Abstract Details

Title Normalization of the Spinal Cord in Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P06 - (-)

Poster/Presentation
Number 106

Objective

Background BACKGROUND: Spinal cord(SC) pathology is common in multiple sclerosis(MS), and measures of SC atrophy are increasingly being utilized. Normalization of SCV is important to remove inter-subject variation unrelated to disease effects, particularly in cross-sectional studies. There is no consensus regarding the optimal method to normalize SCV, with prior studies supporting the use of a number of distinct normalization factors. Using a variety of normalization factors and clinical measures, we sought to assess the effect of SCV normalization on MRI-clinical correlations in MS.

Design/Methods DESIGN/METHODS: 133 individuals with relapsing and progressive MS underwent cervical SC-MRI at 3T and clinical assessment, including the expanded disability status scale(EDSS), multiple sclerosis functional composite(MSFC), and quantitative tests of hip-flexion strength(HFS) and vibration sensation threshold(VST). SCV was measured between C3-C4. SCV normalization was performed by dividing the raw SCV by each normalization factor(subject height, number-of-slices between C3-C4, and intracranial volume(ICV)). Spearman's correlation coefficient([rho]) was used to assess relationships between SCV and individual clinical measures. Multivariable linear regression was used to further investigate the association between the multiple SCV normalization factors and individual clinical measures.

Results RESULTS: There were significant correlations between clinical measures and raw SCV(EDSS:[rho]=-0.20; MSFC: [rho]=0.16; HFS:[rho]=0.35, VST: [rho]=-0.19, all p-values<0.05). Observed clinical-MRI correlations improved with normalization by number-of-slices(EDSS:[rho]=-0.43; MSFC:[rho]=0.33; HFS:[rho]=0.38, VST:[rho]=-0.40, all p-values<0.001) and height(EDSS:[rho]=-0.26; MSFC:[rho]=0.28; HFS:[rho]=0.22, VST:[rho]=-0.29, all p-values<0.01 except HFS p-value=0.02), but diminished with normalization by ICV(EDSS:[rho]=-0.02,p-value=0.81; MSFC:[rho]=-0.16;p-value=0.08; HFS:[rho]=0.11,p-value=0.22; VST:[rho]=-0.19,p-value=0.04). All normalization factors were independently associated with MSFC in a multivariable regression model(all coefficient p-values<0.05).

Conclusions CONCLUSIONS: SCV normalization by number-of-slices and height strengthen clinical-MRI correlations. Normalization of SCV by either of these factors should be performed to maximize the clinical utility of this measure. Normalization of SCV by multiple factors may be of utility when assessing comprehensive clinical measures.

Authors/Disclosures
Jiwon Oh, MD, FAAN (St Michael's Hospital) PRESENTER	Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen-Idec. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD-Serono. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Oh has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen-Idec. Dr. Oh 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. Oh has received research support from Biogen-Idec. The institution of Dr. Oh has received research support from Roche.
	No disclosure on file
Shiv Saidha, MD (Johns Hopkins)	Dr. Saidha has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Setpoint Medical. Dr. Saidha has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Saidha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Saidha has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReWind Therapeutics. Dr. Saidha 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. Saidha has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Pharmaceuticals. Dr. Saidha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Saidha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Saidha 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. Saidha has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Saidha has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal ETC. Dr. Saidha has stock in June Brain. Dr. Saidha has stock in Lapix Therapeutics. The institution of Dr. Saidha has received research support from Biogen. The institution of Dr. Saidha has received research support from Genentech. The institution of Dr. Saidha has received research support from Novartis. The institution of Dr. Saidha has received research support from Lapix Therapeutics. The institution of Dr. Saidha has received research support from Novartis.
Elias S. Sotirchos, MD (Johns Hopkins University)	Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Sotirchos has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Sotirchos has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Sotirchos has received research support from National Institutes of Health. The institution of Dr. Sotirchos has received research support from National Multiple Sclerosis Society. The institution of Dr. Sotirchos has received research support from Sumaira Foundation. The institution of Dr. Sotirchos has received research support from Genentech. The institution of Dr. Sotirchos has received research support from UCB. The institution of Dr. Sotirchos has received research support from Astoria Biologica. The institution of Dr. Sotirchos has received research support from Ad Scientiam. The institution of Dr. Sotirchos has received research support from Alexion. The institution of Dr. Sotirchos has received research support from Corevitas. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Ad Hoc Reviewer with National Institutes of Health.
Kathleen M. Zackowski, PhD, OTR (National MS Society)	Dr. Zackowski has received personal compensation for serving as an employee of National MS Society.
	No disclosure on file
	No disclosure on file
Jerry Prince	No disclosure on file
	No disclosure on file
Peter A. Calabresi, MD, FAAN (Johns Hopkins University)	Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. An immediate family member of Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MyMD. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Myelin Repair Foundation. The institution of Dr. Calabresi has received research support from Genentech. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME.
Daniel Reich, MD, PhD (National Institutes of Health, Neuroimmunology Branch, NINDS)	Dr. Reich has received research support from NIH. The institution of Dr. Reich has received research support from Adelson Medical Research Foundation. The institution of Dr. Reich has received research support from Sanofi. The institution of Dr. Reich has received research support from Abata Therapeutics. The institution of Dr. Reich has received research support from National Multiple Sclerosis Society. The institution of Dr. Reich has received research support from Cure Alzheimer's Fund. Dr. Reich has received intellectual property interests from a discovery or technology relating to health care. Dr. Reich has received personal compensation in the range of $5,000-$9,999 for serving as a CME Faculty with Integrity. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Letters and Sciences. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Academic CME. Dr. Reich has a non-compensated relationship as a Advisor with Sanofi that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Board of Directors with ACTRIMS that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Abata Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with University of Basel RC2NB that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Multiple Sclerosis Society of Canada that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Tuscan Doctorate in Neuroscience that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Editorial Board with Multiple Sclerosis Journal that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Hyperfine that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Imaginab that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Annexon that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Philips that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Siemens that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Calico Life Sciences that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Cognito Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Sudo that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Allumis that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with BioCentury that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Regeneron that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Eli Lilly that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with SetPoint that is relevant to AAN interests or activities.

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