Progression Of White Matter Hyperintensities Research Articles

Correlation of vitamin D levels with burden of white matter lesions in individuals with Prader-Willi syndrome

Objective: Vitamin D has a variety of roles, including bone metabolism, calcium homeostasis, immunomodulation, anti-inflammation, and possibly neuroprotection. Neuroimaging has shown that hypovitaminosis D may cause more rapid progression and increased severity of white matter hyperintensities (WMH) in some populations. Individuals with Prader-WIlli syndrome (PWS) often have inadequate vitamin D intake, so we investigated if the burden of WMH in PWS is associated with hypovitaminosis D. Design/Methods: We evaluated brain MRI’s of 20 individuals with vitamin D levels measured at the time of the scan, who were between ages 5 and 46 years and had PWS (n = 17) or were typical siblings (n = 3). The presence and number of WMH were correlated with vitamin D. Results: Serum vitamin D levels were inversely correlated with the presence and number of WMH (0.025) in individuals with PWS and controls, as well as the progression of WMH ( p = 0.029) in PWS. Additionally, vitamin D levels correlated with cognitive scores in PWS ( p < 0.01). Conclusions: The results of this small study support that vitamin D has neuroprotective effects influencing the development and progression of WMH even in the pediatric population. Studies should be done in children with high prevalence of vitamin D deficiency such as obesity. Normal 0 false false false EN-US ZH-CN X-NONE

Plasma β-amyloid and MRI markers of cerebral small vessel disease: Three-City Dijon study.

We investigated the relation of circulating plasma β-amyloid (Aβ) with MRI markers of small vessel disease (SVD) in dementia-free community persons. Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Aβ measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Aβ levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n = 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure. Low plasma Aβ1-40 levels were associated with increased progression of WMH, and low Aβ1-42 with higher odds of extensive WMH progression over the follow-up (odds ratio = 1.66, 95% confidence interval = 1.16-2.38). Consistently low Aβ1-40 and Aβ1-42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE ε4 genotype. Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma Aβ. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.

Cerebrovascular Biomarker Profile Is Related to White Matter Disease and Ventricular Dilation in a LADIS Substudy

Background: Small vessel disease (SVD) represents a common often progressive condition in elderly people contributing to cognitive disability. The relationship between cerebrospinal fluid (CSF) biomarkers and imaging correlates of SVD was investigated, and the findings were hypothesized to be associated with a neuropsychological profile of SVD. Methods: CSF SVD-related biomarkers [neurofilament light (NF-L), myelin basic protein (MBP), soluble amyloid precursor protein-β (sAPPβ), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinase (TIMP)] were analysed in 46 non-demented elderly with imaging findings of SVD. We assessed the relationship between the CSF biomarkers and white matter hyperintensity (WMH) volume, diffusion-weighted imaging and atrophy as well as their association with neuropsychological profiles. Results: The WMH volume correlated with ventricular dilation, which was associated with executive function and speed and attention. Increased WMH and ventricular dilation were related to increased CSF levels of TIMP-1, NF-L and MBP and to decreased sAPPβ. A positive correlation was found between the CSF biomarker MMP-9 and WMH progression. Conclusions: The link between progressive WMH and MMP-9 suggests an involvement of the enzyme in white matter degeneration. CSF TIMP-1, NF-L, MBP and sAPPβ may function as biological markers of white matter damage.

Progression of white matter hyperintensities of presumed vascular origin increases the risk of falls in older people.

Greater volume of cerebral white matter hyperintensities (WMH) of presumed vascular origin may affect postural control and gait. WMH measured at one time point predicts an increased risk of incident multiple falls. However, it is unknown whether WMH progression increases falls risk. We hypothesized that the progression of WMH would be associated with a greater risk of multiple falls. A population-based sample aged more than 60 years was randomly selected from the electoral roll and followed up 2.5 years apart with two phases of measurement. Magnetic resonance imaging scans from both time points were subjected to automated segmentation to derive WMH volumes. Falls were recorded prospectively over 12 months after the second magnetic resonance imaging measurement. A generalized linear model was used to estimate the relative risk of multiple falls associated with WMH progression adjusted for confounders. There were 187 people (mean age 70.4, SD 6.5) with a mean follow-up of 2.5 (SD 0.4) years. Over 12 months, 35 (18.7%) participants reported multiple falls. A greater progression of WMH was associated with an increased risk of multiple falls (adjusted relative risk 1.30, 95% confidence interval 1.00-1.70, p = .05) independent of baseline WMH volume, duration of follow-up, age, sex, and total intracranial volume. This association was unchanged when adjusted for medical history, peripheral sensorimotor factors, gait speed, cognition, medications, mood, and magnetic resonance imaging infarcts. Greater WMH progression independently increased the risk of multiple falls. Interventions to slow the progression of WMH may be successful in reducing this risk.

Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence

Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the present study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy and cortical thickness). Three hundred three nondemented older adults (mean age = 79.24 ± 5.29) received high-resolution magnetic resonance imaging at baseline and then again 4.6 years (standard deviation = 1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling, we calculated latent difference scores of parietal and nonparietal WMH, hippocampus volumes, and cortical thickness values in AD-related regions. Within the structural equation modeling framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD.

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.

Presence and progression of white matter hyperintensities and cognition: a meta-analysis.

We aimed to quantify the effects of white matter hyperintensities (WMHs) on specific cognitive functions with particular attention to WMH progression and localization. PubMed (January 1990-July 2013) and bibliographies from included articles were used. Studies that were included (1) used MRI; (2) had a population-based or case-control design with a healthy control group that could be used for analysis; (3) matched/adjusted for age, sex, and education; and (4) addressed ≥1 predefined cognitive domains with ≥1 validated neuropsychological tests. Data were independently extracted by 2 investigators. Pearson r was extracted/calculated and used as the common metric for the effect size across studies. Twenty-three cross-sectional and 14 longitudinal studies were included with a total of 8,685 and 7,731 participants. Presence of WMHs was significantly associated with concurrent cognitive deficits in all examined domains: general intelligence (Fisher z -0.10, 95% confidence interval [CI] -0.19 to -0.04), memory (-0.08, -0.13 to -0.06), processing speed (-0.11, -0.17 to -0.07), attention and executive functions (-0.11, -0.16 to -0.07), and perception/construction (-0.15, -0.21 to -0.07). Similar effect sizes were observed for cognitive decline over time. WMH progression was associated with greater cognitive decline, particularly for general intelligence (Fisher z -0.31, 95% CI -0.5 to -0.02) and attention and executive functions (-0.32, -0.34 to -0.28). The small but robust and consistent effects of WMHs on all cognitive domains suggest a more global effect on cognition than previously thought. Progression of WMHs was associated with even worse cognitive functioning, most pronounced in attention and executive functioning.

Prestroke statins, progression of white matter hyperintensities, and cognitive decline in stroke patients with confluent white matter hyperintensities.

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale-initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52cm(3) vs 5.01 ± 6.00cm(3), p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = -0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale-initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.

Blood Pressure, Internal Carotid Artery Flow Parameters, and Age-Related White Matter Hyperintensities

White matter hyperintensities (WMH) are associated with hypertension. We examined interactions among blood pressure (BP), internal carotid artery (ICA) flow velocity parameters, and WMH. We obtained BP measurements from 694 community-dwelling subjects at mean ages 69.6 (±0.8) years and again at 72.6 (±0.7) years, plus brain MRI and ICA ultrasound at age 73±1 years. Diastolic and mean BP decreased and pulse pressure increased, but systolic BP did not change between 70 and 73 years. Multiple linear regression, corrected for vascular disease and risk factors, showed that WMH at the age of 73 years were associated with history of hypertension (β=0.13; P<0.001) and with BP at the age of 70 years (systolic β=0.08, mean β=0.09, diastolic β=0.08; all P<0.05); similar but attenuated associations were seen for BP at the age of 73 years. Lower diastolic BP and higher pulse pressure were associated with higher ICA pulsatility index at the age 73 years (diastolic BP age 70 years: standardized β=-0.24, P<0.001; pulse pressure age 70 years: β=0.19, P<0.001). WMH were associated with higher ICA pulsatility index (β=0.13; P=0.002) after adjusting for BP and correction for multiple testing. Therefore, falling diastolic BP and increased pulse pressure are associated with increased ICA pulsatility index, which in turn is associated with WMH. This suggests that hypertension and WMH may either associate indirectly because hypertension increases arterial stiffness that leads to WMH over time, or coassociate through advancing age and stiffer vessels, or both. Reducing vascular stiffness may reduce WMH progression and should be tested in randomized trials, in addition to testing antihypertensive therapy.

