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Neuromodulation helps paralysed man take independent steps

A patient with complete lower limb paralysis can independently step again following a combination of electronic spinal cord stimulation and rehabilitation therapy, reports a study from Mayo Clinic and UCLA (Nature Medicine 10.1038/s41591-018-0175-7).

Treadmill stepping
Treadmill stepping with and without epidural electrical stimulation. (Courtesy: Zhao et al; Mayo Clinic; Nature Medicine)

Severe spinal cord injuries can functionally disconnect the higher brain centres that guide movement from the spinal cord circuitry, located below the injury, that interacts with skeletal muscle – causing chronic paralysis. In this study, the subject had injured his spinal cord in the middle of his back in a snowmobile accident.

The subject first participated in 22 weeks of physical therapy and then had an electrical spinal stimulation device surgically implanted by co-principal investigator Kendall Lee and his neurosurgery team. The implant was located in the epidural space — the outermost part of the spinal canal — at a specific location below the injured area.

The man next underwent 113 sessions of task-specific, multimodal rehabilitation training over next 43 weeks. In the first week, he used a harness to lower his risk of falling and provide upper body balance. Trainers were positioned at his knees and hips to help him stand, swing his legs and shift his weight. Because he did not regain sensation, he initially used mirrors to view his legs, and the trainers described leg position, movement and balance.

“It was a very rigorous and intensive protocol, but we do believe that this had an impact on the recovery, and think it was very important for recovery,” says co-principal investigator Kristin Zhao, director of Mayo Clinic’s Assistive and Restorative Technology Laboratory. week 25, the man did not need a harness, and trainers offered only occasional help. At the end of the 43-week programme, and with the stimulator turned on, the patient was able to produce intentional contraction of the leg muscles that could support standing and stepping. He was able to step using a front-wheeled walker and on a treadmill, and walked with assistance for a total of 16 minutes, achieving a total of 331 steps and a distance of 102 m. However, when stimulation was off, the man remained paralysed.

“The amount of steps that he was able to take was pretty significant. The total distance was about the length of a football field,” notes Lee, director of Mayo Clinic’s Neural Engineering Laboratories. “I think this is a very important study. If you look at the research that’s been done over the past 50 years in trying to regain functional control, there’s not been much success. Therefore, even though this study was only one patient, being able to regain intentional control is highly significant.”

Lee notes that from a neural engineering side, the team learnt a tremendous amount about the most suitable location for the implant, the surgical procedures involved, the parameters to test and how to program these. “And from this research, we are now able to step back and re-engineer the device – which was initially used for helping patients with pain – to help patients with paralysed limbs,” he explains. “The study gives hope to people faced with paralysis that functional control may be possible.”

The authors conclude that additional research is required to investigate how the rehabilitation training interacts with the electrical stimulation to recover lost motor functions and to confirm whether this approach could be successful in patients with different types or durations of injury.

“We are very early in the research,” says Zhao. “The next stage is [to understand] how this is working, why it is working and who can we help. We hope to continue this line of research at Mayo.”

In a separate study, University of Louisville researchers report that two participants with motor complete spinal cord injury achieved over-ground walking after epidural stimulation paired with daily locomotor training. In addition, these and two other participants achieved independent standing and trunk stability when using the stimulation and maintaining their mental focus (NEJM 10.1056/NEJMoa1803588).

This research was also based on two distinct treatments: epidural stimulation and locomotor training. The epidural stimulation involves application of continuous electrical current at varying frequencies and intensities to specific locations on the lumbosacral spinal cord. The locomotor training, meanwhile, aims to ultimately retrain the spinal cord to “remember” the pattern of walking by repetitively practicing standing and stepping.

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