Non-invasive spinal cord neuromodulation enables volitional anti-gravity leg movements after motor-complete spinal cord injury: responders vs. non-responders

BACKGROUND AND OBJECTIVES: Transcutaneous spinal cord stimulation (tSCS) is an emerging treatment for motor recovery following spinal cord injury (SCI). However, the extent of motor recovery with tSCS and the reasons why some individuals with motor-complete SCI respond less effectively, despite having the same injury classification, remain unclear. Here, we demonstrate that lumbosacral tSCS can enable anti-gravity voluntary movement following motor-complete SCI, and identify markers that distinguish responders from non-responders. METHODS: Ten individuals with chronic cervical and upper thoracic motor-complete SCI received 30 Hz lumbosacral tSCS with a 10 kHz carrier frequency for 60 min, 2-5 times per week, for a minimum of 6 weeks (12-36 sessions). Post-intervention, volitional movement was measured using surface electromyography (EMG) over the quadriceps and tibialis anterior (TA), and knee and ankle joint range of motion. To identify markers of responsiveness, we assessed the integrity of the corticospinal tract (motor evoked potentials; MEPs), ascending sensory pathways (somatosensory evoked potentials; SEPs), spinal cord reflexes (H-reflex), and motor neurons (compound muscle action potential, CMAP), along with muscle morphology using ultrasound echo-intensity. This observational cohort study was reported in accordance with STROBE guidelines. RESULTS: Five of 10 individuals demonstrated voluntary anti-gravity knee extension and ankle dorsiflexion strength in the presence of tSCS. TA MEPs were observed in one responder only and tibial nerve SEPs were not observed in any participants. All participants showed poor TA muscle morphology. Four responders had a soleus H-reflex (compared to 2/5 non-responders) and a normal amplitude fibular CMAPs (compared to 2/5 non-responders). DISCUSSION: These results show that tSCS can enable volitional motor activity against gravity in people with motor-complete SCI, but there is variability in responsiveness. Using conventional neurophysiological techniques, we were unable to consistently demonstrate the pathways facilitating voluntary control or the factors differentiating responders versus non-responders, but trends were observed. Spinal cord reflex and peripheral motor nerve integrity may be important for responding to tSCS but may not distinguish responders from non-responders. Additional assessments are needed to develop biomarkers for stratifying motor responders to tSCS. Trial Registration on ClinicalTrials.gov NCT04726059 (registered: 2021-Jan-22), NCT04604951 (registered: 2020-Oct-25), NCT05369520 (registered: 2022-May-05).