White Matter Hyperintensities Grade Research Articles

Patients with normal pressure hydrocephalus have fewer enlarged perivascular spaces in the centrum semiovale compared to cognitively unimpaired individuals

IntroductionEnlarged perivascular spaces (ePVS) may be an indicator of glymphatic dysfunction. Limited studies have evaluated the role of ePVS in idiopathic normal pressure hydrocephalus (iNPH). We aimed to characterize the distribution and number of ePVS in iNPH compared to controls. MethodsThirty-eight patients with iNPH and a pre-shunt MRI were identified through clinical practice. Age- and sex-matched controls who had negative MRIs screening for intracranial metastases were identified through a medical record linkage system. The number of ePVS were counted in the basal nuclei (BN) and centrum semiovale (CS) using the Wardlaw method blinded to clinical diagnosis. Imaging features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), callosal angle, Fazekas white matter hyperintensity (WMH) grade, and the presence of microbleeds and lacunes were also evaluated. ResultsBoth iNPH patients and controls had a mean age of 74 ± 7 years and were 34% female with equal distributions of hypertension, dyslipidemia, diabetes, stroke, and history of smoking. There were fewer ePVS in the CS of patients with iNPH compared to controls (12.66 vs. 20.39, p < 0.001) but the same in the BN (8.95 vs. 11.11, p = 0.08). This remained significant in models accounting for vascular risk factors (p = 0.002) and MRI features of DESH and WMH grade (p = 0.03). ConclusionsFewer centrum semiovale ePVS may be a biomarker for iNPH. This pattern may be caused by mechanical obstruction due to upward displacement of the brain leading to reduced glymphatic clearance.

Association between carotid artery perivascular fat density and cerebral small vessel disease.

Studies aiming to identify the significance of the carotid artery perivascular fat density are limited. The present study investigated the distribution pattern of pericarotid fat and its association with imaging markers of cerebral small vessel disease (CSVD). In total, 572 subjects who underwent both neck computed tomography angiography and cranial magnetic resonance imaging were analyzed. The pericarotid fat density near the origin of the internal carotid artery (ICA) and imaging markers of CSVD, such as lacunes, white matter hyperintensities (WMHs) and dilated perivascular spaces (PVSs), were assessed. We found that an increased pericarotid fat density was associated with the presence of lacunes and a higher WMH grade in all subjects, but in the patients with acute ischemic stroke, there was a difference only among the WMH grades. There was no significant difference in the pericarotid fat density in different grades of PVSs. The patients with acute ischemic stroke had a significantly higher mean pericarotid fat density than those without stroke. In conclusion, our study provides evidence suggesting that an increased pericarotid fat density is associated with the presence and degree of WMHs and lacunes. Our findings suggested that features that appear to extend beyond the vessel lumen of the ICA may be linked to CSVD.

Prognostic Structural Neural Markers of MRI in Response to Mechanical Thrombectomy for Basilar Artery Occlusion.

Objective: Mechanical thrombectomy (MT) has been an effective first-line therapeutic strategy for ischemic stroke. With impairment characteristics separating it from anterior circulation stroke, we aimed to explore prognostic structural neural markers for basilar artery occlusion (BAO) after MT.Methods: Fifty-four BAO patients with multi-modal magnetic resonance imaging at admission from the multicenter real-world designed BASILAR research were enrolled in this study. Features including volumes for cortical structures and subcortical regions, locations and volumes of infarctions, and white matter hyperintensity (WMH) volumes were recorded from all individuals. The impact features were identified using ANCOVA and logistic analysis. Another cohort (n = 21) was further recruited to verify the prognostic roles of screened prognostic structures.Results: For the primary clinical outcome, decreased brainstem volume and total infarction volumes from mesencephalon and midbrain were significantly related to reduced 90-day modified Rankin score (mRS) after MT treatment. WMH volume, WMH grade, average cortex thickness, white matter volume, and gray matter volume did not exhibit a remarkable relationship with the prognosis of BAO. The increased left caudate volume was obviously associated with early symptomatic recovery after MT. The prognostic role of the ratio of pons and midbrain infarct volume in brainstem was further confirmed in another cohort with area under the curve (AUC) = 0.77.Conclusions: This study was the first to provide comprehensive structural markers for the prognostic evaluation of BAO. The fully automatic and semiautomatic segmentation approaches in our study supported that the proportion of mesencephalon and midbrain infarct volume in brainstem was a crucial prognostic structural neural marker for BAO.

