Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

Background: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke with Proven Occlusion (TEMPO-2): Rational and design of a multicenter, randomized open-label clinical trial.

Background: Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials.

The relationship of small vessel disease burden on cerebral and regional brain atrophy rates and cognitive performance over one year of follow-up after transient ischemic attack.

Background: Stroke, even when minor, increases the risk of dementia. We aimed to determine whether patients with transient ischaemic attack (TIA) exhibit higher rates of cerebral and regional atrophy 1-year after first stroke symptoms and evaluate the relationship with small vessel disease and cognitive performance.

Methods: TIA patients and controls without cognitive symptoms underwent high-resolution T1-weighted MRI and cognitive testing at baseline and 1-year.

Visualization of atrophy of medial temporal lobes and the septal nuclei in patients with transient ischaemic attack and controls.

Introduction: Transient ischaemic attack (TIA) is associated with increased risk of cognitive decline and dementia as early as one-year post-event. Regional brain atrophy measurements may predict future cognitive decline. 1) To determine whether Medial Temporal Atrophy (MTA) scores and interseptal distance (ISD) measurements are greater in patients with TIA compared to controls; and 2) To determine whether MTA and ISD predicts cognitive change one year after TIA.

Vascular Brain Lesions, Cognitive Reserve, and Their Association with Cognitive Profile in Persons with Early-Stage Cognitive Decline.

Background: Cognitive reserve may protect against the effects of brain pathology, but few studies have looked at whether cognitive reserve modifies the adverse effects of vascular brain pathology.

Objective: We determined if cognitive reserve attenuates the associations of vascular brain lesions with worse cognition in persons with subjective concerns or mild impairment.

Methods: We analyzed 200 participants aged 50-90 years from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study.

The Cognitive Sequelae of Transient Ischemic Attacks-Recent Insights and Future Directions.

There is now considerable evidence that Transient Ischemic Attack (TIA) carries important sequelae beyond the risk of recurrent stroke, particularly with respect to peri-event and post-event cognitive dysfunction and subsequent cognitive decline. The occurrence of a TIA could provide an important window in understanding the relationship of early mixed vascular-neurodegenerative cognitive decline, and by virtue of their clinical relevance as a "warning" event, TIAs could also furnish the opportunity to act preventatively not only for stroke prevention but also for dementia prevention. In this review, we discuss the current state of the literature regarding the cognitive sequelae associated with TIA, reviewing important challenges in the field.

Diagnosing Alzheimer's Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe.

Background: Toxic amyloid-β (Aβ) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials.

Objective: To develop a novel method for early Alzheimer's disease (AD) detection, we used blood leukocytes, that could act as "sentinels" after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy.

Quantitative detection of grey and white matter amyloid pathology using a combination of K114 and CRANAD-3 fluorescence.

Background: Alzheimer's disease (AD) is a neurodegenerative disease that exacts a huge toll on the patient, the healthcare system and society in general. Abundance and morphology of protein aggregates such as amyloid β plaques and tau tangles, along with cortical atrophy and gliosis are used as measures to assess the changes in the brain induced by the disease. Not all of these parameters have a direct correlation with cognitive decline.

The neuroimaging of neurodegenerative and vascular disease in the secondary prevention of cognitive decline.

Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent years. Thus, future trials must begin during the preclinical phases of the disease before symptom onset.

White matter tract microstructure and cognitive performance after transient ischemic attack.

Background And Purpose: Patients with transient ischemic attack (TIA) show evidence of cognitive impairment but the reason is not clear. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. We report WM changes using DTI and the relationship with neuropsychological performance in a cohort of transient ischemic attack (TIA) and non-TIA subjects.

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis.

Background: The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear.

Methods: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes.

Recanalization following Endovascular treatment and imaging of PErfusion, Regional inFarction and atrophy to Understand Stroke Evolution-NA1 (REPERFUSE-NA1).

Rationale: Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery.

Aim: The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion.

Temporal evolution and spatial distribution of quantitative T2 MRI following acute ischemia reperfusion injury.

