The progressive decline in mobility that occurs with multiple sclerosis (MS) is attributable to two factors: a reduction in the ability of the nervous system to generate adequate muscle activation signals and a decrease in the level of physical conditioning that results from the development of a more sedentary lifestyle. Exercise programs can provide some relief by reducing the level of deconditioning, but only for individuals with low levels of disability. There are no effective countermeasures for persons with MS who are moderately disabled with limitations in walking performance. To address this knowledge gap, we will examine the effectiveness of an intervention that evokes involuntary contractions in leg muscles with a novel form of neuromuscular electrical stimulation (NMES). Conventional NMES mainly activates motor axons using narrow (0.2-0.5 ms) stimulus pulses, but does not improve the walking performance of persons with MS. As an alternative approach, we will use wide (1 ms) stimulus pulses to activate both motor and sensory axons and thereby modulate the excitability of spinal and cortical neurons to promote the recovery of motor function in the nervous system. The primary outcome will be walking endurance, which will be quantified as the distance walked in 6 min. The participants (n = 30, 18-55 yrs) will be individuals diagnosed with MS who exhibit a clinically defined moderate level of disability. The research design comprises a 6 week (18 sessions), randomized, evaluator-blinded comparison of narrow- and wide-pulse NMES treatment on walking performance and then retention of the gains in walking endurance during 6 months of follow-up. Based on the demonstrated acute effects of wide-pulse NMES in healthy volunteers, the intervention will comprise stimulation of each leg individually with 30 trains of stimulation (20 s on, 20 s off) with a well-tolerated current that elicits a submaximal force (~20% maximum). We will evaluate two hypotheses: H1: Treatment of moderately disabled MS patients with wide-pulse NMES will improve walking endurance more than treatment with narrow-pulse NMES. H2: Improvements in walking endurance will be associated with elevated levels of habitual physical activity that will be retained longer after the treatment ends for the wide-pulse NMES group compared with the narrow-pulse NMES group. We expect wide-pulse NMES to produce greater improvement in walking endurance than narrow-pulse NMES and the gains to be associated with: (1) sustained electromyographic (EMG) activity in leg muscles during walking;(2) improved walking economy;and (3) increases in stride length. If wide-pulse NMES can elicit clinically significant improvements in mobility and quality of life for persons with moderate disability, clinicians will be able to prescribe a meaningful strategy for this underserved group of MS patients. Moreover, the intervention may delay the development of disability in individuals who are less affected by the disease. The outcomes of this feasibility study will suggest directions for subsequent R01 projects.

Public Health Relevance

Electrical stimulation applied over a nerve can do two things: evoke a muscle contraction and produce a sensation about the stimulus. Most often, the therapeutic use of electrical stimulation just focuses on evoking muscle contractions. In contrast, we propose to use electrical stimulation to enhance the sensory aspects of the therapy as a way to produce some recovery of function in the central nervous system of persons with multiple sclerosis. We expect the treatment will improve walking performance and quality of life.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Small Research Grants (R03)
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Pediatrics Subcommittee (CHHD)
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Cruz, Theresa
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University of Colorado at Boulder
Schools of Arts and Sciences
United States
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Almuklass, Awad M; Davis, Leah; Hamilton, Landon D et al. (2018) Pulse Width Does Not Influence the Gains Achieved With Neuromuscular Electrical Stimulation in People With Multiple Sclerosis: Double-Blind, Randomized Trial. Neurorehabil Neural Repair 32:84-93
Almuklass, Awad M; Feeney, Daniel F; Mani, Diba et al. (2017) Peg-manipulation capabilities during a test of manual dexterity differ for persons with multiple sclerosis and healthy individuals. Exp Brain Res 235:3487-3493
Enoka, Roger M; Duchateau, Jacques (2016) Translating Fatigue to Human Performance. Med Sci Sports Exerc 48:2228-2238