Severity Of Periventricular White Matter Lesions Research Articles

Higher High-Mobility Group Box-1 Levels are Associated with White Matter Lesions in Ischemic Stroke Patients.

High-mobility group box-1 (HMGB1) is a useful biomarker for disease severity stratification and prognosis prediction. We aim to explore whether the circulating HMGB1 concentrations are associated with the white matter lesions (WMLs) burden in stroke patients. Between 2022 June and December 2022, patients with acute ischemic stroke were prospectively enrolled. HMGB1 levels were measured by an enzyme-linked immunosorbent assay after admission for all patients. The WMLs severity was assessed by the Fazekas scale. We dichotomized patients into those with moderate-severe WMLs (Fazekas score 3-6) versus those with none-mild WMLs (Fazekas score 0-2). Furthermore, based on the severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs), patients were categorized as none-mild (Fazekas score 0-1) or moderate-severe (Fazekas score 2-3). A total of 287 participants (mean age: 64.9 years; 157 male) were analyzed. The median serum HMGB1 levels were 7.3 ng/mL (interquartile, 4.3 ng/mL-12.3 ng/mL). After adjustment for potential confounders, elevated HMGB1 levels were associated with the presence of moderate-severe WMLs (first quartile vs fourth quartile, odds ratio [OR], 4.101; 95% confidence interval [CI], 1.948-8.633; P = 0.001) and moderate-severe PWMLs (first quartile vs fourth quartile, OR, 9.181; 95% CI, 4.078-20.671; P = 0.001). Similar results were found when the HMGB1 levels were analyzed as a continuous variable. This study demonstrated that increased HMGB1 levels were associated with the severity of WMLs, mainly in the periventricular region.

Cerebrovascular disorders in diabetic patients with resistant hypertension and factors associated with their severity

Abstract Introduction Diabetes mellitus (DM) and hypertension (HTN) are associated with accelerated brain damage that often precedes the development of stroke and dementia. However, little is known about the features of silent brain damages and possible mechanisms of their development in patients with resistant hypertension (RHTN) and type 2 DM. Objective To study the features of MRI- sings of silent brain damage in patients RHTN with type 2 DM and to establish the factors associated with their development. Methods We studied 46 with RHTN and type 2 DM (mean age 60.3±7.9 years; 27 females (59%), mean 24-hour (systolic/diastolic) BP 169.0±16.4/89.0±14.7 mmHg, HbA1c 7.4±1.3%). On average, patients were taking 4.3±1.0 antihypertensive drugs. Patients were subjected to brain MRI (1.5 T), 24-hour BP monitoring, lab tests (HbA1c, TNF-α, hsCRP, leptin, resistin, aldosterone, basal end postprandial serum glucose, insulin, C-peptide). According to MRI linear dimensions of liquor spaces (subarachnoidal spaces (SAS), lateral ventricles, III and IV ventricles), white matter lesions (WMLs), basal ganglia and thalamus abnormalities were assessed. In addition, severity of periventricular WMLs (PWMLs) was evaluated semi-quantitatively on a scale of 0 to 4. Results The frequency of ventricular dilatation was 45%, expansion of SAS – 65%, lacunar infarctions – 25%, focal WMLs (diameter <3 mm) – 52%, PWMLs – 89%. According to the correlation analysis, an increase in density of the MR signal of PWMLs was associated with an increase in levels of TNF-α (r=0.55 p=0.01) and hsCRP (r=0.64 p=0.045). The increase in density of the MR signal from basal ganglia and thalamus correlated with postprandial levels of glucose (r=0,48 p=0,025; r=0.46 p=0.04, respectively), insulin (r=0.54 p=0.011; r=0.52 p=0.017, respectively) and C-peptide (r=0.54 p=0.011; r=0.46 p=0.037, respectively), as well as with basal level of insulin (r=0.52 p=0.007; r=0.48 p=0.012, respectively) and the leptin (r=0.40 p=0.027; r=0.36 p=0.048, respectively). The severity of PWMLs depended on the level of basal glycaemia (r=0.35, p=0.020) and HbA1c (r=0.37, p=0.04). The transverse size of the chiasmal cistern had a relationship with of the resistin level (r=0.43, p=0.03), and the transverse size of the III ventricle correlated with the serum aldosterone level (r=0.51, p=0.13). There were no direct correlations between MRI- sings of silent brain damage and blood pressure levels. Conclusion Thus, diabetic patients with resistant hypertension have a high frequency of white matter lesions and of liquorodynamics dysturbanses. The severity of these changes depends on a complex of metabolic, pro-inflammatory and neurohormonal factors in the absence of a direct relationship with the blood pressure level. Funding Acknowledgement Type of funding sources: None.

