Abstract Details

Title Loss of Brain Iron is Linked to Disability in Multiple Sclerosis - The Difference Between Concentration and Mass of Iron

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-011

Objective To assess changes in the total mass of iron in the deep gray matter (DGM) nuclei of patients with multiple sclerosis (MS) over two years, and compare findings to changes in iron concentration.

Background Numerous studies have reported increasing tissue iron concentrations with disease development in MS. However, an elevated iron concentration does not necessarily imply an influx of iron into the region but, instead, may result only from atrophy of the non-iron containing tissue compartments.

Design/Methods One-hundred twenty (120) MS patients and 40 age- and sex-matched healthy controls were included. Clinical testing and MRI were performed both at baseline and after two years. We calculated the mass of iron in the thalamus, caudate, putamen, and globus pallidus by integrating the iron concentration (obtained via quantitative susceptibility mapping; QSM) over the structure’s volume. Cross-sectional (MS vs. controls) and temporal (baseline vs. follow-up) differences were studied using mixed factorial ANOVA and appropriate t-tests.

Results Cross-sectionally, iron mass was significantly lower in the thalamus of MS patients compared to controls (-24.9%, p<0.001), with progressive MS patients showing lower iron mass than relapsing-remitting patients (-24.2%, p<0.001). Over two years, iron mass decreased in all regions of patients with MS (-3.6% to -0.9%), whereas it increased or remained stable among controls (-0.5% to +3.8%). In the thalamus, decreasing iron mass over two years was associated with increasing EDSS (β = -0.197, p=0.0005).

Conclusions Our findings suggest that disease progression in MS is linked to pathological mechanisms that reduce overall tissue iron in the DGM, similar to recent histopathological evidence of iron loss in the normal appearing white matter. Prospective studies will have to confirm the benefit of iron mass as a potential new imaging outcome measure for disease progression in clinical trials.

Authors/Disclosures
Jesper Hagemeier PRESENTER	No disclosure on file
Michael G. Dwyer III, MD, PhD (Buffalo Neurological Analysis Center)	Dr. Dwyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Keystone Heart, Ltd. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Dwyer has received research support from Novartis. The institution of Dr. Dwyer has received research support from Keystone Heart, Ltd. The institution of Dr. Dwyer has received research support from Bristol Myers Squibb. The institution of Dr. Dwyer has received research support from Roche.
Niels Bergsland (Buffalo Neuroimaging Analysis Center / State University of New York At Buffalo)	Prof. Bergsland has nothing to disclose.
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo)	Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman 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. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)	The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.
Ferdinand Schweser, PhD (SUNY University At Buffalo)	Dr. Schweser 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.

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