Abstract Details

Title Vascular Disease Risk Factors (VDRF) in MS is Associated with Brain ATP Abnormalities: Dysmetabolism May Drive MS Disease Progression.

Topic Multiple Sclerosis

Presentation(s) S55 - MS Basic Science (3:30 PM-3:41 PM)

Poster/Presentation
Number 001

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 To determine if VDRF accelerate disease progression by decreasing cerebral blood flow and brain 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). 7T MRI brain data collected at baseline, 12, 24 and 36 months. Outcome measures include changes in: 1) high energy phosphate metabolites in cerebral gray matter assessed by ³¹P 7T MR imaging (MRSI) and cerebral blood flow and blood volume detected by dynamic contrast-enhanced 7T MRI, 2) brain parenchymal volume assessed using SIENAX, 3) clinical impairment, disability, and quality of life.

Results We preformed cross-sectional analyses of the baseline MRI data was available for 50 subjects. Mean age/gender was 54.5 years with 72% female) (+VDRF, N=28, mean age 56.4 years, 82% female) and -VDRF, N=22, mean age 52.2 years; 59% female). We analyzed a volume of interest in the occipital region for changes in phosphate metabolites using 7T MRSI. Adenosine triphosphate (ATP) to total phosphate signal ratio was decreased in +VDRF subjects by 4.5% (P<0.05) compared with -VDRF subjects. +VDRF female subjects had a 3.9% decrease in normalized brain tissue volume (P=0.02) compared to -VDRF. Cerebral blood flow data and clinical correlates will be presented.

Conclusions This is the first study to assess brain metabolism and cerebral blood flow in MS patients with and without VDRF. We demonstrate here that MS subjects with VDRF have significantly reduced brain ATP compared with MS subjects without VDRF. ATP depletion may reflect mitochondrial dysfunction resulting from cerebral blood flow abnormalities 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.
Allison Fryman	Allison Fryman has nothing to disclose.
Michael A. Lane, MD (OHSU)	Dr. Lane has nothing to disclose.
Frank Bittner, DO	Dr. Bittner has nothing to disclose.
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.
William Rooney, PhD (Oregon Health & Science University)	Dr. Rooney has nothing to disclose.

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