Spinal stimulation enables three people with paraplegia to walk again

Combined with other recent studies, new evidence points to electrical stimulation as a promising treatment for paralysis.

By Emily Waltz, IEEE Spectrum 31 October 2018

Three men with paraplegia are able to walk after being treated with electrical stimulation of their spinal cords. The treatment, combined with physical therapy, enabled the men to overcome years-old spinal cord injuries that had paralyzed their leg muscles.

Researchers at the Swiss Federal Institute of Technology (EPFL) in Lausanne, who conducted the experiments, announced the results today in a pair of papers in Nature and Nature Neuroscience. Combined with recent efforts from other groups in the area of spinal stimulation, the work suggests that paralysis, once considered an incurable condition, is perhaps treatable.

The Swiss research adds to the body of work reported by two other groups that have enabled paralyzed individuals to walk using the experimental electrical treatment. In September, a group from the University of Louisville, in Kentucky, led by Susan Harkema, reported in the New England Journal of Medicine that two people with spinal cord injuries were walking independently, with balance help, after months of electrical stimulation and training.

The same week, a separate group at the Mayo Clinic in Rochester, Minnesota, reported in Nature Medicine that they too had successfully enabled one person with a spinal cord injury to walk the length of a football field, with a walker and physical assistance, after months of stimulation and training.

Now the Swiss group, led by Grégoire Courtine, director of EPFL’s Center for Neuroprosthetics and Brain Mind Institute, says it is adding three more people to that list.

In spinal stimulation, a wireless electrode array is surgically implanted in the epidural space next to the spinal cord. By turning on different electrode combinations at precise times, researchers are able to engage the spinal cord to activate regions of the legs and enable voluntary movement.

David was completely paralyzed in his left leg and had limited control over his right leg before undergoing electrical stimulation treatment with researchers at Swiss Federal Institute of Technology (EPFL) in Lausanne. IEEE Spectrum. Youtube Oct 31, 2018

Exactly how one should stimulate is a matter of debate among the researchers. Courtine’s group used what it calls a “burst” method of stimulation, in which the electrical currents are turned on and off during walking. The stimulation is timed to coincide with the patient’s intent to move a specific region of the leg. Intent to move is monitored using video cameras and sensors placed on the patients’ feet.

“The idea is to modulate the spinal cord as the brain would naturally,” Courtine said in an email to IEEE Spectrum. “Bursts of stimulation activate the region of the spinal cord that the brain is also trying to activate.”

This method differs from “continuous” stimulation, which was employed by the Louisville and Mayo Clinic groups. In that strategy, targeted electrical fields are not completely turned off during walking.

Courtine says he tried the continuous method, but found that it blocked the patients’ proprioception—the ability to perceive the relative position and strength employed in their legs. “Because we stimulate with bursts, it feels more natural and the sensation of walking is more powerful,” Courtine said during a press briefing on Tuesday.

But the Louisville and Mayo groups were able to get the continuous method to work just fine, says Harkema. “ continuous stimulation method wasn’t successful, but ours was,” she told Spectrum.

Moreover, the three men in Courtine’s report had some function in their lower bodies before the experiments, so they had more starting capabilities compared with the participants in the Louisville and Mayo Clinic studies.

For example, before the experiments, one of the participants in the Swiss study—Gerjtan—could very slowly take a few steps, with body weight support, over the course of a few minutes. Another participant—David—was completely paralyzed in his left leg, but had some control over his right leg. The third participant—Sebastian—couldn’t move either leg, but retained voluntary anal contraction.

By contrast, the people in the Louisville and Mayo Clinic studies had no muscle control below their spinal cord injury, and their injuries were all considered by international standards to be “motor complete.” These are important distinctions when assessing a technology like epidural stimulation, says Harkema.

Still, Courtine’s study is important in that it presents more evidence that epidural stimulation works, which is good for patients and for the researchers developing it. “What’s important is that took people with chronic paraplegia, used neuromodulation, and changed their status,” says Harkema.

All three of Courtine’s patients improved. Gerjtan and David were both able to walk independently by the end of the study. Sebastian still needed a gravity assist robot when the paper was written, but now doesn’t need it, Courtine said in an email to Spectrum.

During the media briefing, all three of Courtine’s patients said the stimulation and training has improved their motor capabilities, even, in some instances, when the stimulation isn’t running. “When working on the parallel bars I took  steps without hands and without stimulation and that was really exciting,” said David during the press briefing. “Still, I get lateral stability from the parallel bars so it’s not what I would  ‘proper walking.’ But like the other guys I’m willing to train more to see where we get.”