Sex differences in associations between blood lipids and cerebral small vessel disease

Background and aimsDyslipidemia predicts higher risk of coronary events and stroke and might be associated with cerebral small vessel disease (SVD). Previous studies linking blood lipids and SVD have yielded inconsistent results, which may be attributable to sex differences in lipids metabolism. The aim of this study was to investigate the relationships between blood lipids and SVD in neurologically healthy men and women. Methods and resultsConsecutive 817 people aged 50 years or more were enrolled and underwent magnetic resonance imaging scans to evaluate the periventricular white matter lesions (PVWMLs), deep white matter lesions (DWMLs) and silent brain infarction (SBI). Fasting total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, apolipoprotein A-1 (apoA-1) and apolipoprotein B were assessed. Multivariable logistic regression analyses were performed to determine the associations of blood lipids with PVWMLs, DWMLs and SBI. HDL-C (for PVWMLs: OR 0.36, 95% CI 0.19–0.71; for DWMLs: OR 0.35, 95% CI 0.20–0.63) and apoA-1 (for PVWMLs: OR 0.27, 95% CI 0.11–0.66; for DWMLs: OR 0.22, 95% CI 0.10–0.48) were inversely associated with the severity of PVWMLs and DWMLs in women but not in men after adjustment for age, hypertension, diabetes, current smoking, daily drinking, body mass index and uric acid. Additionally, no blood lipids were significantly associated with SBI. ConclusionsOur findings demonstrate that sex differences may exist in the associations between lipids and SVD. HDL-C and apoA-1 levels were inversely associated with the severity of PVWMLs and DWMLs in women.

Association between serum uric acid levels and cerebral white matter lesions in Chinese individuals

Purpose/aim of the study: We aimed to evaluate the association between serum uric acid (SUA) levels and cerebral white matter lesions (WMLs) in Chinese individuals. Material and methods: We prospectively identified patients aged 50 years and older in neurology department from July 2014 to March 2015. Both periventricular WMLs (P-WMLs) and deep WMLs (D-WMLs) were identified on magnetic resonance imanging (MRI) scans and the severity was graded using the Fazekas method. Multivariate logistic regression analyses were performed to examine the association between SUA and WMLs. Results: A total of 480 eligible participants were enrolled in this study. SUA level in severe group was much higher than that in mild group (for P-WMLs: 320.21 ± 79.97 vs. 286.29 ± 70.18, p = 0.000; for D-WMLs: 314.71 ± 74.74 vs. 290.07 ± 74.04, p = 0.031). Subgroup analyses showed that higher SUA level was associated with higher severity of P-WMLs in women, but not in male patients. Multivariate logistic regression analyses showed that SUA was still associated with increased risk of higher severity of P-WMLs (OR = 1.003, 95% = 1.000–1.006), but not D-WMLs. Conclusion: Elevated SUA level was independently associated with greater odds of higher severity of P-WMLs, particularly in women.

Significance of increased CIMT with coexisting carotid plaques in cerebral white matter lesions in elders

