Stroke

Background and Purpose-The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods-A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results-Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2-6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (β=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (β=-0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions-NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery. © 2020 Lippincott Williams and Wilkins. All rights reserved.Translational Research and Advanced Imaging Laborator

Radiology

Background: A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose: To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods: In this secondary analysis, two prospectively collected independent stroke data sets (2012–2015 and 2017–2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1–3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion–related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results: Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58–80 years]; 207 men) and 173 (median age, 74 years [IQR, 65–82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P =.02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P =.004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P =.20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P =.01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P =.03). Conclusion: Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. © RSNA, 2022.Translational Research and Advanced Imaging Laborator

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Apport des biomarqueurs radiologiques dans la prédiction de la récupération après un infarctus cérébral

Stroke is the first cause of non-traumatic disability, and the second cause of dementia in France. Demographic factors and the characteristics of the stroke lesion are well-known risk factors of post-stroke disability. However, the cerebral parenchyma surrounding stroke might also have a role in the outcome. White matter hyperintensities (WMH) and cerebral atrophy are the radiological biomarkers more usually reported. The aim of the work was to evaluate the influence of cortical atrophy using quantitative tool, and of other new radiological biomarkers in post-ischemic stroke outcome. Study population was recruited from the “Brain Before Stroke” study, a prospective and monocentric study conducted at the Bordeaux University Hospital. The main inclusion criteria were an age > 18 years old, and the diagnosis of an acute ischemic supra-tentorial stroke in subjects free from pre-stroke neurological disability or dementia. A clinical assessment was performed, including cognitive, mood, gait and global functional tests, and patients were followed over one year. A multimodal brain 3 Tesla MRI was performed at baseline. Four biomarkers were analyzed: the cortical volume, the integrity of normal appearing white matter using diffusion tensor imaging, cortical cerebral microinfarcts (CMI), and cerebral amyloid angiopathy biomarkers. One hundred seventy-one to 207 patients were included in the analyses (mean age 65 to 66 ± 13 to 14). The patients with worse performances at baseline had the best improvement at three months. Using a voxel-based morphometry approach, these patients had lower cortical volumes in fronto-temporal regions. The severity of WMH was associated with changes in global cognition scores, and executive functions. Normal appearing white matter integrity in widespread regions was associated with one-year global functional outcome. The number of cortical CMI visually detected was associated with a slowdown improvement of psychomotor speed. The presence of superficial cortical siderosis was associated with a slowdown of attentional functions improvement. To conclude, the detection of radiological biomarkers early after an ischemic stroke enables the identification of patients with a higher risk of a slowdown recovery after one year, and with higher cognitive vulnerability.Les accidents vasculaires cérébraux sont la première cause de handicap non traumatique, et la deuxième cause de démence en France. Outre les facteurs de risque démographiques et les facteurs liés à la lésion elle-même, le parenchyme cérébral en dehors de la lésion aurait un rôle dans la récupération. Les biomarqueurs radiologiques les plus couramment décrits sont les hypersignaux de la substance blanche (HSB) et l’atrophie cérébrale. L’objectif du travail était d’évaluer l’influence de ces biomarqueurs avec des mesures quantitatives objectives sur le pronostic à un an d’un infarctus cérébral, et d’évaluer l’influence d’autres biomarqueurs moins fréquemment rapportés. Les sujets recrutés étaient ceux de l’étude « Brain Before Stroke », une étude prospective monocentrique menée au Centre Hospitalier Universitaire de Bordeaux. Les principaux critères d’inclusion étaient des sujets âgés de plus de 18 ans, ayant présenté un infarctus cérébral supra-tentoriel, sans handicap neurologique ni démence antérieurs. Les patients ont bénéficié d’une évaluation clinique comprenant des scores cognitifs, thymiques, de l’équilibre et fonctionnels, et ont été suivis pendant un an. Une IRM cérébrale 3 Tesla multimodale a été réalisée à la phase initiale. Quatre biomarqueurs ont été analysés : le volume cortical, l’intégrité de la substance d’apparence normale sur les séquences de tenseur de diffusion (fraction d’anisotropie, diffusivité moyenne, axiale et radiale), les microinfarctus cérébraux (MIC) corticaux et les biomarqueurs d’angiopathie amyloïde cérébrale. Cent soixante et onze à 207 patients ont été inclus dans les analyses (âge moyen 65 à 66 ans ± 13 à 14). Les patients avec les moins bonnes performances cognitives à la phase initiale se sont le plus améliorés à trois mois. En utilisant une méthode d’analyse basée sur l’intensité de voxels à voxels, ces patients avaient de plus petits volumes corticaux dans les régions fronto-temporales. La sévérité des HSB était associée à l’évolution des fonctions cognitives globales et exécutives. L’intégrité de la substance blanche d’apparence normale dans des régions diffuses était associée au pronostic fonctionnel à un an. Le nombre de MIC corticaux détectés visuellement était associé à un ralentissement de la récupération de la vitesse psychomotrice. La présence de sidérose corticale superficielle était associée à un ralentissement de la récupération des fonctions attentionnelles. En conclusion, la détection de biomarqueurs radiologiques dès la phase aiguë d’un infarctus cérébral permet d’identifier les patients à risque de récupération plus lente à un an et de plus grande vulnérabilité cognitive

