Volume of Subcortical Grey Matter Structures and Gait Outcomes in Multiple Sclerosis

Background: Research has identified a significant relationship between pallidal and caudate volumes with walking dysfunction in multiple sclerosis (MS). To date, there is little is known about the association between these subcortical gray matter (SGM) structures and gait outcomes in MS.

Objectives: This study examined the associations among SGM structures (thalamus and basal ganglia) and gait outcomes (gait velocity, cadence, step length, and base support) in MS.

Methods: We enrolled 71 persons with MS who underwent brain MRI and completed gait testing that involved two trials of walking at a self-selected pace on a 16-foot GAITRite electronic walkway. Velocity (cm/sec), cadence (steps/min), step length (cm), and base support (cm) were averaged for the two trials. Volumes of the thalamus, caudate, putamen, and pallidum as well as whole-brain white matter (WM) and gray matter (GM) were calculated from 3D T1-weighted structural brain images. We examined the associations using partial (pr) correlations controlling for demographic and clinical variables. We further performed hierarchical linear regression (HLR) for identifying the strongest SGM correlate of the gait parameters. 

Results: Gait velocity was significantly associated with volumes of the thalamus (pr=.29, p=.03), caudate (pr=.38, p<.01), and pallidum (pr=.46, p<.01). Cadence was significantly associated with caudate (pr=.35, p<.01) and pallidal (pr=.43, p<.01) volumes. Volumes of the thalamus (pr=.27, p=.04; pr=-.39, p<.01), caudate (pr=.29, p=.03; pr=-.26, p=.05), and pallidum (pr=.32, p=.02; pr=-.34, p=.01) were significantly associated with step length and base support, respectively. Volumes of the putamen were not significantly associated with any of the gait parameters (p>0.05). Pallidum volume was the strongest SGM correlate of gait velocity (β=.47), cadence (β=.49), step length (β=.31) in HLR. Thalamic volume was the strongest SGM correlate of base support (β=-.44) in HLR.

Conclusions: We provide novel evidence of possible SGM structures, particularly the pallidum and thalamus, as correlates of gait parameters in MS. These results are intriguing in that the pallidum and thalamus may serve as regions of interest for explaining progression of walking dysfunction over time in MS.