A few months ago we were surprised by the news in the press, television and radio about a new treatment that restored walking ability to people who had suffered a spinal cord injury. Some media outlets tend to highlight these findings with headlines highlighting results that are usually in the research and development phase.
When we talk about spinal cord injuries, we are referring to those injuries, whether traumatic or not (such as infection or tumor), that damage the structures of the spinal cord, hindering the connections between the brain and the rest of the body. Depending on the location of the lesion, we will be talking about tetraplegia -when the lesion is located at the level of the cervical spine-, and paraplegia -when the lesion affects the dorsal and lumbar area-. The other factor that defines spinal cord injury is severity, so we refer then to complete lesions (when the lesion totally prevents the transmission of motor and sensory signals), and incomplete lesions (when part of these signals are able to pass through the injured area).
We know that spinal cord injury is accompanied by partial or total loss of mobility, sensitivity, control of urination and defecation functions, sexual dysfunction, as well as possible sequelae, such as pain, spasticity, pressure ulcers and osteoporosis, among others. Of all these possible sequelae, the loss of the ability to walk is the most striking consequence, since the image of the wheelchair is what has the greatest impact from an external point of view. Of course, losing the ability to walk is a great loss, but we know that it is not always the most disabling sequela in terms of quality of life. Even so, a large part of the lines of research are aimed at recovering the ability to walk, and the media find it the most striking, so it is not surprising that when a scientific publication highlights that after a certain intervention a person with spinal cord injury can walk again, the news is served up with big headlines. This is what happened recently with publications in journals of great scientific impact, such as the New England Journal of Medicine and Nature.
Lines of research in spinal cord injury
Among the numerous lines of research in the field of spinal cord injury, spinal cord stimulation using electrical stimuli has been under development for years. Whether intraspinal (electrodes inside the spinal cord), epidural (electrodes placed on the dura mater), percutaneous or transcutaneous, researchers have attempted to induce electrical current in the spinal cord for different therapeutic purposes. Among these, spinal cord electrical stimulation has been used especially for the treatment of chronic pain, but there is also literature with examples in the treatment of spasticity and neurogenic bladder and bowel. In addition, it has been known for years that motor activity can be induced by tonic stimulation in the spinal cord at the lumbar level.
However, it was not until 2011, after years of research, when the group at the University of Louisville in the United States, headed by Dr. Harkema and Dr. Edgerton, from the University of California, Los Angeles (UCLA), showed us in the Lancet some surprising results using a spinal cord stimulator implanted epidurally at the lumbosacral level in a person with complete motor and incomplete sensory paraplegia more than two years after injury. This person had no mobility in his legs, but retained some sensibility. After implantation of the stimulator and seven months of intensive rehabilitation, this person was again able to move his legs voluntarily when the spinal stimulator was on. It was noted that if the stimulator was on, but there was no conscious command to move the legs, they did not move. In the day-to-day life of the person, these findings did not mean a great change in his mobility, which remained in a wheelchair, but it marked the path of a line of research of great impact.
After years of continuity in this project, the same group of Dr. Harkema published in 2014, in the journal Brain, the results of three new cases, also chronic, achieving the same results of voluntary mobility with the spinal cord stimulator on. The novelty in this article is that two of these people had a complete spinal cord injury, both motor and sensory, thus opening the door to more severe injuries.
With other publications in between, we come to 2018, when the same group publishes in the prestigious New England Journal of Medicine the results of four new people with a complete motor spinal cord injury, although in two of them with sensory preservation. In this case, after implantation of the stimulator and long periods of rehabilitation (up to 278 sessions in one of the subjects), the two subjects with complete motor and incomplete sensory lesions were able to walk on the ground, with the help of a walker in one case and canes in the other for short distances. The other two subjects with complete motor and sensory lesion did not manage to walk on the floor, but could take a few steps on the treadmill with partial suspension of body weight and could stand up. It should be noted that the ability to walk occurs only when the spinal stimulator is on and the person intends to walk, i.e., his brain gives the command for his legs to move. If the stimulator was on, but the command to walk was not given, walking was not possible. The exact mechanism of how electrical stimulation at the lumbosacral level favors gait recovery is not exactly known, but it seems that the preservation of part of the sensory pathways favors the results. The activation of the neuronal networks at this level, by means of electrical stimulation, produces an excitatory environment that acts as a “bridge” for the transmission of other signals that were previously unable to cross and produce voluntary movement.
