The NIBIB Rehabilitation Engineering program supports the development of next generation medical rehabilitation devices and systems that presents a paradigm shift from the current state of the art technology. In 2008, NIBIB awarded a 5-year Bioengineering Research Partnership (BRP) grant to the University of California Los Angeles for Dr. Reggie Edgerton and his multidisciplinary team to develop the next generation high density electrode array technology for epidural stimulation of the spinal cord. In this first-in-human study the investigators proposed to explore the possibility of humans regaining standing and stepping functions (as observed previously in animals) through a combination of epidural stimulation with motor training. In year 2 of the award, the first implanted human subject is now able to stand and move his previously paralyzed lower limbs.
Scientists funded in part by the National Institutes of Health report that after intensive physical therapy and electrical stimulation to the spine, a man with a paralyzing spinal cord injury has recovered the ability to stand and move paralyzed muscles when the stimulator is active.
A car accident in 2006 left Rob Summers completely paralyzed from the chest down. Summers, now 26 years old, is participating in a pilot trial that combines locomotor training and epidural stimulation. The locomotor training involves being supported over a treadmill, either in a harness or by hand rails, while a team of physical therapists work with his legs to help him stand and step on the machine. During epidural stimulation, electrical pulses are delivered to the surface of his spinal cord, below the injury.
“While these results are obviously encouraging, we need to be cautious, and there is much work to be done,” said V. Reggie Edgerton, Ph.D., a professor of physiology at the University of California Los Angeles. Dr. Edgerton conducted the new study in collaboration with Susan Harkema, Ph.D., the director of rehabilitation research at the Kentucky Spinal Cord Injury Research Center at the University of Louisville. The team published data on Summers’ improvement in The Lancet.*
The team’s novel approach to rehabilitation was developed through research on animals, supported by NIH’s National Institute of Neurological Disorders and Stroke (NINDS). This first-in-human study as well as a parallel development of the new stimulator technology is supported by a NIH Bioengineering Research Partnership from the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The Christopher and Dana Reeve Foundation also contributed to the study.
Summers’ accident dislocated a segment of his spine between his neck and chest. He lost most movement and sensation below the injury, including the ability to control his legs. He began working with Dr. Edgerton in 2007, and received months of locomotor training with no epidural stimulation. While he hung over the treadmill for hours at a time, physical therapists moved his legs in stepping motions.
The locomotor training by itself did not improve Summers’ ability to stand or walk. But he did improve after December 2009, when electrodes were surgically implanted over the paralyzed area of his spinal cord near the bottom of his ribcage, and used to deliver rhythmic electrical bursts during the locomotor training sessions. During his efforts to stand on the treadmill, his supporting harness was gradually lowered until he was able to stand and fully bear his own weight for up to four minutes at a time. He is not able to walk on the treadmill. While standing with the stimulator on, however, he can bend one leg at the knee, flex his ankle and extend his big toe.
"This study is an example of the convergence of the physical, neurological and clinical sciences to develop novel approaches that could improve the lives of individuals with spinal cord injuries,” said Belinda Seto, Ph.D., deputy director of NIBIB. “There is still much work to be done to optimize the multi-electrode stimulator technology, including determining the most effective stimulation patterns,” added Grace C.Y. Peng, Ph.D., the NIBIB program director who oversees the project.
The investigators do not know precisely how epidural stimulation works. The approach emerged from research on basic spinal cord physiology, largely supported by NINDS. When we decide to move, our brains send signals that travel through our spinal cords and to our muscles. The feel of the movement, for example our feet hitting the ground as we walk, is transmitted back to the spinal cord by sensory nerve cells – and ultimately back to the brain. However, the spinal cord also contains local circuits that are capable of producing and sensing movements even without the brain’s control. The knee jerk reflex is a simple example from everyday life.
Dr. Edgerton’s research on animals with spinal cord injury has shown that local circuits in the spinal cord can also drive more complex movements, such as stepping. In a recent study on rats with spinal cord injury, Dr. Edgerton showed that combining epidural stimulation with sensory input – feeling the motion of a treadmill – helped the rats regain the ability to walk. The rats also received drugs that mimic the effects of serotonin, a chemical messenger that excites nerve cells in the spinal cord.
The serotonin-like drugs that were used in the rats are not suitable for human use and will require further development, the researchers say.
Along with the animal studies, there were hints that people with spinal cord injuries might respond to a similar combination of treadmill training and spine stimulation. Locomotor training, without any epidural stimulation, is routinely used as a rehabilitative technique for people with so-called incomplete spinal cord injuries, which means they still have some ability to move and feel below the injury. Meanwhile, a form of epidural stimulation is used to relieve pain for some patients.
While Summers retained some sensation below his injury, his legs were completely paralyzed. This is the first time researchers have found that locomotor training and epidural stimulation together can help someone with such a severe injury. It is believed that the epidural stimulation and locomotor training have two distinct roles. The stimulation appears to have a non-specific effect, switching on intact circuits in the spinal cord. Meanwhile, the training relays specific information about the body and its position, for example, whether the person is standing or walking.
"These studies show that after a spinal cord injury, the sophisticated circuitry of the spinal cord remains, ready to coordinate complex movements if it receives the right commands," said Naomi Kleitman, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS). "Harnessing that potential has been the goal of decades of research to understand spinal cord function and to find effective ways to restore that function after injury."
One mystery is that for Summers, the physical therapy and stimulation to the spinal cord appeared to do something more than activate the local circuits in his spinal cord. The treatment actually put the power of movement under his control. With the stimulator turned on, he stood up when he wanted to stand, and he could move his legs, feet and toes when asked. The researchers have two theories for how this happened. One possibility is that the stimulation amplifies weak signals that manage to reach the injured spinal cord from the brain, but are not strong enough to produce muscle contractions on their own. Another possibility is that the stimulation helps nerve cells in the cord grow and establish new connections.
Summers is the first of five individuals participating in this trial. The researchers and NIH scientists caution that further study is required to confirm these early, promising results and to understand exactly how the stimulation is working.
"We still have much to learn about how different people will respond to this type of stimulation," said Dr. Kleitman. "Testing of more individuals is needed, as every spinal cord injury and patient is different. Drugs that make the spinal circuits more sensitive to the stimulation may be added to the therapy in the future."
*Harkema S et al. "Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study." The Lancet, published online May 20, 2011.
About the National Institute of Biomedical Imaging and Bioengineering (NIBIB): The NIBIB’s mission is to support multidisciplinary research and research training at the crossroads of engineering and the biological and physical sciences. NIBIB supports emerging technology research and development within its internal laboratories and through grants, collaborations, and training. More information is available at the NIBIB website.
About the National Institute of Neurological Disorders and Stroke (NINDS): The NINDS is the nation’s leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease – a burden borne by every age group, by every segment of society, by people all over the world. More information is available at the NINDS website.
About the National Institutes of Health (NIH): The NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. More information is available at the NIH website.
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