scholarly journals Genetic Architecture of White Matter Hyperintensities Differs in Hypertensive and Nonhypertensive Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (2) ◽  
pp. 348-353 ◽  
Author(s):  
Poneh Adib-Samii ◽  
William Devan ◽  
Matthew Traylor ◽  
Silvia Lanfranconi ◽  
Cathy R. Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Genetic Architecture ◽  
White Matter Hyperintensities

scholarly journals Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke

2019 ◽  
Vol 9 (1) ◽  
pp. 16 ◽  
Author(s):  
Imama Naqvi ◽  
Emi Hitomi ◽  
Richard Leigh
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Stroke ◽  
Blood Brain Barrier ◽  
White Matter Hyperintensities ◽  
Brain Barrier ◽  
Common Finding ◽  
Blood Brain ◽  
History Of ◽  
Iv Tpa

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.

scholarly journals Association between homocysteine and white matter hyperintensities in asymptomatic intracranial arterial stenosis: results from a population-based study

2019 ◽  
Author(s):  
Hao Yin ◽  
Xiang Wang ◽  
Yuan-yuan Zhao ◽  
Xiao-kang Ji ◽  
Shao-wei Sang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
White Matter ◽  
Magnetic Resonance ◽  
White Matter Hyperintensities ◽  
Population Based ◽  
Arterial Stenosis ◽  
Chinese People ◽  
Intracranial Arterial Stenosis ◽  
Population Based Study

Abstract Background: Although homocysteine (Hcy) and white matter hyperintensities (WMH) have been proven to be correlated with increased risks of ischemic stroke, there have been few studies addressing the association between serum Hcy and WMH in a population with asymptomatic intracranial arterial stenosis (aICAS). Thus, the aim of the present study is to describe the association between Hcy and WMH in rural-dwelling Chinese people with aICAS. Methods: In this study, 150 participants diagnosed as aICAS by magnetic resonance angiography were recruited from the Kongcun Town Study, which was a population-based study aimed to investigate the prevalence of aICAS in general population aged 40 to 90 years old, free of ischemic stroke history, and living in the Kongcun town, Pingyin county, Shandong, China. Data on demographics, risk factors, and serum Hcy levels were collected via interview, clinical examination, and laboratory tests. The WMH volumes were calculated through the lesion segmentation tool system for the Statistical Parametric Mapping package based on magnetic resonance imaging. The association between Hcy and WMH volume was analyzed using both linear and logistic regression analysis. Results: After adjusting for all confounders, high Hcy (HHcy) (serum Hcy ≥15umol/L) was significantly associated with severe WMH (the highest quartile in WMH volume) (OR: 2.972, 95%CI: 1.017-7.979, P <0.05). However, with changing of WMH volumes, only trends towards association with HHcy were observed in all 3 models (P values only slightly exceeded 0.05). After being stratified by age, sex, or ever smoking, the association between HHcy and WMH became more significant in participants who were ≥60 years old, male, or ever smoker. Conclusions: HHcy is associated with severe WMH in rural-dwelling Chinese people with aICAS, especially in participants ≥60 years old, male participants, or ever smokers, indicating these may be risk factors that contribute to the association between HHcy and severe WMH.

scholarly journals MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation

Neurology ◽  
2019 ◽  
Vol 92 (21) ◽  
pp. e2432-e2443 ◽  
Author(s):  
Joan Martí-Fàbregas ◽  
Santiago Medrano-Martorell ◽  
Elisa Merino ◽  
Luis Prats-Sánchez ◽  
Rebeca Marín ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Intracranial Hemorrhage ◽  
White Matter Hyperintensities ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Hazard Ratio ◽  
Superficial Siderosis ◽  
Increased Risk

ObjectiveWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.MethodsPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.ResultsWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).ConclusionPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.ClinicalTrials.gov identifierNCT02238470.

scholarly journals Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 2901-2909
Author(s):  
Mukul Sharma ◽  
Robert G. Hart ◽  
Eric E. Smith ◽  
Jacqueline Bosch ◽  
John W. Eikelboom ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Magnetic Resonance ◽  
Cognitive Decline ◽  
Odds Ratio ◽  
White Matter Hyperintensities ◽  
Cerebral Microbleeds ◽  
Cognitive Tests ◽  
Brain Infarcts ◽  
End Point

Background and Purpose: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. Methods: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. Results: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. Conclusions: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

scholarly journals Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities

Stroke ◽  
2020 ◽  
Vol 51 (7) ◽  
pp. 2111-2121 ◽  
Author(s):  
Nicola J. Armstrong ◽  
Karen A. Mather ◽  
Muralidharan Sargurupremraj ◽  
Maria J. Knol ◽  
Rainer Malik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Imaging Genetics ◽  
Genome Wide Association ◽  
Association Analyses ◽  
New Genes ◽  
Genome Wide

Background and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 ( NBEAL ), 10q23.1 ( TSPAN14/FAM231A ), and 10q24.33 ( SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 ( NOS3 ) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction

2016 ◽  
Vol 43 (1-2) ◽  
pp. 17-24 ◽  
Author(s):  
Søren Due Andersen ◽  
Torben Bjerregaard Larsen ◽  
Anders Gorst-Rasmussen ◽  
Yousef Yavarian ◽  
Gregory Y.H. Lip ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Risk Score ◽  
White Matter Hyperintensities ◽  
Stroke Risk ◽  
Risk Scores ◽  
Stroke Recurrence ◽  
Cerebral White Matter ◽  
Clinical Scores ◽  
Recurrence Prediction

Background: Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA2DS2VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. Methods: In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA2DS2VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. Results: White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA2DS2VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed improved C-statistics: the recalibrated CHA2DS2VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). Conclusions: An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA2DS2VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence.

scholarly journals Magnetic Resonance Imaging White Matter Hyperintensities and Mechanism of Ischemic Stroke

Stroke ◽  
1999 ◽  
Vol 30 (10) ◽  
pp. 2053-2058 ◽  
Author(s):  
Riitta Mäntylä ◽  
Hannu J. Aronen ◽  
Oili Salonen ◽  
Tarja Pohjasvaara ◽  
Mauno Korpelainen ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Ischemic Stroke ◽  
White Matter ◽  
Magnetic Resonance ◽  
White Matter Hyperintensities ◽  
Resonance Imaging
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