Cerebral small vessel disease (CSVD) is a common group of neurological conditions that confer a significant burden of morbidity and mortality worldwide. In most cases, CSVD is only recognized in its advanced stages once its symptomatic sequelae develop. However, its significance in asymptomatic healthy populations remains poorly defined. In population-based studies of presumed healthy elderly individuals, CSVD neuroimaging markers including white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and cerebral microinfarcts are frequently detected. While the presence of these imaging markers may reflect unique mechanisms at play, there are likely shared pathways underlying CSVD. Herein, we aim to assess the etiology and significance of these individual biomarkers by focusing in asymptomatic populations at an epidemiological level. By primarily examining population-based studies, we explore the risk factors that are involved in the formation and progression of these biomarkers. Through a critical semi-systematic review, we aim to characterize “asymptomatic” CSVD, review screening modalities, and draw associations from observational studies in clinical populations. Lastly, we highlight areas of research (including therapeutic approaches) in which further investigation is needed to better understand asymptomatic CSVD.
Aged ; Biomarkers ; Cerebral Small Vessel Diseases ; Epidemiology ; Humans ; Leukoaraiosis ; Mass Screening ; Mortality ; Neuroimaging ; Risk Factors ; Siderosis ; Stroke, Lacunar ; White Matter

OBJECTIVES: The significance of leukoaraiosis on brain magnetic resonance imaging (MRI) is uncertain, but it is often seen with vascular risk factors or in the context of cognitive impairment. We aimed to investigate the effect of leukoaraiosis on the severity and course of delirium. METHODS: Periventricular hyperintensity and deep white matter hyperintensity on brain MRI were rated in 42 patients with delirium by semiquantative visual rating scale. Correlations between their grades and the scores of Korean version of Delirium Rating Scale-Revised-98 (K-DRS-R-98) were analyzed, and the interaction effects between the groups according to the levels of leukoaraiosis and two evaluation points were also analyzed. RESULTS: The grade of deep white matter hyperintensity in the occipital lobe was positively correlated with the scores on the total, severity items, cognitive items, and non-cognitive items of K-DRS-R-98. The cognitive items scores of K-DRS-R-98 in the low grade group of periventricular hyperintensity showed significantly steeper decrease than the high grade group. CONCLUSIONS: A difference in severity or recovery speed of delirium according to the level of leukoaraiosis may result from disruption in brain functional connectivity. Our results have a clinical implication in that the severity and course of delirium can be possibly predicted using the level of leukoaraiosis.
Brain ; Cognition Disorders ; Delirium ; Humans ; Leukoaraiosis ; Magnetic Resonance Imaging ; Occipital Lobe ; Risk Factors ; White Matter

To investigate the influence of leukoaraiosis (LA) on the functional outcomes of subcortical stroke in the subacute phase after onset. We retrospectively analyzed 41 patients with subacute subcortical infarct at a single center from 2011 to 2015. We explored the relationship between LA severity at admission/transfer (initial evaluation) and functional outcome at the time of discharge (follow-up evaluation), as assessed using the modified Rankin Scale (mRS), Functional Ambulation Category (FAC), and modified Barthel Index (mBI). LA severity was graded as mild, moderate, or severe according to the Fazekas scale. Scores of the mRS, FAC, and mBI were compared in patients grouped based on LA severity: no LA (n = 12), mild LA (n = 19), and moderate-to-severe LA (n = 10). Significant inter-group differences were observed in all 3 scores at both the initial and follow-up evaluations. After adjustment for age, scores at follow-up evaluation were significantly different between the 2 groups. LA is related to functional outcomes of subcortical stroke in the subacute phase after onset. After adjustment for age, severe LA was correlated with poor functional outcomes in the subacute phase.
Cerebral Infarction ; Follow-Up Studies ; Humans ; Leukoaraiosis* ; Retrospective Studies ; Stroke ; Walking

BACKGROUND AND PURPOSE: An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. METHODS: Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). RESULTS: Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. CONCLUSIONS: Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains.
Alzheimer Disease* ; Atherosclerosis ; Brain ; Carotid Artery Diseases ; Corpus Callosum ; Dementia, Vascular* ; Diffusion Magnetic Resonance Imaging ; Diffusion* ; Humans ; Leukoaraiosis ; Magnetic Resonance Imaging* ; Memory ; Neurons ; Occipital Lobe ; Rabeprazole ; Ultrasonography ; Water