It is very common that increased carotid intima media thickness (CIMT) and carotid plaque coexist in a single subject in elderly patients with white matter lesions (WMLs). In this study we investigated whether the coexistence of increased CIMT and carotid plaque is more strongly associated with the presence and extent of WMLs than either alone. All patients were classified into 1 of the following 4 groups: without either increased CIMT (I) or carotid plaque (P): I(-)P(-); with only increased CIMT: I(+)P(-); with only carotid plaque: I(-)P(+); and with both increased CIMT and carotid plaque: I(+)P(+). The presence and severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs) were assessed and the prevalence of MRI findings by the Cochran-Armitage trend test was calculated. The characteristics of subjects showed that the percentages of patients with increased CIMT and carotid plaque in the DWMLs group and the PWMLs group were significantly higher than those without WMLs group. Both DWMLs and PWMLs were strongly associated with age, carotid plaque and CIMT. Furthermore, the Cochran-Armitage trend test indicated that the prevalence of MRI findings of PWMLs and DWMLs increased in the order of I(-)P(-)< I(+)P(-)< I(-)P(+)< I(+)P(+) (P<0.0001). For the patients with DWMLs, the grades of both I(+)P(-) and I(+)P(+) were increased significantly compared to I(-)P(-) (P<0.0025, P<0.05, respectively) without such a difference found in patients with PWMLs. Our results suggested that the coexistence of increased CIMT and carotid plaque is most closely associated with WMLs, and that increased CIMT is associated with the severity of DWMLs, whereas carotid plaque is related to the presence of WMLs.

Periventricular White Matter Lucencies Relate to Low Vitamin B12 Levels in Patients With Small Vessel Stroke

Blood-brain barrier dysfunction may be an early phenomenon in the development of the small vessel disease, which underlies white matter lesions. Because vitamin B12 plays a role in maintaining the integrity of the blood-brain barrier, we studied serum vitamin B12 level in relation to such lesions. In 124 patients with first lacunar stroke, we measured serum vitamin B12 level and rated the degree of white matter lesions on MRI. Mean vitamin B12 level was 202 pmol/L (SD, 68.9). Thirty-nine patients (31.5%) had a vitamin B12 level less than the lower reference value of 150 pmol/L. Lower vitamin B12 level was (statistically significant) associated with more severe periventricular white matter lesions (odds ratio/100 pmol/L decrease, 1.773; 95% CI, 1.001-3.003), but not with deep white matter lesions (odds ratio/100 pmol/L decrease, 1.441; 95% CI, 0.881-2.358; ordered multivariate regression analysis). More severe periventricular white matter lesions in lacunar stroke patients relate to lower vitamin B12 levels. A possible causal relationship should now be studied prospectively.

White matter lesions on magnetic resonance imaging and their relationship with vascular risk factors in memory clinic attenders

The association between white matter lesions on magnetic resonance imaging (MRI) and the presence of vascular risk factors has been investigated in different populations, and results have varied widely. However, this relationship has not been adequately addressed in memory clinic attenders who have relatively early cognitive impairment. This study was undertaken to determine the relationship between the severity of white matter lesions and vascular risk factors in elderly subjects referred to a Memory Clinic, irrespective of their diagnoses. Patients attending the Memory Clinic had relatively early, mild cognitive impairment and differed, in this respect, from typical unselected community-based samples and from patients with established dementia. The study also investigated whether periventricular and deep white matter lesions differed in their relationship with vascular risk factors. All patients assessed in the Memory Clinic at Leicester General Hospital between April 1998 and October 2000 who had undergone an MRI scan were included in the study. They received a comprehensive clinical and cognitive assessment, a standard dementia laboratory screen and evaluation of vascular risk factors. MRI scans were reviewed by two independent raters and semi-quantitative ratings of the severity of white matter lesions were made using standardised protocols. The relationship between cerebral white matter lesions and vascular risk factor variables was examined by multiple linear regression. One hundred and seventy-seven subjects were included in the study. The mean age was 69.8 and the mean MMSE score was 23.2. Of the risk factors investigated, only age and prior cerebrovascular disease were significantly associated with severe periventricular white matter lesions; age, hypertension and diabetes were significantly associated with severe deep white matter lesions. Periventricular and deep white matter lesions are differentially influenced by vascular risk factors.

The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study.