Prediction of brain age from routine T2-weighted spin-echo brain magnetic resonance images with a deep convolutional neural network

Our study investigated the feasibility and clinical relevance of brain age prediction using axial T2-weighted images (T2-WIs) with a deep convolutional neural network (CNN) algorithm. The CNN model was trained by 1,530 scans in our institution. The performance was evaluated by the mean absolute error (MAE) between the predicted brain age and the chronological age based on an internal test set (n=270) and an external test set (n=560). The ensemble CNN model showed an MAE of 4.22 years in the internal test set and 9.96 years in the external test set. Participants with grade 2–3 white matter hyperintensity (WMH) showed a higher corrected predicted age difference (PAD) than grade 0 WMH (posthoc p<0.001). Participants diagnosed with diabetes mellitus also had a higher corrected PAD than those without diabetes (adjusted p=0.048), although it showed no significant differences according to the diagnosis of hypertension or dyslipidemia. We suggest that routine clinical T2-WIs are feasible to predict brain age, and it might be clinically relevant according to the WMH grade and the presence of diabetes mellitus.

Vitamin D and white matter hyperintensities: results of the population-based Heinz Nixdorf Recall Study and 1000BRAINS.

Cross-sectional studies showed an inverse association between serum 25-hydroxyvitamin D (25OHD) and white matter hyperintensities (WMHs) whereas the few longitudinal studies did not. The association between baseline 25OHD and WMHs at 10-year follow-up in the Heinz Nixdorf Recall Study plus 1000BRAINS was investigated. Data of 505 participants (49% women, 56.2±6.6years) with 25OHD at baseline (2000-2003) and WMH volume and grade of WMHs using the Fazekas classification at 10-year follow-up were analysed. The association between deseasonalized 25OHD and the base-10 logarithm of WMH volume was evaluated by multiple linear regression, adjusted for age, sex, education, smoking, alcohol consumption, sports, diabetes mellitus, systolic blood pressure and total cholesterol. β-estimators were transformed back (10β ). Using multiple logistic regression, odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated to evaluate the association between deseasonalized 25OHD and Fazekas grades (0, absence and 1, punctate foci vs. 2, beginning and 3, large confluence). Mean 25OHD was 17.0±8.2ng/ml, and mean deseasonalized 25OHD was 16.9±7.5ng/ml. Mean WMH volume was 16.6±17.4ml, range 1-132ml. Most grade 2-3 WMHs were found to be periventricular (39% of the participants), parietal (32%) and frontal (31%) (temporal 6%, occipital 3%). The linear regression showed an inverse association between 25OHD and WMH volume. On average, a 25OHD increase of 1ng/ml was associated with a reduced WMH volume by a factor of 0.99 (95% CI 0.98; 1.00) (fully adjusted). There was also some indication for an inverse association between 25OHD and extent of periventricular (OR 0.98 [95% CI 0.96; 1.01]), frontal (0.99 [0.97; 1.02]) and parietal (0.98 [0.95; 1.00]) WMHs according to the Fazekas classification. Lower 25OHD may be a risk factor for the occurrence of WMHs.

Intra-arterial anti-oxidant power negatively correlates with white matter injury, and oxidative stress positively correlates with disability in daily activities

Oxidative stress influences many kinds of diseases. Our hypothesis is that oxidative stress and antioxidant potentials correlate with cognitive function, activities of daily life and white matter injury. (UMIN-CTR R000016770) Thirty-two consecutive patients participated to this study after informed consent. A routine biochemical analysis, modified-Rankin Scale (m-RS), revised Hasegawa Dementia Scale (HDS-R), Mini-Mental State Examination (MMSE) and fluid-attenuated-inversion-recovery imaging (FLAIR) were performed before admission. Derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured photometrically using arterial blood. Statistical analyses were done by analysis variance or logistic regression analysis. Median age was 72 (IQR: 64.3 –– 75.8). The d-ROMS were 367 ± 55.4, and BAP was 1967 ± 284. HDS-R and m-RS deteriorated with d-ROMs elevation (p < 0.05). Uric acid and creatinine decreased with d-ROMs elevation (p < 0.05). Both periventricular hyperintensity grade and deep and subcortical white matter hyperintensity grade worsened with BAP reduction (p < 0.05). Oxidative stress correlates negatively with cognitive function and activities of daily life. Low antioxidative potentials correlate with aggravation of white matter injury. We should control both oxidative stress and antioxidative potential to maintain healthy lives.

Correlation Between Internal Carotid Artery Tortuosity and Imaging of Cerebral Small Vessel Disease.

