Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging: a systematic review and meta-analysis.
ABSTRACT: BACKGROUND:Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. EPVS have been linked to small vessel disease. Some studies have also indicated an association of EPVS to neuroinflammation and/or neurodegeneration. However, there is conflicting evidence with regards to their potential as a clinically relevant imaging biomarker in multiple sclerosis (MS). METHODS:To perform a systematic review and meta-analysis of EPVS as visualized by MRI in MS. Nine out of 299 original studies addressing EPVS in humans using MRI were eligible for the systematic review and meta-analysis including a total of 457 MS patients and 352 control subjects. RESULTS:In MS, EPVS have been associated with cognitive decline, contrast-enhancing MRI lesions, and brain atrophy. Yet, these associations were not consistent between studies. The meta-analysis revealed that MS patients have greater EPVS prevalence (odds ratio?=?4.61, 95% CI?=?[1.84; 11.60], p?=?0.001) as well as higher EPVS counts (standardized mean difference [SMD]?=?0.46, 95% CI?=?[0.26; 0.67], p?
Project description:Enlarged perivascular spaces (ePVS), visible on magnetic resonance imaging (MRI), are associated with aortic pulse wave changes produced by arterial stiffening. However, the relationship between ePVS and cognition is still unclear. We aimed to benchmark current knowledge of associations between ePVS and cognitive function using a meta-analysis of all available published data. We searched three databases for studies examining ePVS and cognition, identified seven studies involving 7,816 participants, plotted multivariate-adjusted odds ratio (OR) and 95% CI and generated summary OR with a fixed effects model. EPVS were related to the risk of impaired cognition (OR?=?1.387, 95% CI?=?1.198-1.606, z=4.38, P<0.001) with low heterogeneity. There was publication bias, which could be corrected by trimming and supplementation (OR=1.297, 95% CI= 1.130-1.490). EPVS were associated with impaired cognition and may be a sign of cognitive impairment rather than particular diseases. More studies are required to validate ePVS as a measurable risk marker for cognition using consistent methods to determinea characteristic appearance of ePVS.
Project description:Small vessel disease (mainly hypertensive arteriopathy and cerebral amyloid angiopathy (CAA)) is an important cause of spontaneous intracerebral haemorrhage (ICH), a devastating and still poorly understood stroke type. Enlarged perivascular spaces (EPVS) are a promising neuroimaging marker of small vessel disease. Based on the underlying arteriopathy distributions, we hypothesised that severe centrum semiovale EPVS are more common in lobar ICH attributed to CAA than other ICH. We evaluated EPVS prevalence, severity and distribution, and their clinical-radiological associations.Retrospective multicentre cohort study of 121 ICH patients. Clinical information was obtained using standardised forms. Basal ganglia and centrum semiovale EPVS on T2-weighted MRI (graded 0-4 (>40 EPVS)), white-matter changes, cerebral microbleeds (CMBs) and lacunes were rated using validated scales.Patients with probable or possible CAA (n=76) had a higher prevalence of severe (>40) centrum semiovale EPVS compared with other ICH patients (35.5% vs 17.8%; p=0.041). In logistic regression age (OR: 1.43; 95% CI 1.01 to 2.02; p=0.045), deep CMBs (OR: 3.27; 95% CI 1.27 to 8.45; p=0.014) and mean white-matter changes score (OR: 1.29; 95% CI 1.17 to 1.43; p<0.0001) were independently associated with increased basal ganglia EPVS severity; only age was associated with increased centrum semiovale EPVS severity (OR: 1.50; 95% CI 1.08 to 2.10; p=0.017).EPVS are common in ICH. Different mechanisms may account for EPVS according to their anatomical distribution. Severe centrum semiovale EPVS may be secondary to, and indicative of, CAA with value as a new neuroimaging marker. By contrast, basal ganglia EPVS severity is associated with markers of hypertensive arteriopathy.
