Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging: a systematic review and meta-analysis
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ORIGINAL COMMUNICATION
Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging: a systematic review and meta‑analysis Tobias Granberg1,2 · Thomas Moridi1 · Judith S. Brand3 · Susanne Neumann1 · Martin Hlavica4 · Fredrik Piehl1,5 · Benjamin V. Ineichen1,2 Received: 25 April 2020 / Revised: 29 May 2020 / Accepted: 1 June 2020 © The Author(s) 2020
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 2 mm [1] or 2 mm) and cognitive decline in MS [17], again without adjustment for potential confounding factors.
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Journal of Neurology
Fig. 4 Pooled analyses of studies assessing absolute differences in enlarged perivascular spaces (EPVS) comparing MS patients to controls. Standardized mean differences were pooled using the random effects inverse-variance weighted method. Pooled analyses were
stratified by unit of measurement: a EPVS area, b EPVS volume and c EPVS count. CI confidence interval, df degrees of freedom, IV inverse variance weighted
Imaging outcomes
The association of EPVS with brain atrophy has been assessed in six out of nine studies. Five out of six studies did not find an association between EPVS and brain volumetry [7–9, 17, 48]. In all these studies, brain volumes have been computed using the package SIENAX from the software FSL [24]. One study including 34 MS patients and 11 healthy controls did, however, detect an association between EPVS and supratentorial brain fraction as computed by the surface-based software FreeSurfer [18]. Notably, it is the only study employing supratentorial brain fraction as outcome. All other studies used whole brain parenchymal fraction (BPF) [40], defined as the ratio of total brain parenchymal volume to the total intracranial volume, as the volumetric outcome. Moreover, the study by Kilsdonk and colleagues employed by far the highest MRI field strength (7 T) for the image acquisition and should thus have a very high EPVS detection s
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