Subcortical White Matter Lesions Research Articles

Brain magnetic resonance image changes in a family with congenital and classic myotonic dystrophy

We present the clinical manifestations, brain magnetic resonance images (MRI), and genetic analysis of a family with 2 siblings with congenital myotonic dystrophy type 1 (DM1) and 4 patients with classic DM1. These 2 patients with congenital DM1 had severe mental retardation and a characteristic feature of hyperintensity of white matter at the posterior-superior trigone (HWMPST), in addition to ventricular dilatation in T2-weighted images (T2WI) of brain MRI. In 2 of the 4 classic DM1 patients, brain T2WI MRI showed hyperintensity lesions in the bilateral frontal and/or temporal regions, which were absent in congenital DM1. In conclusion, we suggest that the HWMPST in brain MRI is a characteristic finding in congenital DM1, and that the severe cognitive impairments are not only attributable to the subcortical white matter lesions. In congenital DM1, the cognitive function is a diffuse impairment, which is different from that in classic DM1.

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.

March 2004: a 24-year-old woman with bifrontal headaches.

A 24-year-old woman with bifrontal headaches was found to have a well-circumscribed lesion in the frontal lobe subcortical white matter. Microscopic examination showed clusters of small round cells separated by hypocellular neuropil-like areas, and a distinct border between tumor and surrounding white matter. Synaptophysin was diffusely positive in neuropil-like areas, and many tumor cells expressed NeuN. Based on these findings, a diagnosis of "extraventricular neurocytoma" was made. A double-label immunofluorescence stain was performed with NeuN and Ki-67 antibodies to determine if NeuN+ cells remained in the mitotic cycle. No colocalization of these markers was found, thus supporting the hypothesis that neuronal differentiation (as marked by NeuN expression) is incompatible with continued proliferation of tumor cells, as well as normal neurons.

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...

Topographical and cytopathological lesion analysis of the white matter in Binswanger?s disease brains

The purpose of the present study was to document the topographical and cytopathological lesions in the white matter (WM) of Binswanger's disease (BD) brains. Subcortical WM lesions in each lobe and fiber bundle lesions related to the medial thalamic and hippocampal structures in clinicopathologically proven BD brains were evaluated by Klüver-Barrera staining using a grading score. Lesions in the frontal subcortical WM of BD brains, brains from non-neurological patients, and brains with cerebral hemorrhage or large cortical infarcts were also examined immunohistochemically using molecular markers for axonal flow damage: amyloid precursor protein (APP); and for demyelinating axonopathy: encephalitogenic peptide (EP). Our results indicated that the WM lesions in BD were significantly more prominent in the frontal periventricular and subcortical regions as compared with other subcortical WM lesions, in the order of the parietal, occipital and temporal lobes. Fiber bundle lesions in the capsular genu, including the anterior thalamic peduncle, were also significantly more prominent in BD brains as compared with the other bundle lesions. Furthermore, the frequency of damaged nerve fibers labeled by the EP antiserum and APP immunoreactive fibers was significantly higher in BD brains as compared with the control brains. The grading scores for the WM damage correlated significantly with those for the APP and EP immunoreactive fibers in all brains, including the control brains. The axonal damage in the frontal WM lesions of the BD brains was clearly revealed in our study using immunohistochemistry for APP and EP.

Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects

Background Several studies have linked geriatric depression with cerebrovascular disease. The apolipoprotein E gene (APOE) ε4 allele has been associated with a variety of late-life neuropsychiatric disorders, including Alzheimer’s disease, vascular dementia, and depression. Methods The sample consisted of 145 elderly depressive individuals and 100 nondepressed elderly control subjects. After a standardized clinical assessment, all subjects underwent a magnetic resonance imaging brain scan. Volumes of subcortical white and gray matter lesions were determined using a semi-automated method. Apolipoprotein E genotype was determined on blood sample using a standard protocol. A series of linear regression models were developed to assess the relationships between APOE genotype and white and gray matter lesion volumes. Results Older age, lower Mini-Mental State Examination score, and having any APOE ε4 allele were each correlated with gray-matter lesion volume in depressed patients. Apolipoprotein E genotype was not associated with any lesion volume among control subjects. In a subsequent linear regression model, gray matter lesion volume was associated with older age, having at least one APOE ε4 allele, and white matter lesion volume among depressed patients. Conclusions These results are consistent with previous reports linking cerebrovascular disease and APOE genotype. Further studies are needed to replicate this finding in elderly depressive individuals and to explain the relationship between the APOE locus and development of central nervous system vascular pathology.

