Abstract Details

Title Vascular Disease Risk Factors in Multiple Sclerosis (MS) is Associated with Brain Adenosine Triphosphate Abnormalities: Dysmetabolism May Drive MS Disease Progression

Topic Multiple Sclerosis

Presentation(s) S2 - Advances in MS Imaging (2:32 PM-2:40 PM)

Poster/Presentation
Number 004

Background VDRF, such as hyperlipidemia, hypertension, obesity, diabetes, and heart disease, appear to significantly increase the risk of disability progression in MS, however the underlying mechanisms are not well understood.

Objective

Determine if the presence of VDRF affects the disease progression and brain phosphate metabolism in people with MS.

Design/Methods This is a 3-year prospective, observational, single-site, study with two arms (MS subjects with and without VDRF). We collect 7T MRI brain data at baseline, 12, 24 and 36 months (V1, V2, V3 and V4 visits, respectively) and clinical and biomarkers data every 6 months. Outcome measures include changes in: 1) high energy phosphate metabolites in cerebral gray matter assessed by ³¹P 7T MR imaging (MRSI) and 2) brain parenchymal volume, 3) clinical impairment, disability, and quality of life.

Results We preformed cross-sectional and longitudinal analyses of MRI data (52 V1 and 37 V3 subjects). Mean age/gender was 54.6 years with 71% female) (+VDRF, N=29, mean age 56.3 years, 83% female) and -VDRF, N=23, mean age 52.4 years; 57% female) at baseline. We analyzed a volume of interest in the occipital region for changes in phosphate metabolites (V1 and V3) using 7T MRSI. We observed decrease in Adenosine triphosphate (ATP) to total phosphate signal ratio in +VDRF subjects by 3.3% (P<0.05) compared with -VDRF. +VDRF subjects showed a larger reduction in parenchymal volume fraction (0.01544, P=0.025) over time (between V1 and V3) compared to -VDRF (0.00423). No significant group differences in temporal changes in phosphate metabolites are seen. Additional analyses are underway.

Conclusions This is the first study to assess brain metabolism and volume in MS patients with and without VDRF. +VDRF MS subjects have significantly reduced brain ATP compared with -VDRF. ATP depletion may reflect mitochondrial dysfunction and contribute to MS disease progression as suggested by the increased brain atrophy in those with VDRF.

Authors/Disclosures
Vijayshree Yadav, MD, FAAN (OHSU) PRESENTER	Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb Foundation. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD-Serono . The institution of Dr. Yadav has received research support from Department of Veterans Affairs. Dr. Yadav has received research support from NIH. Dr. Yadav has received research support from PCORI. Dr. Yadav has received research support from NMSS. The institution of Dr. Yadav has received research support from Department of Veterans Affairs. The institution of Dr. Yadav has received research support from Tykeson Family Foundation Endowed Professorship.
Michael A. Lane, MD (OHSU)	Dr. Lane has nothing to disclose.
Allison Fryman	No disclosure on file
Manoj K. Sammi, PhD (Oregon Health & Science Univ)	Dr. Sammi has received research support from Race to Erase MS. Dr. Sammi has received research support from Myelin Repair Foundation. Dr. Sammi has received research support from Revalesio. Dr. Sammi has received research support from Paul G. Allen Family Foundation. Dr. Sammi has received research support from Conrad F Hilton Foundation Innovation Fund. Dr. Sammi has received research support from NIH/NIDDK.