Abstract Details

Title Identifying Phenotypes Based on MRI-Defined Cerebral Lesions and Atrophy in Patients with Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) (-)

Poster/Presentation
Number 001

Objective

Background While clinical phenotypes of multiple sclerosis (MS) are well established, there remains heterogeneity among patients within the clinical definitions. MRI-defined lesions and atrophy show only moderate inter-correlations, suggesting that, in part, they represent different processes in MS.

Design/Methods We studied 175 MS patients [age (mean±SD) 42.7±9.1 years, EDSS score 2.5±2.3, n=18 clinically-isolated syndrome (CIS), n=115 relapsing-remitting (RR), and n=42 secondary progressive (SP)]. Brain MRI measures included T2-hyperintense lesion volume (T2LV), the ratio of T1-hypointense LV (T1LV) to T2LV, and brain parenchymal fraction (BPF). The median was used to create bins for each MRI parameter, with patients assigned a score of low or high severity.

Results Four broad categories emerged from the analysis: Type I=low LV/mild atrophy (n=67; CIS=14, RR=47, SP=6). Type II=high LV/mild atrophy (n=21; RR=19, SP=2); Type III=low LV/high atrophy (n=21; CIS=4, RR=16, SP=1); Type IV=high LV/high atrophy (n=66; RR=33, SP=33). Within each type, a subgroup, a or b, was defined by low or high proportion of T1LV. Type IVb showed higher EDSS (4.2±2.4 vs. 1.7±2.1), different clinical composition [(RR=21, SP=28) vs. (CIS=9, RR=32, SP=6)] and longer disease duration (14.7±9.6 vs. 6.0±5.9 years) vs. Type Ia (all p<0.05).

Conclusions We show the feasibility of MRI-categorization of lesions and atrophy to identify phenotypes in MS. Most patients have congruent extremes related to the degree of lesions and atrophy. However, many other patients have a dissociation between inflammation and atrophy, with either one being higher than the other. Longitudinal studies will help define the uniqueness of these patterns and their clinical relevance regarding risk stratification and treatment response.

Authors/Disclosures
Shahamat Tauhid, MD (Brigham & Women's Hospital) PRESENTER	Dr. Tauhid has nothing to disclose.
Mohit Neema, MD	No disclosure on file
Antonia Ceccarelli, MD, PhD (Epicura Centre Hospitalier, VUB)	No disclosure on file
Amy L. Phillips, PharmD (EMD Serono)	Amy L. Phillips, PharmD has received personal compensation for serving as an employee of EMD Serono, Inc.
Brian C. Healy	The institution of Mr. Healy has received research support from Analysis Group. The institution of Mr. Healy has received research support from Bristol-Myers Squibb. The institution of Mr. Healy has received research support from Verily Life Sciences. The institution of Mr. Healy has received research support from Novartis. The institution of Mr. Healy has received research support from Merck Serono. The institution of Mr. Healy has received research support from Genzyme.
Ashish Arora, MD (The Moses H Cone Memorial Hospital)	No disclosure on file
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..
Rohit Bakshi, MD, FAAN	Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Bakshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. The institution of Dr. Bakshi has received research support from Bristol Myers Squibb. The institution of Dr. Bakshi has received research support from EMD Serono. The institution of Dr. Bakshi has received research support from Novartis.

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