cSVD Score Research Articles

Optical coherence tomography angiography as a potential screening tool for cerebral small vessel diseases

BackgroundThe retina and the brain share anatomic, embryologic, and physiologic characteristics. Therefore, retinal imaging in patients with brain disorders has been of significant interest. Using optical coherence tomography angiography (OCTA), a novel quantitative method of measuring retinal vasculature, we aimed to evaluate radial peripapillary capillary (RPC) network density and retinal nerve fiber layer (RNFL) thickness in cognitively impaired patients and determine their association with brain imaging markers.MethodsIn this prospective cross-sectional study, a total of 69 patients (138 eyes) including 29 patients with amyloid-positive Alzheimer’s disease-related cognitive impairment (ADCI), 25 patients with subcortical vascular cognitive impairment (SVCI), and 15 amyloid-negative cognitively normal (CN) subjects were enrolled. After excluding eyes with an ophthalmologic disease or poor image quality, 117 eyes of 60 subjects were included in the final analyses. Retinal vascular [capillary density (CD) of the radial peripapillary capillary (RPC) network] and neurodegeneration markers [retinal nerve fiber layer (RNFL) thickness at four quadrants] were measured using OCTA and OCT imaging. Brain vascular (CSVD score) and neurodegeneration markers (cortical thickness) were assessed using 3D brain magnetic resonance imaging. The CD and RNFL thickness and their correlation with brain imaging markers were investigated.ResultsThe SVCI group showed lower CD in the temporal quadrant of the RPC network compared to the CN group (mean (SD), 42.34 (6.29) vs 48.45 (7.08); p = 0.001). When compared to the ADCI group, the SVCI showed lower CD in the superior quadrant (mean (SD), 60.14 (6.42) vs 64.15 (6.39); p = 0. 033) as well as in the temporal quadrant (ADCI 45.76, SVCI 42.34; p = 0.048) of the RPC network. The CD was negatively correlated with CSVD score in the superior (B (95%CI), − 0.059 (− 0.097 to − 0.021); p = 0.003) and temporal (B (95%CI), − 0.048 (− 0.080 to − 0.017); p = 0.003) quadrants of the RPC network. RNFL thickness did not differ among the groups nor did it correlate with cortical thickness.Conclusions and relevanceThe microvasculature of the RPC network was related to the CSVD burden. However, the RNFL thickness did not reflect cerebral neurodegeneration. Noninvasive and rapid acquisition of the OCTA image might have the potential to be used as a screening tool to detect CSVD.

Prediction for the Total MRI Burden of Cerebral Small Vessel Disease With Retinal Microvascular Abnormalities in Ischemic Stroke/TIA Patients

Background and Purpose: The association of retinal microvascular abnormalities with the total cerebral small vessel disease (cSVD) burden found on brain MRI has not been determined. In the present study, we examined whether the retinopathy score could predict the total cSVD burden in ischemic stroke/transient ischemic attack (TIA) patients. A simple practical diagnostic tool may help identify candidates for MRI screening.Methods: We consecutively collected clinical data including retinal photography and cerebral MRI of ischemic stroke/TIA patients from August 2016 to August 2017 at our stroke center. The retinopathy score was assessed by the Keith-Wagener-Barker grading system for analyzing retinal microvascular abnormalities. To evaluate the total cSVD burden, the total cSVD score was assessed by awarding one point for the presence of each marker of cSVD on MRI. The clinical characteristics and retinopathy score were analyzed across patients for each total cSVD score. The association between the retinopathy score and the total cSVD score was analyzed.Results: Among the 263 enrolled patients, the frequency of hypertension in patients with a total cSVD score of 2, 3, or 4 was higher than that in patients with a score of 0 (69.5, 71.7, and 89.2% vs. 45.2% respectively, all P < 0.05). The retinopathy score was related to the total cSVD score (r = 0.687, P < 0.001). Adjusted multivariate ordinal regression showed that the retinopathy score was independently correlated with the total cSVD score (odds ratio [OR], 4.18; 95% confidence interval [CI], 3.07–5.70) after adjustment for age, history of hypertension, previous stroke/TIA and current smoking. The c statistics were 0.30 (95% CI, 0.24–0.37; P < 0.05), 0.46 (95% CI, 0.39–0.53; P = 0.303), 0.79 (95% CI, 0.72–0.86; P < 0.001), and 0.81 (95% CI, 0.74–0.88; P < 0.001) for predicting the total cSVD score of 1, 2, 3, and 4 respectively.Conclusions: These results suggest that retinal microvascular abnormalities have predictive value for severe total cSVD burden in ischemic stroke/TIA patients.

