Pre-existing White Matter Hyperintensity Lesion Burden and Diagnostic Certainty of Transient Ischemic Attack.
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ABSTRACT:
SUBMITTER: Nagy M
PROVIDER: S-EPMC6441369 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:IntroductionTo determine the influence of white matter hyperintensity (WMH) burden on functional outcome, rate of symptomatic intracerebral hemorrhage (sICH), and procedural success in patients with acute ischemic stroke (AIS) treated by mechanical thrombectomy (MT) with current stentriever/aspiration devices.MethodsPatients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. WMH volumes were obtained by semiautomated planimetric segmentation and tested in association with the rate of favorable outcome (90-day functional independence), substantial recanalization after MT, and sICH.ResultsA total of 496 participants were included between 2015 and 2018 (50% female, mean age 68.1 ± 15.0 years). Overall, 434 (88%) patients presented with detectable WMH (mean ± SD 4.93 ± 7.7). Patients demonstrated increasingly worse outcomes with increasing WMH volumes (odds ratio [aOR]1.05 per 1-cm3 increase for unfavorable outcome, 95% confidence interval [CI] 1.01-1.06, p = 0.014). Fifty-seven percent of patients in the first quartile of WMH volume vs 28% in the fourth quartile demonstrated favorable outcome (p < 0.001). WMH severity was not associated with sICH rate (aOR 0.99, 95% CI 0.93-1.04, p = 0.66), nor did it influence recanalization success (aOR 0.99, 95% CI 0.96-1.02, p = 0.84).ConclusionOur study provides evidence that in patients with AIS due to LVO and high burden of WMH as assessed by pretreatment MRI, the safety and efficacy profiles of MT are similar to those in patients with lower WMH burden and confirms that they are at higher risk of unfavorable outcome. Because more than a quarter of patients in the highest WMH quartile experienced favorable 3 months outcome, WMH burden may not be a good argument to deny MT.Clinicaltrialsgov identifierNCT01062698.
| S-EPMC6815208 | biostudies-literature
Project description:BackgroundTransient ischemic attack (TIA) is a known risk factor for stroke. Abnormal alterations in the low-frequency range of the gray matter (GM) of the brain have been studied in patients with TIA. However, whether there are abnormal neural activities in the low-frequency range of the white matter (WM) in patients with TIA remains unknown. The current study applied two resting-state metrics to explore functional abnormalities in the low-frequency range of WM in patients with TIA. Furthermore, a reinforcement learning method was used to investigate whether altered WM function could be a diagnostic indicator of TIA.MethodsWe enrolled 48 patients with TIA and 41 age- and sex-matched healthy controls (HCs). Resting-state functional magnetic resonance imaging (rs-fMRI) and clinical/physiological/biochemical data were collected from each participant. We compared the group differences between patients with TIA and HCs in the low-frequency range of WM using two resting-state metrics: amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The altered ALFF and fALFF values were defined as features of the reinforcement learning method involving a Q-learning algorithm.ResultsCompared with HCs, patients with TIA showed decreased ALFF in the right cingulate gyrus/right superior longitudinal fasciculus/left superior corona radiata and decreased fALFF in the right cerebral peduncle/right cingulate gyrus/middle cerebellar peduncle. Based on these two rs-fMRI metrics, an optimal Q-learning model was obtained with an accuracy of 82.02%, sensitivity of 85.42%, specificity of 78.05%, precision of 82.00%, and area under the curve (AUC) of 0.87.ConclusionThe present study revealed abnormal WM functional alterations in the low-frequency range in patients with TIA. These results support the role of WM functional neural activity as a potential neuromarker in classifying patients with TIA and offer novel insights into the underlying mechanisms in patients with TIA from the perspective of WM function.
| S-EPMC9592236 | biostudies-literature
Project description:ObjectiveTo determine the time of acceleration in white matter hyperintensity (WMH) burden, a common indicator of cerebrovascular pathology, in relation to conversion to mild cognitive impairment (MCI) in the elderly.MethodsA total of 181 cognitively intact elderly volunteers from the longitudinal, prospective, Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MRIs were analyzed for imaging markers of neurodegeneration: WMH and ventricular CSF (vCSF) volumes. The time before MCI, when the changes in WMH and vCSF burden accelerate, was assessed using a mixed-effects model with a change point for subjects who developed MCI during follow-up.ResultsDuring a follow-up duration of up to 19.6 years, 134 subjects converted to MCI. Acceleration in %WMH volume increase occurred 10.6 years before MCI onset. On average, the annual rate of change in %WMH increased an additional 3.3% after the change point. Acceleration in %vCSF volume increase occurred 3.7 years before the onset of MCI. Out of 63 subjects who converted to MCI and had autopsy, only 28.5% had Alzheimer disease (AD) as the sole etiology of their dementia, while almost just as many (24%) had both AD and significant ischemic cerebrovascular disease present.ConclusionsAcceleration in WMH burden, a common indicator of cerebrovascular disease in the elderly, is a pathologic change that emerges early in the presymptomatic phase leading to MCI. Longitudinal changes in WMH may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease-modifying therapies prior to dementia onset.
