White matter tract disruption is associated with ipsilateral hand impairment in subacute stroke: a diffusion MRI study.

Purpose: The ipsilateral hand (ILH) is impaired after unilateral stroke, but the underlying mechanisms remain unresolved. Based on the degeneracy theory of network connectivity that many connectivity patterns are functionally equivalent, we hypothesized that ILH impairment would result from the summation of microstructural white matter (WM) disruption in the motor network, with a task-related profile. We aimed to determine the WM disruption patterns associated with ILH impairment.

Solving the Evidence Interpretability Crisis in Health Technology Assessment: A Role for Mechanistic Models?

Health technology assessment (HTA) aims to be a systematic, transparent, unbiased synthesis of clinical efficacy, safety, and value of medical products (MPs) to help policymakers, payers, clinicians, and industry to make informed decisions. The evidence available for HTA has gaps-impeding timely prediction of the individual long-term effect in real clinical practice. Also, appraisal of an MP needs cross-stakeholder communication and engagement.

Ipsilateral hand impairment predicts long-term outcome in patients with subacute stroke.

Background: Ipsilateral hand (ILH) impairment is documented following motor stroke, but its impact on long-term outcome remains unknown. We assessed ILH impairment in subacute stroke and tested whether ILH impairment predicted long-term outcome.

Methods: We performed a longitudinal study in 209 consecutive patients with unilateral stroke and sensorimotor deficit at admission.

Using numerical modeling and simulation to assess the ethical burden in clinical trials and how it relates to the proportion of responders in a trial sample.

In order to propose a more precise definition and explore how to reduce ethical losses in randomized controlled clinical trials (RCTs), we set out to identify trial participants who do not contribute to demonstrating that the treatment in the experimental arm is superior to that in the control arm. RCTs emerged mid-last century as the gold standard for assessing efficacy, becoming the cornerstone of the value of new therapies, yet their ethical grounds are a matter of debate. We introduce the concept of unnecessary participants in RCTs, the sum of non-informative participants and non-responders.

Lateropulsion After Hemispheric Stroke: A Form of Spatial Neglect Involving Graviception.

Objective: To test the hypothesis that lateropulsion is an entity expressing an impaired body orientation with respect to gravity in relation to a biased graviception and spatial neglect.

Methods: Data from the DOBRAS cohort (ClinicalTrials.gov: NCT03203109) were collected 30 days after a first hemisphere stroke.

Recovery of balance and gait after stroke is deteriorated by confluent white matter hyperintensities: Cohort study.

Background: White matter hyperintensities (WMHs) are well known to affect post-stroke disability, mainly by cognitive impairment. Their impact on post-stroke balance and gait disorders is unclear.

Objectives: We aimed to test the hypothesis that WMHs would independently deteriorate post-stroke balance and gait recovery.

Balance, Lateropulsion, and Gait Disorders in Subacute Stroke.

Objective: To test the hypothesis that impaired body orientation with respect to gravity (lateropulsion) would play a key role in poststroke balance and gait disorders.

Methods: Cohort study of 220 individuals consecutively admitted to a neurorehabilitation ward after a first hemisphere stroke (DOBRAS cohort [Determinants of Balance Recovery After Stroke] 2012-2018, ClinicalTrials.gov: NCT03203109), with clinical data systematically collected at 1 month, then at discharge.

Blood-based biomarkers and stem cell therapy in human stroke: a systematic review.

Stroke is one of the main causes of death and disability worldwide. Cell therapy represents a promising therapeutic approach to improve stroke outcome. Measurement of blood-based biomarkers might serve as a proof-of-concept to monitor the mechanisms undergirding these treatments, and such compounds could be used as surrogate biomarkers to monitor the safety and efficacy of cell therapies in the future.

Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial.

While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up.

Controlled clinical trials of cell therapy in stroke: Meta-analysis at six months after treatment.

Background Cell therapy is promising in experimental studies and has been assessed only in a few studies on humans. Aims To evaluate the effect of cell therapy in humans. Methods We included clinical trials with a control group that reported safety and efficacy six months following treatment.

Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke.

While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke.

How to Measure Recovery? Revisiting Concepts and Methods for Stroke Studies.

In clinical trials, assessing efficacy is based on validated scales, and the primary endpoint is usually based on a single scale. The aim of the review is to revisit the concepts and methods to design and analyze studies focused on restoration, recovery and or compensation. These studies are becoming more frequent with the development of restorative medicine.

Intravenous Injection of Clinical Grade Human MSCs After Experimental Stroke: Functional Benefit and Microvascular Effect.

Stroke is the leading cause of disability in adults. Many current clinical trials use intravenous (IV) administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs). This autologous graft requires a delay for ex vivo expansion of cells.

Positive Predictive Value of French Hospitalization Discharge Codes for Stroke and Transient Ischemic Attack.

Background: We aimed at measuring the positive predictive value (PPV) of data in the French Hospital Medical Information Database (FHD).