Cerebral small vessel disease score and atherosclerosis burden – A population study in community-dwelling older adults

ObjectiveCerebral small vessel disease (cSVD) and large artery atherosclerosis (LAA) are related to different pathogenetic mechanisms. However, relationships between single biomarkers of cSVD and LAA affecting isolated vascular beds have been reported. Using the Atahualpa Project cohort, we aimed to assess the association between cSVD score categories and LAA burden in community-dwelling older adults. Patients and methodsAtahualpa individuals aged ≥60 years undergoing assessment of the cSVD score and LAA in the peripheral, carotid extracranial, and intracranial vascular beds (n = 333) were included. Multivariate models were fitted to assess independent associations between the cSVD score and LAA burden. ResultsThe cSVD score was 0 points in 62 % individuals, 1 point in 19 %, 2 points in 13 %, and 3–4 points in 7 %. LAA involved the extracranial carotid bed in 43 % individuals, the intracranial bed in 36 %, and the peripheral bed in 20 %. One vascular bed was involved in 111 (33 %) individuals, two beds in 75 (23 %), and three beds in 23 (7 %). The remaining 124 (37 %) had no atherosclerosis. Ordinal logistic regression models showed progressively greater associations between higher categories of cSVD score and the odds of having more beds involved with LAA. Multinomial logistic regression models showed associations between categories of cSVD score and LAA burden, but only when two or three vascular beds were involved. ConclusionThis study demonstrates robust associations between the cSVD score and LAA, which become evident at the upper end of the spectrum of cSVD score (3–4 points) and LAA burden (2–3 vascular beds involved).

Effect of Heart Rate Variability on the Association Between the Apnea-Hypopnea Index and Cerebral Small Vessel Disease.

Background and Purpose- The apnea-hypopnea index (AHI) is associated with cerebral small vessel disease (cSVD), but pathogenesis of this association is elusive. We aimed to assess the effect of nighttime heart rate variability (HRV)-as a proxy of sympathetic upregulation-on the aforementioned association. Methods- Atahualpa residents aged ≥60 years undergoing brain magnetic resonance imaging, polysomnography, and 24-hour Holter monitoring (N=176) were included. The presence of moderate-to-severe white matter hyperintensities, deep cerebral microbleeds, lacunar infarcts, and >10 enlarged basal ganglia perivascular spaces were added for estimating the cSVD score. Interaction models were fitted to assess the effect modification of nighttime HRV in the association between the AHI and the cSVD score, and mediation analysis was utilized to assess the proportion of total effect by nighttime HRV on this association. Results- Generalized linear models showed a significant association between the AHI and the cSVD score (P=0.025), as well as a significant inverse association between nighttime HRV and the cSVD score (P=0.002), but no association between daytime HRV and the cSVD score (P=0.097). Interaction models showed a significant interaction of nighttime HRV on the association between AHI and the cSVD score (P=0.001), and mediation analysis found that the percent of total effect between AHI and cSVD score mediated by HRV was 30.8%. Predictive marginal means of the cSVD score were highly significant when the 10th percentile of nighttime HRV was compared across categories of 10th and 90th percentiles of the AHI (cSVD score margins, 0.61 [95% CI, 0.37-0.86] versus 1.67 [95% CI, 1.26-2.09]). Contour plots showed the effect of nighttime (but not daytime) HRV on the association between AHI and the cSVD score. Conclusions- This study shows an important effect of nighttime HRV on the association between the AHI and the cSVD score and provides further support for the role of sympathetic overactivity on this association.

