Quantitative measures of walking and strength provide insight into brain corticospinal tract pathology in multiple sclerosis

Abstract

At least 85% of individuals with multiple sclerosis report walking dysfunction as their primary complaint. Walking and strength measures are common clinical measures to mark increasing disability or improvement with rehabilitation. Previous studies have shown an association between strength or walking ability and spinal cord MRI measures, and strength measures with brainstem corticospinal tract magnetization transfer ratio. However, the relationship between walking performance and brain corticospinal tract magnetization transfer imaging measures and the contribution of clinical measurements of walking and strength to the underlying integrity of the corticospinal tract has not been explored in multiple sclerosis. The objectives of this study were explore the relationship of quantitative measures of walking and strength to whole-brain corticospinal tract-specific MRI measures and to determine the contribution of quantitative measures of function in addition to basic clinical measures (age, gender, symptom duration and Expanded Disability Status Scale) to structural imaging measures of the corticospinal tract. We hypothesized that quantitative walking and strength measures would be related to brain corticospinal tract-specific measures, and would provide insight into the heterogeneity of brain pathology.Twenty-nine individuals with relapsing-remitting multiple sclerosis (mean(SD) age 48.7 (11.5) years; symptom duration 11.9(8.7); 17 females; median[range] Expanded Disability Status Scale 4.0 [1.0–6.5]) and 29 age and gender-matched healthy controls (age 50.8(11.6) years; 20 females) participated in clinical tests of strength and walking (Timed Up and Go, Timed 25 Foot Walk, Two Minute Walk Test ) as well as 3 T imaging including diffusion tensor imaging and magnetization transfer imaging.Individuals with multiple sclerosis were weaker (p = 0.0024) and walked slower (p = 0.0013) compared to controls. Quantitative measures of walking and strength were significantly related to corticospinal tract fractional anisotropy (r > 0.26; p < 0.04) and magnetization transfer ratio (r > 0.29; p < 0.03) measures. Although the Expanded Disability Status Scale was highly correlated with walking measures, it was not significantly related to either corticospinal tract fractional anisotropy or magnetization transfer ratio (p > 0.05). Walk velocity was a significant contributor to magnetization transfer ratio (p = 0.006) and fractional anisotropy (p = 0.011) in regression modeling that included both quantitative measures of function and basic clinical information.Quantitative measures of strength and walking are associated with brain corticospinal tract pathology. The addition of these quantitative measures to basic clinical information explains more of the variance in corticospinal tract fractional anisotropy and magnetization transfer ratio than the basic clinical information alone. Outcome measurement for multiple sclerosis clinical trials has been notoriously challenging; the use of quantitative measures of strength and walking alon...

Diffusion tensor imaging and disability progression in multiple sclerosis: A 4‐year follow‐up study

“…Conversely, the association between diffusivity in the frontal NAWM and disability as measured by the MS Functional Composite Scale has been found in primaryprogressive MS (Schmierer et al, 2004 We did not observe any associations in the IC between baseline DTI and disability progression. Our finding is supported by studies where no correlation between DTI indices in the corticospinal tract and disability progression expressed by an EDSS increase has been observed (Fritz, Keller, Calabresi, & Zackowski, 2017;Lin et al, 2007). This result indicates that diffusivity abnormalities may already exist in the IC, but they progress at different rates, and image disability progression distinctly than in the CC (Ge et al, 2004).…”

“…Conversely, the association between diffusivity in the frontal NAWM and disability as measured by the MS Functional Composite Scale has been found in primaryprogressive MS (Schmierer et al, 2004 (Ge et al, 2004). Our finding is supported by studies where no correlation between DTI indices in the corticospinal tract and disability progression expressed by an EDSS increase has been observed (Fritz, Keller, Calabresi, & Zackowski, 2017;Lin et al, 2007).…”

Associations of functional connectivity and walking performance in multiple sclerosis

“…The networks associated with gait velocity in the DT condition demonstrated significantly greater FC in supplementary motor and prefrontal regions, when compared to the normal walking condition (Yuan et al, 2015). In persons with MS, two previous studies demonstrated that corticospinal motor pathway damage, measured using diffusion tensor imaging, was associated with walking performance (Hubbard et al, 2016, Fritz et al, 2017 in persons with MS. However, these studies did not examine the neural correlates of walking performance in persons with MS at the cortical level.…”

Effect of High-Intensity Exercise on Multiple Sclerosis Function and Phosphorous Magnetic Resonance Spectroscopy Outcomes

“…The symptomatic and neuroanatomic benefits of physical activity in MS are also evident. Cross-sectional studies in MS reveal positive associations between levels of physical activity and walking performance with fatigue, cognitive processing speed, brain volumes, and tract integrity (10)(11)(12). Longitudinal studies of aerobic exercise generally, although not invariably, demonstrate improvements in fitness and MS symptoms (3,13,14).…”