Design, data management, and population baseline characteristics of the PERFORM magnetic resonance imaging project

Quantitative information from magnetic resonance imaging (MRI) may substantiate clinical findings and provide additional insight into the mechanism of clinical interventions in therapeutic stroke trials. The PERFORM study is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke. We report on the design of an exploratory longitudinal MRI follow-up study that was performed in a subgroup of the PERFORM trial. An international multi-centre longitudinal follow-up MRI study was designed for different MR systems employing safety and efficacy readouts: new T2 lesions, new DWI lesions, whole brain volume change, hippocampal volume change, changes in tissue microstructure as depicted by mean diffusivity and fractional anisotropy, vessel patency on MR angiography, and the presence of and development of new microbleeds. A total of 1,056 patients (men and women ≥55years) were included. The data analysis included 3D reformation, image registration of different contrasts, tissue segmentation, and automated lesion detection. This large international multi-centre study demonstrates how new MRI readouts can be used to provide key information on the evolution of cerebral tissue lesions and within the macrovasculature after atherothrombotic stroke in a large sample of patient

The Virtual International Stroke Trials Archive

BACKGROUND AND PURPOSE: Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. METHODS: Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. RESULTS: Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on \u3e15,000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69+/-12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. CONCLUSIONS: This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning

Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen stroke study, a population-based stroke registry

Background: Stroke etiology in ischemic stroke guides preventive measures and etiological stroke subgroups may show considerable differences between both sexes. In a population-based stroke registry we analyzed etiological subgroups of ischemic stroke and calculated sex-specific incidence and mortality rates. Methods: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke registry. Multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Modified TOAST ( Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for subgroup analysis in ischemic stroke. Results: Out of 626 patients with first-ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 8 12.6 years) than men (n = 299; 69.7 8 11.5 years; p < 0.001). The age-adjusted incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI 1.20–1.56) than in women (1.12; 95% CI 0.97–1.29; p = 0.04). Cardioembolism (n = 219; 35.0%), smallartery occlusion (n = 164; 26.2%), large-artery atherosclerosis (n = 98; 15.7%) and ‘probable atherothrombotic stroke’ (n = 84; 13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p 85 years) was detected. Conclusions: Cardioembolism is the main source for ischemic stroke in our population. Etiology of ischemic stroke differs between sexes, with large-artery atherosclerotic stroke and associated diseases (coronary artery disease and peripheral artery disease) being more common in men

The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate

Background: In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 106 cells, this could also be a consequence of engrafted cell number. The aim of this study was therefore to investigate the effect of different doses of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke outcome measured in vivo using 9.4-T high-field magnetic resonance imaging (MRI). Methods: Male Wistar rats (n = 43) underwent a middle cerebral artery occlusion (MCAo) for 45 or 90 min, followed by IA delivery of either saline or 1 × 106, 3 × 105, or 5 × 104 ASCs pre-labelled with very small superparamagnetic iron oxide particles (VSOPs). MRI (9.4-T) analysis was performed 48 h and 9 days post-MCAo. Lesion volumes were assessed by analysis of T2-weighted images and cell signal tracking showing cell engraftment and active cell migration by an improved T2*-analysis. Results: The ASC-derived signal intensity increased in the affected hemisphere 48 h post MCAo with injected cell number (p < 0.05). The analysis of stroke volumes revealed an increased infarction after injection of 1 × 106 ASCs compared to controls or application of 5 × 104 ASCs (p < 0.05). At 9 days post-MCAo, injection of 3 × 105 ASCs resulted in reduced infarct volumes (p < 0.05). Correspondingly, MRI analysis revealed no changes in cell numbers between both MRI examinations but showed active ASC migration to the site of infarction. Conclusion: Our results confirm that IA injection is an efficient way of targeting damaged brain tissue but its usefulness strongly depends on the right dose of delivered stem cells since this factor has a strong influence on migration rate and infarct volume, with better results for doses below 1 × 106 cells. Future challenges will include the determination of therapeutic doses for best cellular engraftment and stroke outcome

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

Confirmatory factor analysis of the Neuropsychological Assessment Battery of the LADIS study: a longitudinal analysis

WOS:000315985900004Age-related white matter changes have been associated with cognitive functioning, even though their role is not fully understood. This work aimed to test a 3-factor model of the neuropsychological assessment battery and evaluate how the model fit the data longitudinally. Confirmatory factor analysis (CFA) was used to investigate the dimensions of a structured set of neuropsychological tests administered to a multicenter, international sample of independent older adults (LADIS study). Six hundred and thirty-eight older adults completed baseline neuropsychological, clinical, functional and motor assessments, which were repeated each year for a 3-year follow-up. CFA provided support for a 3-factor model. These factors involve the dimensions of executive functions, memory functions, and speed and motor control abilities. Performance decreased in most neuropsychological measures. Results showed that executive functioning, memory and speed of motor abilities are valid latent variables of neuropsychological performance among older adults, and that this structure is relatively consistent longitudinally, even though performance decreases with time.info:eu-repo/semantics/acceptedVersio

Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

Objective To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes

Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: Results from the ACSRS study

Objectives. This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. Methods. Patients (n = 1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. Results. The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 μmol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). Conclusions. Linearity between ECST percent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy. © 2005 Elsevier Ltd. All rights reserved

Global burden of small vessel disease-related brain changes on MRI predicts cognitive and functional decline

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (PPeer reviewe

Compilation of Giant Electric Dipole Resonances Built on Excited States

Giant Electric Dipole Resonance (GDR) parameters for gamma decay to excited states with finite spin and temperature are compiled. Over 100 original works have been reviewed and from some 70 of which more than 300 parameter sets of hot GDR parameters for different isotopes, excitation energies, and spin regions have been extracted. All parameter sets have been brought onto a common footing by calculating the equivalent Lorentzian parameters. The current compilation is complementary to an earlier compilation by Samuel S. Dietrich and Barry L. Berman (At. Data Nucl. Data Tables 38(1988)199-338) on ground-state photo-neutron and photo-absorption cross sections and their Lorentzian parameters. A comparison of the two may help shed light on the evolution of GDR parameters with temperature and spin. The present compilation is current as of January 2006.Comment: 31 pages including 1 tabl