Walking disability measures in multiple sclerosis patients: Correlations with MRI-derived global and microstructural damage

BACKGROUND: The relationship between walking disability in multiple sclerosis (MS) patients and their macro- and microstructural MRI-derived measures still remains unclear.

OBJECTIVE: To assess the correlations between walking disability and MRI-derived lesion, atrophy, and microstructural/axonal integrity outcomes.

METHODS: Seventy-one (71) MS patients were clinically examined, the expanded timed get-up and go (ETGUG), and timed 25-foot walk (T25FW) tests were assessed. Additionally, the Symbol Digit Modalities Test (SDMT) was obtained. Normalized brain (NBV), gray matter (GMV), white matter (WMV), cortex (CV), and deep GM (DGM) volumes, as well as lesion volumes (LV) and diffusion tensor imaging (DTI) scalar maps of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated. Spearman correlation, partial correlation and stepwise regression analyses were performed.

RESULTS: T25FW and ETGUG were associated with T2-LV (p < .001), global (NBV, p < .001), tissue-specific (GMV and CV, p < .001) and regional (DGM p < .001; and thalamus p < .001) volumes. The ETGUG remained correlated with T1-LV, GMV, CV and total DGM volume (all p < .001) after age, sex, and disease duration adjustment. The WMV was not associated with walking disability. Similarly, DTI measures did not show significant association with the walking tests. The regression analysis outlined DMG volume as best predictor of T25FW (Adj R2 = 0.231, standardized β = -0.435, and p = .001), and CV for ETGUG (Adj R2 = 0.176, standardized β = -0.417, and p = .004). SDMT was associated with both T25FW (p = .004) and ETGUG (p = .013).

CONCLUSION: Despite the low disability levels, walking as measured by T25FW and ETGUG, is largely explained by the loss of cortical and nuclei specific GM volumes.