Non-invasive Spinal Cord Stimulation - Paralyzed Move Legs
- Publish Date: 2015/07/30 - (Rev. 2018/05/01)
- Author: NIH/National Institute of Biomedical Imaging & Bioengineering(i)
- Contact : www.nibib.nih.gov
Outline: Transcutaneous stimulation delivers electrical current to the spinal cord by way of electrodes placed on the skin of the lower back.
Five men with complete motor paralysis were able to voluntarily generate step-like movements thanks to a new strategy that non-invasively delivers electrical stimulation to their spinal cords, according to a new study funded in part by the National Institutes of Health.
Spinal cord injury (SCI) - Defined as an injury to the spinal cord resulting in a change, either temporary or permanent, in the cord's normal motor, sensory, or autonomic function A spinal cord injury, damage to any part of the spinal cord or nerves at the end of the spinal canal, often causes permanent changes in strength, sensation and other body functions below the site of the injury. The spinal cord does not have to be severed in order for a loss of function to occur. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence.
Neuromodulation - Defined by the International Neuromodulation Society as "the alteration of nerve activity through the delivery of electrical stimulation or chemical agents to targeted sites of the body," and is carried out to normalize, or modulate, nerve function.
Transcutaneous electrical nerve stimulation (TENS) - Defined as the use of electric current produced by a device to stimulate the nerves for therapeutic purposes. TENS, by definition, covers the complete range of transcutaneously applied currents used for nerve excitation although the term is often used with a more restrictive intent, namely to describe the kind of pulses produced by portable stimulators used to treat pain.
The strategy, called transcutaneous stimulation, delivers electrical current to the spinal cord by way of electrodes strategically placed on the skin of the lower back. This expands to nine the number of completely paralyzed individuals who have achieved voluntary movement while receiving spinal stimulation, though this is the first time the stimulation was delivered non-invasively. Previously it was delivered via an electrical stimulation device surgically implanted on the spinal cord.
In the study, the men's movements occurred while their legs were suspended in braces that hung from the ceiling, allowing them to move freely without resistance from gravity. Movement in this environment is not comparable to walking; nevertheless, the results signal significant progress towards the eventual goal of developing a therapy for a wide range of individuals with spinal cord injury.
This image shows the range of voluntary movement prior to receiving stimulation compared to movement after receiving stimulation, physical conditioning, and buspirone. The subject's legs are supported so that they can move without resistance from gravity. The electrodes on the legs are used for recording muscle activity - Picture Credit Edgerton lab/UCLA
"These encouraging results provide continued evidence that spinal cord injury may no longer mean a life-long sentence of paralysis and support the need for more research," said Roderic Pettigrew, Ph.D., M.D., director of the National Institute of Biomedical Imaging and Bioengineering at NIH. "The potential to offer a life-changing therapy to patients without requiring surgery would be a major advance; it could greatly expand the number of individuals who might benefit from spinal stimulation. It's a wonderful example of the power that comes from combining advances in basic biological research with technological innovation."
The study was conducted by a team of researchers at the University of California, Los Angeles; University of California, San Francisco; and the Pavlov Institute, St. Petersburg, Russia. The team was led by V. Reggie Edgerton, Ph.D., a distinguished professor of integrative biology and physiology at UCLA and Yury Gerasimenko, Ph.D., director of the laboratory of movement physiology at Pavlov Institute and a researcher in UCLA's Department of Integrative Biology and Physiology. They reported their results in the Journal of Neurotrauma.
In a study published a little over a year ago, Edgerton - along with Susan Harkema, Ph.D., and Claudia Angeli, Ph.D., from the University of Louisville, Kentucky - reported that four men with complete motor paralysis were able to generate some voluntary movements while receiving electrical stimulation to their spinal cords. The stimulation came from a device called an epidural stimulator that was surgically implanted on the surface of the men's spinal cords. On the heels of that success, Edgerton and colleagues began developing a strategy for delivering stimulation to the spinal cord non-invasively, believing it could greatly expand the number of paralyzed individuals who could potentially benefit from spinal stimulation.
"There are a lot of individuals with spinal cord injury that have already gone through many surgeries and some of them might not be up to or capable of going through another," said Edgerton. "The other potentially high impact is that this intervention could be close to one-tenth the cost of an implanted stimulator."
During this most recent study, five men - each paralyzed for more than two years - underwent a series of 45 minute sessions, once a week, for approximately 18 weeks, to determine the effects of non-invasive electrical stimulation on their ability to move their legs.
In addition to stimulation, the men received several minutes of conditioning each session, during which their legs were moved manually for them in a step-like pattern. The goal of the conditioning was to assess whether physical training combined with electrical stimulation could enhance efforts to move voluntarily.
For the final four weeks of the study, the men were given the pharmacological drug buspirone, which mimics the action of serotonin and has been shown to induce locomotion in mice with spinal cord injuries. While receiving the stimulation, the men were instructed at different points to either try to move their legs or to remain passive.
At the initiation of the study, the men's legs only moved when the stimulation was strong enough to generate involuntary step-like movements. However, when the men attempted to move their legs further while receiving stimulation, their range of movement significantly increased. After just four weeks of receiving stimulation and physical training, the men were able to double their range of motion when voluntarily moving their legs while receiving stimulation. The researchers suggest that this change was due to the ability of electrical stimulation to reawaken dormant connections that may exist between the brain and the spinal cord of patients with complete motor paralysis.
Surprisingly, by the end of the study, and following the addition of buspirone, the men were able to move their legs with no stimulation at all and their range of movement was - on average - the same as when they were moving while receiving stimulation.