Cerebral white matter lesions are frequently observed on magnetic resonance imaging (MRI) scans in elderly people and are associated with stroke and dementia. Elevated blood pressure is presumed one of the main risk factors, although data are almost exclusively derived from cross-sectional studies. We assessed in 10 European cohorts the relation between concurrently and previously measured blood pressure levels, hypertension, its treatment, and severe cerebral white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years were sampled from ongoing community-based studies that were initiated 5 to 20 years before the MRI. White matter lesions in the periventricular and subcortical region were rated separately using semiquantitative measures. We performed logistic regression analyses adjusted for potential confounders in 1625 people with complete data. Concurrently and formerly assessed diastolic and systolic blood pressure levels were positively associated with severe white matter lesions. Both increases and decreases in diastolic blood pressure were associated with more severe periventricular white matter lesions. Increase in systolic blood pressure levels was associated with more severe periventricular and subcortical white matter lesions. People with poorly controlled hypertension had a higher risk of severe white matter lesions than those without hypertension, or those with controlled or untreated hypertension. Higher blood pressure was associated with an increased risk of severe white matter lesions. Successful treatment of hypertension may reduce this risk; however, a potential negative effect of decreasing diastolic blood pressure level on the occurrence of severe periventricular white matter lesions should be taken into account.

Arterial oxygen saturation, COPD, and cerebral small vessel disease

Objective: To study whether lower arterial oxygen saturation (SaO2) and chronic obstructive pulmonary disease (COPD) are associated with cerebral white matter lesions and lacunar infarcts. Methods: We measured SaO2 twice...

Migraine as a risk factor for subclinical brain lesions.

Clinical series have suggested an increased prevalence of cerebral infarction and white matter lesions (WMLs) in migraine patients. It is not known whether these lesions are prevalent in the general migraine population. To compare the prevalence of brain infarcts and WMLs in migraine cases and controls from the general population and to identify migraine characteristics associated with these lesions. Cross-sectional, prevalence study of population-based sample of Dutch adults aged 30 to 60 years. Randomly selected patients with migraine with aura (n = 161), patients with migraine without aura (n = 134), and controls (n = 140), who were frequency matched to cases for age, sex, and place of residence. Nearly 50% of the cases had not been previously diagnosed by a physician. Brain magnetic resonance images were evaluated for infarcts, by location and vascular supply territory, and for periventricular WMLs (PVWMLs) and deep WMLs (DWMLs). The odds ratios (ORs) and 95% confidence intervals (CIs) of these brain lesions compared with controls were examined by migraine subtype (with or without aura) and monthly attack frequency (<1 attack, > or =1 attack), controlling for cardiovascular risk factors and use of vasoconstrictor migraine agents. All participants underwent a standard neurological examination. No participants reported a history of stroke or transient ischemic attack or had relevant abnormalities at standard neurological examination. We found no significant difference between patients with migraine and controls in overall infarct prevalence (8.1% vs 5.0%). However, in the cerebellar region of the posterior circulation territory, patients with migraine had a higher prevalence of infarct than controls (5.4% vs 0.7%; P =.02; adjusted OR, 7.1; 95% CI, 0.9-55). The adjusted OR for posterior infarct varied by migraine subtype and attack frequency. The adjusted OR was 13.7 (95% CI, 1.7-112) for patients with migraine with aura compared with controls. In patients with migraine with a frequency of attacks of 1 or more per month, the adjusted OR was 9.3 (95% CI, 1.1-76). The highest risk was in patients with migraine with aura with 1 attack or more per month (OR, 15.8; 95% CI, 1.8-140). Among women, the risk for high DWML load (top 20th percentile of the distribution of DWML load vs lower 80th percentile) was increased in patients with migraine compared with controls (OR, 2.1; 95% CI, 1.0-4.1); this risk increased with attack frequency (highest in those with > or =1 attack per month: OR, 2.6; 95% CI, 1.2-5.7) but was similar in patients with migraine with or without aura. In men, controls and patients with migraine did not differ in the prevalence of DWMLs. There was no association between severity of PVWMLs and migraine, irrespective of sex or migraine frequency or subtype. These population-based findings suggest that some patients with migraine with and without aura are at increased risk for subclinical lesions in certain brain areas.

Endothelial cell activation is associated with cerebral white matter lesions in patients with cerebrovascular disease.

