The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative

Abstract

At present, the diagnosis of multiple sclerosis (MS) relies heavily on the use of MRI, which can demonstrate disease dissemination in space and time [1][2][3][4] . The current 2010 McDonald criteria have enabled earlier diagnosis 5,6 and initiation of disease-modifying treatment, with substantial benefits for disease outcome 7,8 , but they still have imperfect sensitivity and specificity 9,10 . The limited accuracy of the criteria results in challenging cases and misdiagnosis, which are prevalent problems in MS 11,12 . Therefore, more-accurate and pathologically specific MRI criteria are still needed to exclude other disorders that can mimic MS 13,14 .The MRI-detectable central vein inside white matter lesions has recently been proposed as a biomarker of inflammatory demyelination and, thus, may aid the diagnosis of MS 15 . The 'central vein sign' (CVS) has been investigated in various neurological conditions by several groups, and evidence has accumulated that the CVS may have the ability to accurately differentiate MS from its mimics [15][16][17][18][19][20][21] . As a consequence, recent guidelines from the Magnetic Resonance Imaging in MS (MAGNIMS) group 1,4 and the Consortium of MS Centers (CMSC) task force 22 have acknowledged the potential of the CVS and its dedicated MRI acquisitions for the differential diagnosis of MS, while calling for further research before considering a possible modification of the diagnostic criteria. However, the lack of standardization for the definition and imaging of the CVS, as well as a dearth of large-scale prospective studies evaluating the CVS for MS diagnosis, are currently preventing the clinical validation of this potential biomarker 1,23 .This Consensus Statement aims to provide recommendations for the definition, standardization and clinical evaluation of the CVS in the diagnosis of MS. These statements are based on a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative. E X P E RT C O N S E N S U S D O C U M E N T on behalf of the NAIMS CooperativeAbstract | Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Mult...

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies

“…Our analysis was limited to the brain and did not consider the spinal cord in the assessement of dissemination in space MRI criteria for MS. Of note, in vivo imaging reports of the central vein sign in the spinal cord are lacking, due in part to the challenge of obtaining high‐quality T2*‐weighted images of the cord 14. Patients with primarily confluent lesions were excluded from the study, and therefore it may not be possible to generalize our results to such patients.…”

“…Several studies conducted with 3T and 7T MRI clearly showed that in MS, the association between brain WM venules and lesions (perivenular lesions), also named the “central vein sign,”17 can be efficiently visualized; in MS, the proportion of lesions that have clear central veins is high 14, 15. These data suggest that high frequency of perivenular lesions is pathologically specific to MS, and therefore this marker is an important candidate for improving MRI diagnostic criteria14 and for reducing the still too high rate of MS misdiagnosis, with its considerable clinical consequences 18, 19…”

Radiologically isolated syndrome or subclinical multiple sclerosis: MAGNIMS consensus recommendations

“…They are often localized in the anterior, deep WM, subcortical, juxtacortical brain regions, are rarely present in the infratentorial regions, and usually do not progress over time (13). In this context, the demonstration of the perivenular distribution within subclinical MS-like lesions can be particularly helpful (14).…”

Morphology-Specific Discrimination between MS White Matter Lesions and Benign White Matter Hyperintensities Using Ultra-High-Field MRI

“…6 However, the presence of nonspecific WML, which increase with age and with certain risk factors, confounds a confirmatory diagnosis of MS. A number of studies have proposed perivenous WM lesion count (herein referenced as a percentage of total perivenous white matter lesion count [%PVWML]), as de-perivenous lesions has led to some uncertainty in evaluating %PVWML as an imaging biomarker. The recently published consensus statement by the North American Imaging in Multiple Sclerosis committee promotes a more controlled evaluation of the perivenous lesions 13 by suggesting several exclusion criteria in defining the central vein sign (CVS); specifically, the exclusion of lesions that are Ͻ3 mm in diameter in any plane, are confluent, have multiple distinct veins, or have poor visibility. Additionally, the consensus statement calls for the investigation of a standard radiologic definition of the CVS.…”