White Matter Correlates of Reactive Stepping in People with Multiple Sclerosis

Abstract

Background and Purpose Reactive steps are rapid protective responses after balance challenges. People with MS (PwMS) demonstrate impaired stepping, which can increase fall-risk, and these deficits may be caused by white matter (WM) loss. However, the specific neural mechanisms contributing to reactive stepping in PwMS are poorly understood. We aimed to determine WM correlates of reactive stepping and responsiveness to step training. Methods 14 PwMS participated in an 18-week multiple-baseline study. Participants attended 2 baseline assessments (B1 and B2) before training, a 2-week, 6-session training protocol, and a post-training assessment (P1). Each assessment consisted of 3 backward reactive step trials. Training consisted of 32 stepping trials. Outcomes included the anterior-posterior margin of stability (MOS), step length, and step latency. Tract-Based Spatial Statistics (TBSS) was performed to investigate the WM microstructure by correlating fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) with baseline reactive step performance (B1) and immediate responsiveness to training (P1). Results The FA of the right superior longitudinal fasciculus (R-SLF) was associated with baseline step length (p=0.048) and MOS (p=0.048). Corpus Callosum (p=0.047) and right anterior corona radiata (R-ACR) (p=0.047) FA were also related to baseline MOS during backward stepping. FA of the corticospinal tract was also associated with baseline step length (p=0.048). The FA (p=0.047) and the MD (trending- p=0.082) of the L-ACR were also related to step length. No significant associations were found between WM and training responsiveness, but a trend showed an association between the right uncinate fasciculus and a change in step latency (p=0.072). Discussion We identified several WM loci associated with baseline stepping involved in the rapid integration of sensory information and the execution of motor responses. A better understanding of the neural control of reactive stepping may lead to developing more effective rehabilitation strategies and ultimately reducing fall-risk in PwMS. Reactive steps are rapid protective responses after balance challenges. People with MS (PwMS) demonstrate impaired stepping, which can increase fall-risk, and these deficits may be caused by white matter (WM) loss. However, the specific neural mechanisms contributing to reactive stepping in PwMS are poorly understood. We aimed to determine WM correlates of reactive stepping and responsiveness to step training. 14 PwMS participated in an 18-week multiple-baseline study. Participants attended 2 baseline assessments (B1 and B2) before training, a 2-week, 6-session training protocol, and a post-training assessment (P1). Each assessment consisted of 3 backward reactive step trials. Training consisted of 32 stepping trials. Outcomes included the anterior-posterior margin of stability (MOS), step length, and step latency. Tract-Based Spatial Statistics (TBSS) was performed to investigate the WM microstructure by correlating fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) with baseline reactive step performance (B1) and immediate responsiveness to training (P1). The FA of the right superior longitudinal fasciculus (R-SLF) was associated with baseline step length (p=0.048) and MOS (p=0.048). Corpus Callosum (p=0.047) and right anterior corona radiata (R-ACR) (p=0.047) FA were also related to baseline MOS during backward stepping. FA of the corticospinal tract was also associated with baseline step length (p=0.048). The FA (p=0.047) and the MD (trending- p=0.082) of the L-ACR were also related to step length. No significant associations were found between WM and training responsiveness, but a trend showed an association between the right uncinate fasciculus and a change in step latency (p=0.072). We identified several WM loci associated with baseline stepping involved in the rapid integration of sensory information and the execution of motor responses. A better understanding of the neural control of reactive stepping may lead to developing more effective rehabilitation strategies and ultimately reducing fall-risk in PwMS.