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.
Subject(s)
Exoskeleton Device , Multiple Sclerosis , Exercise Therapy , Humans , Multiple Sclerosis/complications , Pilot Projects , WalkingABSTRACT
Multiple sclerosis (MS) is a non-traumatic, immune-mediated neurodegenerative disease of the central nervous system (CNS), affecting more than 2 million individuals globally and approximately one million in the United States [1], [2]. This autoimmune inflammatory disease of the CNS featuring both neuroinflammatory and neurodegenerative aspects [3], often results in mobility and cognitive impairment. Rehabilitation has been suggested as the best [4], and perhaps, one of few methods for restoring function in MS [5]. The goal of the present investigation is to examine the effects of 4 weeks of supervised, over-ground gait training using a robotic exoskeleton (RE) compared with a control condition (conventional gait therapy, CGT) in persons with MS with ambulatory and cognition disabilities. Four subjects (mean age=50 years, three females) with relapsing-remitting MS (RRMS) participated in this study and completed a total of eight sessions (1-hour/session) gait training in a standard therapy gym either using a RE supervised by an RE training physical therapist (PT) or with the CGT supervised by a PT. Outcome measures (walking speed and temporal-spatial parameters) were measured on a level surface without RE using an instrumented walkway, for both groups, pre- and post-intervention. The two participants in the RE group were also tested in the same testing environment, while wearing a RE pre- and post-intervention. Cognitive processing speed was assessed using the Symbol Digit Modalities Test (SDMT) pre- and post-intervention. Subjects in the RE group tested without a RE increased average walking speed, stride length, and step length with decreased stride width and step time bilaterally after the 8-session of RE training. The two participants in the CGT group only had modest improvements in walking performance. Furthermore, while the CGT group had no improvements in the processing speed (SDMT scores), an average of 80% improvement in the processing speed was noted in the RE group.