Summary: This retrospective multicenter study included 31 hospitals from where 56 hospital stays were randomly selected among all hospitalizations for the years 2009 and 2010 with at least 1 principal diagnosis of stroke or transient ischemic attack (TIA). Three algorithms were evaluated.

Imaging of functional and structural alterations of large arteries after acute ischaemic atherothrombotic stroke or acute coronary syndromes.

Background: Non-invasive methods allow the evaluation of structural and functional arterial abnormalities. So far, no study has focused on the comparison of vascular parameters by type of cardiovascular event.

Methods: In this pilot study, cardiovascular risk factors, carotid parameters, carotid-to-femoral pulse wave velocity (PWV), brachial flow-mediated dilation and ambulatory blood pressure were assessed in patients who presented with acute coronary syndromes (ACS) or ischaemic atherothrombotic stroke (IAS).

Upper limb recovery after stroke is associated with ipsilesional primary motor cortical activity: a meta-analysis.

Background And Purpose: Although neuroimaging studies have revealed specific patterns of reorganization in the sensorimotor control network after stroke, their role in recovery remains unsettled. To review the existing evidence systematically, we performed activation likelihood estimation meta-analysis of functional neuroimaging studies investigating upper limb movement-related brain activity after stroke.

Methods: Twenty-four studies using sensorimotor tasks in standardized coordinates were included, totaling 255 patients and 145 healthy controls.

Depression: cognition relations after stroke.

Background: Poststroke depression and cognitive dysfunction are common and are independent predictors of poor recovery.

Aims: We assessed whether and how depression and cognition were correlated in the subacute period after stroke.

Method: We prospectively recruited 207 nondemented patients (Mini Mental State Examination ≥ 23) presenting with a first-ever ischemic stroke (127 males), mean age of 48·5 years (16·4 standard deviation), median 12 days after infarction, as assessed on magnetic resonance imaging.

Magnetic resonance imaging and fluorescence labeling of clinical-grade mesenchymal stem cells without impacting their phenotype: study in a rat model of stroke.

Human mesenchymal stem cells (hMSCs) have strong potential for cell therapy after stroke. Tracking stem cells in vivo following a graft can provide insight into many issues regarding optimal route and/or dosing. hMSCs were labeled for magnetic resonance imaging (MRI) and histology with micrometer-sized superparamagnetic iron oxides (M-SPIOs) that contained a fluorophore.

How accurate is the reporting of stroke in hospital discharge data? A pilot validation study using a population-based stroke registry as control.

Population-based stroke registries can provide valid stroke incidence because they ensure exhaustiveness of case ascertainment. However, their results are difficult to extrapolate because they cover a small population. The French Hospital Discharge Database (FHDDB), which routinely collects administrative data, could be a useful tool for providing data on the nationwide burden of stroke.

Pathophysiologic cascades in ischemic stroke.

Many advances have been achieved in terms of understanding the molecular and cellular mechanisms of ischemic stroke. But thus far, clinically effective neuroprotectants remain elusive. In this minireview, we summarize the basics of ischemic cascades after stroke, covering neuronal death mechanisms, white matter pathophysiology, and inflammation with an emphasis on microglia.

Improving stroke care: a French health-care organiser's perspective.

The French national action plan: 'Stroke 2010-2014' results from years of increasing concern related to stroke, initially carried by stoke physicians and progressively shared by all other health professionals and more recently by administration and politicians. Its aim is the development not only of stroke care networks, but also of prevention and health education. Its success will mainly depend on the reactivity of the regional health agencies; therefore it is important to maintain political momentum and pressure.

In silico study of the influence of intensity and duration of blood flow reduction on cell death through necrosis or apoptosis during acute ischemic stroke.

Ischemic stroke involves numerous and complex pathophysiological mechanisms including blood flow reduction, ionic exchanges, spreading depressions and cell death through necrosis or apoptosis. We used a mathematical model based on these phenomena to study the influences of intensity and duration of ischemia on the final size of the infarcted area. This model relies on a set of ordinary and partial differential equations.

Predicting cognitive dysfunctioning in nondemented patients early after stroke.

Background: Cognitive dysfunctioning (CDF) is an important issue in stroke, interfering with recovery and social dysfunctioning. We aimed to investigate the clinical and imaging correlates of CDF in patients with a first-ever subacute ischemic stroke and no dementia.

Methods: We evaluated CDF 15 days after stroke in a prospective cohort of consecutive patients with a Mini Mental State Examination score > or =23 using a comprehensive neuropsychological battery.

Intravenous administration of 99mTc-HMPAO-labeled human mesenchymal stem cells after stroke: in vivo imaging and biodistribution.

Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after stroke. To deliver these cells, an IV injection appears safer than a local graft. We aimed to assess the whole-body biodistribution of IV-injected (99m)Tc-HMPAO-labeled hMSC in normal rats (n = 9) and following a right middle cerebral artery occlusion (MCAo, n = 9).