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are frequently observed on MRI in ischemic stroke patients as well as in normal elderly individuals. Besides the progression of WMH, the regression of WMH has been rarely reported. Thus, we aimed to investigate how WMH change over time in patients with ischemic stroke, particularly focusing on regression. METHODS: We enrolled ischemic stroke patients who underwent brain MRI more than twice with at least a 6 month time-interval. Based on T2-weighted or FLAIR MRI, WMH were visually assessed, followed by semiautomatic volume measurement. Progression or regression of WMH change was defined when 0.25 cc increase or decrease was observed and it was also combined with visible change. A statistical analysis was performed on the pattern of WMH change over time and factors associated with change. RESULTS: A total of 100 patients were enrolled. Their age (mean+/-SD) was 67.5+/-11.8 years and 63 were male. The imaging time-interval (mean) was 28.0 months. WMH progressed in 27, regressed in 9 and progressed in distinctive regions and regressed in others in 5 patients. A multiple logistic regression model showed that age (odds ratio[OR] 2.51, 90% confidence interval[CI] 1.056-5.958), male gender (OR 2.957, 95% CI 1.051-9.037), large vessel disease (OR 1.955, 95% CI 1.171-3.366), and renal dysfunction (OR 2.900, 90% CI 1.045-8.046) were associated with progression. Regarding regression, no significant factor was found in the multivariate analysis. CONCLUSIONS: In 21.5% of ischemic stroke patients, regression of WMH was observed. WMH progression was observed in a third of ischemic stroke patients.
Aged ; Brain ; Humans ; Leukoaraiosis ; Logistic Models ; Magnetic Resonance Imaging ; Male ; Multivariate Analysis ; Stroke*

OBJECTIVE: To determine whether cognitive function is associated with white matter hyperintensities (WMH) in patients with infratentorial stroke. METHODS: This was a retrospective, cross-sectional study. Twenty-four first-ever infratentorial stroke patients between 18 and 60 years of age were enrolled. WMH was evaluated by the Fazekas scale and the Scheltens scale. Cognitive functions were assessed using the Korean Mini-Mental Status Examination (K-MMSE), Rey-Osterrieth Complex Figure Test, and the Seoul Computerized Neuropsychological Test Battery (SCNT) at one month after stroke. All participants were divided into two groups based on the presence of WMH (no-WMH group and WMH group). General characteristics and cognitive functions were compared between the groups. RESULTS: There were no significant differences in general characteristics, such as age, stroke type, hypertension history, and education level between the two groups. However, K-MMSE in the WMH group was significantly lower compared to the no-WMH group (p<0.05). The verbal learning test score in SCNT was significantly higher in the no-WMH group compared to the WMH group (p<0.05). Executive function in the no-WMH group tended to be higher compared to the WMH group. CONCLUSION: Impairment of cognitive function in patients with infratentorial stroke appeared to be associated with WMH. WMH should be carefully evaluated during rehabilitation of infratentorial stroke patients.
Cognition ; Cross-Sectional Studies ; Education ; Executive Function ; Humans ; Hypertension ; Leukoaraiosis ; Leukoencephalopathies ; Neuropsychological Tests ; Rehabilitation ; Retrospective Studies ; Seoul ; Stroke* ; Verbal Learning

BACKGROUND: Impaired renal function may contribute to development of stroke and small vessel pathology in the brain. We investigated whether stroke subtype, initial stroke severity, early neurologic outcomes, time to cerebral infarction occurrence, and the presence of small vessel pathology in the brain are different between patients with end stage renal disease (ESRD) and those with renal transplantation (RT). METHODS: A total of 57 consecutive de novo RT patients (RT group) and 120 patients undergoing dialysis due to ESRD (ESRD group) who developed a first-ever acute cerebral infarction were enrolled. We compared stroke subtypes based on the Trial of Org 10172 in Acute Stroke Treatment classification, the presence of small vessel pathology (cerebral microbleed, leukoaraiosis and silent lacunar infarction) on MRI, stroke severity based on the National Institutes of Health Stroke Scale (NIHSS) and in-hospital mortality between the groups. RESULTS: The stroke subtypes, NIHSS scores at admission and in-hospital mortality were not different between the two groups. On multivariate analysis, the presence of high grade periventricular white matter changes tended to be more frequently detected in the ESRD group than the RT (P=0.078). The time from starting dialysis to stroke was longer in the RT group (129.9+/-60.9 months) than in the ESRD group (51.1+/-46.1 months). CONCLUSIONS: The stroke patterns, severity and short term outcomes were not different between RT and ESRD. The risk of cerebral infarction and high grade periventricular white matter changes may be reduced after RT in patients with ESRD.
Brain ; Cerebral Infarction ; Chondroitin Sulfates ; Dermatan Sulfate ; Dialysis ; Glycosaminoglycans ; Heparitin Sulfate ; Hospital Mortality ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Leukoaraiosis ; Multivariate Analysis ; National Institutes of Health (U.S.) ; Stroke

OBJECTIVETo explore the syndrome factors of leukoaraiosis patients with mild cognitive impairment (LACI), thus providing evidence for syndrome typing.