Project description:<h4>Objective</h4>To examine the association between enlarged perivascular spaces (EPVS) and the prevalence and extent of small acute diffusion-weighted imaging (DWI) lesions (SA-DWIL) in patients with spontaneous supratentorial intracerebral hemorrhage (ICH).<h4>Methods</h4>We conducted a retrospective review of a consecutive cohort of 201 patients with spontaneous supratentorial ICH who had brain MRI with DWI within 1 month of ICH onset. We compared the clinical and imaging characteristics, including EPVS, of patients with and without SA-DWIL. We used univariate and multivariate logistic regression analyses to determine the variables associated with SA-DWIL.<h4>Results</h4>Small acute DWI lesions were detected in 27.9% (n = 56) of patients. Intraventricular and subarachnoid extension of ICH (p ≤ 0.001), high centrum semiovale (CSO)-EPVS (p < 0.001), high basal ganglia-EPVS (p = 0.007), overall extent of white matter hyperintensity (p = 0.018), initial ICH volume (p < 0.001), and mean change in mean arterial blood pressure (δ MAP = MAP at admission - the lowest MAP before MRI scan) (p = 0.027) were associated with SA-DWIL on univariate analyses. On multivariate logistic regression analyses, larger ICH volume (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.06; p = 0.006) and high CSO-EPVS (OR 12.56; 95% CI 4.40-35.85; p < 0.001) were independently associated with the presence of SA-DWIL.<h4>Conclusions</h4>In our cohort, high EPVS, in particular CSO-EPVS, and larger hematoma volume emerged as independent predictors for SA-DWIL after ICH. Our findings might provide a new explanation for the pathophysiologic mechanisms predisposing to SA-DWIL after ICH.
Project description:Enlarged perivascular spaces (EPVS) are widely considered as a feature of cerebral small vessel diseases (SVD), but its underlying pathology is still under active investigation. The aim of this study was to explore the association between hemoglobin level and the severity of EPVS. Consecutive patients with acute ischemic stroke who underwent baseline MRI scan and hemoglobin testing were evaluated. EPVS in basal ganglia (BG) and central semiovale (CS) were rated with a validated 4-point semiquantitative scale (0?=?none; 1?=?1-10; 2?=?11-20; 3?=?21-40; and 4???40). Bivariate logistic regression models were used to identify the associations of hemoglobin with predefined high-degree (score?>?1) CS-EPVS and BG-EPVS. Multinomial logistic regression models were used to analyze the associations between hemoglobin and CS-/BG-EPVS predominance patterns. A total of 401 patients were included in the final analysis, 94 patients (23.4%) had a high degree of CS-EPVS and 45 patients (11.2%) had a high degree of BG-EPVS. Compared with tertile 1 of hemoglobin, tertile 3 of hemoglobin was independently associated with high degree of CS-EPVS after adjusting for other features of SVD (odds ratio [OR] 2.399, 95% confidence interval [CI] 1.315-4.379, P?=?0.004) and potential confounding factors (OR 2.611, 95% CI 1.346-5.066, P?=?0.005). In multinomial logistic regression models, compared with tertile 1 of hemoglobin, tertile 2 (OR 2.463, 95% CI 1.195-5.075, P?=?0.015) and tertile 3 (OR 2.625, 95% CI 1.102-6.251, P?=?0.029) of hemoglobin were associated with higher odds of BG-EPVS?=?CS-EPVS pattern, and tertile 3 of hemoglobin (OR 2.576, 95% CI 1.004-6.608, P?=?0.049) was associated with higher odds of BG-EPVS?<?CS-EPVS pattern. Elevated hemoglobin level was independently associated with high degree of CS-EPVS and higher odds of CS-EPVS predominance pattern, but not with BG-EPVS, which support that the topography of EPVS is characteristic. However, the pathogenesis linking hemoglobin and CS-EPVS is unclear and still needs further investigation.
