Abstract

BackgroundPerivascular 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).MethodsTo 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.ResultsIn 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 < 0.001) and larger volumes (SMD = 0.88, 95% CI = [0.19; 1.56], p = 0.01) compared to controls.ConclusionsAvailable literature suggests a higher EPVS burden in MS patients compared to controls. The association of EPVS to neuroinflammatory or -degenerative pathology in MS remains inconsistent. Thus, there is currently insufficient evidence supporting EPVS as diagnostic and/or prognostic marker in MS. In order to benefit future comparisons of studies, we propose recommendations on EPVS assessment standardization in MS. PROSPERO No: CRD42019133946.

Highlights

  • Perivascular spaces surround blood vessel walls penetrating the brain parenchyma through the subarachnoid space and are mostly microscopical [43]

  • Perivascular spaces have been proposed as lymphatic efflux pathways from the brain [29], which is devoid of lymphatic vessels and has long been considered as “immune-privileged” organ [13]

  • enlarged perivascular spaces (EPVS) are detectable on T2- and on T1-weighted MR images as cerebrospinal fluid (CSF)-isointense structures which are correlated with perforating brain vessels [5]

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Summary

Introduction

Perivascular spaces surround blood vessel walls penetrating the brain parenchyma through the subarachnoid space and are mostly microscopical [43]. Perivascular spaces can become detectable on magnetic resonance imaging (MRI), referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces [45]. Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. 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. These associations were not consistent between studies.

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