Circulating Inflammatory Markers Are Associated With Magnetic Resonance Imaging-Visible Perivascular Spaces But Not Directly With White Matter Hyperintensities

White matter hyperintensities (WMH) and perivascular spaces (PVS) are features of small vessel disease, found jointly on MRI of older people. Inflammation is a prominent pathological feature of small vessel disease. We examined the association between inflammation, PVS, and WMH in the Lothian Birth Cohort 1936 (N=634). We measured plasma fibrinogen, C-reactive protein, and interleukin-6 and rated PVS in 3 brain regions. We measured WMH volumetrically and visually using the Fazekas scale. We derived latent variables for PVS, WMH, and Inflammation from measured PVS, WMH, and inflammation markers and modelled associations using structural equation modelling. After accounting for age, sex, stroke, and vascular risk factors, PVS were significantly associated with WMH (β=0.47; P<0.0001); Inflammation was weakly but significantly associated with PVS (β=0.12; P=0.048), but not with WMH (β=0.02; P=NS). Circulating inflammatory markers are weakly associated with MR-visible PVS, but not directly with WMH. Longitudinal studies should examine whether visible PVS predate WMH progression and whether inflammation modulators can prevent small vessel disease.

Ankle-Brachial Pressure Index and Pulse Wave Velocity as Markers of White Matter Hyperintensities and Cognitive Impairment

Vascular disease is associated with cognitive impairment. White matter hyperintensities (WMHs), as detected by brain magnetic resonance imaging (MRI), are associated with cognitive impairment and considered to be a marker of cerebral microvascular abnormality. Ankle-brachial pressure index (ABI) and pulse wave velocity (PWV) are noninvasive methods to assess blockage and stiffness in peripheral arteries, respectively. We investigated the associations of ABI and PWV with WMHs and cognition. We included 242 subjects representing 56 controls, 75 patients with mild cognitive impairment, and 111 patients with Alzheimer’s disease. We assessed brachial-ankle PWV (baPWV), ABI, general cognitive status with the Korean Mini-Mental State Examination (K-MMSE), and WMHs with brain MRI. The mean age of subjects correlated with values of baPWV (r=0.432, p<0.001) and ABI (r=-0.192, p=0.002). Among vascular risk factors, baPWV was positively associated with the presence of intracerebral artery stenosis (r=0.102, p=0.028) and ABI was negatively correlated with the presence of hypertension (r=-0.150, p=0.017) and smoking (r=-0.176, p=0.005), independent of age. After adjusting for age and vascular risk factors, baPWV was associated with WMHs (r=0.192, p=0.002), and ABI was associated with the K-MMSE score (r=0.14, p=0.028). There was no association of ABI with WMHs and of baPWV with K-MMSE. An increased baPWV was associated with the severity of WMHs, and a lower ABI was associated with cognitive impairment. Management of peripheral vascular disease may help prevent the progression of WMHs or cognitive decline.

Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: a prospective longitudinal study

Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally, radiological abnormalities expressed as white matter hyperintensities (WMH) and cerebral atrophy (CA) can develop. In this study, these functional and morphological parameters are evaluated, and their relation is investigated. After surgery, HGG patients underwent chemo-irradiation for six weeks, followed by six cycles of temozolomide. Assessments were performed before chemo-irradiation, post-concomitantly, after the third and sixth adjuvant cycle, and 3 and 7 months after treatment. Degree of WMH and CA was scored on MRI. Patients' neuropsychological performance was compared to healthy matched controls, yielding six cognitive domain z-scores. Development or progression of pre-existing WMH and CA during follow-up was observed in 36 and 45 % of the patients (n = 39) respectively. Cognitive functioning remained stable or improved in 70 % of the patients and deteriorated in 30 % of the patients (n = 33). Of the cognitive decliners, 80 % had tumor progression within 4 months thereafter. No clear association between cognitive functioning and WMH or CA was found. Central neurotoxic effects of combined modality treatment in HGG patients expressed by radiological abnormalities are encountered in approximately 40 % of patients. However, functional impact as indexed by cognitive functioning was found to be limited. Furthermore, development or progression of pre-existing WMH and CA does not consistently result in functional impairment as measured by cognitive tests.

