Magnetization Transfer Imaging in Brain Corticospinal Tract Is Associated with Clinical Walking Performance in Multiple Sclerosis

Background: Walking is a common measure of physical function in individuals with multiple sclerosis (MS). Previous studies have shown an association between spinal cord MRI measures (e.g., magnetization transfer ratio (MTR)) and strength or walking ability, and brain corticospinal tract (CST) MTR with strength measures. However, the relationship between brain CST MTR measures and walking performance has not been explored in MS. 

Objectives: The objective of this study was to examine the relationship between clinical measures of walking and CST-specific measures of myelin (MD, MTR) and axonal integrity (FA). 

Methods: Seventeen individuals with relapsing remitting MS (age 50.3 ± 9.9 years; 9 females; EDSS of 4.1±1.5) and 12 age and gender-matched healthy controls (age 51.7 ± 10.4 years; 8 females) participated in clinical tests of strength (hand-held dynamometer), sensation (Vibratron II) and walking (Timed Up and Go (TUG), Timed 25 Foot Walk (T25W), Two Minute Walk Test (2MWT)) as well as 3T imaging (DTI, MT). T-tests and Pearson’s correlation coefficients were used to assess statistical significance. 

Results: Individuals with MS had weaker hip flexion strength (p=0.0024), poorer vibration sensation (p=0.0001), walked slower (TUG: p=0.0013; T25W: p=0.0112; velocity: p=0.0033) and had reduced endurance demonstrated by shorter distance walked on the 2MWT (p=0.0055) than controls. Subjects with MS also had a lower MTR in the CST (p <0.0001). There is a strong relationship between CST MTR and TUG (r=-0.50), T25W (r=-0.58) and walk velocity (r=0.51), and between CST FA and TUG (r=-0.47), T25W (r=-0.58) and walk velocity (r=0.49). Both CST MTR and FA were only weakly correlated with the 2MWT. Hip flexion strength is correlated with CST MTR (r=0.42), but walking measures demonstrated stronger associations. Although EDSS is also highly correlated with walking measures, it is only minimally related to CST MTR or FA, which may reflect the specificity of the CST for walking measures. 

Conclusions: CST measures of MTR and FA are highly correlated with clinical walking performance in our MS cohort. Surprisingly, our data links brain CST to walking measures and highlights MTR as an important addition to structural MRI protocols. Evaluating structure-function relationships is a first step in the development of appropriate quantitative outcome measures; our next step is to determine the predictive value of these measures in evaluating intervention responsiveness.