Background and Purpose: An association between artery tortuosity and neuroimaging of cerebral small vessel disease (SVD) has been reported, especially in the posterior circulation. However, few studies involved the whole magnetic resonance imaging (MRI) spectrum of SVD in association with anterior circulation arterial tortuosity. This study aimed to investigate the relationship between internal carotid artery (ICA) tortuosity and the neuroimaging of SVD.Methods: Data of 1,264 consecutive patients in whom cerebral vessel diseases were suspected and who underwent both MRI and computed tomography angiography were reviewed from a prospective registry. Internal carotid artery tortuosity was evaluated using the tortuosity index (TI), which was defined as the ratio of the vessel centerline length divided by the straight length. Magnetic resonance imaging was used to assess cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVSs), and lacunes.Results: The TIs of the ICA for patients with and without SVD MRI markers were 1.81 ± 0.42 and 1.72 ± 0.33, respectively (P < 0.001). Univariate analysis showed that the ICA TI were positively correlated with each SVD MRI marker (P < 0.001), and the correlation coefficients (rs) were 0.57, 0.42, 0.30, and 0.26 for EPVSs, WMHs, CMBs, and lacunes, respectively. The adjusted ORs of the ICA TI were 1.52 (95% CI 1.44–1.60, P < 0.001) for EPVS grade 1, 2.05 (95% CI 1.93–2.18, P < 0.001) for EPVS grades 2–4, and 1.09 (95% CI 1.03–1.15, P = 0.004) for WMH grade 3.Conclusions: The TI of ICA was higher in patients with neuroimaging of SVD. Internal carotid arteries tortuosity was associated with MRI-defined markers of SVD, including EPVS and high-grade WMH, and positively correlated with EPVS severity. Arterial tortuosity might be a risk factor for SVD. This finding may have potential clinical significance for identifying patients with suspected SVD.

Microvascular Brain Disease Progression and Risk of Stroke: The ARIC Study.

Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts, and their progression over time for the prediction of stroke are scarce. We studied associations between the progression in combined measures of microvascular brain disease and risk of stroke in the ARIC study (Atherosclerosis Risk in Communities). Prospective analysis of 907 stroke-free ARIC participants who underwent a brain magnetic resonance imaging (MRI) in 1993 to 1995, a second brain MRI in 2004 to 2006, and were subsequently followed for stroke incidence through December 31, 2017 (median [25%-75%] follow-up 12.6 [8.9-13.4] years). A combined measure of microvascular brain disease was defined at each visit and categorized by progression from first to second brain MRI as no progression; mild progression (increase of ≥1 unit in WMH grade or new lacune), and moderate progression (increase of ≥1 unit in WMH grade and new lacune). All definite/probable ischemic or hemorrhagic incident strokes occurring after this second MRI, and through 2017, were included. Associations between microvascular brain disease, progression in the combined measures, and stroke incidence were studied with Cox proportional hazard models, adjusting for age, sex, race, education level, time from first to second MRI, body mass index, smoking, hypertension, diabetes mellitus, and coronary heart disease. At the second brain MRI (mean age 72), the distribution of the combined measure was 37% WMH grade <2 and no lacune; 57% WMH grade ≥2 or lacune; and 6% WMH grade ≥2 and lacune. No progression in the combined measures was observed in 38% of participants, 57% showed mild progression and 5% showed moderate progression. Sixty-four incident strokes occurred during the follow-up period. Compared with no change in the combined measure, moderate progression of microvascular brain disease was significantly associated with higher risk of stroke (adjusted hazard ratio, 3.00 [95% CI, 1.30-6.94]). Progression of microvascular brain disease, manifesting as both new lacunes and increase in WMHs grade, is related to substantial increase in long-term risk of stroke.

Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events: Neuroimaging and Prognostic Associations.

