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. 2018 Apr 27;4(2):2055217318773540.
doi: 10.1177/2055217318773540. eCollection 2018 Apr-Jun.

Myelin status is associated with change in functional mobility following slope walking in people with multiple sclerosis

E M King  1   2 , M J Sabatier  2 , M Hoque  2 , T M Kesar  2 , D Backus  3 , M R Borich  2
Affiliations

Myelin status is associated with change in functional mobility following slope walking in people with multiple sclerosis

E M King et al. Mult Scler J Exp Transl Clin. .

Abstract

Background: The level of myelin disruption in multiple sclerosis patients may impact the capacity for training-induced neuroplasticity and the magnitude of therapeutic response to rehabilitation interventions. Downslope walking has been shown to increase functional mobility in individuals with multiple sclerosis, but it is unclear if myelin status influences therapeutic response.

Objective: The current study aimed to examine the relationship between baseline myelin status and change in functional mobility after a walking intervention.

Methods: The Timed Up and Go test was used to measure functional mobility before and after completion of a repeated, six-session slope walking intervention in 16 participants with relapsing-remitting multiple sclerosis. Multi-component T2 relaxation imaging was used to index myelin water fraction of overall water content in brain tissue compartments.

Results: Results demonstrated that the ratio of the myelin water fraction in lesion to normal-appearing white matter (myelin water fraction ratio) significantly predicted 31% of the variance in change in Timed Up and Go score after the downslope walking intervention, where less myelin disruption was associated with greater intervention response.

Conclusions: Myelin water content fraction ratio may offer a neural biomarker of myelin to identify potential responders to interventions targeting functional impairments in multiple sclerosis.

Keywords: Multiple sclerosis; downslope walking; magnetic resonance imaging; mobility; myelin; myelin water fraction.

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Figures

Figure 1.
Figure 1.
Study design. Left: Timeline of study design. Right: example of treadmill walking protocol during the first downslope walking (DSW) intervention visit. The same protocol was followed for all treadmill walking sessions (Days 3–9). Expanded Disability Status Scale (EDSS) and Timed Up and Go (TUG) test were administered on Day 1. Follow-up TUG test was performed on Day 10. MRI: magnetic resonance imaging. LW: level walking.
Figure 2.
Figure 2.
Magnetic resonance imaging (MRI) data processing pipeline. Normal-appearing white matter (NAWM) and lesion region of interest (ROI) masks were co-registered to the gradient- and spin-echo (GRASE) scan for each subject using FMRIB Software Library (FSL) FMRIB's Linear Registration Tool (FLIRT). Lesion masks were then subtracted from the NAWM mask to prevent overlap. Mean myelin water fraction (MWF) values were extracted for each ROI in each participant. FAST: FMRIB's Automated Segmentation Tool.
Figure 3.
Figure 3.
Mean normal-appearing white matter (NAWM) and lesion myelin water fraction (MWF) values across individuals. Mean lesion MWF was significantly lower than mean NAWM MWF (p < 0.001). Error bars represent standard deviation.
Figure 4.
Figure 4.
Myelin water fraction (MWF) ratio was associated with change in Timed Up and Go test (TUGT) score after downslope walking intervention (R2=0.31, p=0.047). Less myelin disruption in lesions, represented by higher MWF ratios, was associated with greater improvement (reduction in TUGT times) in functional mobility following the intervention. Participant ID numbers are provided beside each data point.
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