Primary angiitis of the central nervous system: MRI features and clinical presentation.

We report the MRI features in a series of four patients with primary angiitis of the central nervous system (PACNS). Based on MRI features, clinical presentation, paraclinical investigations and laboratory tests, including cerebrospinal fluid (CSF) analysis, various differentials were considered. In two patients with MRI findings of cortical, subcortical and deep white matter lesions, lack of mass effect, focal areas of bleed and heterogeneous parenchymal, leptomeningeal or pial enhancement and a normal magnetic resonance angiography, a differential diagnosis of primary angiitis of the CNS was also considered. In all patients, an open brain biopsy was advised to establish a definitive diagnosis of PACNS. Here, we briefly discuss the MRI features, correlation with clinical presentation and paraclinical parameters for the diagnosis of this entity. We also briefly review the literature.

MR Imaging and Proton MR Spectroscopy of the Brain in Behçet's Disease

Cerebral MR imaging (MR) and proton-MR spectroscopy (H-MRS) data are lacking in neurologically asymptomatic patients with Behçet's disease (BD). Aim of the following work was to assess MR and H-MRS characteristics of brain involvement over time in patients with BD without clinical neurological involvement. Forty cerebral MR and 12 H-MRS examinations obtained over a one to nine year follow-up in 17 patients with (group A n=9) or without (group B n=8) neurological involvement were retrospectively reviewed. Four group-B patients had a normal first MR examination whereas all group-A and four group-B patients showed single (n?3) or multiple (n=10) subcortical white matter foci of signal change. Large midbrain, basal ganglia or subcortical white matter lesions were depicted in six group-A patients. Comparison between initial and last MR examinations revealed 28 new small-to-medium size lesions. Over the course of the study, lesion enhancement was seen in five patients all belonging to group A. NAA/Cr and Cho/Cr ratios of supraventricular white matter did not show significant differences between patients and healthy controls or between group-A and group-B patients. Clinically silent cerebral involvement in the form of small-to-medium size subcortical lesions may be present at MR examination in BD patients. Large brainstem and basal ganglia lesions associated with overt neurological symptoms are characteristic of the disease. H-MRS of cerebral normal-appearing white matter does not show any significant metabolic change in BD.

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.

Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study.

Previous studies have reported an association between cerebrovascular disease and depressive symptoms. The Cardiovascular Health Study (CHS) provides an opportunity to examine the relationship between vascular brain pathology seen on neuroimaging and changes in depressive symptoms. The sample included 3236 CHS participants who had an MRI brain scan. Demographic variables, medical history, functional status, and apolipoprotein E genotype were obtained at baseline. Annual scores on a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale were obtained initially and up to 7 years subsequently. After controlling for important covariates, occurrence of depressive symptoms (defined as modified CES-D score of >7) was associated with small lesions in the basal ganglia, large cortical white-matter lesions, and severe subcortical white-matter grade. Neuroimaging variables did not predict incident depression among those who were nondepressive at the time of MRI. Persistence of depressive symptoms across 2 consecutive time points was associated with small basal ganglia lesions and large cerebral cortical white-matter lesions. Worsening of depression (increase in CES-D score of > or =5) was associated with subcortical white-matter lesions. These findings suggest that cerebrovascular disease at baseline is related to depression symptoms over time. Further studies are needed to investigate the differential effects of subcortical white- versus gray-matter lesions on mood.

Evidence for an ischaemic origin of deep white matter lesions in the ageing brain

