Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease

Background and Purpose— Nonfocal transient neurological attacks (TNAs), such as unsteadiness, bilateral weakness, or confusion, are associated with an increased risk of stroke and dementia. Cerebral ischemia plays a role in their pathogenesis, but the precise mechanisms are unknown. We hypothesized that cerebral small vessel disease is involved in the pathogenesis of TNAs and assessed the relation between TNAs and manifestations of cerebral small vessel disease on magnetic resonance imaging. Methods— We included participants from the HBC (Heart-Brain Connection) study. In this study, hemodynamic and cardiovascular contributions to cognitive impairment have been studied in patients with heart failure, carotid artery occlusion, or possible vascular cognitive impairment, as well as in a reference group. We excluded participants with a history of stroke or transient ischemic attacks. The occurrence of the following 8 TNAs was assessed with a standardized interview: unconsciousness, confusion, amnesia, unsteadiness, bilateral leg weakness, blurred vision, nonrotatory dizziness, and paresthesias. The occurrence of TNAs was related to the presence of lacunes or white matter hyperintensities (Fazekas score, ≥2; early confluent or confluent lesions) in logistic regression analysis, adjusted for age, sex, and hypertension. Results— Of 304 participants (60% men; mean age, 67±9 years), 63 participants (21%) experienced ≥1 TNAs. Lacunes and early confluent or confluent white matter hyperintensities were more common in participants with TNAs than in participants without TNAs (35% versus 20%; adjusted odds ratio, 2.32 [95% CI, 1.22–4.40] and 48% versus 27%; adjusted odds ratio, 2.65 [95% CI, 1.44–4.90], respectively). Conclusions— In our study, TNAs are associated with the presence of lacunes and early confluent or confluent white matter hyperintensities of presumed vascular origin, which indicates that cerebral small vessel disease might play a role in the pathogenesis of TNAs.

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Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

Brain Communications ◽

10.1093/braincomms/fcaa111 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Fanny Quandt ◽

Felix Fischer ◽

Julian Schröder ◽

Marlene Heinze ◽

Iris Lettow ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Functional Connectivity ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

White Matter Lesion ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Lesion Load ◽

Vessel Disease

Abstract Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

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Blood Pressure Variability and Cerebral Small Vessel Disease

Stroke ◽

10.1161/strokeaha.119.026739 ◽

2020 ◽

Vol 51 (1) ◽

pp. 82-89 ◽

Cited By ~ 6

Author(s):

Yuan Ma ◽

Alex Song ◽

Anand Viswanathan ◽

Deborah Blacker ◽

Meike W. Vernooij ◽

...

Keyword(s):

Blood Pressure ◽

White Matter ◽

Odds Ratio ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Meta Analysis ◽

Random Effect ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

Background and Purpose— Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia. Methods— A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models. Results— These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 [95% CI, 1.06–1.50]). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 [95% CI, 0.74–1.16]) and the presence of microbleeds (odds ratio, 1.13 [95% CI, 0.89–1.44]) were not statistically significant. Conclusions— A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.

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Cerebral Small Vessel Disease, Risk Factors, and Cognition in Tenants of Precarious Housing

Stroke ◽

10.1161/strokeaha.120.030446 ◽

2020 ◽

Vol 51 (11) ◽

pp. 3271-3278

Author(s):

Lily W. Zhou ◽

William J. Panenka ◽

Ghadeer Al-Momen ◽

Kristina M. Gicas ◽

Allen E. Thornton ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Risk Factors ◽

White Matter ◽

Odds Ratio ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Resonance Imaging ◽

Vessel Disease

Background and Purpose: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing. Methods: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance. Results: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3–63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05–1.15], P <0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01–1.09], P =0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07–9.16], P =0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain. Conclusions: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.

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Abstract W P345: Increased Risk of Gastrointestinal Bleeding Associated With Antiplatelet Therapy in Patients With Cerebral Small Vessel Disease

Stroke ◽

10.1161/str.45.suppl_1.wp345 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Sang-mi Noh ◽

Jong S. Kim

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Bleeding Risk ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Gi Bleeding ◽