Effect of Normal Aging Versus Hypertension, Abnormal Body Mass Index, and Diabetes Mellitus on White Matter Hyperintensity Volume

The natural history of white matter hyperintensity (WMH) progression resulting from normal aging versus comorbid vascular insults remains unclear. Therefore we investigated age-related differences in WMH volumes among a group with comorbid hypertension, abnormal body mass index, and diabetes mellitus to a normal aging group drawn from the same population lacking any of these comorbidities. WMH volumes were acquired using 3T MRI for 2011 Dallas Heart Study participants. The slope of the WMH versus age regression was compared between normal and comorbidity groups<50 and ≥50 years of age where a change in slope was demonstrated. Aging was linearly associated with greater log WMH volume for both normal (P=0.02) and comorbidity (P<0.0001) groups. Beyond 50 years of age, more rapid increases in WMH volumes for age were seen in the group with comorbidities (P<0.0001) but not in the normal group (P=0.173). The between-group difference in slope of expected WMH for age was significantly greater in the comorbidity groups≥50 years of age (P=0.0008) but not <50 years of age (P=0.752). After 50 years of age, but not before, comorbid hypertension, obesity, and diabetes mellitus were associated with significantly larger WMH volumes for age compared with a normal aging group lacking these conditions. These results support the assertion that age-related differences in WMH volumes are significantly increased in the presence of comorbidities, but the effect is only detectable after 50 years of age.

A physiologic biomarker for cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA), a common small-vessel disease of older adults characterized by accumulation of amyloid-β in leptomeningeal and cortical blood vessels, is a well-established cause of intracerebral hemorrhage.(1) Recent years have seen the emergence of clinical research reports establishing associations between CAA, ischemic brain injury, and vascular cognitive impairment (VCI). CAA patients had a higher load of chronic microvascular white matter hyperintensities (WMH), small infarcts, as well as a high degree of WMH progression.(2,3) A more recent report showed that vascular amyloid load strongly correlated with ischemic WMH in CAA.(4.)

Migraine and white matter hyperintensities

Migraine is associated with white matter hyperintensities (WMH) cross-sectionally, but its effect on WMH progression is uncertain. Participants in the Atherosclerosis Risk in Communities cohort study (n = 10,924) completed a standardized headache questionnaire between 1993 and 1995. A subset of participants (n = 1,028) received 2 MRIs 8 to 12 years apart: once at the time of headache ascertainment, and again from 2004 to 2006. WMH were quantified using both a visually graded score (0-9) and semiautomated volumetric analysis. Linear and logistic regression models adjusted for age, sex, and other vascular risk factors were constructed. Individuals who had migraine without aura were cross-sectionally associated with an 87% greater odds of having a WMH score ≥3 than individuals without headache (adjusted odds ratio = 1.87; 95% confidence interval [CI]: 1.04, 3.37). Participants with migraine had an average of 2.65 cm(3) more WMH than those without headache (95% CI: 0.06, 5.24). However, there was no significant difference in WMH progression over the study period between individuals with and without migraine (1.58 cm(3) more progression for individuals with migraine compared to those without; 95% CI: -0.37, 3.53). Migraine is associated with WMH volume cross-sectionally but not with WMH progression over time. This suggests that the association between migraine and WMH is stable in older age and may be primarily attributable to changes occurring earlier in life, although further work is needed to confirm these findings.

