Two of the four participants (Participants 3 and 4, both AIS grade B) were able to walk over ground with assistive devices after intensive physical training with electrical stimulation of the lower spinal cord. The other two (Participants 1 and 2, both AIS grade A) achieved some components of independent stepping on the treadmill with body-weight support but not over-ground walking. All four participants could not do these actions in trials when the stimulator was off. Motor and sensory scores for three participants did not change from the scores before implantation. In Participant 3, the motor score improved from 23 to 24 and the sum of the sensory scores from 83 to 86 (Table 1, and Fig. S1 in the Supplementary Appendix).

Participant 1 had a spontaneous hip fracture (he was stepping on the treadmill with body-weight support) after 1 week of training, without a fall, and resumed training 1 year later. He had a total of 176 sessions over a period of 62 weeks, after which he could stand with a walker. Participant 2 was able to produce continuous steps on the treadmill with one leg at a time after 40 sessions over a period of 14 weeks with 60% body-weight support and treadmill speeds of 0.22 to 0.67 m per second. He achieved unsupported sitting and standing with a walker but not over-ground walking after a total of 159 sessions over a period of 41 weeks.

Figure 2. Figure 2. Walking over Ground. Panel A shows a series of photographs of independent walking. Participant 3 (top) is walking with parallel poles for trunk stability. Participant 4 (bottom) is walking using a rolling walker. Panel B shows standing without stimulation (before and after training) and with stimulation (after training) for Participant 3 (top) and Participant 4 (bottom). Panel C shows Participant 3 performing trunk extension without and with stimulation after 89 locomotor training sessions and sitting without and with stimulation.

Participant 3 was able to step the right leg independently on the treadmill with 35% body-weight support after 160 sessions over a period of 36 weeks. The transition to over-ground walking occurred after achievement of independent stepping of the right leg and an independent extension of the left leg on the treadmill after 278 total training sessions over a period of 85 weeks. This participant was able to walk over ground during epidural stimulation while using horizontal poles for balance or when holding hands with two persons (one on each side) (Figure 2A, and , available at NEJM.org). Muscle activation during walking was timed appropriately to the step cycle, as detected by surface EMG recording (Fig. S2A in the Supplementary Appendix). During epidural stimulation, he could walk over ground only when he intended to walk, not otherwise, and the pattern of EMG activation was different when he intended to step on the treadmill than when he did not intend to (Figs. S3 and S4 in the Supplementary Appendix). When this participant stopped his mental intention to walk, he was unable to move his legs.

Walking speed (Fig. S2B in the Supplementary Appendix) and continuous walking distance improved in Participant 3 during the next 80 over-ground walking sessions, reaching 90.5 continuous meters without a rest and a total of 362 m during an interrupted 1-hour session. He reached a maximum speed of 0.19 m per second and was limited in speed and distance by imbalance and fatigue. He also regained the ability to stand independently using a walker during epidural stimulation (Figure 2B and ) and to sit independently for 5 minutes (Figure 2C and , and Fig. S5 in the Supplementary Appendix).

Participant 4 achieved independent right-leg stepping on the treadmill with 50% body-weight support after 5 sessions over a period of 1 week. She transitioned to over-ground walking after 81 sessions over a period of 15 weeks and was able to achieve independent stepping of the right leg and an independent extension of the left leg on the treadmill (Figure 2A and ). At session 147, she was able to walk over ground with a walker and with no contact assistance from trainers. She also achieved independent standing for approximately 50 minutes at a time while holding on to elastic bands during epidural stimulation only (Figure 2B and ). She was completely independent during standing, without balance support by the arms, for 7 to 10 seconds at a time (Figure 2B).

The only serious adverse event was a hip fracture in Participant 1, noted earlier. On the participant’s return to the study, after 68 sessions, ankle edema developed on the right side. Adverse events are reported in Table S1 in the Supplementary Appendix.