Stroke Patients ◽

Vessel Disease ◽

Increased Risk

Background: Gastrointestinal (GI) bleeding is a major complication of aniplatelets in patients with stroke. Although underlying gastrointestinal disease is an important factor for increased bleeding risk, the presence of cerebral small vessel disease (SVD) may also be a factor because it may indicate systemic small vessel pathologies. We assessed the association of cerebral SVD and GI bleeding in patients who are under treatment with antiplatelets for secondary stroke prevention. Methods: We compared stroke patients who visited our clinic between May 2007 and May 2013 who developed GI bleeding while receiving antiplatelets with age and sex matched patients who did not. Control subjects were randomly selected among those who were visited out-patients clinic on the same day as the study subjects. Patients who received anticoagulants were excluded. MRIs were evaluated for the presence of white matter changes (Fazeka scale) and microbleeds. Results: During the study period, 47 patients in the bleeding group and 94 patients in the control group were enrolled. No differences were found in baseline characteristics between the two groups including stroke subtypes and the number of antiplatelets (mono vs dual therapy). The prevalence of SVD (microbleeds or white matter hyperintensities) (p = 0.004), white matter hyperintensities (p = 0.008), but not microbleeds alone (p = 0.221), were significantly higher in the bleeding group. Multivariate analysis showed that the presence of SVD was independently associated with increased GI bleeding risk (OR 3.3, 95% confidence interval 1.5-7.3). Conclusions: Our data show the presence of cerebral SVD is a marker for increased GI bleeding risk in patients receiving antiplatelets in stroke patients, perhaps related with systemic small vessel pathology in this group of patients. Physicians may have to consider this association when antiplatelets are used for the secondary prevention of stroke.

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Suffering from cerebral small vessel disease with and without metabolic syndrome

Open Medicine ◽

10.1515/med-2019-0051 ◽

2019 ◽

Vol 14 (1) ◽

pp. 479-484

Author(s):

Tatjana Bošković Matić ◽

Gordana Toncev ◽

Aleksandar Gavrilović ◽

Dejan Aleksić

Keyword(s):

Metabolic Syndrome ◽

Cognitive Impairment ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitively Impaired ◽

Vessel Disease ◽

Neurology Clinic

AbstractBackgroundCerebral small vessel disease (CSVD) and metabolic syndrome were separately associated with cognitive impairment and depression. However, whether metabolic syndrome adds to cognitive impairment and depression in patients who already have CSVD remained unanswered.ObjectiveThe aim of our study was to investigate the association of metabolic syndrome with cognitive impairment and depression in patients with CSVD who have lacunar lesions or white matter hyperintensities.MethodsThis prospective cohort study was conducted at Neurology Clinic, Clinical Center, Kragujevac, Serbia. Main outcomes of the study were cognitive assessment, and assessment of depression among hospitalized patients with or without CSVD.ResultsThe study included 74 inpatients, 25 of them having lacunary infarctions, 24 with the white matter hyperintensities, and 25 control patients without CSVD. The CSVD was accompanied by impairment of cognition and depression, the patients with lacunary lesions being more cognitively impaired and more depressive than the patients with the white matter hyperintensities. The patients with CSVD who also had metabolic syndrome were more cognitively impaired and depressed than the patients with CSVD alone.ConclusionsIn conclusion, our study showed that metabolic syndrome is associated with further worsening of already impaired cognition and existing depression in patients with CSVD.

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Microstructural Predictors of Cognitive Impairment in Cerebral Small Vessel Disease and the Conditions of Their Formation

Diagnostics ◽

10.3390/diagnostics10090720 ◽

2020 ◽

Vol 10 (9) ◽

pp. 720

Author(s):

Larisa A. Dobrynina ◽

Zukhra Sh. Gadzhieva ◽

Kamila V. Shamtieva ◽

Elena I. Kremneva ◽

Bulat M. Akhmetzyanov ◽

...

Keyword(s):

Blood Flow ◽

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Venous Blood Flow ◽

Csf Flow ◽

Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.

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Cognitive consequences of regression of cerebral small vessel disease

European Stroke Journal ◽

10.1177/2396987318820790 ◽

2018 ◽

Vol 4 (1) ◽

pp. 85-89 ◽

Cited By ~ 6

Author(s):

Esther MC van Leijsen ◽

Mayra I Bergkamp ◽

Ingeborg WM van Uden ◽

Sjacky Cooijmans ◽

Mohsen Ghafoorian ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Disease Markers ◽

Total Brain

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.

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Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease

Stroke ◽

10.1161/strokeaha.119.027661 ◽

2020 ◽

Vol 51 (5) ◽

pp. 1404-1410 ◽

Cited By ~ 3

Author(s):

Michelle P. Lin ◽

Thomas G. Brott ◽

David S. Liebeskind ◽

James F. Meschia ◽

Kevin Sam ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Cerebral Microbleeds ◽

Large Vessel ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Poor Recruitment

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.

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Adverse effects of pre-existing cerebral small vessel disease on cognitive improvement after carotid endarterectomy

International Journal of Stroke ◽

10.1177/1747493019874732 ◽

2019 ◽

Vol 15 (6) ◽

pp. 657-665 ◽

Cited By ~ 2

Author(s):

Jun Yoshida ◽

Fumio Yamashita ◽

Makoto Sasaki ◽

Kunihiro Yoshioka ◽

Shunrou Fujiwara ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Carotid Endarterectomy ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitive Improvement ◽

Vessel Disease

Background Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. Aims The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. Methods Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. Results Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74–3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01–0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. Conclusion Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.

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