Project description:<b>Background:</b> Enlarged perivascular spaces (ePVS) are common finding on magnetic resonance imaging (MRI) in elderly. ePVS are thought to be associated with cerebral small vessel disease (SVD) such as white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs). However, the different location of SVD and its relationship to ePVS distribution requires further investigation. <b>Objective:</b> To study the association between location and severity of SVD with ePVS from memory clinic and population-based settings. <b>Methods:</b> This study includes patients from an ongoing memory clinic based case-control study and participants from the population-based: Epidemiology of Dementia in Singapore study (EDIS). All participants underwent a comprehensive standardized evaluation including physical, medical and neuropsychological assessment and a brain MRI. CMBs and lacune location were categorized into strictly lobar, strictly deep and mixed, and ePVS location into centrum semiovale and basal ganglia. WMH volume was automatically segmented and was classified into anterior and posterior distribution. Negative binomial regression models were constructed to analyse associations between SVD and ePVS and the rate ratios (RR) and 95% confidence intervals (CI) were reported. <b>Results:</b> Of 375 patients (median age = 73 years) from memory clinic and 583 participants (median age = 70 years) from EDIS, the median total ePVS count was 17.0 and 7.0, respectively. Increased severity of SVD was not associated with total ePVS counts in both memory clinic and EDIS study. Analysis with the location of SVD and ePVS also showed similar results. However, in EDIS study, presence of ?2 lacunes [RR = 1.61, 95% CI = 1.3, 2.30, <i>p</i> = 0.009], presence of ?2 CMBs [RR = 1.40, 95% CI = 1.08, 1.83, <i>p</i> = 0.012], and higher volume of WMH [RR = 1.41, 95% CI = 1.10, 1.81, <i>p</i> = 0.006] were associated with basal ganglia ePVS independent of age, gender and vascular risk factors. <b>Conclusion:</b> In this study, we found that the ePVS were not associated with the location and severity of SVD in the memory-clinic patients. However, only severity of SVD was associated with basal ganglia ePVS in the population-based setting. Our findings will need to be studied further in different cohorts so as to understand the mechanism underlying different SVD types in subclinical and clinical phases as well as for predicting cognitive decline.
Project description:This study investigated whether genetic factors involved in Alzheimer's disease (AD) are associated with enlargement of Perivascular Spaces (ePVS) in the brain. A total of 680 participants with T2-weighted MRI scans and genetic information were acquired from the ALFA study. ePVS in the basal ganglia (BG) and the centrum semiovale (CS) were assessed based on a validated visual rating scale. We used univariate and multivariate logistic regression models to investigate associations between ePVS in BG and CS with <i>BIN1</i>-rs744373, as well as <i>APOE</i> genotypes. We found a significant association of the <i>BIN1</i>-rs744373 polymorphism in the CS subscale (<i>p</i> value = 0.019; OR = 2.564), suggesting that G allele carriers have an increased risk of ePVS in comparison with A allele carriers. In stratified analysis by <i>APOE</i>-<i>ε4</i> status (carriers vs. non-carriers), these results remained significant only for ε4 carriers (<i>p</i> value = 0.011; OR = 1.429). To our knowledge, the present study is the first suggesting that genetic predisposition for AD is associated with ePVS in CS. These findings provide evidence that underlying biological processes affecting AD may influence CS-ePVS.
Project description:In secondary progressive multiple sclerosis (SPMS) significance of enlarged perivascular spaces (ePVS) is unknown. Objectives, Methods: Analysis of associations between vascular co-morbidities, clinical outcomes, and volumetrics with categorical ePVS scores in midbrain, basal ganglia (BG), and centrum semiovale (CSO) in SPMS(n-46). Results, Conclusion: In BG, advancing age (Z?=?2.68) and lower Expanded Disability Status Scale (Z?=?-2.04) were associated with increasing ePVS score. In CSO, advancing age (Z?=?2.66) and male gender (Z?=?2.45) were associated with increasing ePVS score. No associations between ePVS score and vascular co-morbidities or volumetrics existed; ePVS may not be an informative marker for SPMS.
Project description:Recent studies reported that 24-hour ambulatory blood pressure variability (ABPV) was associated with lacunar infarction and white matter hyperintensities (WMH). However, the relationship between ABPV and enlarged perivascular spaces (EPVS) has not been investigated. Thus, our study aimed to investigate whether ABPV is associated with EPVS by 24-hour ambulatory blood pressure monitoring (ABPM).We conducted this study as a cross-sectional study.The study was based on patients who presented for physical examinations in our hospital from May 2013 to June 2016.Patients with both brain MRI scans and 24-hour ABPM were included and patients with acute stroke, a history of severe stroke and some other severe diseases were excluded. A total of 573 Chinese patients were prospectively enrolled in this study.EPVS in basal ganglia (BG) and white matter (WM) were identified on MRI and classified into three categories by the severity. WMH were scored by the Fazekas scale. Coefficient of variation (CV) and SD were considered as metrics of ABPV. Spearman correlation analysis and ordinal logistic regression analysis were used to assess the relationship between ABPV and EPVS.There were statistical differences among the subgroups stratified by the severity of EPVS in BG in the following ABPV metrics: SD and CV of systolic blood pressure (SBP), CV of diastolic blood pressure (DBP) in 24?hours, daytime and nighttime and SD of DBP in nighttime. The above ABPV metrics were positively associated with the degree of EPVS. The association was unchanged after adjusting for confounders. Spearman correlation analysis showed ABPV was not related to the degree of EPVS in the WM.ABPV was independently associated with EPVS in BG after controlling for blood pressure, but not in the WM. Pathogenesis of EPVS in BG and WM might be different.
