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Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis.

ABSTRACT: The presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH.We investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6-9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ? 3.Among 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12-2.00, p = 0.007) higher death rate compared to those without. In the older age group (?65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15-2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association.The degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.

SUBMITTER: Baik M

PROVIDER: S-EPMC5726763 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis.

Baik Minyoul M Kim Kyoungsub K Yoo Joonsang J Kim Hyeon Chang HC Jeong Seong Ho SH Kim Ki Hoon KH Park Hyung Jong HJ Kim Young Dae YD Heo Ji Hoe JH Nam Hyo Suk HS

PloS one 20171212 12

<h4>Background</h4>The presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH.<h4>Methods</h4>We investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6-9.7). The degree of WMH was a ...[more]

PMID: 29232701

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Project description:BackgroundThe progression of FLAIR white matter hyperintensities (WMHs) on MRI heralds vascular-mediated cognitive decline. Even before FLAIR WMH progression, adjacent normal appearing white matter (NAWM) already demonstrates microstructural deterioration on diffusion tensor imaging (DTI). We hypothesized that elevated DTI free water (FW) would precede FLAIR WMH progression, implicating interstitial fluid accumulation as a key pathological step in the progression of cerebral small vessel disease.MethodsParticipants at least 3 months after an ischemic stroke or TIA with WMH on MRI underwent serial brain MRIs every 3 months over the subsequent year. For each participant, the WMHs were automatically segmented, serial MRIs were aligned, and a region of WMH penumbra tissue at risk was defined by dilating lesions at any time point and subtracting baseline lesions. Penumbra voxels were classified as either stable or progressing to WMH if they were segmented as new lesions and demonstrated increasing FLAIR intensity over time. Aligned DTI images included FW and FW-corrected fractional anisotropy (FATissue) and mean diffusivity (MDTissue). Logistic regression and area under the receiver-operator characteristic curve (AUC) were used to test whether baseline DTI predicted voxel-wise classification of stable penumbra or progression to WMH while covarying for clinical risk factors.ResultsIn the included participants (n = 26, mean age 71 ± 9 years, 31% female), we detected a median annual voxel-wise WMH growth of 2.9 ± 2.6 ml. Each baseline DTI metric was associated with lesion progression in the penumbra, but FW had the greatest AUC of 0.732 (0.730 - 0.733) for predicting voxel-wise WMH progression pooled across participants.DiscussionBaseline increased interstitial fluid, estimated as FW on DTI, predicted the progression of NAWM to WMH over the following year. These results implicate the presence of FW in the pathogenesis of cerebral small vessel disease progression.

Project description:Background This study was conducted to compare frequencies of chronic brain infarctions (CBIs) and white matter hyperintensities (WMHs) as well as their associations with established early recurrence risk scores in patients with transient ischemic attack (TIA) and stroke mimics compared with ischemic stroke. Methods and Results Single-center cohort study including consecutive patients with TIA, stroke mimics, and acute ischemic stroke, with available magnetic resonance imaging from January 2015 to December 2017. Blinded raters adjudicated WMH (age-related white matter changes score) and CBI according to established definitions. A total of 2112 patients (median [Q1-Q3] age 71 [59-80] years, 43% women, National Institutes of Health Stroke Scale score of 2 [1-7], 80% ischemic stroke, 18% TIA, 2% stroke mimics) were included. While CBIs were present in only 10% of patients with stroke mimic, they were detected in 28% of TIAs and 38% of ischemic strokes (P<0.001). WMHs were less pronounced (0, 0-1) in patients with stroke mimic, but there was no difference between TIA (1, 1-2) and ischemic stroke (0, 1-2) patients. CBIs (adjusted odds ratio, 0.3; 95% CI, 0.1-0.9) were associated with a lower rate of stroke mimic as the final diagnosis, while WMHs were not (adjusted odds ratio per point, 1.3; 95% CI, 0.7-2.2). WMH (β per point, 0.4; 95% CI, 0.3-0.6) and presence of CBI (β, 0.6; 95% CI, 0.3-0.9) were associated with a higher cardiovascular risk profile according to the ABCD3-I score. The accuracy of prediction was good for high-risk TIA (cross-validated area under the receiver operating characteristic curve, 0.89; 95% CI, 0.79-0.93) on the basis of brain imaging, age, and sex. Conclusions CBI and WMH differ between patients with stroke mimic and patients with TIA/ischemic stroke and are closely associated with established recurrence risk scores. Prospective studies need to clarify whether including brain frailty markers may contribute to the refinement of current management algorithms and risk stratifications.

Project description: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. 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. 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. 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. 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.

Project description:Background: White matter hyperintensities of presumed vascular origin (WMH) are a common finding in elderly people and a growing social malady in the aging western societies. As a manifestation of cerebral small vessel disease, WMH are considered to be a vascular contributor to various sequelae such as cognitive decline, dementia, depression, stroke as well as gait and balance problems. While pathophysiology and therapeutical options remain unclear, large-scale studies have improved the understanding of WMH, particularly by quantitative assessment of WMH. In this review, we aimed to provide an overview of the characteristics, research subjects and segmentation techniques of these studies. Methods: We performed a systematic review according to the PRISMA statement. One thousand one hundred and ninety-six potentially relevant articles were identified via PubMed search. Six further articles classified as relevant were added manually. After applying a catalog of exclusion criteria, remaining articles were read full-text and the following information was extracted into a standardized form: year of publication, sample size, mean age of subjects in the study, the cohort included, and segmentation details like the definition of WMH, the segmentation method, reference to methods papers as well as validation measurements. Results: Our search resulted in the inclusion and full-text review of 137 articles. One hundred and thirty-four of them belonged to 37 prospective cohort studies. Median sample size was 1,030 with no increase over the covered years. Eighty studies investigated in the association of WMH and risk factors. Most of them focussed on arterial hypertension, diabetes mellitus type II and Apo E genotype and inflammatory markers. Sixty-three studies analyzed the association of WMH and secondary conditions like cognitive decline, mood disorder and brain atrophy. Studies applied various methods based on manual (3), semi-automated (57), and automated segmentation techniques (75). Only 18% of the articles referred to an explicit definition of WMH. Discussion: The review yielded a large number of studies engaged in WMH research. A remarkable variety of segmentation techniques was applied, and only a minority referred to a clear definition of WMH. Most addressed topics were risk factors and secondary clinical conditions. In conclusion, WMH research is a vivid field with a need for further standardization regarding definitions and used methods.

Dataset Information

Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis.

Publications

Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis.

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