Rapid Buildup of Brain White Matter Hyperintensities Over 4 Years Linked to Ambulatory Blood Pressure, Mobility, Cognition, and Depression in Old Persons

Brain white matter hyperintensities (WMH) are associated with functional decline in older people. We performed a 4-year cohort study examining progression of WMH, its effects on mobility, cognition, and depression with the role of clinic and 24-hour ambulatory systolic blood pressure as a predisposing factor. Ninety-nine subjects, 75-89 years were stratified by age and mobility, with the 67 completing 4-years comprising the cohort. Mobility, cognition, depressive symptoms, and ambulatory blood pressure were assessed, and WMH volumes were determined by quantitative analysis of magnetic resonance images. WMH increased from 0.99±0.98% of intracranial cavity volume at baseline to 1.47±1.2% at 2 years and 1.74±1.30% after 4 years. Baseline WMH was associated with 4-year WMH (p < .0001), explaining 83% of variability. Small, but consistent mobility decrements and some evidence of cognitive decline were noted over 4 years. Regression analyses using baseline and 4-year WMHs were associated with three of five mobility measures, two of four cognitive measures and the depression scale, all performed at 4 years. Increases in ambulatory systolic blood pressure but not clinic systolic blood pressure during the initial 2 years were associated with greater WMH accrual during those years, while ambulatory systolic blood pressure was related to WMH at 4 years. Declines in mobility, cognition, and depressive symptoms were related to WMH accrual over 4 years, and WMH was related to out-of-office blood pressure. This suggests that prevention of microvascular disease, even in asymptomatic older persons, is fundamental for preserving function. There may be value in tighter 24-hour blood pressure control in older persons although this requires further investigation.

Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women

To determine the association of conventional cardiovascular risk factors, markers of platelet activation, and thrombogenic blood-borne microvesicles with white matter hyperintensity (WMH) load and progression in recently menopausal women. Women (n = 95) enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study underwent MRI at baseline and at 18, 36, and 48 months after randomization to hormone treatments. Conventional cardiovascular risk factors, carotid intima-medial thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and thrombogenic microvesicles were measured at baseline. WMH volumes were calculated using a semiautomated segmentation algorithm based on fluid-attenuated inversion recovery MRI. Correlations of those parameters with baseline WMH and longitudinal change in WMH were adjusted for age, months past menopause, and APOE ε4 status in linear regression analysis. At baseline, WMH were present in all women. The WMH to white matter volume fraction at baseline was 0.88% (0.69%, 1.16%). WMH volume increased by 122.1 mm(3) (95% confidence interval: -164.3, 539.5) at 36 months (p = 0.003) and 155.4 mm(3) (95% confidence interval: -92.13, 599.4) at 48 months (p < 0.001). These increases correlated with numbers of platelet-derived and total thrombogenic microvesicles at baseline (p = 0.03). Associations of platelet-derived, thrombogenic microvesicles at baseline and increases in WMH suggest that in vivo platelet activation may contribute to a cascade of events leading to development of WMH in recently menopausal women.

Abstract WP122: The Coexisting Leukoaraiosis In Ischemic Stroke Patients: How Does It Change Over Time?

Background: The prevalence of leukoaraiosis or white matter hyperintensities (WMH) is getting higher with the easy accessibility of brain imaging. Their clinical significance has not been known yet. Herein, we aimed to investigate how they progress or regress over time in patients with ischemic stroke. Methods: We consecutively enrolled ischemic stroke patients who underwent brain MRI (T2-weighted image or fluid-attenuated inverse recovery (FLAIR) image) more than twice with at least a 6 month time-interval. Patients with pathologic lesions which cannot be distinguished from WMH were excluded. Clinical variables (age, sex, risk factors, stroke subtypes, and imaging time) were obtained by reviewing medical records. T2-weighted image or FLAIR image was used to assess the presence of WMH. WMH was visually measured with use of modified Fazekas grading by an independent investigator. The change of WMH was interpreted as 1)no change, 2)progress, 3)regression, 4)distinctive progress and regression. The descriptive analysis of the pattern of WMH change over time and factors associated with each pattern were analyzed. Results: The total number of enrolled patients were 100. Their age (mean±SD) was 67.5±11.8 years and 63 were male. The most common stroke subtype was small vessel disease (SVD, 43%), followed by large vessel disease (LVD, 27%), and cardioembolism (9%). The imaging time-interval (mean±SD) was 28.0±16.6 months. In 64 patients, WMH was observed on brain MRI. Among them, the WMH pattern didn’t change in 25 patients, progressed in 28, regressed in 10 and progressed in distinctive region and regressed in others in 4 patients. Three patients had newly developed WMH on their follow-up MRI. 51.9% (14/27) of patients with LVD showed progress, whereas 30.2% (13/43) of SVD showed progress. Regarding regression, 16.3% (7/43) of patients with SVD, 11.1% (3/27) of LVD showed regression. The presence of LVD was significantly associated with WMH progression (14/27 vs. 18/73, p=0.015). The WMH changing pattern was not affected by risk factors. Conclusions: Over half of patients with stroke showed progress of WMH on their follow-up MRI. In addition, regression of WMH was also observed in 21.8% patients. Stroke subtype of LVD was associated with WMH progression.