BackgroundIt is likely that a proportion of poststroke cognitive impairment is sometimes attributable to unidentified prestroke decline; prestroke cognitive function is also clinically relevant because it is associated with poor functional outcomes, including death. We investigated the radiological and prognostic associations of preexisting cognitive impairment in patients with ischemic stroke or transient ischemic attack associated with atrial fibrillation.Methods and ResultsWe included 1102 patients from the prospective multicenter observational CROMIS‐2 (Clinical Relevance of Microbleeds in Stroke 2) atrial fibrillation study. Preexisting cognitive impairment was identified using the 16‐item Informant Questionnaire for Cognitive Decline in the Elderly. Functional outcome was measured using the modified Rankin scale. Preexisting cognitive impairment was common (n=271; 24.6%). The presence of lacunes (odds ratio [OR], 1.50; 95% CI, 1.03–1.05; P=0.034), increasing periventricular white matter hyperintensity grade (per grade increase, OR, 1.38; 95% CI, 1.17–1.63; P<0.0001), deep white matter hyperintensity grade (per grade increase, OR, 1.26; 95% CI, 1.05–1.51; P=0.011), and medial temporal atrophy grade (per grade increase, OR, 1.61; 95% CI, 1.34–1.95; P<0.0001) were independently associated with preexisting cognitive impairment. Preexisting cognitive impairment was associated with poorer functional outcome at 24 months (mRS >2; adjusted OR, 2.43; 95% CI, 1.42–4.20; P=0.001).ConclusionsPreexisting cognitive impairment in patients with atrial fibrillation–associated ischemic stroke or transient ischemic attack is common, and associated with imaging markers of cerebral small vessel disease and neurodegeneration, as well as with longer‐term functional outcome.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02513316.

Association of Blood Pressure Variability and Intima-Media Thickness With White Matter Hyperintensities in Hypertensive Patients

Background and Purpose: Ambulatory blood pressure variability (ABPV), ABP, and carotid intima-media thickness (IMT) are closely associated with white matter hyperintensities (WMH), and few studies focused on establishing effective models based on ABP, ABPV, and IMT to predict the WMH burden. We aimed to evaluate the value of a predictive model based on the metrics of ABP, ABPV, and IMT, which were independently associated with the WMH burden.Methods: We retrospectively enrolled 140 hypertensive inpatients for physical examinations in Shanghai East Hospital, Tongji University School of Medicine between February 2018 and January 2019. The basic clinical information of all subjects was recorded, and we also collected the metrics of ABP, ABPV, and IMT. Patients with Fazekas scale grade ≥2 were classified into heavy burden of WMH group. Then, we analyzed the association between all characteristics and the WMH burden. Multivariate analysis was performed to assess whether the metrics of ABP, ABPV, and IMT were independently associated with WMH, and we used receiver operating characteristic (ROC) to evaluate the value of predictive model based on the metrics of ABP, ABPV, and IMT.Results: Higher WMH grade was associated with increasing age, diabetes mellitus, higher total cholesterol (TC), higher low-density lipoprotein (LDL), higher IMT, higher 24-h systolic blood pressure (SBP), higher daytime SBP, higher nocturnal SBP, 24-h and daytime standard deviation (SD) of SBP, and 24-h SBP weight SD; 24-h SBP, 24-h SBP-SD, and IMT were independently related to the burden of WMH even after adjusting for the clinical variables. In addition, we also established a model that has a higher predictive capacity using 24-h SBP, 24-h SBP-SD, and IMT in the ROC analysis to assess the WMH burden in hypertensive patients.Conclusions: Higher 24-h SBP, higher 24-h SBP-SD, and larger IMT were independently associated with a greater burden of WMH among elderly primary hypertension Asian patients. Establishing a model based on these factors might provide a new approach for enhancing the accuracy of diagnosis of WMH using metrics in 24-h ABPM and carotid ultrasound.

Correlation Between Intracranial Arterial Calcification and Imaging of Cerebral Small Vessel Disease.

Background and Purpose: Vascular calcification is part of the atherosclerotic process. Intracranial artery calcification is closely associated with cerebral small vessel disease (SVD). The present study aimed to investigate the distribution pattern of intracranial arterial calcification and its association with magnetic resonance imaging (MRI) markers of SVD in patients with acute ischemic cerebrovascular disease.Methods: Two hundred and seventy six consecutive patients with transient ischemic attack (TIA) or acute ischemic stroke who underwent both computed tomography (CT) angiography and MRI were enrolled in this study. Intracranial arterial calcium scores were evaluated using Agatston method. MRI was performed to assess cerebral infarction, white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVSs).Results: Intracranial artery calcification was present in 200 (72.46%) patients, with the highest prevalence in the internal carotid arteries (ICA) (64.8%). The severity of intracranial arterial calcification was associated with the presence of WMHs (P = 0.0001), lacunes (P = 0.0001), and CMBs (P = 0.0001); however, there was no association between calcifications and the presence of EPVSs (P = 0.058). The correlation coefficients (rs) were 0.350, 0.142, 0.285, and 0.251 for WMHs, EPVSs, lacunes, and CMBs, respectively. The adjusted odds ratios (ORs) of intracranial arterial calcification were: 2.747 for WMH (grade 1–2), 3.422 for WMH (grade 3), 2.902 for lacunes, 2.449 for CMB, 0.88 for EPVS (grade 1), and 0.295 for EPVS (grade 2–4).Conclusion: Intracranial artery calcification is common in patients with ischemic cerebrovascular disease and the intracranial carotid artery is most frequently affected. Intracranial arterial calcifications might be associated with imaging markers of SVD and are highly correlated with WMHs, lacunes, and CMBs. Quantification of calcification on CT provides additional information on the pathophysiology of SVD. Intracranial arterial calcification could act as a potential marker of SVD.

