Prevalence of Grey Matter Pathology in Early Multiple Sclerosis Assessed by Magnetization Transfer Ratio Imaging

Lydie Crespy,Françoise Reuter,Jean Pelletier,Sylviane Confort-Gouny,Jean-Philippe Ranjeva,Irina Malikova,Wafaa Zaaraoui,Anthony Faivre,Bertrand Audoin,Patrick J Cozzone,Audrey Rico,Mathias Lemaire,Shaolin Yang

doi:10.1371/journal.pone.0024969

Abstract

The aim of the study was to assess the prevalence, the distribution and the impact on disability of grey matter (GM) pathology in early multiple sclerosis. Eighty-eight patients with a clinically isolated syndrome with a high risk developing multiple sclerosis were included in the study. Forty-four healthy controls constituted the normative population. An optimized statistical mapping analysis was performed to compare each subject's GM Magnetization Transfer Ratio (MTR) imaging maps with those of the whole group of controls. The statistical threshold of significant GM MTR decrease was determined as the maximum p value (p<0.05 FDR) for which no significant cluster survived when comparing each control to the whole control population. Using this threshold, 51% of patients showed GM abnormalities compared to controls. Locally, 37% of patients presented abnormalities inside the limbic cortex, 34% in the temporal cortex, 32% in the deep grey matter, 30% in the cerebellum, 30% in the frontal cortex, 26% in the occipital cortex and 19% in the parietal cortex. Stepwise regression analysis evidenced significant association (p = 0.002) between EDSS and both GM pathology (p = 0.028) and T2 white matter lesions load (p = 0.019). In the present study, we evidenced that individual analysis of GM MTR map allowed demonstrating that GM pathology is highly heterogeneous across patients at the early stage of MS and partly underlies irreversible disability.

Highlights

Pathological studies have clearly demonstrated that multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by macroscopic inflammatory lesions of white matter (WM) and grey matter (GM) associated with a diffuse microscopic inflammatory process of the CNS [1]
The large majority of these studies have explored patients suffering from MS for several years, some recent studies using magnetization transfer ratio (MTR) or voxel based morphometry imaging have demonstrated that GM pathology occurs from the onset of the disease [4,7,14,15]
Sensitivity of individual MTR statistical mapping analysis At the same threshold used to detect local GM abnormalities in patients, (p,0.05, FDR corrected; k = 10), we observed significant clusters in the modified MTR maps of controls starting at 3% of artificial decrease in MTR for 3 out of the 6 controls

Summary

Introduction

Pathological studies have clearly demonstrated that multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by macroscopic inflammatory lesions of white matter (WM) and grey matter (GM) associated with a diffuse microscopic inflammatory process of the CNS [1]. The large majority of these studies have explored patients suffering from MS for several years, some recent studies using MTR or voxel based morphometry imaging have demonstrated that GM pathology occurs from the onset of the disease [4,7,14,15]. These techniques have not been optimized to give sensitive individual assessments of GM pathology according to their inability to clearly separate pathological from normal values at the individual level

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Conclusion