Extracranial Artery Stenosis Is Associated With Total MRI Burden of Cerebral Small Vessel Disease in Ischemic Stroke Patients of Suspected Small or Large Artery Origins.

Background and Purpose: Extracranial artery stenosis (ECAS) is related to individual imaging markers of cerebral small vessel disease (cSVD). However, little has been reported on the association between ECAS and the total burden of cSVD as assessed by magnetic resonance imaging (MRI). The purpose of this study was to investigate the relationship between ECAS and cSVD burden in patients with ischemic stroke of suspected small or large artery origin.Methods: We reviewed consecutive patients with ischemic stroke of suspected small or large artery origin who underwent color Doppler ultrasonography and brain MRI. Bilateral extracranial cerebral arteries including common carotid artery, internal carotid artery (ICA), and proximal vertebral artery (VA, ostium, V2–3 segments) were assessed using color Doppler ultrasonography. ECAS severity was classified as no/mild stenosis, moderate stenosis, severe stenosis, or occlusion. The total cSVD score was assessed by awarding one point according to the load of each of these cSVD markers as determined using MRI; lacunar infarction, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces. The relationship between ECAS severity and cSVD burden according to MRI was examined.Results: Two hundred and twenty one patients were included in this study (mean age 61 ± 12 years, 75.6% male). Hypertension, current smoking, hyperlipidaemia, and diabetic mellitus were frequent among the patients (67.4, 45.7, 43.9, and 36.7%, respectively), while the other vascular risk factors including previous stroke or TIA and alcohol excess were less frequent (19.0 and 15.4%, respectively). Patients with higher total cSVD burden was significantly older and had severer ECAS. The frequency of hypertension was significantly higher in patients with higher total cSVD burden. This analysis indicated that that increasing ECAS severity (from no stenosis through to 100%) was independently associated with increasing total cSVD score after adjusting for other vascular risk factors (odds ratio 1.76, 95% CI [1.16–2.69]).Conclusions: In this study, high levels of ECAS from ultrasound evidence were associated with coexisting advanced cerebral cSVD in ischemic stroke patients of suspected small or large artery origin. Further studies are required to determine if and how extracranial arterial imaging helps reduce cSVD burden or improves cognitive function.

Association between remote diffusion-weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage.

The aim of this study was to examine the association amongst remote diffusion-weighted imaging lesions (R-DWILs), imaging markers of cerebral small vessel disease (cSVD) and total cSVD burden in patients with primary intracerebral haemorrhage (ICH). In total, 344 consecutive primary ICH patients were enrolled prospectively. R-DWILs on magnetic resonance imaging as well as four imaging markers of cSVD, including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), lacunes and enlarged perivascular spaces, were rated with validated scales. The total cSVD score was calculated by adding up these four markers. Univariate and multivariate analyses were performed. Remote DWI lesions were detected in 57 (16.6%) primary ICH patients. On multivariate logistic regression analysis, the presence of CMBs [odds ratio (OR) 5.26, 95% confidence interval (CI) 1.72-16.12], of high-grade WMHs (OR 4.68, 95% CI 2.01-10.90), the presence of lacunes (OR 2.69, 95% CI 1.20-6.06), mixed CMBs (OR 2.93, 95% CI 1.35-6.36), mixed lacunes (OR 3.60, 95% CI 1.25-10.37), periventricular WMHs (OR 2.19, 95% CI 1.40-3.44), deep WMHs (OR 1.92, 95% CI 1.24-2.97) and total WMHs (OR 1.52, 95% CI 1.20-1.94) were associated with the presence of R-DWILs. A significant association was also found between high-grade total cSVD score and R-DWILs (OR 1.97, 95% CI 1.36-2.84). This association remained significant in patients stratified by an age of 60years or more than 60 years. Remote DWI lesions are correlated with the severity of each imaging marker of cSVD and with the total burden of cSVD.

Left ventricular ejection fraction is associated with small vessel disease in ischaemic stroke patients.