Early Prediction of Functional Outcome after Cerebral Small Arteries Infarctions Using Diffusion Tensor MRI Tractography

AbstractBackground: Lacunar Infarctions (LIs) are ischemic strokes caused by occlusion of the deep penetrating arteries. They constitute about 25% of all ischemic strokes and have variable consequences based on affected tracts disruptions.Aim of Study: Were to assess the role of MRI Diffusion Tensor Imaging (DTI) fiber tractography as an early biomarker of LIs prognosis.Patients and Methods: This work was conducted on 42 first-ever symptomatic motor or sensorimotor LIs patients (3 1 male and 11 female) submitted to stroke severity assess-ment using the National Institute of Health Stroke Scale (NIHSS), carotid duplex, brain MRI to determine LIs dimeter and occult small vessel disease imaging markers. Corticospinal Diffusion Tensor Tractography (CS-DTT) was done within 48 hours from stroke onset. Thirty-eight patients continued a 3-months follow-up schedule, at the end of which their physical dependences were assessed using the Modified Barthel Index (MBI) scale which were compared with the baseline assessment parameters to determine the prognostic biomarkers.Results: Dependent patients' group showed significant increase in their age, BMI, carotid intima media thickness and white matter hyperintensities grade than independent patients' group. The FA ratio was the earliest parameter showed significant changes which were lower in dependent than independent patients' groups. On the other hand, each of ipsilateral DTI fractional anisotropy, mean diffusivity and fiber number showed non-significant differences.Conclusion: Factors associated with poorer functional outcome after newly diagnosed LIs include advanced age, hypertension, obesity, premorbid physical inactivity, increased CIMT and the presence of imaging biomarkers of occult SVD. Reduced ipsilateral/contralateral FA ratio of the CS-DTT is a reliable early predictor of short-term functional outcome and motor disability after motor and sensorimotor LIs.

Abstract WP178: Impact of White Matter Hyperintensity on Severity and Outcome of Acute Ischemic and Hemorrhagic Stroke: The Japan Stroke Data Bank

Introduction: Extensive forms of white matter hyperintensity (WMH) are a consequence of and indicative for advanced cerebral small vessel disease, and thus are reportedly associated with higher risks for stroke, dementia, and mortality. Our aim was to analyze impact of WMH on severity and outcome in patients with acute ischemic and hemorrhagic stroke using data from a nationwide stroke registration. Methods: We studied patients hospitalized with acute stroke in 103 participating centers of the Japan Stroke Data Bank from 2001 to 2015. Deep WMH was evaluated with magnetic resonance imaging (MRI) and classified with Fazekas grade. We examined associations of WMH with National Institutes of Health Stroke Scale (NIHSS) on admission and poor outcome (modified Rankin Scale of 3 - 6) at discharge using multivariable models. Results: We studied a total of 28,469 patients with MRI imformation. In patients with ischemic stroke (n = 24,591; women, 40%; and age, 72.5±12.1 years), median NIHSS was 4 (interquartile range [IQR] 2-9); and 10,073 (41%) had poor outcome. WMH grades of 0, 1, 2, and 3 were observed in 23%, 45%, 25%, and 6%, respectively. In multivariate analysis adjusted by age and sex, WMH grade was independently related to higher admission NIHSS (incidence rate ratio [IRR] of grade 3 versus 0, 1.33; 95% confidence interval [CI], 1.30-1.35, P for trend &lt;0.001). In multivariate analysis adjusted by age, sex, and admission NIHSS, WMH grade was related to poor outcome (odds ratio [OR] of grade 3 versus 0, 3.08; 95% CI 2.63-3.60; P for trend &lt;0.001). In patients with intracerebral hemorrhage (n = 3,878; women, 42%; and age, 66.9±14.2), median NIHSS was 10 (IQR 4-20); and 2,393 (62%) had poor outcome. WMH grade of 0, 1, 2 and 3 were observed in 28%, 43%, 22%, and 7%, respectively. In multivariate analysis adjusted by age and sex, WMH was independently related to higher NIHSS (IRR of grade 3 versus 0, 1.35; 95%CI, 1.30-1.40). In multivariate analysis adjusted by age, sex, and admission NIHSS, WMH grade was related to poor outcome (OR of grade 3 versus 0, 1.99; 95% CI 1.28-3.11; P for trend &lt;0.001). Conclusions: Extensive forms of WMH influenced on severity and outcome in both acute ischemic stroke and intracerebral hemorrhage in a nationwide hospital-based patient cohort.

