Comparing mismatch strategies for patients being considered for ischemic stroke tenecteplase trials.

Background: Currently there are multiple variations of imaging-based patient selection mismatch methods in ischemic stroke. In the present study, we sought to compare the two most common mismatch methods and identify if there were different effects on the outcome of a randomized clinical trial depending on the mismatch method used.

Aims: Investigate the effect of clinical and imaging-based mismatch criteria on patient outcomes of a pooled cohort from randomized trials of intravenous tenecteplase versus alteplase.

Patient-Specific iPSC Model of a Genetic Vascular Dementia Syndrome Reveals Failure of Mural Cells to Stabilize Capillary Structures.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common form of genetic stroke and vascular dementia syndrome resulting from mutations in NOTCH3. To elucidate molecular mechanisms of the condition and identify drug targets, we established a patient-specific induced pluripotent stem cell (iPSC) model and demonstrated for the first time a failure of the patient iPSC-derived vascular mural cells (iPSC-MCs) in engaging and stabilizing endothelial capillary structures. The patient iPSC-MCs had reduced platelet-derived growth factor receptor β, decreased secretion of the angiogenic factor vascular endothelial growth factor (VEGF), were highly susceptible to apoptotic insults, and could induce apoptosis of adjacent endothelial cells.

Arterial branching and basal ganglia lacunes: A study in pure small vessel disease.

Introduction: Lacunes are defined morphologically by size and location, but radiological characteristics alone may be unable to distinguish small vessel disease aetiology from alternative mechanisms. We investigated the branching order of arterial vessels associated with basal ganglia lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in order to improve the understanding of their pathogenesis in pure cerebral small vessel disease.

Patients And Methods: Adults with a confirmed diagnosis of CADASIL were included.

Tenecteplase in ischemic stroke offers improved recanalization: Analysis of 2 trials.

Objective: To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated with tenecteplase compared to alteplase.

Methods: Pooled clinical and imaging data from 2 phase 2 randomized trials comparing tenecteplase with alteplase allowed CT angiography (CTA) scans to be assessed centrally for occlusion status at baseline and at 24 hours post thrombolysis using the modified thrombolysis in cerebral infarction (TICI) scale. Twenty-four-hour poststroke NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores were also compared between treatment groups using linear regression to generate odds ratios (ORs).

Vasoreactivity in CADASIL: Comparison to structural MRI and neuropsychology.

Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. A total of 22 adults with CADASIL gave informed consent to participate in an exploratory study of vascular function in CADASIL.

The Impact of CT Perfusion Threshold on Predicted Viable and Nonviable Tissue Volumes in Acute Ischemic Stroke.

Background And Purpose: Perfusion imaging is used for patient selection in clinical practice and trials. Postprocessing and definitions of tissue viability are nevertheless not standardized. We compared the lesion volumes generated with two well-recognized perfusion tissue definitions in a single-center phase 2 thrombolysis study.

Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials.

Background: We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging.

Methods: We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios.

Clinicopathological case: progressive cognitive decline with gait disturbance in a steel worker.

A 57-year-old male steel plant worker presented with fatigue and altered liver function tests. Over the next two years, he developed cognitive decline, parkinsonism and seizures. This paper reports the clinicopathological conference at the 37th Edinburgh Advanced Neurology Course 2015 and outlines what we can learn from this case.

Respiratory challenge MRI: Practical aspects.

Respiratory challenge MRI is the modification of arterial oxygen (PaO2) and/or carbon dioxide (PaCO2) concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging.

Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.

Oxygen challenge magnetic resonance imaging in healthy human volunteers.

Oxygen challenge imaging involves transient hyperoxia applied during deoxyhaemoglobin sensitive (T2*-weighted) magnetic resonance imaging and has the potential to detect changes in brain oxygen extraction. In order to develop optimal practical protocols for oxygen challenge imaging, we investigated the influence of oxygen concentration, cerebral blood flow change, pattern of oxygen administration and field strength on T2*-weighted signal. Eight healthy volunteers underwent multi-parametric magnetic resonance imaging including oxygen challenge imaging and arterial spin labelling using two oxygen concentrations (target FiO of 100 and 60%) administered consecutively (two-stage challenge) at both 1.

Coagulation and Fibrinolytic Activity of Tenecteplase and Alteplase in Acute Ischemic Stroke.

Background And Purpose: We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage.

Methods: Venous blood samples from a subgroup of participants in the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann-Whitney tests for between-group differences.

Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study.

Background: In most countries, alteplase given within 4·5 h of onset is the only approved medical treatment for acute ischaemic stroke. The newer thrombolytic drug tenecteplase has been investigated in one randomised trial up to 3 h after stroke and in another trial up to 6 h after stroke in patients selected by advanced neuroimaging. In the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST), we aimed to assess the efficacy and safety of tenecteplase versus alteplase within 4·5 h of stroke onset in a population not selected on the basis of advanced neuroimaging, and to use imaging biomarkers to inform the design of a definitive phase 3 clinical trial.

Insular cortex hypoperfusion and acute phase blood glucose after stroke: a CT perfusion study.

Background And Purpose: Insular cortex ischemia is proposed to mediate a sympathetic stimulus that leads to acute hyperglycemia after stroke.

Methods: We retrospectively analyzed insular perfusion on perfusion CT (median 180 minutes after onset) in 35 patients.

Results: We found no association of hypoperfusion (relative cerebral blood flow <0.