The contribution of radiological biomarkers in the prediction of recovery after an ischemic stroke

Les accidents vasculaires cérébraux sont la première cause de handicap non traumatique, et la deuxième cause de démence en France. Outre les facteurs de risque démographiques et les facteurs liés à la lésion elle-même, le parenchyme cérébral en dehors de la lésion aurait un rôle dans la récupération. Les biomarqueurs radiologiques les plus couramment décrits sont les hypersignaux de la substance blanche (HSB) et l’atrophie cérébrale. L’objectif du travail était d’évaluer l’influence de ces biomarqueurs avec des mesures quantitatives objectives sur le pronostic à un an d’un infarctus cérébral, et d’évaluer l’influence d’autres biomarqueurs moins fréquemment rapportés. Les sujets recrutés étaient ceux de l’étude « Brain Before Stroke », une étude prospective monocentrique menée au Centre Hospitalier Universitaire de Bordeaux. Les principaux critères d’inclusion étaient des sujets âgés de plus de 18 ans, ayant présenté un infarctus cérébral supra-tentoriel, sans handicap neurologique ni démence antérieurs. Les patients ont bénéficié d’une évaluation clinique comprenant des scores cognitifs, thymiques, de l’équilibre et fonctionnels, et ont été suivis pendant un an. Une IRM cérébrale 3 Tesla multimodale a été réalisée à la phase initiale. Quatre biomarqueurs ont été analysés : le volume cortical, l’intégrité de la substance d’apparence normale sur les séquences de tenseur de diffusion (fraction d’anisotropie, diffusivité moyenne, axiale et radiale), les microinfarctus cérébraux (MIC) corticaux et les biomarqueurs d’angiopathie amyloïde cérébrale. Cent soixante et onze à 207 patients ont été inclus dans les analyses (âge moyen 65 à 66 ans ± 13 à 14). Les patients avec les moins bonnes performances cognitives à la phase initiale se sont le plus améliorés à trois mois. En utilisant une méthode d’analyse basée sur l’intensité de voxels à voxels, ces patients avaient de plus petits volumes corticaux dans les régions fronto-temporales. La sévérité des HSB était associée à l’évolution des fonctions cognitives globales et exécutives. L’intégrité de la substance blanche d’apparence normale dans des régions diffuses était associée au pronostic fonctionnel à un an. Le nombre de MIC corticaux détectés visuellement était associé à un ralentissement de la récupération de la vitesse psychomotrice. La présence de sidérose corticale superficielle était associée à un ralentissement de la récupération des fonctions attentionnelles. En conclusion, la détection de biomarqueurs radiologiques dès la phase aiguë d’un infarctus cérébral permet d’identifier les patients à risque de récupération plus lente à un an et de plus grande vulnérabilité cognitive.Stroke is the first cause of non-traumatic disability, and the second cause of dementia in France. Demographic factors and the characteristics of the stroke lesion are well-known risk factors of post-stroke disability. However, the cerebral parenchyma surrounding stroke might also have a role in the outcome. White matter hyperintensities (WMH) and cerebral atrophy are the radiological biomarkers more usually reported. The aim of the work was to evaluate the influence of cortical atrophy using quantitative tool, and of other new radiological biomarkers in post-ischemic stroke outcome. Study population was recruited from the “Brain Before Stroke” study, a prospective and monocentric study conducted at the Bordeaux University Hospital. The main inclusion criteria were an age > 18 years old, and the diagnosis of an acute ischemic supra-tentorial stroke in subjects free from pre-stroke neurological disability or dementia. A clinical assessment was performed, including cognitive, mood, gait and global functional tests, and patients were followed over one year. A multimodal brain 3 Tesla MRI was performed at baseline. Four biomarkers were analyzed: the cortical volume, the integrity of normal appearing white matter using diffusion tensor imaging, cortical cerebral microinfarcts (CMI), and cerebral amyloid angiopathy biomarkers. One hundred seventy-one to 207 patients were included in the analyses (mean age 65 to 66 ± 13 to 14). The patients with worse performances at baseline had the best improvement at three months. Using a voxel-based morphometry approach, these patients had lower cortical volumes in fronto-temporal regions. The severity of WMH was associated with changes in global cognition scores, and executive functions. Normal appearing white matter integrity in widespread regions was associated with one-year global functional outcome. The number of cortical CMI visually detected was associated with a slowdown improvement of psychomotor speed. The presence of superficial cortical siderosis was associated with a slowdown of attentional functions improvement. To conclude, the detection of radiological biomarkers early after an ischemic stroke enables the identification of patients with a higher risk of a slowdown recovery after one year, and with higher cognitive vulnerability