Findings of Vascular Brain Injury and Structural Loss from Cranial Magnetic Resonance Imaging in Elderly American Indians: The Strong Heart Study

Background: The Cerebrovascular Disease and its Consequences in American Indians study conducted cranial MRI examination of surviving participants of the Strong Heart Study, a longitudinal cohort of elderly American Indians. Methods: Of the 1,033 recruited participants, some were unable to complete the MRI (n = 22), some scans were unusable due to participant motion or technical errors (n = 13), and one community withdrew consent after data collection (n = 209), leaving 789 interpretable MRI scan images. Six image sequences were obtained in contiguous slices on 1.5T scanners. Neuroradiologists graded white matter hyperintensities (WMH), sulci, and ventricles on a 0- to 9-point scale, and recorded the presence of infarcts and hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were estimated by automated image processing. Results: The median scores for graded measures were 2 (WMH) and 3 (sulci, ventricles). About one-third of participants had lacunar (20%) or other infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy were also prevalent. Statistical analyses indicated significant associations between older age and findings of vascular injury and atrophy; male gender was associated with findings of cortical atrophy. Conclusions: Vascular brain injury is the likely explanation in this elderly American Indian population for brain infarcts, hemorrhages, WMH grade, and WMH volume. Although vascular brain injury may play a role in other findings, independent degenerative other disease processes may underlie abnormal sulcal widening, ventricular enlargement, hippocampal volume, and total brain volume. Further examination of risk factors and outcomes with these findings may expand the understanding of neurological conditions in this understudied population.

Association of Leukoaraiosis With Convalescent Rehabilitation Outcome in Patients With Ischemic Stroke.

We investigated the factors influencing inpatient convalescent rehabilitation outcomes in patients with ischemic stroke, particularly severity of leukoaraiosis on magnetic resonance imaging. Participants included 520 patients with ischemic stroke (317 men and 203 women; mean age, 72.8±8.4 years) who were transferred from acute care hospitals for inpatient convalescent rehabilitation. Ischemic stroke subtypes included lacunar infarction (n=41), atherothrombosis (n=223), artery-to-artery embolism (n=67), cardiogenic embolism (n=97), undetermined embolism (n=76), and uncategorized ischemic stroke (n=16). Leukoaraiosis was graded according to periventricular hyperintensity (PVH) and deep white matter hyperintensity on magnetic resonance imaging. Functional Independence Measure scores were assessed on admission and at discharge. Multiple regression analysis revealed that rehabilitation outcomes, measured as total Functional Independence Measure scores, were significantly associated with leukoaraiosis estimated by PVH grade. This association was observed after adjustment for factors such as severity, age, and poststroke history. In all patients, PVH grades were associated with Functional Independence Measure motor scores (P<0.001), whereas in patients with artery-to-artery embolism or cardiogenic embolism and deep white matter hyperintensity grades were associated with Functional Independence Measure cognitive scores (P<0.05). Our study revealed that the degree of leukoaraiosis was associated with inpatient convalescent rehabilitation outcome in patients with ischemic stroke. Furthermore, the PVH grade was associated with motor function outcome, whereas the deep white matter hyperintensity grade correlated with cognitive function outcome, likely because the progression patterns and anatomic backgrounds of PVH and deep white matter hyperintensity differ according to ischemic stroke subtype.