Grégoire Courtine, director of the Swiss Federal Institute of Technology’s Center for Neuroprosthetics and Brain Mind Institute, talks about using electrical stimulation of the spinal cord to treat patients with paraplegia. IEEE Spectrum. Youtube Oct 31, 2018

In an accompanying perspective article in Nature Neuroscience, Chet Moritz, at the University of Washington in Seattle, says that the Swiss, Louisville, and Mayo Clinic reports, taken together, represent a “breakthrough in the treatment of paralysis.” He noted that the “differences in stimulation approaches by these three groups will need to be sorted out” as they move toward larger clinical trials.

Adds Harkema: Collectively, the work shows “that fundamental control of movement exists in the spinal circuitry,” and doesn’t necessarily have to come from the brain, she says. Because of that, “we need to start rethinking paralysis.”

In future studies, Courtine says he hopes to enroll people soon after spinal cord injury to see if greater improvements in mobility can be achieved. He also hopes to be able to implant more precise electrodes. The array and stimulator he and others currently use was developed for pain treatment and Parkinson’s disease. “The next generation being developed by start-ups will be much more precise with much more rapid changes in stimulation parameters and a broader range of capabilities,” he said in the press briefing. “So that will be the technology we will test in the next two or three years.”

Source IEEE Spectrum

References

Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury, Emanuele Formento, Karen Minassian, Fabien Wagner, Jean Baptiste Mignardot, Camille G. Le Goff-Mignardot, Andreas Rowald, Jocelyne Bloch, Silvestro Micera, Marco Capogrosso & Gregoire Courtine. Nature Neuroscience (2018) doi: 10.1038/s41593-018-0262-6 Published: 31 October 2018

Targeted neurotechnology restores walking in humans with spinal cord injury, Fabien B. Wagner, Jean-Baptiste Mignardot, Camille G. Le Goff-Mignardot, Robin Demesmaeker, Salif Komi, Marco Capogrosso, Andreas Rowald, Ismael Seáñez, Miroslav Caban, Elvira Pirondini, Molywan Vat, Laura A. McCracken, Roman Heimgartner, Isabelle Fodor, Anne Watrin, Perrine Seguin, Edoardo Paoles, Katrien Van Den Keybus, Grégoire Eberle, Brigitte Schurch, Etienne Pralong, Fabio Becce, John Prior, Nicholas Buse, Rik Buschman, Esra Neufeld, Niels Kuster, Stefano Carda, Joachim von Zitzewitz, Vincent Delattre, Tim Denison, Hendrik Lambert, Karen Minassian, Jocelyne Bloch & Grégoire Courtine. Nature volume 563, pages 65–71 (2018). doi:10.1038/s41586-018-0649-2. Published 31 October 2018

Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury, Claudia A. Angeli PhD, Maxwell Boakye MD.Rebekah A. Morton BS, Justin Vogt BS, Kristin Benton BS, Yangshen Chen PhD, Christie K. Ferreira BS, and Susan J. Harkema Ph.D. September 27, 2018 N Engl J Med 2018; 379:1244-1250 doi: 10.1056/NEJMoa1803588

Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia, Megan L. Gill, Peter J. Grahn, Jonathan S. Calvert, Margaux B. Linde, Igor A. Lavrov, Jeffrey A. Strommen, Lisa A. Beck, Dimitry G. Sayenko, Meegan G. Van Straaten, Dina I. Drubach, Daniel D. Veith, Andrew R. Thoreson, Cesar Lopez, Yury P. Gerasimenko, V. Reggie Edgerton, Kendall H. Lee & Kristin D. Zhao. Nature Medicine (2018) doi:10.1038/s41591-018-0175-7. Published: 24 September 2018

A giant step for spinal cord injury research, Chet Moritz. Nature Neuroscience (2018) doi:10.1038/s41593-018-0264-4. Published: 31 October 2018

Bioinspired neuron-like electronics, Yang X, Zhou T, Zwang TJ, Hong G, Zhao Y, Viveros RD, Fu TM, Gao T, Lieber CM. Nat Mater. 2019 May;18(5):510-517. doi: 10.1038/s41563-019-0292-9. Epub 2019 Feb 25.

Also see
Thanks to Spinal Stimulation, Paralyzed Man Walks the Length of a Football Field IEEE Spectrum
Paralysed people walk again after spinal-cord stimulation Nature
A paralyzed man makes great strides with spinal stimulation and rehab Science News