"It's as if we've reawakened some networks so that once the individuals learned how to use those networks, they become less dependent and even independent of the stimulation," said Edgerton.
The researchers also made extensive recordings of electrical signals generated in the calf muscle and the muscle directly below the calf while the men attempted to flex their feet during stimulation. Over time, these signals increased with the same amount of stimulation, further supporting the hypothesis of re-established communication between the brain and spinal cord.
Edgerton has already initiated a new study to see whether these same men can be trained with non-invasive spinal stimulation to fully bear their weight, a feat that the four men with surgically implanted stimulators have already achieved. In addition, he is interested in determining whether, similar to epidural stimulation, non-invasive stimulation can help individuals regain some autonomic functions lost due to paralysis such as the ability to sweat, regulate blood pressure, and control bladder, bowel, and sexual function.
The hope is that further research can help determine whether non-invasive stimulation can restore function that will truly impact patient lives.
Edgerton also wants to test non-invasive stimulation on individuals who have partial paralysis. "We have focused on individuals with complete paralysis throughout this whole process because we knew that was going to be the toughest patient population to see changes in. We've always thought, and we have every reason to believe, that those individuals with partial injuries have even more room for improvement," said Edgerton.
Though a non-invasive stimulation could offer advantages over a surgically implanted device, Edgerton says both need to continue to be developed. For example, a non-invasive stimulator might be useful in determining whether a patient will be receptive to neuromodulation, which could then help determine whether undergoing surgery to implant a stimulator is warranted. Alternatively, Edgerton speculates it may be possible early after an injury for non-invasive stimulation to help patients achieve a certain level of motor control that then allows them to continue to improve with physical rehabilitation and avoid surgery altogether.
"All patients are going to need something slightly different, and maybe non-invasive stimulation is going to be best in some cases and epidural stimulation in others," said Edgerton. "What we need to do is maximize the clinical tool box that we have so that the physician and the patient can select a therapy that is best for them."
This research was supported in part by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Neurological Disorders and Stroke, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Advancing Translational Sciences at NIH under award numbers EB015521, EB007615, and TR000124, the Christopher and Dana Reeve Foundation, the Walkabout Foundation, the F. M. Kirby Foundation, the Russian Foundation for Basic Research grant ?13-04-12030, the Russian Scientific Fund project 14-45-00024, the J. Yang and Family Foundation, and the Paul and Daisy Soros New American Fellowship.
Today, improved emergency care for people with spinal cord injuries, antibiotics to treat infections, and aggressive rehabilitation can minimize damage to the nervous system and restore function to varying degrees. Advances in research are giving doctors and people living with SCI hope that spinal cord injuries will eventually be repairable. With new surgical techniques and developments in spinal nerve regeneration, cell replacement, neuro-protection, and neuro-rehabilitation, the future for spinal cord injury survivors looks brighter than ever.
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- In the United States there are about 700,000 persons with a disability involving their spinal cord. The disabilities these people have include Multiple Sclerosis, Traumatic Spinal Cord Injury, Poliomyelitis, Spina Bifida, Syningomelia, and Amyotrophic Lateral Sclerosis (ALS).
- Somewhere in America a person sustains a spinal cord injury every forty-one minutes. Approximately eleven-thousand people in America experience a spinal cord injury every year.
- The first year after a person experiences a spinal cord injury is the most expensive medically, costing from $209,000 to $710,000. Each year afterward, medical expenses may range from $14,000 to $127,000 depending on the individual. For a person who has sustained a SCI at age twenty-five, lifetime medical costs may range from $624,000 to $2.8 million.
- Approximately 400,000 people in America have Multiple Sclerosis (MS)). Ten-thousand people face a diagnosis of MS each year. MS is a progressive disease which attacks the myelin sheath surrounding nerve cells in a person's nervous system, blocking transmission of motor signals to their limbs. For unknown reasons, MS affects two to three times as many women as it does men.
- Approximately 70,000 people are living in America with Spina Bifida at this time. Spina Bifida is a neural tube birth defect that causes the spinal column in the person to close incompletely. There are various forms of Spina Bifida.
- Approximately 5,600 people in America are diagnosed with Amyotrophic Lateral Sclerosis, or ALS every year. The incidence of ALS is two-thirds as high as that of MS, and five-times as high as that of Huntington's disease. About 30,000 Americans have ALS, which affects persons of any race or ethnic background.
- 1 - Reflex Control Could Improve Walking after Incomplete Spinal Injuries | National Institutes of Health (NIH) | 2013/03/10
- 2 - Human Spine and Spinal Cord Picture C1 - S5 Vertebra | Disabled World | 2017/12/01
- 3 - Spinal Cord Neural Stem Cells Show Diverse Promise for SCI | University of California - San Diego | 2018/08/14
- 4 - Majority of Patients with Unknown Spinal Cord Disease Later Given Specific Diagnosis | Mayo Clinic | 2018/01/09
- 5 - New Hope of Spinal Cord Injury (SCI) Recovery | American Friends of Tel Aviv University | 2018/07/28
- 6 - Experimental Drug Restores Some Bladder Function After SCI | Ohio State University | 2018/06/05
- 7 - Non-invasive Spinal Cord Stimulation - Paralyzed Move Legs | NIH/National Institute of Biomedical Imaging & Bioengineering | 2015/07/30
- 8 - Non-Invasive Spinal Stimulation Enables Paralyzed People to Regain Use of Hands | University of California - Los Angeles | 2018/04/26
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