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Three more patients with complete lower-body paralysis regained some ability to move their legs and feet voluntarily with electrical stimulation to their spinal cords, researchers said.

After obtaining such results in one patient, the subject of a , a team based at the University of Louisville repeated the stimulation procedure in three more patients with even better success, they reported Brain.

Whereas the first patient, then 25-year-old Rob Summers, required 7 months of stimulation before he showed any signs of voluntary movement in his lower extremities, the three subsequent patients were all moving their legs, feet, and/or toes within days of starting the treatment.

The intervention in all four patients consisted of a 16-electrode array implanted at vertebrae T11 and T12, over spinal cord segments L1 to S1, according to the report from , and colleagues. Epidural stimulation was delivered at varying voltages with frequencies of 25 or 30 Hz.

In addition to the stimulation, patients underwent standing and stepping training with body weight support, in the clinic or at home, for more than a year in Summers' case and for up to 38 weeks in the newer patients.

All four had been paralyzed for at least 2 years. Two retained some sensory function in their lower extremities but no motor ability; the other two had neither sensory nor motor function.

With these new data, Angeli and colleagues have changed their minds about the likely reasons for the intervention's success.

Summers was one of those who still had feeling in his legs. In the 2011 Lancet report, the researchers speculated that the remaining sensory connections were somehow harnessed to restore motor control.

But now that the intervention appeared to work in patients with no sensory function, Angeli and colleagues suggested another mechanism.

"Anatomical connections may have persisted after the injury that were previously 'silent' because of loss of conduction as a result of disruption of myelin or the ionic channels of the neurons," they wrote -- connections that were then awakened with the epidural stimulation.

Angeli and colleagues indicated that it was conceivable that nerve axons may have regenerated across the lesions, but they called it unlikely, given the quick development of motor control seen with initiation of stimulation in the recent patients.

The three new patients -- all victims of motor vehicle accidents -- had to meet strict inclusion criteria. Among them:

• Spinal cord injury at least 1 year previously
• Stable medical condition without cardiopulmonary or autonomic abnormalities that would prohibit standing or stepping exercises
• No infections, fractures, contractures, or other skin or musculoskeletal conditions that could interfere with such training
• No clinical depression or substance use disorders
• No botulinum toxin injections in the past 6 months
• Stable spinal cord injury
• Complete lack of lower-extremity motor response to transcranial magnetic stimulation
• Sensory evoked potentials either absent or delayed bilaterally
• No voluntary ability to induce movement in lower extremities
• Segmental reflexes retained below the spinal cord lesion
• No electromyographic evidence of brain influence on spinal reflexes

In fact, all four patients, including Summers, suffered their injuries more than 2 years before starting the stimulation. One was 33 years old, the others were in their 20s. All were male. Injury levels ranged from C6 to T6, with neurological levels from C7 to T5.

The three new patients were voluntarily moving their legs and/or feet within 11 days of beginning the epidural stimulation, Angeli and colleagues reported. In one patient, voluntary control appeared in just 4 days. The level of stimulation needed to allow voluntary movements decreased as training continued over several months.

One patient eventually was able to flex his leg without the stimulator being switched on. The others continued to require some stimulation to exert voluntary control.

with the Brain paper showed a patient flexing his left leg vigorously and also rotating one of his feet.

In addition to the visible leg movements, other measures also confirmed the restoration of motor function. Electromyographic recordings showed essentially no activity in patients' lower bodies without stimulation, but strong responses when the stimulators were turned on.

Although standing for short periods became possible, none of the patients has yet regained an ability to walk. On the other hand, Angeli and colleagues reported, "all four of these individuals have found unique ways to incorporate their ability to move their trunk and legs into daily activities."

For example, a video distributed to the media by the University of Louisville showed one patient catching a heavy ball while seated on a table -- clearly using his legs for balance in a way that a truly paraplegic individual could not.

Notably, however, the study did not include any blinding or control condition such as sham stimulation in these or other patients.

Other limitations included the small number of patients as well as the strict inclusion criteria.

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