Gait Change Is Associated with Cognitive Outcome after an Acute Ischemic Stroke

Background: Cognition and gait have often been studied separately after stroke whereas it has been suggested that these two domains could interact through a cognitive-motor interference.Objective: To evaluate the influence of gait changes on cognitive outcome after an ischemic stroke (IS).Methods: We conducted a prospective and monocentric study including patients admitted for an acute supratentorial IS with a National Institute of Health Stroke Score ≤ 15. Cognition, gait and motor disability were evaluated at baseline, 3 months and 1 year post-stroke, using the Montreal Cognitive Assessment (MoCA), the 10-m walking test (10-MWT) and the Fugl-Meyer motor assessment (FMMA). The effect of changes in 10-MWT over the year of follow-up on MoCA changes was estimated using a generalized linear mixed model with FMMA, age and gender as covariates.Results: Two hundred and Twelve patients were included (71% male, age 64 ± 13 years old). 10-MWT improved from baseline to 1 year (p < 0.001), as did MoCA (p < 0.001) and FMMA (p < 0.001) scores. Ninety-nine patients (47%) had a MoCA <26 at 1 year. Changes in 10-MWT were independently associated with changes in MoCA (β = −0.2, 95% CI −0.24 to −0.07, Bonferroni-corrected p-value = 0.002). Analyses of MoCA sub-scores suggested that changes in gait performance was associated with changes in executive functions and recall.Conclusion: Gait performance is associated with cognitive outcome after a mild to moderate IS, suggesting that they should be managed together to improve post-stroke independence