Introduction: The pathogenesis of white matter lesions (WMLs) is not established. Evidence from clinical,. pathological and pathophysiological studies favours a vascular mechanism for subcortical WMLs (DWML) and a nonischaemic origin for periventricular (PV) hyperintensities. Small vessel degeneration giving rise to ischaemia is the hypothetical origin for subcortical WMLs.Methods: PV lesions (PVL) and deep subcortical lesions (DWML) demonstrated in MRI scans of fixed coronal brain slices, from elderly postmortem brain donors to the MRC CFAS(N) cohort, were sampled together with nonlesional WM from the same brains. Immunohistochemistry was performed to detect activated microglia (CD68), endothelial activation (ICAM‐1), capillary basement membrane (Collagen IV), and hypoxia‐inducible factor‐1α (HIF‐1α) expression. Quantitative analysis of microvasculature was performed with digital images using Image Pro Plus software. The sample consisted of 18 PV (seven nonlesional) and 23 DWML (11 nonlesional) regions from 15 subjects. Statistical analysis was performed using SPSS software.Results: Vascular changes in arterioles were related to ML and not to dementia. DWML arterioles had thicker walls (P < 0.001; 95%CI = 5.6–8.4), bigger external diameters (P < 0.001; 95%CI = 7.7–17.8) and larger perivascular spaces (P < 0.05; 95%CI = 13.3–19.4) than nonlesional areas. Vascular lumen diameters remained the same. The ICAM‐1/Collagen 4 ratio was significantly elevated in lesional DWML (P = 0.001) but not in the periventricular regions (P = 0.85) reflecting capillary endothelial activation. HIF‐1α expression (P = 0.004) and presence of activated microglia (P = 0.001) were more frequent in DWML. The prevalence (χ2 = 0.053; P = 0.82) and absolute counts (P = 0.07) of HIF‐1α expression, and the presence of activated microglia (P = 0.95) in PVL were not increased over control WM.Discussion: DWML show vascular degenerative changes in arterioles, reactive changes in capillaries and persistent HIF expression, all consistent with chronic ischaemia. The study raises the possibility that an age‐related impairment of the neovascular response to ischaemia results in WM lesions.

Hypertension and cerebral white matter lesions in a prospective cohort study.

White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hyper tension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross-sectional studies. We studied prospectively the association of these lesions with the duration and treatment of hypertension. We randomly sampled 1077 subjects aged between 60 and 90 years from two prospective population-based studies. One-half of the study subjects had their blood pressure measured between 1975 and 1978 and the other half between 1990 and 1993. All subjects underwent 1.5 T MRI scanning; white matter lesions in the subcortical and periventricular regions were rated separately. Subjects with hypertension had increased rates of both types of white matter lesion. Duration of hypertension was associated with both periventricular and subcortical white matter lesions. This relationship was influenced strongly by age. For participants with >20 years of hypertension and aged between 60 and 70 years at the time of follow-up, the relative risks for subcortical and periventricular white matter lesions were 24.3 [95% confidence interval (CI) 5.1-114.8] and 15.8 (95% CI 3.4-73.5), respectively, compared with normotensive subjects. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk 3.3, 95% CI 1.3-8.4 and 2.6, 95% CI 1.0-6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these relative risks were 8.4 (95% CI 3.1-22.6) and 5.8 (95% CI 2.1-16.0), respectively. In conclusion, we found a relationship between long-standing hypertension and the presence of white matter lesions. Our findings are consistent with the view that effective treatment may reduce the rates of both types of white matter lesion. Adequate treatment of hypertension may therefore prevent white matter lesions and the associated cognitive decline.

Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study.

Silent brain infarcts and white matter lesions are frequently seen on magnetic resonance imaging in healthy elderly people and both are associated with an increased risk of stroke and dementia. Plasma total homocysteine may be a potentially modifiable risk factor for stroke and dementia. We examined whether elevated total homocysteine levels are associated with silent brain infarcts and white matter lesions. The Rotterdam Scan Study is a population-based study of 1,077 people aged 60 to 90 years who had cerebral magnetic resonance imaging. The cross-sectional relation of total homocysteine with silent infarcts and white matter lesions was analyzed with adjustment for cardiovascular risk factors. The mean plasma total homocysteine level was 11.5 micromol/l (standard deviation 4.1). The risk of silent brain infarcts increased with increasing total homocysteine levels (odds ratio 1.24/standard deviation increase, 95% confidence interval 1.06-1.45). The severity of periventricular white matter lesions and extent of subcortical white matter lesions were also significantly associated with total homocysteine levels, even after excluding those with silent brain infarcts. The overall risk of having either a silent brain infarct or severe white matter lesions was strongly associated with total homocysteine levels (odds ratio 1.35/standard deviation increase, 95% confidence interval 1.16-1.58). We concluded that total homocysteine levels are associated with silent brain infarcts and white matter lesions independent of each other and of other cardiovascular risk factors.

Subcortical white matter lesions and functional impairment in geriatric depression.

