Abstract Details

Title Slowly-Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression

Topic Multiple Sclerosis

Presentation(s) S26 - MS Imaging (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Background Chronic active lesions contribute to MS severity, but their association with long-term disease progression has not been evaluated yet. White matter (WM) lesions showing linear expansion over time on serial T1- and T2-weighted scans (i.e., SELs) have been proposed as a marker of chronic inflammation.

Objective

To evaluate whether slowly-expanding lesion (SEL) burden and microstructural abnormalities are associated to Expanded Disability Status Scale (EDSS) worsening and secondary progressive (SP) multiple sclerosis (MS) evolution over a long-term follow-up (FU) in relapsing-remitting (RR) MS patients.

Design/Methods Fifty-two RRMS patients underwent 3T brain MRI scans at baseline, month 6, 12 and 24. SELs were identified among baseline WM lesions by linearly fitting the Jacobian of the non-linear deformation field between timepoints obtained using T1- and T2-weighted scans. Logistic regression analysis was applied to investigate the associations of SEL burden, magnetization transfer ratio (MTR) and T1 intensity over the first two years with EDSS worsening or SPMS conversion at long-term FU.

Results After a median FU of 9.1 years (IQR=7.6;9.4), 20/52 (38%) RRMS patients showed EDSS worsening, and 13/52 (25%) evolved to SPMS. Baseline EDSS (for point higher: odds ratio [OR]=3.153 [95% confidence interval=1.612;8.375], p=0.003), proportion of SELs among baseline lesions (for each % increase: OR=1.221 [1.044;1.575], p=0.04) and baseline MTR values of SELs (for each % higher: OR=0.659 [0.405;0.920], p=0.033) were significant independent predictors of EDSS worsening at FU (c-index=0.892). Baseline EDSS (for point higher: OR=6.371 [1.978;20.526], p=0.002) and baseline MTR values of SELs (for each % higher: OR=0.476 [0.254;0.893], p=0.02) independently predicted SPMS conversion (c-index=0.947).

Conclusions Proportion of SELs is associated with MS progression after 9 years. More severe SEL microstructural abnormalities independently predict EDSS worsening and SPMS conversion. The quantification of SEL burden and damage using T1-, T2-weighted and MTR sequences may identify RRMS patients at higher risk of long-term disability progression and SPMS conversion.

Authors/Disclosures
Paolo Preziosa (Ospedale San Raffaele) PRESENTER	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Elisabetta Pagani	No disclosure on file
Alessandro Meani	No disclosure on file
Lucia Moiola, MD, PhD (Fondazione Centro San Raffaele)	Dr. Moiola has nothing to disclose.
	No disclosure on file
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi;. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi- Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.