“It’s an amazing feeling,” says David Mzee, whose left leg was paralyzed in 2010. Mzee has now regained some ability to walk thanks to a breakthrough in spinal-cord stimulation technology. “I can do a knee extension of my left leg... flex my hip and even move my toes.”
Mzee is one of three participants in a study that used a new technique to overcome spinal-cord injury and restore walking ability in patients with varying degrees of paralysis. The results, published in Nature and Nature Neuroscience today, are dramatic. All three patients recovered some degree of walking ability, and their progress in physical-therapy sessions has translated to improved mobility in their daily lives.
The basis of the technique, called epidural electrical stimulation (EES), is not new at all—it’s been investigated as a potential treatment for paralysis for decades, with a lot of success in animals. And in September this year, two separate papers reported breakthroughs in allowing patients with paralysis to walk, with assistance, as a result of EES.
But the earlier patients made progress only after months of intensive rehabilitation—in the best case, after four months, and in others, closer to a year. What Grégoire Courtine, Jocelyne Bloch, and a large team of researchers report today is a huge leap forward: their patients were able to walk (with assistance) after only a few days.
Blocking the feedback loop
The difference lies in how constant the electrical stimulation is. EES works by implanting a device that delivers electrical signals to the spinal cord. When an injury interrupts the connection between the spinal cord and brain, it prevents signals from reaching below the site of the injury, EES can help to bridge the gap by providing electrical signals to the spinal cord below the injury site.
In rodents, cats, and even monkeys, EES has allowed “standing, walking in various directions, and even running,” write Courtine and his colleagues. They suggest that this technique has been less successful in humans because the electrical stimulation has been continuous, preventing feedback from the body to the brain, and effectively blocking the brain’s sense of where the limbs are in space. Physiological differences between humans and rats—including just the difference in body size—could explain why this affects humans and not rats, they suggest.
The systems needed to get more precise. And so the researchers set about understanding how the nervous system responded to movements in every joint in healthy individuals, building up a “map” of what these activation patterns looked like. Then they worked out where exactly the electrodes were needed to provide stimulation to match these activation patterns and built a system that would deliver shifting signals only to where they needed to be.
The researchers had to adjust the details for each of the three patients in the study, adapting to the individual measurements of each person’s spinal cord. They even built personalized model spinal cords to lie in an electricity-conducting salty fluid, allowing the team to work out precisely where each electrode needed to be inserted during surgery. Then the pattern of electrical signals was calibrated for each individual.
“All the patients could walk using body weight support within one week,” says Blotch. In ongoing tests of the system, the patients were able to adjust the length and speed of their strides and to walk on a treadmill for an hour—traveling the equivalent of up to one kilometer. All movement was under voluntary control; EES doesn’t generate movement on its own.
“The participants are constantly challenged to voluntarily generate the appropriate leg movements,” says co-author Karen Minassian. “They need to be mentally active all the time in order to close the loop with the electrical stimulation that ultimately produces the muscle activity.”
Because of that engagement, the treatment also resulted in voluntary movement being restored over time, as connections through the nervous system were re-established. Mzee, whose left leg had been completely paralyzed after a gymnastics accident, had undergone extensive rehabilitation treatment, but with little progress. After five months, he was able to take a few steps on his own, completely unassisted. With EES switched on, he’s able to walk using a walker.
Gert-Jan Oskam, who lost the use of both his legs in a cycling accident, had also made very limited progress in rehabilitation before the study. “Now I can walk short distances with the help of electrical stimulation and even without electrical stimulation,” he says. While he can take a few steps with crutches or stand up with another person for support, “I should be able to have a BBQ standing on my own in the near future.”
Even within the small group of three patients, the results have been markedly different. For Sebastian Tobler, the five months haven’t been long enough to restore much voluntary movement without EES. But he’s able to lift his legs while lying down without EES, and he says that he’s noticed better core stability in his daily life. He plans to continue training.
The degree of success for the treatment will depend on a range of factors, including the severity of the injury and the degree of residual movement. For some, like Mzee, it could result in a dramatic improvement in voluntary mobility in a short space of time; for others, this might not be the case. Understanding the results in a larger population is a crucial next step.
For Courtine, Bloch, and their colleagues, the next step is to explore results in people with recent injuries, where “the potential for plasticity is elevated and the neuromuscular system has not yet undergone the atrophy that follows chronic paralysis,” they write. While they point to the current study as a validation of the idea that continuous EES would have limited success in humans, future studies would need to work on understanding and predicting which patients would be likely to benefit most—this technique is far from ready to be rolled out across the board.
And essential, they add, is ensuring that the treatment translates outside of the hospital. The researchers developed a voice-activated system that allowed their patients to switch EES on and off themselves, and they calibrated it to different modes for walking, standing, or cycling on a hand-and-leg-powered tricycle. Getting EES working is one thing, but they also have an eye on making it possible for patients to use at home—supporting “rehabilitation in clinical settings and use in the community.”