Cerebral MRI scanning frequently shows white matter lesions in elderly people. They are related to cognitive impairment and may result in dementia. Although vascular risk factors are associated with the presence of white matter lesions, the exact pathogenesis remains unclear. Animal studies have indicated involvement of endothelial cells in the pathogenesis of white matter lesions and possibly dementia. We investigated the relation between endothelial cell activation and white matter lesions in individuals with cerebrovascular disease. In 29 patients with an acute stroke (n = 11) or TIAs associated with a symptomatic internal carotid artery stenosis (n = 18), markers of endothelial cell activation such as intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, and sP-selectin were measured by means of ELISA. All individuals underwent 1.5-T MRI scanning. White matter lesions were rated for the periventricular and the subcortical region separately. Individuals with severe periventricular white matter lesions had higher levels of sP-selectin (245.5 ng/mL vs. 172.7 ng/mL, p = 0.01) and sVCAM-1 (547.8 ng/mL vs. 454.0 ng/mL, p = 0.04) than those without. This association was only found in individuals with a symptomatic carotid artery stenosis. No such association was found for subcortical white matter lesions. We did not detect any relation between sICAM-1 and sE-selectin and white matter lesions. Endothelial cell activation may play a role in the pathogenesis of white matter lesions, especially in periventricular white matter. Possibly, this activation represents the influence of vascular factors on the cerebral endothelium as a prelude to increasingly severe small vessel disease.

Periventricular cerebral white matter lesions predict rate of cognitive decline.

The prospect of declining cognitive functions is a major fear for many elderly persons. Cerebral white matter lesions, as commonly found with magnetic resonance imaging, have been associated with cognitive dysfunction in cross-sectional studies. Only a few longitudinal studies using small cohorts confirmed these findings. We examined the relation between severity of white matter lesions and cognitive decline over a nearly 10-year period in 563 elderly subjects sampled from the general nondemented Dutch population. Severity of white matter lesions was scored for periventricular and subcortical regions separately using an extensive semiquantitative scale. Cognitive function was measured by the Mini-Mental State Examination at regular time intervals during 1990 to 2000, and magnetic resonance imaging scans were made in 1995 to 1996. More severe white matter lesions were associated with more rapid cognitive decline over a mean follow-up period of 7.3 years (standard deviation, 1.5). After adjusting for age, gender, educational level, measures of depression, and brain atrophy and infarcts, subjects with severe periventricular white matter lesions experienced cognitive decline nearly three times as fast (0.28 Mini-Mental State Examination points/year [95% confidence interval, 0.20-0.36]) as the average (0.10 points/year [95% confidence interval, 0.09-0.11]). There was no independent relationship between severity of subcortical white matter lesions and rate of cognitive decline.

Serum carotenoids and cerebral white matter lesions: the Rotterdam scan study.

To study the relation between serum levels of carotenoids and white matter lesions (WMLs) on magnetic resonance imaging (MRI). Evaluation of cross-sectional data from a cohort study. The Rotterdam Scan Study. Two hundred and three nondemented older persons, age 60 to 90, from the Rotterdam Scan Study. Serum levels of carotenoids were determined. WMLs on MRIs were rated separately into periventricular and subcortical WMLs. Odds ratios (ORs) for the presence of severe WMLs (upper decile) were calculated per standard deviation (SD) increase in serum carotenoid level and per SD increase in overall carotenoid serum level. Effect modification by smoking status was studied through stratified analyses. Increasing levels of all the separate carotenoids were associated with less severe periventricular WMLs, which reached statistical significance for the overall carotenoid serum level (OR 0.4 per SD; 95% confidence interval (CI) = 0.2-0.9). We found no association between carotenoid levels and the presence of severe subcortical WMLs (OR 1.2 per SD; 95% CI = 0.7-2.0). The association of carotenoid levels with severe periventricular WMLs was more marked in those who ever smoked (OR 0.1 per SD; 95% CI = 0.0-0.9) than in those who had never smoked (OR 0.9 per SD; 95% CI = 0.4-2.1). These findings are compatible with the view that high levels of carotenoids may protect against WMLs in the periventricular region, in particular in smokers. Longitudinal studies with repeated measurements of both carotenoids and WMLs are necessary to explore this hypothesis further.

Atrial fibrillation and the risk of cerebral white matter lesions.