| S-EPMC3421153 | biostudies-literature
Project description:ObjectivesSmall subcortical infarcts (SSI) frequently coexist with brain white matter hyperintensity (WMH) lesions. We sought to determine whether preexisting WMH burden relates to SSI volume, SSI etiology, and 90-day functional outcome.Materials and methodsWe retrospectively studied 80 consecutive patients with acute SSI. Infarct volume was determined on diffusion weighted imaging, and WMH burden was graded on fluid-attenuated inversion recovery sequences according to the Fazekas scale. SSI etiology was categorized as small vessel disease (SVD) vs non-SVD related. Multivariable linear and logistic regression models were constructed to determine whether WMH burden was independently associated with the SSI volume and a poor 90-day outcome (modified Rankin scale [mRS] score >2), respectively.ResultsIn unadjusted analyses, patients with non-SVD-related SSI were older (P=.002) and more frequently had multiple infarcts (P<.001) than patients with SVD-related SSI. In the fully adjusted model, WMH severity (Coefficient 0.07; 95%-CI 0.029-0.117; P=.002) but not SSI etiology (P>.1) was independently associated with the SSI volume. On multivariable logistic regression, worse WMH (OR 2.28; 95%-CI 1.04-4.99; P=.040), SSI etiology (OR 9.20; 95%-CI 1.04-81.39; P=.046), preadmission mRS (OR 8.96; 95%-CI 2.65-30.27; P<.001), and SSI volume (OR 1.98; 95%-CI 1.14-3.44; P=.016) were associated with a poor 90-day outcome.ConclusionsGreater WMH burden is independently associated with a larger SSI volume and a worse 90-day outcome.
| S-EPMC5332524 | biostudies-literature
Project description:Background and purposeThe purpose of this study was to replicate the top loci associated with white matter hyperintensity (WMH) phenotypes identified by large genome-wide association studies and the loci identified from the previous candidate gene studies.MethodsA total of 946 Geisinger MyCode patients with acute ischemic stroke with validated European ancestry and magnetic resonance imaging data were included in this study. Log-transformed WMH volume, as a quantitative trait, was calculated by a fully automated quantification process. The genome-wide association studies was carried out by a linear mixed regression model (GEMMA). A candidate-single nucleotide polymorphism analysis by including known single nucleotide polymorphisms, reported from a meta-analysis and several large GWAS for WMH, was conducted in all cases and binary converted extreme cases.ResultsNo genome-wide significantly associated variants were identified. In a candidate-single nucleotide polymorphism study, rs9515201 (COL4A2) and rs3744028 (TRIM65), 2 known genetic loci, showed nominal or trend of association with the WMH volume (β=0.13 and P=0.001 for rs9515201; β=0.094 and P=0.094 for rs3744028), and replicated in a subset of extreme cases versus controls (odds ratio=1.78, P=7.74×10-4 for rs9515201; odds ratio=1.53, P=0.047 for rs3744028, respectively). MTHFR677 cytosine/thymine (rs1801133) also showed an association with the binary WMH with odds ratio=1.47 for T allele (P=0.019).ConclusionsReplication of COL4A1/2 associated with WMH reassures that the genetic risk factors for monogenic and polygenic ischemic stroke are shared at gene level.
| S-EPMC8336687 | biostudies-literature
Project description:White matter hyperintensities (WMHs) are associated with progressive age-related cognitive decline and cardiovascular risk factors, but their biological relevance as indicators of generalized white matter injury is unclear. Diffusion tensor imaging provides more sensitive indications of subtle white matter disruption and can therefore clarify whether WMHs represent foci of generalized white matter damage that extends over a broader neighborhood.Two hundred eight participants from the University of California, Davis Alzheimer's Disease Center received a comprehensive clinical evaluation and brain MRI including fluid-attenuated inversion recovery and diffusion tensor imaging sequences. Voxelwise maps of WMHs were produced from fluid-attenuated inversion recovery using a standardized WMH detection protocol. Fractional anisotropy maps were calculated from diffusion tensor imaging. All WMH and fractional anisotropy maps were coregistered to a standardized space. For each normal-appearing white matter voxel in each subject fluid-attenuated inversion recovery scan, a neighborhood white matter injury score was calculated that increased with increasing number and proximity of WMH in the vicinity of the normal-appearing white matter voxel. Fractional anisotropy was related to neighborhood white matter injury using a nonlinear mixed effect model controlling for relevant confounding factors.Fractional anisotropy was found to decrease as neighborhood white matter injury increased (? = -0.0017/%, P < 0.0001) with an accelerated rate (P < 0.0001) for neighborhood white matter injury >0.4. An increase of 1% in neighborhood white matter injury score was associated with a decrease in mean fractional anisotropy of 0.012 (P < 0.001).WMH may represent foci of more widespread and subtle white matter changes rather than distinct, sharply delineated anatomic abnormalities. We use the term white matter hyperintensities penumbra to explain this phenomenon.