Geriatric depression is associated with significant functional impairment. There is also growing evidence linking vascular brain changes to depression in late life. We sought to examine the relationship between cerebrovascular disease and impairment in basic activities of daily living (BADL) and instrumental activities of daily living (IADL) in a group of older depressives. The sample consisted of 224 depressed adults aged 60 years and above enrolled in Duke's Mental Health Clinical Research Center. All subjects had unipolar major depression and were free of other major psychiatric and neurological illness, including dementia. In a structured interview, subjects reported their medical history and ability to perform both BADL and IADL. Geriatric psychiatrists assessed cognition using the Mini Mental State Examination (MMSE) and depression severity using the Montgomery Asberg Depression Rating Scale (MADRS). Subjects had a standardized magnetic resonance imaging (MRI) brain scan. MRI scans were processed using a semi-automated method to determine volumes of subcortical white matter lesions (WML) and subcortical gray matter lesions (GML). Logistic regression was used to examine effects of WML and GML controlling for demographic and clinical factors. Greater volume of WML was associated with impairment in both BADL and IADL, while GML was associated with IADL impairment. In logistic models, WML remained significantly associated with IADL after controlling for the effects of age, gender, depression severity, and medical comorbidity. We concluded that white matter lesions are independently associated with functional impairment. Further studies are needed to understand how these lesions affect function, e.g., through effects on cognition or motor skills.

MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease.

Causes of cognitive impairment in subcortical ischemic vascular disease (SIVD) are less well understood than in AD, but have been thought to result from direct effects of subcortical lacunes and white matter lesions, perhaps related to disruption of important cortical-subcortical pathways. To examine the relation between cognitive abilities and quantitative MRI measures of subcortical cerebrovascular disease and cortical and hippocampal atrophy. Subjects were 157 participants in a multicenter study of SIVD and AD who included cognitively normal, cognitively impaired, and demented individuals with and without subcortical lacunar infarcts. Dependent variables were neuropsychological tests of global cognitive function, memory, language, and executive function. Independent variables were quantitative MRI measures of volume of lacunar infarcts in specific subcortical structures, volume of white matter lesion (WML), volume of cortical gray matter (cGM), and total hippocampal volume (HV). Multiple regression analyses were used to identify MRI predictors of cognition. Subcortical lacunes were not related to cognitive measures independent of effects of other MRI variables. WML was independently related to selected, timed measures. HV and cGM were strong and independent predictors of cognitive variables, with effects that did not differ in subjects with and without subcortical lacunes. Results suggest that cognitive impairment associated with subcortical ischemic vascular disease is primarily a result of associated hippocampal and cortical changes.

Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions.

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: Type I lesions were contiguous with subcortical white matter lesions; Type II lesions were small, confined to the cortex, and often perivascular; Type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from 8 and 7 patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3-positive lymphocytes (195 vs 2,596/mm3 of tissue) and 6 times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm3 in active cortical lesions, 1,107/mm3 in chronic active cortical lesions, 25/mm3 in chronic inactive cortical lesions, 8/mm3 in myelinated MS cortex, and 1/mm3 in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.

Angiotensinogen polymorphism M235T, carotid atherosclerosis, and small-vessel disease-related cerebral abnormalities.

The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. We studied the role of this polymorphism as a risk factor for carotid atherosclerosis and small-vessel disease-related brain abnormalities. A total of 431 randomly selected community-dwelling subjects without clinical evidence for strokes underwent angiotensinogen genotyping and carotid Duplex scanning; 1.5-T brain magnetic resonance imaging (MRI) was done in 396 individuals. At 3-year follow-up, we reexamined 343 and 267 study participants by ultrasound and brain MRI, respectively. Carotid atherosclerosis was graded on a 5-point scale. Small-vessel disease-related brain abnormalities were deep or subcortical white matter lesions or lacunes. Progression of carotid atherosclerosis and MRI findings was rated by direct imaging comparison by 3 independent raters. The M/M, M/T, and T/T genotypes were seen in 20.9%, 52.9%, and 18.1% of subjects, respectively. The M235T polymorphism was neither associated with baseline carotid findings nor with progression of carotid atherosclerosis. There was a trend toward more frequent small-vessel disease-related MRI abnormalities in the T/T than in the other genotypes at the baseline examination. Progression of brain lesions occurred significantly more commonly in T/T than in M/M and M/T carriers (P<0.001). Logistic regression analysis identified the T/T genotype (odds ratio, 3.19; P=0.002) and arterial hypertension (odds ratio, 3.06; P=0.03) as significant independent predictors of lesion progression. These data suggest that the angiotensinogen T/T genotype at position 235 is a genetic marker for brain lesions from and progression of small vessel disease but not for extracranial carotid atherosclerosis.

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.

Neuropsychiatric Significance of Subcortical Hyperintensity

Neuropsychiatric Significance of Subcortical Hyperintensity