The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients. Consecutive first-ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid-attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose-response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated. A total of 841 patients were included [median WMH volume 2.98 (1.22-10.50)ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF (B=-0.052, P<0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR)0.978, P=0.012], CMBs (aOR=0.96, P<0.001) and moderate to severe EPVSs (aOR=0.94, P<0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes (P=0.026), CMBs (P<0.001) and EPVSs (P=0.002). The total cSVD score also showed a negative association with LVEF in a dose-response manner (P<0.001). The burden of cSVD is negatively correlated with the LVEF in a dose-response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.

Total MRI burden of cerebral vessel disease correlates with the progression in patients with acute single small subcortical strokes.

BackgroundThe patients of single small subcortical strokes (SS) commonly have neurological worsening with risk factors, and mechanisms remain unclear. Asymptomatic lacunes, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces are MRI markers of cerebral small vessel disease (cSVD). Previous studies mostly explored the association between the neurological deterioration and presence of above markers separately. The relationship between progressive single small SS and the simultaneous presence of multiple markers of cSVD has not been fully identified. We aimed to investigate whether total burden of cSVD detected with MRI was associated with progressive small SS in this study.MethodsPatients with single small SS (2.0 cm in diameter) were prospectively recruited during January 2016 and May 2018. Progression was defined as worsening by ≥1 point in National Institutes Health Stroke Scale (NIHSS) motor score within 72 hr from onset. The presence and burden of cSVD were determined by brain MRI, producing a score between 0 and 4. Besides, the patients' characteristics, clinical data, medical treatments during hospitalization stay were collected and statistically analyzed. Associations with progression were tested with forward stepwise regression analyses.ResultsFifty‐seven (35.6%) patients underwent progression. No significant difference was observed in the distribution of any single vascular risk factor and its related laboratory data among these patients. After adjustment for age, sex, NIHSS score at admission, and time from stroke to MRI in separate models, severe WMHs (OR = 4.892; 95% CI = 2.011–11.904, p = 0.016), moderate‐ and high‐grade basal ganglia EPVS (OR = 2.970; 95% CI = 1.861–6.121, p = 0.009), and total cSVD score (OR = 3.359; 95% CI = 2.016–5.599, p = 0.010) were associated with progression.ConclusionThis study demonstrated that total MRI cSVD burden was independently associated with progression after single small subcortical strokes.

Arterial stiffness and total cerebral small vessel disease score in community-dwelling older adults: Results from the Atahualpa Project.

Information on the association between arterial stiffness and cerebral small vessel disease (cSVD) is limited and confined to white and Asian populations. More regional information is needed to confirm this association in different ethnic groups. Using the Atahualpa Project cohort, we aimed to assess whether the aortic pulse wave velocity (PWV) is associated with the total cSVD score, as well as with each of the neuroimaging signatures of cSVD, in a population of Amerindians living in rural Ecuador. Atahualpa residents aged ⩾ 60 years were offered a brain magnetic resonance imaging scan (MRI) and aortic PWV determination. An ordinal logistic regression model, adjusted for demographics and cardiovascular risk factors, was constructed to predict the total cSVD score by levels of aortic PWV. The association between the neuroimaging signatures of cSVD and the aortic PWV was assessed by adjusted logistic regression models. Of 437 candidates, 303 (69%) underwent a brain MRI and aortic PWV determinations. The total cSVD score was 0 points in 65% of individuals, 1 point in 18%, 2 points in 11%, and 3-4 points in 6%. The mean aortic PWV was 10.4 ± 1.8 m/s, which increased from 9.8 ± 1.2 to 12.3 ± 1.8 m/s in individuals with a cSVD score of 0 and 3-4, respectively ( p < 0.001). An ordinal logistic regression model showed significant association between the PWV and the cSVD score. A change of one unit of the aortic PWV increased the odds of having a higher total cSVD score by 1.73 (95% CI: 1.28-2.35; p < 0.001). In addition, individual neuroimaging signatures of cSVD, with the exception of lacunar infarcts, were associated with the aortic PWV. This study shows a significant association between the aortic PWV and total cSVD score and most of its individual components in older Amerindians.