White Matter Lesions Grade Research Articles

Cystatin C as an index of cerebral small vessel disease: results of a cross‐sectional study in community‐based Japanese elderly

Recent studies have shown that kidney dysfunction is associated with cerebral small vessel disease (SVD). Although creatinine-based estimating equations have been used as the standard measure for the evaluation of kidney function, the accuracy of these is limited in the elderly because of muscle mass decrease with aging. Cystatin C is a more useful measurement than creatinine-based estimating equations for evaluating kidney function, however, the relationship amongst cystatin C, cognitive dysfunction, and cerebral SVD has not been fully examined in community-based elderly. We performed a cross-sectional study using MRI to determine the relationship amongst cystatin C, cognitive function, and cerebral SVD in a total of 604 community-based Japanese elderly. In this study, subjects with higher cystatin C levels tended to have more lacunas and higher grades of white matter lesions. Although a decline of the Mini-Mental State Examination (MMSE) scores was associated with SVD-related lesions, the relationship between the tertiles of cystatin C and mean MMSE scores was not statistically significant. In the logistic regression analysis, the association between cystatin C and SVD-related lesions was statistically significant, even after adjustment for conventional risk factors and high-sensitivity C-reactive protein. Furthermore, subjects with higher cystatin C levels accompanied with albuminuria had a greater risk for the presence of subclinical cerebral SVD than those with lower cystatin C levels without albuminuria. The present study suggests that there is a close relationship between cystatin C and subclinical cerebral SVD, independently of conventional risk factors, in community-based elderly.

Cerebral small vessel disease and chronic kidney disease (CKD): Results of a cross-sectional study in community-based Japanese elderly

Chronic kidney disease (CKD) is known as a risk factor for cardiovascular disease. In recent years, several experimental and epidemiological studies have suggested that CKD is associated with endothelial dysfunction; thereby, a CKD state may initiate both large and small vessel damage. The association between renal dysfunction and asymptomatic lacunar infarction was reported in a hospital-based study, whereas the relationship between cerebral small vessel disease (SVD)-related lesions and CKD could not be clarified in a community-based study. We performed a cross-sectional study to determine the relationship between silent cerebral SVD-related lesions and CKD in a total of 625 community-based Japanese elderly. In this study, subjects with lower estimated glomerular filtration rate levels tended to have more lacunar infarcts and higher grades of white matter lesions (WMLs). In addition, the mean grades of WMLs or the mean numbers of lacunar infarction in the subjects with albuminuria were greater than those in subjects without albuminuria. In the logistic regression analysis, the association between the presence of CKD and lacunar infarction or moderate WMLs (Fazekas grades 2 and 3) was statistically significant (odds ratio [OR]: 1.86 and 1.50, respectively). Furthermore, as we performed additional analysis, excluding the subjects with stage 2 hypertension (those with casual blood pressure >or=160/100 mm Hg) or diabetes, CKD remained to be an independent risk for cerebral SVD-related lesions. This is the first study showing the relationship between silent SVD-related brain lesions and the presence of CKD, independently of conventional cardiovascular risk factors, in community-based elderly.

Cystatin C expression in ischemic white matter lesions

To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs). Cystatin C levels in the cerebrospinal fluid (CSF) of patients with cerebrovascular disease, and also in primary and established human neural cell cultures were investigated. For pathologic analysis, cystatin C immunoreactivity was investigated in the white matter of patients with severe WMLs, mild WMLs or controls. Cystatin C levels in the CSF of patients with Fazekas WML grade 3 [14 with hypertension; W/HT(+) and nine without hypertension; W/HT(-)] were lower than those in 38 patients with grade 0-1 (P = 0.0022 and P < 0.0001 respectively). Immunohistochemical study showed that the cystatin C immunoreactivity was found in astrocytes, and the number of astrocytes in the white matter in the severe WML group was decreased when compared with that in controls (P = 0.0027) and in the mild WML group (P = 0.0024). In human neural cell cultures, treatments with thrombin, matrix metalloproteinases and interleukin 1 beta increased the expression of cystatin C mRNA in human astrocytes and hybrid neurons, but an enzyme-linked immunosorbent assay revealed that only thrombin significantly increased the production and secretion of cystatin C in astrocytes. These results suggest that low levels of CSF cystatin C in ischemic WMLs might be due to the decreased number of astrocytes that secrete cystatin C in response to the stimuli of proteases and inflammatory cytokines.