The Association of Brain MRI Characteristics and Postoperative Delirium in Cardiac Surgery Patients

PurposeDelirium is common after cardiac surgery and is associated with adverse consequences, including cognitive decline. Identification of vulnerable older adults might allow for early implementation of delirium-prevention strategies. Brain MRI findings provide insight into structural brain changes that may identify vulnerable patients. The purpose of this study was to examine the association between brain MRI characteristics potentially associated with delirium vulnerability and the development of postoperative delirium in a nested cohort of patients undergoing cardiac surgery. MethodsWe identified 79 cardiac surgery patients who had brain MRI imaging after cardiac surgery, as part of an ongoing randomized trial evaluating the efficacy of blood pressure management based on cerebral autoregulation monitoring versus standard management for improving neurological outcomes. Cerebral lateral ventricular size, cortical sulcal width, and white matter hyperintensities (WMH) on brain MRI scans were graded on a validated 0 to 9 scale, and categorized into tertiles. New ischemic lesions were characterized as present or absent. Delirium was assessed using a validated chart-review. Neuropsychological testing performed before surgery was used to establish preoperative cognitive baseline. Multivariable logistic regression was used to assess the independent association between MRI characteristics and postoperative delirium. FindingsThe average age of patients was 70.1 ± 7.8 years old, and 72% were male. Twenty-eight of 79 (35.4%) patients developed postoperative delirium. Patients with delirium had higher unadjusted ventricular size (median 4 vs. 3, P = 0.003), and there was a trend towards higher sulcal sizes and WMH grades. Increasing tertiles of ventricular size (Odds Ratio [OR] 3.59; 95% Confidence Interval [CI] 1.59-8.12; P = 0.002) and sulcal size (OR 2.15; 95%CI 1.13-4.12; P = 0.02) were associated with postoperative delirium, with a trend for tertiles of WMH grade (OR 1.91; 95%CI 0.99-3.68; P = 0.05). In multivariable models adjusted for logistic EuroSCORE, baseline cognitive status, bypass time, and any postoperative complication, each tertile of ventricular size was associated with increased odds of postoperative delirium (OR 3.23 per tertile increase in ventricular size; 95%CI 1.21-8.60; P = 0.02). There were no differences in odds of delirium by tertiles of sulcal grade, tertiles of white matter grade, or presence of new ischemic lesions, in adjusted models. ImplicationsIncreased brain ventricular size was independently associated with delirium after cardiac surgery. These results suggest that cerebral atrophy may contribute to increased vulnerability for postoperative delirium. Baseline brain MRIs may be useful in identifying cardiac surgery patients at high risk for postoperative delirium, who might benefit from targeted perioperative approaches to prevent delirium. ClinicalTrials.gov identifier: NCT00981474.

N-glycome Profile Levels Relate to Silent Brain Infarcts in a Cohort of Hypertensives.

BackgroundSilent brain infarcts (SBIs) are highly prevalent in the aged population and relate to the occurrence of further stroke and dementia. Serum N‐glycome levels have been previously associated with aging and they might be related as well to the presence of SBIs and age‐related white matter hyperintensities.Methods and ResultsWe determined the serum N‐glycome profile in a cohort study comprising 972 subjects and evaluated the relationship between N‐glycome levels and the presence and number of SBIs and with age‐related white matter hyperintensities grades, assessed by brain magnetic resonance imaging. Decreasing concentrations of bigalacto core‐α‐1,6‐fucosylated biantennary glycan and increasing concentrations of branching α‐1,3‐fucosylated triantennary glycan remained as independent predictors of SBIs (odds ratio 0.4, 95% CI 0.3–0.7 and odds ratio 1.8, 95% CI 1–3.2, respectively), after controlling for the presence of age and classic vascular risk factors. A similar pattern was found to be related to an increasing number of SBIs and white matter hyperintensities grade.ConclusionsN‐glycome levels might be potentially useful as biomarkers for the presence of silent cerebrovascular disease.

Abstract W P184: Echocardiographic Left Ventricular Hypertrophy is Associated with Severity of Cerebral White Matter Hyperintensities in Acute Ischemic Stroke

