled trials. We examined whether commonly used stroke outcome measures captured aspects of QoL.&lt;p&gt;&lt;/p&gt; Methods—We examined primary outcomes by National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and modified Rankin Scale (mRS), and QoL by Stroke Impact Scale (SIS) and European Quality of Life Scale (EQ-5D) from the Virtual International Stroke Trials Archive (VISTA). Using Spearman correlations and logistic regression, we described the relationships between QoL mRS, NIHSS, and BI at 3 months, stratified by respondent (patient or proxy). Using χ2 analyses, we examined the mismatch between good primary outcome (mRS &#8804;1, NIHSS &#8804;5, or BI &#8805;95) but poor QoL, and poor primary outcome (mRS &#8805;3, NIHSS &#8805;20, or BI &#8804;60) but good QoL.&lt;p&gt;&lt;/p&gt; Results—Patient-assessed QoL had a stronger association with mRS (EQ-5D weighted score n=2987, P&#60;0.0001, r=−0.7, r2=0.53; SIS recovery n=2970, P&#60;0.0001, r=−0.71, r2=0.52). Proxy responses had a stronger association with BI (EQ-5D weighted score n=837, P&#60;0.0001, r=0.78, r2=0.63; SIS recovery n=867, P&#60;0.0001, r=0.68, r2=0.48). mRS explained more of the variation in QoL (EQ-5D weighted score=53%, recovery by SIS v3.0=52%) than NIHSS or BI and resulted in fewer mismatches between good primary outcome and poor QoL (P&#60;0.0001, EQ-5D weighted score=8.5%; SIS recovery=10%; SIS-16=4.4%).&lt;p&gt;&lt;/p&gt; Conclusions—The mRS seemed to align closely with stroke survivors’ interests, capturing more information on QoL than either NIHSS or BI. This further supports its recommendation as a primary outcome measure in acute stroke randomized controlled trials

Interdependence of stroke outcome scales: reliable estimates from the Virtual International Stroke Trials Archive (VISTA)

Background and Purpose Clinical deficits from stroke are diverse, prompting measurement in trials by a range of outcome scales. Statistical and clinical advantage can be gained by combining scales into a global outcome provided combinations are chosen with limited correlations. We aimed to clarify the interdependence of outcome scales by systematic review of published data and by novel analysis of data from completed acute trials. Summary of Review We systematically searched ScienceDirect and PubMed to summarize published data on correlations between stroke outcome scales. We generated new data on correlations among salient scales at 90 days poststroke in patients from the Virtual International Stroke Trials Archive (VISTA). We calculated Pearson and Spearman‐Rank correlation coefficients for continuous and ordinal measures, respectively. We also assessed partial correlations, adjusted for baseline National Institute of Health Stroke Scale (NIHSS), and age. Published estimates of interdependence were limited to small single‐trial cohorts and gave divergent results. From the more extensive VISTA dataset, we found that the modified Rankin Scale at 90 days poststroke explained 80.8% of the National Institute of Health Stroke Scale at 90 days poststroke and 86·5% of the European Stroke Scale. National Institute of Health Stroke Scale explained 75.9% of the Barthel Index and 81·2% of the Scandinavian Stroke Scale. After adjustment, modified Rankin Scale explained 56.6% of National Institute of Health Stroke Scale, 75.2% of Barthel Index. National Institute of Health Stroke Scale explained 60.2% of Barthel Index. Conclusion Correlations and partial correlations among stroke outcome scales in trial datasets are higher than previously reported. The new estimates are more reliable for trial planning due to the sample size and diversity