Background: Determining mechanisms of secondary stroke injury related to cerebral blood flow and the severity of microvascular injury contributing to edema and blood-brain barrier breakdown will be critical for the development of adjuvant therapies for revascularization treatment.

Aim: To characterize the heterogeneity of the ischemic lesion using quantitative T2 imaging along with diffusion-weighted magnetic resonance imaging (DWI) within five hours of treatment.

Methods: Quantitative T2 magnetic resonance imaging was acquired within 5 h (baseline) and at 24 h (follow-up) of stroke treatment in 29 patients.

Longitudinal Brain Atrophy Rates in Transient Ischemic Attack and Minor Ischemic Stroke Patients and Cognitive Profiles.

Patients with transient ischemic attack (TIA) and minor stroke demonstrate cognitive impairment, and a four-fold risk of late-life dementia. To study the extent to which the rates of brain volume loss in TIA patients differ from healthy controls and how they are correlated with cognitive impairment. TIA or minor stroke patients were tested with a neuropsychological battery and underwent T1 weighted volumetric magnetic resonance imaging scans at fixed intervals over a 3 years period.

Diffusion-weighted imaging lesion growth occurs despite recanalization in acute ischemic stroke: Implications for future treatment trials.

Background: A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment.

Aims: Infarct growth may occur even after successful recanalization and could represent an appropriate endpoint for future stroke therapy trials.

Methods: Magnetic resonance diffusion-weighted imaging lesion volumes were obtained at 5 h (initial posttreatment) and 24 h (follow-up) after acute stroke treatment for n = 33 in ischemic stroke patients.

A longitudinal magnetic resonance imaging study of neurodegenerative and small vessel disease, and clinical cognitive trajectories in non demented patients with transient ischemic attack: the PREVENT study.

Background: Late-life cognitive decline, caused by progressive neuronal loss leading to brain atrophy years before symptoms are detected, is expected to double in Canada over the next two decades. Cognitive impairment in late life is attributed to vascular and lifestyle related risk factors in mid-life in a substantial proportion of cases (50%), thereby providing an opportunity for effective prevention of cognitive decline if incipient disease is detected earlier. Patients presenting with transient ischemic attack (TIA) commonly display some degree of cognitive impairment and are at a 4-fold increased risk of dementia.

Validation of a proteomic biomarker panel to diagnose minor-stroke and transient ischaemic attack: phase 2 of SpecTRA, a large scale translational study.

Objective: To validate our previously developed 16 plasma-protein biomarker panel to differentiate between transient ischaemic attack (TIA) and non-cerebrovascular emergency department (ED) patients.

Method: Two consecutive cohorts of ED patients prospectively enrolled at two urban medical centers into the second phase of SpecTRA study (training, cohort 2A, n = 575; test, cohort 2B, n = 528). Plasma samples were analyzed using liquid chromatography/multiple reaction monitoring-mass spectrometry.

Diffusion-Weighted MRI Stroke Volume Following Recanalization Treatment is Threshold-Dependent.

Purpose: Infarct lesion segmentation has been problematic as there are a wide range of relative and absolute diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) thresholds that have been used for this purpose. We examined differences of stroke lesion volume and evolution evaluated by magnetic resonance imaging (MRI) during the immediate post-treatment phase (<5 h) and at 24 h.

Methods: In this study 33 acute ischemic stroke patients were imaged with MRI <5 h and 24 h post-reperfusion treatment.

Dementia risk and prevention by targeting modifiable vascular risk factors.

The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society.

Infarct in a New Territory After Treatment Administration in the ESCAPE Randomized Controlled Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

Background And Purpose: Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

Methods: The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging.

Recurrent mild cerebral ischemia: enhanced brain injury following acute compared to subacute recurrence in the rat.

Background: In the current study, a transient cerebral ischemia producing selective cell death was designated a mild ischemic insult. A comparable insult in humans is a transient ischemic attack (TIA) that is associated with functional recovery but can have imaging evidence of minor ischemic damage including cerebral atrophy. A TIA also predicts a high risk for early recurrence of a stroke or TIA and thus multiple ischemic insults are not uncommon.

Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial.

Background And Purpose: The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume.

Methods: The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation.