Abstract Details

Title Axonal and myelin volume fractions and imaging g-ratio in pediatric MS and MOG-associated disorders.

Topic Autoimmune Neurology

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

Poster/Presentation
Number 053

Objective To investigate advanced MRI correlates of axonal and myelin density and myelin thickness in pediatric multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-associated disorders (MOGad).

Background Previous studies have described extensive microstructural brain tissue abnormalities in the normal-appearing white matter (NAWM) of pediatric MS patients. However, previously applied techniques could not distinguish the extent to which such abnormalities are due to axonal loss or demyelination. Little is known about microstructural brain tissue changes in MOGad.

Design/Methods We acquired standardized 3T brain MRI in 26 healthy controls (HC) (58% females (F), mean age [years (y) (range)] 14.9y (9.1-19.1)); 16 MS (69% F, 16.8y (14.2-18.1), disease duration (DD) 2.6y (0.6-6.5), time from last relapse (TLR) 1.7y (0.2-6.2)); and 11 MOGad (72% F, 12.4y (8.3-17.8), DD 2.7y (0.2-6.1), TLR 1.1y (0.2-2.8), 8/11 relapsing). The corpus callosum (CC) was manually segmented. Multi-shell DWI processing was performed with FSL and DMIPy; magnetization transfer saturation (MT_sat), myelin and axonal volume fractions (MVF and AVF) and imaging g-ratio (the ratio between inner and outer diameter of the myelin sheath) were computed using the Jargon data management system. We used general linear models to model average MVF, AVF, and g-ratio in the NAWM of the CC of each group, including the factors age, DD, and the interaction term group*DD. Models including sex were tested, and all exhibited lower AIC.

Results Relative to HC, MS showed decreased MVF (-0.018/y, p=0.0304) and AVF (-0.0069/y; p=0.053) and corresponding increased g-ratio with increased DD (0.0084/y, p=0.059). Relative to HC, MOGad showed decreased MVF (-0.017/y, p=0.0304) and AVF with increased DD (-0.0081/y, p=0.014), without significant g-ratio changes.

Conclusions Both pediatric MS and MOGad exhibited MRI correlates of axonal loss and demyelination in the CC NAWM. Our measures of axonal loss in MOGad reinforces recent work warning of potentially long-term impacts on the brain from non-MS demyelinating pathologies.

Authors/Disclosures
Giulia Longoni, MD (The Hospital for Sick Children) PRESENTER	Dr. Longoni has nothing to disclose.
	No disclosure on file
Robert A. Brown, PhD (ShadowLab Reseaerch)	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
	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
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.
	No disclosure on file

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