Walking Speed and Brain Glucose Uptake are Uncoupled in Patients with Multiple Sclerosis

Abstract

Motor impairments of the upper and lower extremities are common symptoms of multiple sclerosis (MS). While some peripheral effects like muscle weakness and loss of balance have been shown to influence these symptoms, central nervous system activity has not been fully elucidated. The purpose of this study was to determine if alterations in glucose uptake were associated with motor impairments in patients with multiple sclerosis. Eight patients with multiple sclerosis (four men) and eight sex matched healthy controls performed 15 min of treadmill walking at a self-selected pace, during which ≈322 MBq of the positron emission tomography (PET) glucose analog [(18)F]-fluorodeoxyglucose (FDG) was injected. Immediately after the cessation of walking, participants underwent PET imaging. Patients with MS had lower FDG uptake in ≈40% of the brain compared to the healthy controls (p FWE-corr < 0.001, q FDR-corr < 0.001, k e = 93851) and walked at a slower speed [MS, 1.1 (0.2), controls 1.4 (0.1), m/s, P = 0.014]. Within the area of lower FDG uptake 15 regions were identified. Of these 15 regions, 13 were found to have strong to moderate correlations to walking speed within the healthy controls (r > -0.75, P < 0.032). Within patients with MS only 3 of the 15 regions showed significant correlations: insula (r = -0.74, P = 0.036), hippocampus (r = -0.72, P = 0.045), and calcarine sulcus (r = -0.77, P = 0.026). This data suggest that walking impairments in patients with MS may be due to network wide alterations in glucose metabolism. Understanding how brain activity and metabolism are altered in patients with MS may allow for better measures of disability and disease status within this clinical population.

Keywords: brain activity; glucose uptake; movement disorder; multiple sclerosis; positron emission tomography; walking.

Figure 1

Representative image of the experimental timeline.

Figure 2

Brain regions where patients with MS have lower FDG uptake after walking challenge. Walking speed has been modeled out as a nuisance factor. Data are thresholded at P < 0.01, FDR corrected.

Figure 3

SPM output of the areas of lower FDG uptake in patients with MS compared to controls. Within cluster information is displayed for the large cluster (p_FWE-corr < 0.001, q_FDR-corr < 0.001, k_e = 93851) identified during analysis.

Figure 4

Visual representation of correlations between walking speed and brain region FDG uptake. In each case, the strength of the correlation is less in patients with MS compared to controls. As well as correlations being weaker, patients with MS show no statistical significance while correlations for the control group all reach statistical significance. (A) Motor cortex, (B) frontal cortex, (C) cerebellum, (D) anterior cingulate.