Myelin Water Fraction of Slowly Evolving Lesions is Associated With Disability in Multiple Sclerosis
Rebecca Zhuang1, Irene Vavasour1, Colm Elliott2, Douglas Arnold3, David Clayton4, Stefano Magon5, Ulrike Bonati5, Corrado Bernasconi5, Laura Gaetano5, Anthony Traboulsee1, Shannon Kolind1
1University of British Columbia, 2NeuroRx Research, 3Montreal Neurological Institute, McGill Univ, 4Genentech Inc, 5F.Hoffmann-La Roche Ltd
Objective:

To investigate the relationship between Expanded Disability Status Scale (EDSS) and myelin water fraction (MWF)/quantitative T1 (QT1) of lesions in relapsing Multiple Sclerosis (RMS) participants with and without slowly growing lesions (SELs).

Background:

SELs in Multiple Sclerosis (MS) may represent areas of chronic inflammation and demyelination. It is not well understood whether SELs are associated with more severe disease and disability. We hypothesize that SELs may be a biomarker of greater focal and global tissue injury in the MS brain. Previous work using MRI has shown that SELs are characterized by decreased MWF and increased QT1. 

Design/Methods:

Forty-nine participants with RMS (31 females; median age: 39; median EDSS: 2) participating in a substudy of OPERA II (NCT01412333) had mcDESPOT MRI acquired at 3T. MWF and QT1 maps were obtained from the mcDESPOT images. SELs were derived from T1- and T2-weighted images. Non-SELs were defined as all pre-existing T2 lesions not identified as SELs. Correlation between EDSS and MWF/QT1 was measured by Spearman correlation.

Results:

Thirty-two out of 49 participants had at least one SEL (SEL+), and 17 had no SELs (SEL-). Median (range) EDSS for SEL+/SEL- participants was 2(0-4.5)/2(0-4). Mean (standard deviation) MWF for SEL+ SELs was 0.12(0.03), SEL+ non-SELs 0.13(0.02), and SEL- non-SELs 0.15(0.02); QT1 for SEL+ SELs was 1615(232)ms, SEL+ non-SELs 1530(163)ms, and SEL- non-SELs 1415(128)ms. For SEL+ SELs, EDSS correlated with MWF (r=-0.36, p=0.04) and QT1 (r=0.35, p=0.05), while for SEL+ non-SELs, trends toward correlation were found between EDSS and MWF (r=-0.31, p=0.089) and QT1 (r=0.32, p=0.076). For SEL- non-SELs, there was no significant correlation between EDSS and MWF or QT1 .

Conclusions:

Greater tissue damage within SELs is associated with worse baseline disability. Tissue damage and demyelination in T2 lesions in participants with at least one SEL may have a stronger association with disability compared to participants who have no SELs.

10.1212/WNL.0000000000201853