Invest Radiol

BACKGROUND: Gadolinium leakage in ocular structures (GLOS) was recently observed in fluid-attenuated inversion recovery (FLAIR) images obtained the day after an initial gadolinium injection in stroke patients. The specificity of GLOS to stroke and its mechanisms remain unclear. OBJECTIVE: We investigated the factors associated with GLOS in a cohort of patients presenting with acute neurological deficits. MATERIALS AND METHODS: This retrospective study included consecutive patients admitted to our stroke unit for acute neurological deficit between July 2017 and August 2018 who underwent baseline brain magnetic resonance imaging with the injection of a macrocyclic gadolinium agent and another scan without injection within 72 hours. The patients were separated into a stroke group and a stroke mimic group based on diffusion-weighted images. Gadolinium leakage in ocular structures was defined as a bright signal in the vitreous in follow-up FLAIR compared with baseline FLAIR (pregadolinium). Clinical data were collected together with imaging features from the baseline scans, including the volume of the infarct and of hypoperfusion if applicable, white matter hyperintensities, the number of lacunes, and the number of microbleeds, which were combined to yield a small vessel disease (SVD) score. We compared the prevalence of GLOS in both groups using the χ2 test. In the entire cohort, univariate and multivariate regression models were used to test the associations between GLOS and the collected data. RESULTS: Among the 467 patients included in the study, GLOS was observed in similar proportions in the stroke group (32.2%, 136/422) and the stroke mimic group (28.9%, 13/45; mean difference, 3.3%; 95% confidence interval, -10.9 to 17.6; P = 0.65). In univariate analysis, GLOS was associated with older age, increased prevalence of vascular risk factors, brain imaging features of SVD (white matter hyperintensities, lacunes, microbleeds), as well as with impairment of renal function and increased dose of gadolinium. No associations were found with factors related to stroke, such as its volume, acute treatment, or rate of recanalization. Multivariate analyses showed that aging (P < 0.001), diabetes (P = 0.010), severe renal failure (P = 0.004), and increased dose of gadolinium (P < 0.001) were independent contributors to GLOS. CONCLUSIONS: Gadolinium leakage in ocular structures, which occurs more commonly at higher concentrations of gadolinium, is not specific to stroke and may represent increased permeability of the blood-retinal barrier associated with age- and vascular risk factor-related SVD

Association between neurological outcome and poststroke comorbid mood and anxiety disorders: A real‐life experience

Abstract Introduction Poststroke depression (PSD) and anxiety (PSA) are prevalent and have a strong impact on functional outcome. Beside stroke severity, little is known on their clinical determinants. This study investigated the association between stroke mechanism, neurological poststroke complications and remaining vascular risk factors and the presence of comorbid PSD and PSA, termed poststroke emotional distress (PSED). Methods This was a retrospective analysis of a prospectively compiled medical records database of consecutive patients evaluated during a follow‐up visit 3‐ to 4‐month poststroke. HAD scale was used to define PSED category (PSD+PSA vs. NoPSD+NoPSA). Stroke mechanism and poststroke complications were identified clinically or using appropriate scales. Their association with PSED was tested using a multivariate logistic regression model. Results The sample included 2,300 patients (male: 64.8%); 19% had a PSED and 56.39% were free of any depression or anxiety. The most frequent poststroke complications were fatigue/fatigability (58.4%), sleep problems (26.7%), and pain (20.4%). While no association was observed between PSED and stroke mechanism, higher functional disability (OR:1.572), lower cognitive abilities (OR:0.953), sleep problems (OR:2.334), pain (OR:1.478), fatigue/fatigability (OR:2.331), and abnormal movements (OR:2.380) were all independent risk factors. Persisting tobacco consumption (OR:1.360) was the only vascular significant risk factor. Conclusions The frequency of comorbid PSED remains high (1/5 patient) despite improved awareness of these conditions. The association between poststroke complications and the presence of PSED emphasizes the need for standardized neurological and psychological evaluations at follow‐up. These results foster the need to improve the management of addictive behaviors to reduce the burden of PSED