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Abstract Details

MRI Changes Over the Disease Course in a Large Multiple Sclerosis Clinical Cohort
Multiple Sclerosis
S45 - Multiple Sclerosis: Imaging (3:30 PM-3:42 PM)
001
To describe longitudinal changes in T2 lesion volume (T2LV) and gray matter fraction (GMF) over the disease course in a large multiple sclerosis (MS) cohort.
Quantitative MRI measures are used as indicators of disease status and therapeutic response. Understanding the evolution of these metrics is key for interpretation of change in practice.
Demographics, disease history, and MRI were collected from MS patients at a single site. Patients with ≥2 MRI assessments were included. T2LV and GMF annualized rate of change compared to the baseline scan were analyzed. Multivariate mixed-effects models were used to evaluate longitudinal MRI changes, adjusting for age at onset, sex, and patient-determined disease steps (PDDS) with a random subject intercept. Models with restricted cubic splines using 2-5 knots were tested for nonlinearity in the relationship between MRI outcome and disease duration, and were compared based on Akaike Information Criterion.

1107 patients were included:71.4% female, 70.6% relapsing-remitting, mean±SD age at disease onset 32.1±10.7, age at baseline MRI 45.7±11.1 years, disease duration 13.6±10.1 years, number of MRIs 3.07±1.2, median[IQR] PDDS 1.0 [1.0-3.0]. Male sex (β=3.40) and PDDS>3 (β=6.31) were associated with greater T2LV (best fit: restricted cubic spline with 3 knots, p<0.05). T2LV annualized rate of change increased monotonically up until year 8 of disease duration (best fit: cubic spline with 4 knots). Longer disease duration (β=-0.0017), male sex (β=-0.014) and older age at onset (β=-0.014) were significant linear predictors of GMF (p<0.05). No non-linear effect of disease duration on cumulative GMF loss was observed. The GMF annualized rate of change remained stable overall (best fit: cubic spline with 3 knots).

The dynamics of T2LV are variable throughout the disease course, whereas GMF decreases at a stable rate. These results suggest T2LV accumulation reflects fluctuating inflammatory activity, while GMF loss reflecting underlying primary neurodegeneration occurs at a steady rate.
Authors/Disclosures
Gabrielle Macaron, MD
PRESENTER 		Dr. Macaron has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD-Serono. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MedEdge. Dr. Macaron has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Macaron has received research support from National MS Society/International Progressive Multiple Sclerosis Alliance .
Kunio Nakamura, PhD (Cleveland Clinic) Dr. Nakamura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INmune Bio. The institution of Dr. Nakamura has received research support from Biogen. The institution of Dr. Nakamura has received research support from PCORI. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from Novartis. The institution of Dr. Nakamura has received research support from DOD. Dr. Nakamura has received intellectual property interests from a discovery or technology relating to health care.
Kedar Mahajan, MD, PhD Dr. Mahajan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Mahajan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech.
No disclosure on file
Scott Husak No disclosure on file
Nicholas Thompson Nicholas Thompson has nothing to disclose.
Robert A. Bermel, MD, FAAN (Cleveland Clinic) Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck Serono. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astra Zeneca. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LabCorp. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care.
Jeffrey A. Cohen, MD (Cleveland Clinic) Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage.
Daniel Ontaneda, MD, PhD, FAAN (Cleveland Clinic) Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech/Roche. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Ontaneda has received research support from NIH. The institution of Dr. Ontaneda has received research support from PCORI. The institution of Dr. Ontaneda has received research support from NMSS. The institution of Dr. Ontaneda has received research support from Genetech.