A pilot randomized controlled trial of robotic exoskeleton-assisted exercise rehabilitation in multiple sclerosis
Ghaith J.AndrowisabBrian M.SandroffabPeterNiewrzolaFarrisFakhourycGlenn R.WylieabGuangYueabJohnDeLucaab
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https://doi.org/10.1016/j.msard.2021.102936
Highlights
•Mobility and cognitive impairment co-occur in persons with multiple sclerosis (PwMS).
•Robotic-exoskeleton assisted exercise rehabilitation (REAER) may benefit PwMS.
•This study tested REAER effects on mobility, cognition, and fMRI outcomes in 10 PwMS.
•REAER improved mobility, cognition, and brain connectivity based on effect sizes.
•REAER represents a promising rehabilitation approach in PwMS.
Abstract
Background
Co-occurring mobility and cognitive impairments are common, debilitating, and poorly-managed with pharmacological therapies in persons with multiple sclerosis (MS). Exercise rehabilitation (ER), particularly walking ER, has been suggested as one of the best approaches for managing these manifestations of MS. However, there is a focal lack of efficacy of ER on mobility and cognitive outcomes in persons with MS who present with substantial neurological disability. Such severe neurological disability oftentimes precludes the ability for participation in highly-intensive and repetitive ER that is necessary for eliciting adaptations in mobility and cognition. To address such a concern, robotic exoskeleton-assisted ER (REAER) might represent a promising intervention approach for managing co-occurring mobility and cognitive impairments in those with substantial MS disability who might not benefit from traditional ER.
Methods
The current pilot single-blind, randomized controlled trial (RCT) compared the effects of 4-weeks of REAER with 4-weeks of conventional gait training (CGT) as a standard-of-care control condition on functional mobility (timed up-and-go; TUG), walking endurance (six-minute walk test; 6MWT), cognitive processing speed (CPS; Symbol Digit Modalities Test; SDMT), and brain connectivity (thalamocortical resting-state functional connectivity (RSFC) based on fMRI) outcomes in 10 persons with substantial MS-related neurological disability.
Results
Overall, compared with CGT, 4-weeks of REAER was associated with large improvements in functional mobility (ηp2=.38), CPS (ηp2=.53), and RSFC between the thalamus and ventromedial prefrontal cortex (ηp2=.72), but not walking endurance (ηp2=.01). Further, changes in RSFC were moderately associated with changes in TUG, 6MWT, and SDMT performance, respectively, whereby increased thalamocortical RSFC was associated with improved functional mobility, walking endurance, and CPS (|ρ|>.36).
Conclusion
The current pilot RCT provides initial support for REAER as an approach for improving functional mobility and CPS, perhaps based on adaptive and integrative central nervous system plasticity, namely increases in RSFC between the thalamus and ventromedial prefrontal cortex, in a small sample of persons with substantial MS disability. Such a pilot trial provides proof-of-concept data for the design and implementation of an appropriately-powered RCT of REAER in a larger sample of persons with MS who present with co-occurring impairments in both mobility and cognitive functioning.