Abstract Details

Title MRI Characterization of Damage in and Around Lesions in Pediatric MS and MOG-associated disorders

Topic Autoimmune Neurology

Presentation(s) Autoimmune Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 052

Objective To quantify damage to axons and myelin in and around white matter (WM) lesions in pediatric multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-associated disorders (MOGad).

Background Magnetization transfer saturation provides a good myelin measure, and multishell diffusion is sensitive to the axon + myelin assembly. Together, these can be modelled to estimate myelin volume fraction (MVF), axonal volume fraction (AVF) and imaging g-ratio.

Design/Methods 15 MS [67% females(F), mean(range) age[years (y)]: 17y(14-18), disease duration (DD) 3y(0-6), time from last relapse (TLR) 2y(0-6)] and 7 MOGad [86%F, 13y(8-18), DD 3y(0-6), TLR 1y(0-3), 6/7 relapsing] participants received 3T brain MRI. Euclidean distance transforms labelled voxels in normal-appearing WM with the distance to the nearest lesion voxel, and voxels inside lesions with the distance to the nearest non-lesional WM voxel. Mean MVF, AVF and g-ratio were computed on each isodistant surface. Data were modeled using linear mixed models with distance, diagnosis, and their interaction. Knots were used at 0 and 2mm distance.

Results MVF decreased towards the center of lesions (MOGad:-0.03/mm; MS:-0.05/mm; p values (ps)<0.002; difference n.s.) as did AVF (MOGad:-0.03/mm; MS:-0.01/mm; ps<0.0002; difference p=0.02); this graded damage extended to 2mm outside lesions. Inside lesions, g-ratio increased towards the center in MS (0.03/mm, p<10-6) and decreased in MOGad (p=0.15; MOGad-MS difference p<10-4). G-ratio rose with distance outside lesions (MOGad:0.001/mm; MS:0.0004/mm; ps<10-4; difference p<10-5). AVF and g-ratio were similar between groups (within 2%) at 20mm from lesions; MVF was higher in MS (14%, p=0.08).

Conclusions MS and MOGad showed myelin and axonal loss of decreasing severity with distance from lesion center, and this damage extended outside visible lesions. However, MOGad exhibited more severe axonal loss within and near lesions. The corresponding decreasing g-ratio relative to MS may indicate preferential loss of small axons in MS, or relatively better remyelination in MOGad.

Authors/Disclosures
Robert A. Brown, PhD (ShadowLab Reseaerch) PRESENTER	Dr. Brown has received stock or an ownership interest from ShadowLab Research Inc.. Dr. Brown has received intellectual property interests from a discovery or technology relating to health care. Dr. Brown has a non-compensated relationship as a consultant with the Population Council that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Julia O'Mahony (The Hospital for Sick Children)	Ms. O'Mahony has nothing to disclose.
Sridar Narayanan (Montreal Neurological Institute)	Sridar Narayanan has received personal compensation for serving as an employee of NeuroRx Research. Sridar Narayanan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech Inc.. The institution of Sridar Narayanan has received research support from Immunotec Inc.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or 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. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Ruth-Ann Marrie, MD, PhD (University of Manitoba)	The institution of Dr. Marrie has received research support from CIHR. The institution of Dr. Marrie has received research support from MS Canada. The institution of Dr. Marrie has received research support from National MS Society. The institution of Dr. Marrie has received research support from Crohn's and Colitis Canada. The institution of Dr. Marrie has received research support from US Department of Defense. The institution of Dr. Marrie has received research support from The Arthritis Society. The institution of Dr. Marrie has received research support from CMSC.
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.
Brenda L. Banwell, MD, FAAN (Johns Hopkins University)	Dr. Banwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Banwell has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Banwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Banwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Banwell has received research support from National MS Society. The institution of Dr. Banwell has received research support from NIH.
	No disclosure on file
	No disclosure on file
E. Ann Yeh, MD, MA, FRCPC (Hospital for Sick Children)	Dr. Yeh has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pipeline therapeutics. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Yeh has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for SCN. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Yeh has received research support from CIHR. The institution of Dr. Yeh has received research support from National MS Society. The institution of Dr. Yeh has received research support from SickKids Foundation. The institution of Dr. Yeh has received research support from MSSC. The institution of Dr. Yeh has received research support from Garry Hurvitz Foundation. The institution of Dr. Yeh has received research support from Leong Centre. The institution of Dr. Yeh has received research support from OMSLife. The institution of Dr. Yeh has received research support from Canada's Drug Agency. Dr. Yeh has received personal compensation in the range of $0-$499 for serving as a Author with Medscape. Dr. Yeh has a non-compensated relationship as a Editorial Board with Neurology that is relevant to AAN interests or activities. Dr. Yeh has a non-compensated relationship as a Editorial Board with MSJ that is relevant to AAN interests or activities.
Giulia Longoni, MD (The Hospital for Sick Children)	Dr. Longoni has nothing to disclose.

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