Motor improvements enabled by spinal cord stimulation combined with physical training after spinal cord injury: review of experimental evidence in animals and humans

Abstract

Electrical spinal cord stimulation (SCS) has been gaining momentum as a potential therapy for motor paralysis in consequence of spinal cord injury (SCI). Specifically, recent studies combining SCS with activity-based training have reported unprecedented improvements in motor function in people with chronic SCI that persist even without stimulation. In this work, we first provide an overview of the critical scientific advancements that have led to the current uses of SCS in neurorehabilitation: e.g. the understanding that SCS activates dormant spinal circuits below the lesion by recruiting large-to-medium diameter sensory afferents within the posterior roots. We discuss how this led to the standardization of implant position which resulted in consistent observations by independent clinical studies that SCS in combination with physical training promotes improvements in motor performance and neurorecovery. While all reported participants were able to move previously paralyzed limbs from day 1, recovery of more complex motor functions was gradual, and the timeframe for first observations was proportional to the task complexity. Interestingly, individuals with SCI classified as AIS B and C regained motor function in paralyzed joints even without stimulation, but not individuals with motor and sensory complete SCI (AIS A). Experiments in animal models of SCI investigating the potential mechanisms underpinning this neurorecovery suggest a synaptic reorganization of cortico-reticulo-spinal circuits that correlate with improvements in voluntary motor control. Future experiments in humans and animal models of paralysis will be critical to understand the potential and limits for functional improvements in people with different types, levels, timeframes, and severities of SCI.

Fig. 1

How can spinal cord stimulation lead to functional improvements in SCI? a SCS provides a prosthetic effect that enables activation of previously paralyzed muscles. b The prosthetic effect of SCS enables prolonged activation of paralyzed muscles in a physical therapy setting. c Long-term practice with activity-based training and SCS results in increases clinical measures of function in chronic SCI. Modified with permission from (Wagner et al. 2018)

Fig. 2

Post-stimulation depression of evoked responses confirms elicitation of posterior root-muscle (PRM) reflexes. a Electrode position for elicitation of muscle responses via transcutaneous SCS. b Afferent stimulation is confirmed by the depression and partial recovery of the PRM reflex using a paired-pulse paradigm (Minassian et al. ; Hofstoetter et al. ; Kagamihara et al. ; Hofstoetter et al. 2020). Exemplary electromyographic responses of the leg muscles when the time between stimuli is set to 30, 50, and 100 ms. Responses to the second stimulus are completely eliminated at interstimulus intervals of 30 ms and partially recover at 100 ms (Hofstoetter et al. 2019). Modified with permission from (Hofstoetter et al. 2021)

Fig. 3

Functional improvements after long-term training with SCS and activity-based training. Summary of recovery outcomes extracted from Table 1 as a function of lesion severity assessed by AIS classification at study enrollment. Transparent circles indicate not all participants with that AIS classification achieved the outcome. Adjacent ratios indicate the partial number