Vascular Disease Risk Factors and MS Progression: A Study of Brain Metabolism

Background: There is growing evidence that vascular disease risk factors (VDRF), such as hyperlipidemia, hypertension, obesity, diabetes, and heart disease, can significantly increase the risk of disability progression in MS. Recent research has shown MS subjects with one or more VDRF at diagnosis required unilateral assistance to walk at earlier times (a median of 6 years) than those without any VDRF. In addition, there appeared to be a dose-response relationship between VDRF and MS disability with presence of a single VDRF increasing the risk of early gait disability by 51% and presence of 2 of these conditions increasing the risk by 228%.

Objectives: To study how vascular disease risk factors affect cerebral blood flow and brain metabolism measured by DCE MRI and ³¹P MRSI in people with MS.

Methods: We are conducting a 3-year long observational controlled study with a single-site, mixed design (cross sectional and longitudinal) with two arms. The study includes prospective brain MRI and clinical disease progression outcome measurements. MRI data is collected at baseline, 12, 24 and 36 months. We enrolled a total of 60 MS subjects consisting of 35 subjects with VDRF (VDRFP) and 25 subjects without VDRF (VDRFN). The outcome measures include changes in the VDRFP and VDRFN groups in the following: 1) cerebral blood flow and blood volume detected by 7T MRI and high energy phosphate metabolites in cerebral gray matter (GM) assessed by ³¹P 7T magnetic resonance spectroscopic imaging (MRSI), 2) brain atrophy, 3) clinical impairment, disability, and quality of life.

Results: A cross-sectional analyses of baseline data was performed. The average age of the 50 subjects, whose MR data were analyzed, was 54.5 years (SD: 7.5); 72% female). Twenty-seven subjects have VDRFP (average age 55.5 years (SD: 7.2); 70% female) and 23 subjects were VDRFN (average age 53.4 years (SD: 7.8); 32% female).  There was a significant decrease in ATP signal normalized to total phosphate signal (3.5%; P < 0.05) in a volume of interest defined in occipital brain region.  There was no significant difference in between two groups for both parenchymal volume fraction ( PVF[VDRFN]=0.782±0.040, PVF[VDRFP]=0.769±0.050 ) and EDSS score ( EDSS[VDRFN]=3.9±1.4, EDSS[VDRFP]=4.2±1.1 ). Semi-automated lesion segmentation is in progress and will be used to analyze tissue atrophy and phosphate distribution in GM. 

Conclusions: Our preliminary results support the view of an impaired metabolic state in VDRFP MS subjects that may potentially increase risk of neurodegeneration.