In parallel, from the Mayo Clinic in the United States, Drs. Lee and Zhao and also Dr. Edgerton, from UCLA, were working on a similar project and during 2018 published their results in the journal Nature Medicine. In this case it was a person with a complete motor and sensory dorsal injury of three years of evolution who after the implantation of the epidural stimulator and intensive rehabilitation (43 weeks) managed to walk on the ground with the assistance of a walker and the help of another person at the hips to maintain balance.
Shortly thereafter, in October 2018, Dr. Courtine’s team from Switzerland, well known for their work in basic research publishes similar results in the journal Nature. Dr. Gregoire Courtine, after a training period in the United States in the field of spinal cord stimulation and various animal studies, establishes his research center in Lausanne. In this project, they also implanted a spinal cord epidural stimulator at the lumbosacral level, but in this case, the patients had an incomplete motor and sensory spinal cord injury. There are three people participating in this study, all with more than four years of injury. Two of them were able to voluntarily mobilize their legs, but this mobility was slight and did not allow them to walk on the floor. The third person had no leg mobility, but was considered incomplete motor as he had voluntary contraction of the anal sphincter. After the implant and an intense rehabilitation program during five months, the first two patients were able to walk on the ground with the help of crutches and without having the spinal cord stimulator on, while the third person, the most affected, was able to walk with the help of a walker and the stimulator on.
In this study, unlike the two previous studies carried out in the United States, the patients had less severe lesions (incomplete motor) and the spinal cord stimulation in this case was not continuous but “targeted”, with characteristics that allow selective stimulation of different areas of the spinal cord depending on the moment of the gait cycle. What is most striking in this case is that the benefits obtained with this combined technique of intensive rehabilitation and spinal cord stimulation are also maintained, although to a lesser extent, with the spinal cord stimulator turned off. This suggests that, in these chronically injured individuals, the proposed intervention has facilitated an unexpected neurological recovery after years of injury, which is a remarkable advance in the field of spinal cord injury research.
The results obtained by these three research groups independently mark a new stage in the long road to recovery from spinal cord injury, but we must not forget that we are still in a research phase and that the possibility of these techniques becoming standard clinical practice requires a long period of additional research in order to know more precisely the type of patient who can benefit most, the type of stimulator and its appropriate parameters, as well as the rehabilitation that should accompany this process, which as we have seen is a fundamental key in the findings obtained.
In a similar vein, the team of Dr. Edgerton, at UCLA, developed a high-frequency, transcutaneous – hence noninvasive – spinal cord stimulator aimed at stimulating neural networks at the spinal cord level without having to operate on the person to implant a stimulator as in previous studies. During 2018, he published his latest results in the Journal of Neurotrauma aimed at upper extremity recovery in cervical spinal cord injuries. In this case, there were six people who completed the study, all of them with a spinal cord injury at the cervical level of more than one year of evolution, and three of them incomplete sensory and three incomplete motor and sensory. After four weeks of transcutaneous stimulation (eight sessions) and rehabilitation treatment, all patients showed an improvement in the strength of their upper extremities and in some of the activities requiring the use of their hands.
The Institut Guttmann won two research projects, one with ERA-NET NEURON and the other from La Marató de TV3. Through collaboration with Dr. Guillermo García Alias, who worked closely with Dr. Edgerton during his stay in the United States, and who is currently at the Autonomous University of Barcelona.
With these projects, and using the non-invasive spinal cord stimulator developed by Dr. Edgerton’s team, we intend to study in depth how to use this technique combined with rehabilitation, including robotic arms, with the aim of improving the functionality of spinal cord injured patients at the cervical level. This study will begin shortly, once all the bureaucratic procedures required for the use of this new device have been completed.
We are at a key moment, in the midst of the development of a new line of intervention that could bring about a major change in the approach to neurorehabilitation, and more specifically in the quality of life of people who have suffered a spinal cord injury. However, as with any research process, it will take time to complete the necessary studies to make these techniques accessible to everyone. It will take time, but we have a feeling that these interventions will be an important step in resolving some of the issues that occur after spinal cord injury that until now have been taken for granted.