Project description:Enlarged perivascular spaces (EPVS), specifically in stroke patients, has been shown to strongly correlate with other measures of small vessel disease and cognitive impairment at 1 year follow-up. Typical grading of EPVS is often challenging and time consuming and is usually based on a subjective visual rating scale. The purpose of the current study was to develop an interpretable, 3D neural network for grading enlarged perivascular spaces (EPVS) severity at the level of the basal ganglia using clinical-grade imaging in a heterogenous acute stroke cohort, in the context of total cerebral small vessel disease (CSVD) burden. T2-weighted images from a retrospective cohort of 262 acute stroke patients, collected in 2015 from 5 regional medical centers, were used for analyses. Patients were given a label of 0 for none-to-mild EPVS (< 10) and 1 for moderate-to-severe EPVS (≥ 10). A three-dimensional residual network of 152 layers (3D-ResNet-152) was created to predict EPVS severity and 3D gradient class activation mapping (3DGradCAM) was used for visual interpretation of results. Our model achieved an accuracy 0.897 and area-under-the-curve of 0.879 on a hold-out test set of 15% of the total cohort (n = 39). 3DGradCAM showed areas of focus that were in physiologically valid locations, including other prevalent areas for EPVS. These maps also suggested that distribution of class activation values is indicative of the confidence in the model's decision. Potential clinical implications of our results include: (1) support for feasibility of automated of EPVS scoring using clinical-grade neuroimaging data, potentially alleviating rater subjectivity and improving confidence of visual rating scales, and (2) demonstration that explainable models are critical for clinical translation.
Project description:<h4>Background</h4>Intracerebral hemorrhage (ICH) recurrence risk is known to be higher in patients with cerebral amyloid angiopathy (CAA) as compared to other causes of ICH. Risk factors for ICH recurrence are not completely understood, and our goal was to study specific imaging microangiopathy markers.<h4>Methods</h4>Retrospective case-control study of patients with non-traumatic ICH admitted to a single center between 2014 and 2017 who underwent magnetic resonance imaging (MRI). Clinical characteristics of the index event and occurrence of death and ICH recurrence were collected from clinical records. MRI images were independently reviewed by 2 neuroradiologists. Groups of patients with CAA-related and CAA-unrelated ICH defined were compared. Presence of CAA was defined according to the Boston modified criteria. Survival analysis with Kaplan-Meier curves and Cox-regression analyses was performed to analyze ICH recurrence-free survival.<h4>Results</h4>Among 448 consecutive patients with non-traumatic ICH admitted during the study period, 104 were included in the study, mean age 64 years (±13.5), median follow-up of 27 months (interquartile range, IQR 16-43), corresponding to 272 person-years of total follow-up. CAA-related ICH patients presented higher burden of lobar microbleeds (p < 0.001), higher burden of enlarged perivascular spaces (EPVS) in centrum semiovale (p < 0.001) and more frequently presented cortical superficial siderosis (cSS; p < 0.001). ICH recurrence in patients with CAA was 12.7 per 100 person-years, and no recurrence was observed in patients without CAA. Variables associated with ICH recurrence in the whole population were age (hazard ratio [HR] per 1-year increment = 1.05, 95% CI 1.00-1.11, p = 0.046), presence of disseminated cSS (HR 3.32, 95% CI 1.09-10.15, p = 0.035) and burden of EPVS in the centrum semiovale (HR per 1-point increment = 1.80, 95% CI 1.04-3.12, p = 0.035).<h4>Conclusions</h4>This study confirms a higher ICH recurrence risk in patients with CAA-related ICH and suggests that age, disseminated cSS, and burden of EPVS in the centrum semiovale are associated with ICH recurrence.