Abstract TP135: White Matter Hyperintensities in Relation to Severity of Intracranial Atherosclerotic Stenosis

Background &amp; Objectives: White matter hyperintensities (WMH) is regarded as a small-vessel disease because the accompanying silent infarcts are predominantly lacunes and share the same pathological basis with WMH. Endothelial dysfunction is known to play a cardinal role in progression of WMH. Accordingly, atherosclerotic burden might be associated with the development of WMH. Because metabolic syndrome (MetS) is associated with an increased risk of WMH and with intracranial atherosclerotic stenosis (ICAS), we assessed the hypothesis that WMH might be related to ICAS in ischemic stroke patients. We compared a severity of WMH among the ICAS, extracranial (ECAS), and no cerebral atherosclerotic stenosis (NCAS) groups. Methods: We conducted a cross-sectional study in 605 Korean patients with acute ischemic stroke (mean age 67.7±12.8; 347 males), who underwent brain MRI/MRA. The severity of deep WMH (d-WMH, n=495) and periventricular WMH (pv-WMH, n=521) was rated separately. Irrespective of index stroke mechanisms, patients were classified into three groups: ICAS (n=294), extracranial (ECAS, n=63), and no cerebral atherosclerotic stenosis (NCAS, n=248). Stenosis groups and demographics, including the presence of MetS, were compared between patients with d-/pv-WMH and without. Results: The ICAS group showed a higher d-WMH / pv-WMH grade (1.61±0.85 / 1.64±0.80) than both the ECAS (1.29±0.87 / 1.21±0.77) and NCAS (1.15±0.92 / 1.21±0.82) groups ( P &lt;0.001 for all). Patients with more severe ICAS were more likely to have higher grades of d-WMH and pv-WMH ( P &lt;0.001 for all). Patients with higher grades of d-WMH and pv-WMH had a higher incidence of ICAS ( P &lt;0.001 for all) but not of ECAS or NCAS. Patients with a greater number of MetS components were more likely to have higher grades of d-WMH and pv-PWMH ( P &lt;0.001 for all). With a multivariable analysis, a dose-response relationship was observed between the presence of ICAS and the WMH: (1) for d-WMH, OR=3.25 (95% CI, 1.18-8.96) for 2 ICAS, OR=6.39 (1.84-22.14) for ≥3 ICAS, (2) for pv-WMH, OR=2.22 (95% CI, 1.25-3.95) for 2 ICAS, OR=3.40 (1.89-6.09) for ≥3 ICAS versus 1 ICAS. Conclusions: ICAS, rather than ECAS or NCAS is a predictor of d-/pv-WMH. ICAS burden might be the substrate for chronic cerebral hypoperfusion.

Blood–Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

Increased blood-brain barrier (BBB) permeability occurs in cerebral small vessel disease. It is not known if BBB changes predate progression of small vessel disease. We followed-up patients with nondisabling lacunar or cortical stroke and BBB permeability magnetic resonance imaging after their original stroke. Approximately 3 years later, we assessed functional outcome (Oxford Handicap Score, poor outcome defined as 3-6), recurrent neurological events, and white matter hyperintensity (WMH) progression on magnetic resonance imaging. Among 70 patients with mean age of 68 (SD ± 11) years, median time to clinical follow-up was 39 months (interquartile range, 30-45) and median Oxford Handicap Score was 2 (interquartile range, 1-3); poor functional outcome was associated with higher baseline WMH score (P<0.001) and increased basal ganglia BBB permeability (P=0.046). Among 48 patients with follow-up magnetic resonance imaging, WMH progression at follow-up was associated with baseline WMH (ANCOVA P<0.0001) and age (ANCOVA P=0.032). Further long-term studies to evaluate the role of BBB dysfunction in progression of small vessel disease are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age.