MRI white Matter Lesions in a Stroke Clinic Population: Correlation with Increased Carotid Intima-media Thickness on Ultrasonography

Cerebral white matter lesions (WML) on MRI have been related not only to age but also to cerebrovascular disorders. This study aimed to determine the prevalence of WML in a population of patients attending a stroke clinic and relate it to the presence of carotid atherosclerosis as determined by increased carotid intima-media thickness (IMT) on ultrasonography. Subjects were recruited from patients attending a stroke clinic at the National Hospital for Neurology and Neurosurgery, Queen square, London. The patients had cranial MRI and carotid ultrasonography (amongst other investigations). WML on MRI were graded according to the rating scale of the Task force on age-related white matter changes and a WML score was obtained based on the WML grades and geographical distribution. Patients with carotid intima-media thickness > 1cm on ultrasonography were considered to have increased intima-media thickness. WML was present in 63.46% of subjects. Patients with WML had a significantly higher mean age than those without (67.5 vs 53.5 years). Increased carotid IMT was found in 33.3% of those with WML and in 15.8% of those without. The difference was not statistically significant. There was no significant association between the presence of any grade of WML and increased carotid IMT. Similarly, the mean WML scores for patients with and without increased carotid IMT were not significantly different. A high proportion of patients in the stroke clinic had WML on MRI. Presence of WML was not associated with the presence of carotid atherosclerosis as shown by increased carotid intima-media thickness. Nigerian Medical Practitioner Vol. 52 (2) 2007: pp. 38-41

Past adult lead exposure is linked to neurodegeneration measured by brain MRI

To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes. MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as microg lead per gram of bone mineral (microg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated. A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 microg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (> or = 5 vs < 5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula. These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.

Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Atherosclerosis Risk in Communities Study.

White matter lesions (WML) may result from cerebral hypoperfusion or ischemia. We investigated the association of WML with blood pressure, hypertension, and its treatment and control. A random sample of 1920 participants aged 55 to 72 years in the Atherosclerosis Risk in Communities Study (ARIC) was examined. Spin-density 1.5-T MRI scan images were coded from 0 for normal to 9 for most severe WML. Hypertension was defined as systolic or diastolic pressure > or = 140/90 mm Hg or use of antihypertensive medication. The percentages of persons with WML grades 0 through 2 and 3 through 9, respectively, were as follow: normotensive, 92.4% and 7.6%, versus all hypertensive subjects, 83% and 17% (P < .001); and treated controlled hypertensive, 86% and 14%, versus treated uncontrolled hypertensive subjects, 76% and 24% (P = .003). Multivariable adjusted odds ratios (95% confidence intervals) for WML grade > or = 3 relative to normotensive subjects was 2.34 (1.71 to 3.20) for all hypertensives, 1.99 (1.19 to 3.08) for untreated hypertensives, 1.94 (1.32 to 2.85) for treated controlled hypertensives, and 3.40 (2.30 to 5.03) for treated uncontrolled hypertensives. After additional adjustment for hypertension duration, treatment, and control status, the odds ratios (95% confidence intervals) for a 1 SD increase of systolic and diastolic blood pressure were 1.43 (1.11 to 1.85) and 1.16 (0.94 to 1.43), respectively. Hypertension is associated with increased odds of WML, and treated uncontrolled hypertensive subjects have greater odds of WML than those with treated controlled hypertension. The data suggest that the level of blood pressure, especially systolic blood pressure, is related to WML, additional to the effects of categorically defined hypertension and its treatment and control status.