Locomotor function following transcutaneous electrical spinal cord stimulation in individuals with hemiplegic stroke

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Project Abstract Approximately 70% of the more than 7.2 million U.S. stroke survivors experience persistent gait deficits, including reduced walking speed, asymmetrical walking patterns, and reduced lower limb coordination, which limit their capacity for community ambulation. Current rehabilitation approaches are based on the assumption that stroke impairs motor cortex function while the spinal cord is preserved and thus focus on stimulating the ipsilateral or contralateral motor cortex during gait training to activate dormant or new pathways. Although animal models of stroke reveal secondary degeneration of the cervical and lumbar spinal cord, suggesting that damage to the spinal cord may effect functional recovery, little or no research has been done to elucidate spinal cord changes in humans after stroke. Our objective is to evaluate the effects of spinal stimulation combined with gait training after stroke and to investigate mechanisms underlying these effects. In preliminary work, we measured spinally evoked motor potentials (sEMPs) generated by non-invasive, transcutaneous electrical spinal stimulation in 10 stroke survivors, 10 age-matched healthy controls, and 10 young healthy subjects. Stimulation thresholds were significantly higher in stroke survivors than in controls and latency was significantly delayed in the paretic side compared to the non-paretic side, indicating secondary effects of stroke on downstream spinal circuitry and descending pathways. We also showed that spinal stimulation + symmetry-focused gait training (n=4) compared to gait training alone (n=4), significantly improved step-length symmetry, walking speed (10-meter walk test, 10MWT), and walking endurance (6-minute walk test, 6MWT); these improvements exceeded the minimal clinically important difference for chronic stroke. These results support our hypothesis that spinal stimulation may increase gait training efficacy. In Aim 1, we will evaluate the short-term effects of spinal stimulation and sham stimulation, with or without symmetry-focused gait training, on gait function (primary outcome: step-length symmetry) and corticospinal circuitry in 25 stroke survivors. In Aim 2, we will conduct a randomized clinical trial to evaluate the long-term effects of symmetry-focused gait training with stim or sham stimulation in stroke survivors (n=25 per group). The primary outcome will be step-length symmetry; secondary outcomes include temporal gait symmetry, speed (10MWT), muscle activation (electromyography), walking endurance (6MWT), energy expenditure (Cosmed K4B2), upper and lower limb function (Fugl-Meyer Assessment), health status (Stroke Impact Scale-16), and community activity (wearable sensors, Actigraph LLC). We will also investigate mechanisms underlying the effects of spinal stimulation by examining sEMPs elicited in lower limb muscles by cortical/subcortical stimulation of corticospinal axons and intracortical inhibition. This work will (i) identify short- and long-term effects of spinal stimulation, (ii) validate spinal stimulation as a non-invasive method to restore gait in chronic stroke, (iii) identify clinical measures that may determine response to spinal stimulation, and (iv) identify underlying neuromodulatory mechanisms, which may provide additional treatment options.