BACKGROUND &amp; OBJECTIVE: White matter hyperintensities (WMH) indicate an increased risk of cerebrovascular events. Echocardiographic left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular morbidity. We aimed to investigate the association between higher left ventricular mass index (LVMI) and severity of WMH in acute ischemic stroke. METHODS: We evaluated 868 consecutive acute ischemic stroke or transient ischemic attack (TIA) patients who were admitted within 7 days after onset of stroke and underwent magnetic resonance imaging (MRI) and transthoracic echocardiography. LVH was defined as a left ventricular mass index (LVMI) of &gt; 115 g/m2 for men and &gt; 95 g/m2 for women. Periventricular and deep white matter hyperintensities were systematically analyzed and rated according to the modified Fazekas scale (grade 0, 1, 2, and 3) on the baseline MRI. RESULTS: A total of 841 patients were included in this analysis. Numbers of WMH patients are 66 (7%) in grade 0, 546 (65%) in grade 1, 159 (20%) in grade 2, and 70 (8%) in grade 3. Mean LVMIs in each grade of WMH are 86 (SD 18) in grade 0, 95 (SD 22) in grade I, 104 (SD 29) in grade 2, and 100 (SD 28) in grade 3. LVH and 4th quartile of LVMI were associated with grade 2 (OR 2.3, 95% CI 1.1 to 5.0 and OR 3.2, 95% CI 1.4 to 7.2) and grade 3 (OR 2.5, 95% CI 1.1 to 5.9 and OR 2.7, 95% CI 1.1 to 6.6). Binary logistic regression analysis (WMH grade 0-1 versus grade 2-3) showed that age per year (OR 1.09, 95% CI 1.07 to 1.12, p&lt;0.001), hypertension (OR 1.8, 95% CI 1.2 to 2.7, p=0.004), previous stroke or TIA history (OR 2.3, 95% CI 1.5 to 3.4, p&lt;0.001) and increased LVMI per 10 g/m2 (OR 1.15; 95% CI 1.06 to 1.24, p&lt;0.001) were independently associated with grade 2-3 WMH. CONCLUSIONS: Our results demonstrate that higher LVMI or LVH are independently associated with moderate to severe WMH in acute ischemic stroke and TIA patients even after adjusting of established cardiovascular risk factors. Further studies to evaluate whether regression of LVH slows the progression of WMH will be needed.

Mechanical stresses, arterial stiffness, and brain small vessel diseases: Shimanami Health Promoting Program Study.

Arterial stiffness, a risk factor of brain small vessel diseases (SVD), causes hemodynamic changes. Mechanical stresses, circumferential wall tension (WT), and shear stress (SS) may change with arterial stiffness and be related to SVD. We investigated the associations between mechanical stresses and arterial stiffness and SVD. A total of 1296 subjects without apparent cardiovascular diseases were recruited. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an arterial stiffness index. Silent lacunar infarction and deep subcortical white matter hyperintensity were evaluated as SVD indices. Circumferential WT and SS at peak systole and end diastole were measured at the common carotid artery. Second peak of systolic blood pressure was obtained from the radial waveform and used as a central systolic blood pressure substitute. baPWV was associated positively with WT (P<0.0001) and negatively with SS (P=0.0007) even after correction for confounding parameters including baPWV. SVD was associated with significantly higher WT (P<0.0001) and lower SS (P<0.0001). After adjustment for confounding parameters (including baPWV), second peak of systolic blood pressure WT (odds ratio, 1.30; P=0.0017) and end diastolic WT (odds ratio, 1.60; P=0.0038) were related to presence of silent lacunar infarction, whereas peak systolic (odds ratio, 0.95; P=0.014) and end diastolic SS (odds ratio, 0.94; P=0.014) were associated with presence of deep subcortical white matter hyperintensity grade >3. Regression lines between blood pressure and WT were significantly steeper in subjects with SVD than without SVD (β=0.02; P<0.0001). These findings indicate that SVD is phenotype-specifically associated with alterations in WT and SS independently of arterial stiffness.

Vitamin D and subclinical cerebrovascular disease: the Atherosclerosis Risk in Communities brain magnetic resonance imaging study.

Vitamin D deficiency has been associated with hypertension, diabetes mellitus, and incident stroke. Little is known about the association between vitamin D and subclinical cerebrovascular disease. To examine the relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular abnormalities as assessed on brain magnetic resonance imaging (MRI) among participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study. Participants were white and black adults aged 55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at ARIC visit 3 (n = 1622) and a second cerebral MRI approximately 10 years later (n = 888). The 25(OH)D level was measured by mass spectrometry at visit 3, with levels adjusted for calendar month and categorized using race-specific quartiles. The cross-sectional and prospective associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI-defined infarcts were investigated using multivariable regression models. The mean age of the participants was 62 years, 59.6% were women, and 48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH score of severity, prevalent high-grade WMH score (≥3), or prevalent infarcts in cross-sectional, multivariable-adjusted models (all P > .05). Similarly, no significant prospective associations were found for lower 25(OH)D levels with change in WMH volume, incident high WMH score (≥3), or incident infarcts on the follow-up MRI, which occurred approximately 10 years later. A single measure of 25(OH)D was not cross-sectionally associated with WMH grade or prevalent subclinical infarcts and was not prospectively associated with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart. These findings do not support optimizing vitamin D levels for brain health.