| S-EPMC3125449 | biostudies-literature
Project description:Prior intracerebral hemorrhage (ICH) is associated with increased risk of ischemic stroke. Since white matter hyperintensity (WMH) is associated with ischemic stroke and ICH, this study aimed to evaluate the relationship between ICH and the risk of recurrent stroke by WMH severity. From a prospective multicenter database comprising 1454 noncardioembolic stroke patients with cerebral small-vessel disease, patients were categorized by presence or absence of prior ICH and WMH severity: mild-moderate WMH (reference); advanced WMH; ICH with mild-moderate WMH; and ICH with advanced WMH. Among patients with ICH, the association with stroke outcomes by WMH burden was further assessed. The primary endpoint was ischemic stroke and hemorrhagic stroke. The secondary endpoint was major adverse cardiovascular events (MACE): stroke/coronary heart disease/vascular death. During the mean 1.9-year follow-up period, the ischemic stroke incidence rate per 100 person-years was 2.7, 4.0, 2.5, and 8.1 in increasing severity, and the rate of hemorrhagic stroke was 0.7, 1.3, 0.6, and 2.1, respectively. The risk of ischemic stroke was higher in ICH with advanced WMH (adjusted HR 2.62; 95% CI 1.22-5.60) than the reference group, while the risk of hemorrhagic stroke trended higher (3.75, 0.85-16.53). The risk of MACE showed a similar pattern in ICH with advanced WMH. Among ICH patients, compared with mild WMH, the risk of ischemic stroke trended to be higher in advanced WMH (HR 3.37; 95% CI 0.90‒12.61). Advanced WMH was independently associated with an increased risk of hemorrhagic stroke (HR 33.96; 95% CI 1.52-760.95). Given the fewer rate of hemorrhagic stroke, the risk of hemorrhagic stroke might not outweigh the benefits of antiplatelet therapy for secondary prevention.
| S-EPMC8408204 | biostudies-literature
Project description:White matter hyperintensities of presumed vascular origin (WMH) are a prevalent form of cerebral small-vessel disease and an important risk factor for post-stroke cognitive dysfunction. Despite this prevalence, it is not well understood how WMH contributes to post-stroke cognitive dysfunction. Preliminary findings suggest that increasing WMH volume is associated with total hippocampal volume in chronic stroke patients. The hippocampus, however, is a complex structure with distinct subfields that have varying roles in the function of the hippocampal circuitry and unique anatomical projections to different brain regions. For these reasons, an investigation into the relationship between WMH and hippocampal subfield volume may further delineate how WMH predispose to post-stroke cognitive dysfunction. In a prospective study of acute ischemic stroke patients with moderate/severe WMH burden, we assessed the relationship between quantitative WMH burden and hippocampal subfield volumes. Patients underwent a 3T MRI brain within 2-5 days of stroke onset. Total WMH volume was calculated in a semi-automated manner. Mean cortical thickness and hippocampal volumes were measured in the contralesional hemisphere. Total and subfield hippocampal volumes were measured using an automated, high-resolution, ex vivo computational atlas. Linear regression analyses were performed for predictors of total and subfield hippocampal volumes. Forty patients with acute ischemic stroke and moderate/severe white matter hyperintensity burden were included in this analysis. Median WMH volume was 9.0 cm3. Adjusting for intracranial volume and stroke laterality, age (β = -3.7, P < 0.001), hypertension (β = -44.7, P = 0.04), WMH volume (β = -0.89, P = 0.049), and mean cortical thickness (β = 286.2, P = 0.006) were associated with total hippocampal volume. In multivariable analysis, age (β = -3.3, P < 0.001) and cortical thickness (β = 205.2, P = 0.028) remained independently associated with total hippocampal volume. In linear regression for predictors of hippocampal subfield volume, increasing WMH volume was associated with decreased hippocampal-amygdala transition area volume (β = -0.04, P = 0.001). These finding suggest that in ischemic stroke patients, increased WMH burden is associated with selective hippocampal subfield degeneration in the hippocampal-amygdala transition area.
| S-EPMC7649326 | biostudies-literature
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.
| S-EPMC9238476 | biostudies-literature
Project description:Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.
| S-EPMC7585696 | biostudies-literature