Cerebral white matter lesions are often observed on MRI scans of elderly nondemented and demented persons. Their pathogenesis is not fully understood but cerebral hypoperfusion may be involved. Atrial fibrillation is a common finding in elderly subjects and may lead to a reduced cardiac output with cerebral hypoperfusion. The authors investigated the association between atrial fibrillation and the presence of white matter lesions. From 1995 through 1996, the authors randomly sampled 1077 subjects from two ongoing prospective population-based studies. From each participant, an electrocardiogram (ECG) was recorded; atrial fibrillation and left ventricular hypertrophy were diagnosed with a computer program. For one of the two groups (553 subjects), earlier ECGs were available (mean follow-up 4.7 years). All subjects underwent 1.5-T MRI scanning; white matter lesions were separately rated for the periventricular and subcortical regions. The prevalence of atrial fibrillation was 1.9% among subjects younger than 75 years and 5.5% in subjects older than 75 years. The total number of subjects with atrial fibrillation was 28. Subjects with atrial fibrillation had severe periventricular white matter lesions more than twice as often as subjects who did not (RR 2.2; 95% CI 1.0 to 5.2) but had no increased risk of subcortical white matter lesions (RR 1.1; 95% CI 0.4 to 2.6). For seven subjects with atrial fibrillation both at baseline and at follow up, these relative risks were 6.3 (95% CI 1.1 to 37.1) and 0.7 (95% CI 0.1 to 3.7). Atrial fibrillation is associated with periventricular white matter lesions, but not with subcortical white matter lesions.

Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study.

Cerebral white matter lesions (WMLs) have been associated with cognitive dysfunction. Whether periventricular or subcortical WMLs relate differently to cognitive function is still uncertain. In addition, it is unclear whether WMLs are related to specific cognitive domains such as memory or psychomotor speed. We examined the relationship between periventricular and subcortical WMLs and cognitive functioning in 1,077 elderly subjects randomly sampled from the general population. Quantification of WMLs was assessed by means of an extensive rating scale on 1.5-T magnetic resonance imaging scans. Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed, memory performance, and global cognitive function. When analyzed separately, both periventricular and subcortical WMLs were related to all neuropsychological measures. When periventricular WMLs were analyzed conditional on subcortical WMLs and vice versa, the relationship between periventricular WMLs and global cognitive function remained unaltered whereas the relationship with subcortical WMLs disappeared. Subjects with most severe periventricular WMLs performed nearly 1 SD below average on tasks involving psychomotor speed, and more than 0.5 SD below average for global cognitive function. Tasks that involve speed of cognitive processes appear to be more affected by WMLs than memory tasks.

Computed tomography--but not magnetic resonance imaging--identified periventricular white-matter lesions predict symptomatic cerebrovascular disease in probable Alzheimer's disease.

To examine the clinical consequences of periventricular white-matter lesions on computed tomography (CT) and magnetic resonance imaging (MRI) scans in probable Alzheimer's disease. Case series, 12-month follow-up. Multidisciplinary behavioral neurology research clinic. We longitudinally evaluated the clinical characteristics of 27 patients with probable AD for whom both CT and MRI scans had been performed at baseline. None. The presence of abnormal neurological signs was examined at baseline and at a 12-month examination. Periventricular white-matter lesions were observed with CT in 12 patients (44%) and with MRI in 21 patients (78%). Computed tomography did not detect lesions of 1 to 3 mm, as were seen on MRI scans, and CT also did not detect lesions of 4 to 10 mm when they occurred in the deep subcortical white matter and were not part of a greater confluent lesion. There was no relationship between the severity of periventricular white-matter lesions with either neuroimaging method and the presence of abnormal neurological signs. However, there was a greater frequency of periventricular white-matter lesions shown on CT scans than on MRI scans at baseline in patients in whom abnormal neurological signs (eg, abnormal gait, asymmetric deep tendon reflexes, focal motor deficits, abnormal plantar response) developed at 12-month follow-up. Although MRI may be more sensitive in detecting periventricular white-matter lesions, CT is more specific in predicting subsequent symptomatic cerebrovascular disease.