METHODSThe prospective schedule was adopted including 103 LACI patients (as the LACI group) and 100 leukoaraiosis patients without mild cognitive impairment (as the control group). Syndrome factors were extracted from the patients' symptoms with frequency statistics and factor analysis.

RESULTSFifteen common factors were extracted from the LACI group, and 12 common factors from the control group. After analyzed the distribution of syndrome factors in the LACI group, the most common factors were ranked as follows: yang deficiency (33.98%), phlegm (22.33%), yin deficiency (19.42%), qi deficiency (10.68%), fire (9.71%), blood deficiency and blood stasis (3.88%). As for the control group, the most common factors were ranked as follows: yang deficiency (31.00%), qi deficiency (27.00%), yin deficiency and fire (24.00%), blood deficiency and blood stasis (12.00%), phlegm and yang deficiency and blood deficiency (6.00%).

CONCLUSIONSThe main syndrome factors of LACI were yang deficiency, phlegm, yin deficiency, and fire. The secondary syndrome factors were qi deficiency, blood deficiency, and blood stasis. It was mainly involved with Shen and Pi, with secondary organs as Gan and Xin. Deficiency syndrome is its pathogenesis. Phlegm and fire, and other pathological factors are essential for its development and aggravation, with more syndrome factors accompanied in complex condition.

Aged ; Aged, 80 and over ; Case-Control Studies ; Cognition Disorders ; diagnosis ; Female ; Humans ; Leukoaraiosis ; diagnosis ; psychology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Prospective Studies

With an increasing proportion of the elderly, dementia due to severe cerebral white matter change is frequently observed. Because these patients cannot express their symptoms effectively, the recognition of stroke can be delayed. In addition, clinical characteristics of their stroke might be different. We reported on three patients with severe leukoaraiosis, who exhibited altered consciousness after acute lacunar infarction in the corona radiata. This clinico-radiological discrepancy may have resulted from different susceptibility to ischemia in patients with severe white matter change.
Aged ; Cerebral Infarction ; Consciousness ; Dementia ; Dementia, Vascular ; Humans ; Ischemia ; Leukoaraiosis ; Stroke ; Stroke, Lacunar

BACKGROUND: Chronic subclinical ischemia has been considered as one of major causes of leukoaraiosis, although its trigger is unknown. The vascular endothelium plays a major role in maintaining cerebral perfusion through autoregulation. In this study we evaluated the endothelial bioavailability of nitric oxide (NO) in patients with leukoaraiosis. METHODS: We enrolled consecutive patients with lacunar syndrome or transient ischemic attack; the control group comprised age- and sex-matched patients with hypertension but with no neurological abnormality. All participants underwent flow-mediated dilatation of the brachial artery (FMD) to evaluate endothelial function. Leukoaraiosis was defined as ill-defined patches with high signal intensities on FLAIR and low signal intensities on T1-weighted images. Patients were defined as having ischemic leukoaraiosis if they presented with leukoaraiosis and lacunar infarction. Leukoaraiosis only was defined when patient had leukoaraiosis without lacunar infarction leukoaraiosis without lacunar infarction. RESULTS: In total, 75 patients (37 with leukoaraiosis and 38 controls) were enrolled in this study. The demographic and clinical characteristics were similar in the two groups. FMD was lower in patients with leukoaraiosis than in controls (p<0.05), and lower in patients with only leukoaraiosis and in those who also had ischemic leukoaraiosis than in the controls (p<0.05). However, FMD did not differ significantly between patients with leukoaraiosis only and those who also had ischemic leukoaraiosis (p>0.05). CONCLUSIONS: The bioavailability of NO in the vascular endothelium is decreased in patients with leukoaraiosis only and in those who also have ischemic leukoaraiosis compared to controls. These results are suggestive of a causative role of endothelial dysfunction in the pathomechanism of leukoaraiosis.
Biological Availability ; Brachial Artery ; Dilatation ; Endothelium ; Endothelium, Vascular ; Homeostasis ; Humans ; Hypertension ; Ischemia ; Leukoaraiosis ; Nitric Oxide ; Perfusion ; Stroke, Lacunar ; Vasodilation