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More than ten years ago, the words of the late Christopher Reeve prompted Grégoire Courtine, Ph.D., associate professor at the Swiss Federal Institute of Technology Lausanne (EPFL), to guide his research in the field of the spinal cord improve the lives of patients. Today, his laboratory's report that three patients with chronic paraplegia have regained the ability to become familiar with targeted neurotechnology shows that he is on track to achieve this goal.
The three participants in the STImulation Movement Overground (STIMO), who had cervical spine injuries many years ago, can now walk on crutches or walkers.
"Our results are based on a deep understanding of the underlying mechanisms we have acquired over the years of research on animal models. We were able to imitate in real time how the brain naturally activates the spinal cord, "says Dr. Courtine.
The work is published in two articles, published today, which deal with different aspects of the project.
An article published in Nature, entitled "Targeted Neurotechnology Restores Gait in Humans with a Spinal Cord Injury", describes how the Swiss team introduced targeted neurotechnologies for spinal cord stimulation that voluntarily controlled the of people who have had a spinal cord injury more than four years ago.
How did they do it? The authors explain that they used an implanted pulse generator with real-time triggering capabilities to deliver selective stimulation trains into the lumbosacral spinal cord with synchronization that coincided with the desired movement.
The participants were implanted surgically with a network of 16 electrodes on the lumbar region of the spinal cord, outside the protection zone. dura. This electrode array is connected to an implantable pulse generator that can be controlled with a custom voice – activated watch to administer short bursts of electricity. Because different areas of the spinal cord are activated during the different movements associated with walking, this system allows preferential activation of these areas when the participant tries to walk.
"All patients could walk using weight support in the space of a week. I immediately knew that we were on the right track, "recalls Jocelyne Bloch, MD, a neurosurgeon at the University Hospital of Lausanne (CHUV), who performed the surgical placement of implants in patients. Indeed, within a week, this spatio-temporal stimulation had restored the adaptive control of the paralyzed muscles during the walking on the ground and the improved locomotor performance during the reeducation.
"One of the most interesting things about this work," says Peter Grahn, Ph.D., senior engineer at Mayo Clinic's Neuroengineering Laboratory, "observing lasting functional gains when stimulation has been turned off." . After a few months, participants regained voluntary control of their previously paralyzed muscles without stimulation and could walk or cycle in ecological environments during spatio-temporal stimulation.
This is not the first time this type of research has allowed previously paralyzed people to walk. Indeed, a little over a month ago, two articles caused a sensation in the same field: one from the Mayo Clinic, published in Medicine of nature and the Harkema Laboratory of the Kentucky Spinal Cord Injury Research Center at the University of Louisville, published in NEJM.
So, what makes this paper different? Edelle Field-Fote, Ph.D., director of Hulse's Spinal Injury Research Laboratory and professor at Emory University School of Medicine, says, "The difference in this approach is that previous groups have stimulated everything in the region. " She says it's like cooking a jar of beans in a jar. "What other groups have done, is to turn on all the stove burners to heat a jar of beans. But Dr. Courtine's group found a way to light the necessary burner. By targeting only the stimulation on important areas, his group has piloted the activation that stems from the brain. "
Dr. Field-Fote points out that there is rarely the case of a spinal cord injury, even serious, that there is no activity below the level of the lesion. Epidural electrical stimulation (ESA) still activates the circuits with which the brain wants to communicate but can not, either because enough signals can not pass or because of the demyelination of the axons, which brings them closer to the threshold necessary to their operation. .
The accompanying document published in Nature Neuroscience "Stimulation of the spinal cord must preserve proprioception to allow the mobility of humans suffering from spinal cord injury". In this article, the authors hypothesize that one of the reasons that the EES is limited to date is due to interference between EES and proprioception, or the ability to know where your members (or other parts of the body) are in the space. The results suggest that the SEA blocks a significant amount of proprioceptive inputs in humans, but not in the rat.
Dr. Field-Fote explains that this finding makes the targeted approach to Dr. Courtine's stimulation much more striking. In fact, previous approaches to more general stimulation, in which proprioception could have been blocked, could have created an obstacle that patients had to overcome. This may also explain why the previous methods require longer training schemes to see an improvement. With this information, Dr. Courtine's team was able to identify stimulation parameters that do not block proprioceptive information.
Dr. Field-Fote says that she "tends to be rather critical, but this group has really done a good job" and that the work has "a lot of value for the actual function, mainly because it" does not require months of training. "He also extends the evidence to people with different classifications of spinal cord severity that, to our knowledge, had not been studied before, according to Kristin Zhao, Ph.D., director of the Mayo Clinic Rehabilitation and Rehabilitation Technologies Laboratory.
Dr. Courtine calls this "a proof of principle" and makes sure to set realistic expectations for patients with spinal cord. Dr. Zhao tells GEN that "the application of epidural electrical stimulation to allow the loss of functions due to a spinal cord injury is in its infancy," adding that the next steps "will involve a better understanding of the relationship between physical therapy, pacing parameters and plasticity of the spinal cord a long-term stimulation and the choice of patients who will respond successfully to the intervention ". The goal of Dr. Courtine is to begin the process in patients earlier, immediately after the injury.
"These results are exciting, but there are still many hurdles to overcome before large-scale translation of this technology can become a reality," said Dr. Grahn. "For example, before regulatory approval can be obtained for widespread use in humans with spinal cord injury, lesion patterns responding to neuromodulation of the spine must be clearly defined."
According to Dr. Grahn, "as research continues to improve the technology and scientific knowledge of vertebral neuromodulation after paralysis, there is great potential to translate these findings into feasible therapeutics." Dr. Zhao adds that "the field in advance, it's an exciting experience. A promising time for people with spinal cord injury. However, it is important to calibrate expectations, and Dr. Zhao adds the important note that "these methods are only available as part of research protocols and not as clinical treatment."
Nevertheless, Dr. Courtine has made tremendous progress in a short time. In her 2013 TED speech, "The Paralyzed Rat Who Walked," Dr. Courtine explains that the neural network needed and sufficient to coordinate locomotion is present under most injured spinal cords. But, they are dormant because the entrance to the brain is interrupted. His idea was always to wake up this network and he proved that he could do it in the rat. Five years later, he is able to do it in humans.
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