Weeks after winning the College World Series with Oregon State University, 20-year-old Rob Summers was rendered paralyzed from the chest down when he was struck by a hit-and-run driver. The injury to his spinal cord was so severe that he saw only minimal improvement after many months of training. But an experimental approach that combines physical therapy and electrical stimulation of the spinal cord enabled him to recover beyond his dreams. For the first time since his injury, Rob was able to stand up on his own and move his legs at will.
“It was completely unexpected,” says V. Reggie Edgerton, professor of integrative biology and physiology, and neurobiology at the University of California, Los Angeles. Until that time, scientists believed that patients with a completely severed spinal cord would never be able to regain voluntary control of their paralyzed limbs.
Tapping into the Spinal Cord’s Hidden Potential
When a foot is placed down on a surface, local spinal circuits pick up the sensory information and generate a stepping motion without requiring any input from the brain. The sensory information goes to the spinal cord, which can sense it and recognize it and knows what to do with it. “The brain has no idea what’s happening,” says Edgerton.
Edgerton has been studying this phenomenon in animals paralyzed after a spinal cord injury. He found that if he stimulated spinal circuits using electrodes placed under the membrane that surrounds the spinal cord (so-called epidural stimulation), the spinal circuits could register and respond to sensory information. Depending on the location and pattern of stimulation, injured rats and cats can step in different directions and at different speeds.
Importantly, the level of stimulation supplied to the spinal circuitry is too low to trigger muscle movement by itself. The stimulation simply engages the spinal circuitry to receive and process sensory information coming from the legs when researchers place the animal’s feet on a moving treadmill. “As it practices, the circuitry basically re-learns how to stand and step,” says Edgerton, adding that movement of our limbs is largely automatic and does not require much direction from the brain.
A New Application for an Established Technology
To see if epidural stimulation could be successful in people, Edgerton’s collaborators at California Institute of Technology (Caltech) and University of Louisville tested a 16-electrode array that is normally used to treat back pain. “We can place different patterns of electrical stimulation across those 16 electrodes. We can decide which electrodes are turned off and on, and we can vary the frequency that’s applied to those electrodes,” indicates Edgerton’s collaborator Joel Burdick, a professor of mechanical engineering and bioengineering at Caltech who develops new technologies and computer algorithms that help in the recovery of spinal cord injury patients.
To qualify for the study performed at the University of Louisville under the direction of Dr. Susan Harkema, Rob had to show that conventional rehabilitation could not improve his ability to stand or walk. So prior to having the device implanted in his lower back, Rob underwent extensive physical therapy — more than 80 standing and 80 stepping sessions over a period of 26 months resulting in no signs of improvement. This conventional therapy also served to prepare his body for what lay ahead — countless hours of training in a stand frame or on a treadmill while his spinal cord was being stimulated.
The hard work and persistence paid off spectacularly. After four years of being bound to his wheelchair, Rob now can push himself up to a standing position and remain standing for a few minutes while receiving epidural stimulation. With the support of a harness and some help from therapists, he can make stepping motions on the treadmill, but cannot yet step independently. Other functions impaired by his injury have also improved—blood pressure control, body temperature regulation, bladder control, and sexual response. Three additional patients with complete spinal cord injury have also been treated and reported similar results.
The researchers supposed that Rob’s modest ability to feel sensations in his legs contributed to his recovery. However, positive results from three additional patients suggest that even a person with complete sensory dysfunction can respond to the treatment. “Even [Rob] could not accurately sense the detail of the sensory information.”
Patient Rob Summers and investigators Susan Harkema, Reggie Edgerton, Joel Burdick, and Jonathan Hodes address a press conference.
The degree of Rob’s recovery amazed and puzzled the researchers. How can the brain command the legs in a person with a clinically defined “complete” spinal cord injury? “One hypothesis is that we’ve been able to reawaken connections that were there but not functional,” says Edgerton. Some connections between Rob’s brain and the part of the spinal cord below the point of the injury may have been spared. It is also conceivable that the therapy encouraged nerve cells to make new connections. The investigators are planning human and animal studies to explore the biological mechanism for recovery of voluntary movement.
Edgerton wonders how many people diagnosed with complete spinal cord injuries may actually have residual connections so that some function could be regained with epidural stimulation. “We are beginning a series of experiments to determine whether the same phenomenon can be used with the upper limbs,” he says. He is also exploring whether epidural stimulation could be used to improve gait in victims of stroke and Parkinson’s disease.
On the technology end, the research team of Burdick and Y.C. Tai is working on a new generation of stimulating circuits that would allow better control over the lower nervous system. The electrodes will be redesigned as well. “We are trying to model how the electric field penetrates into the spinal cord in order to activate the neurons. We are using that information to know how many electrodes we need, how big they should be, what shape they should be, and precisely where we should place them,” says Burdick. Modeling is also a critical tool to help tailor the stimulation for each specific patient and to modify these parameters as they undergo therapy.
Robotic technologies have recently enabled paralyzed people to stand and walk. Unlike those approaches where a computer orchestrates movements, epidural stimulation actively engages the patient’s nervous system, potentially leading to lasting recovery. “This is obviously not a cure; it is a therapy,” Burdick cautions. Combined with other biological approaches, such as stem cell therapy, it may one day come close to a cure, at least for some patients. And for the millions living with paralysis, this research signifies a giant step toward a better quality of life.
This work is supported in part by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Neurological Disorders and Stroke, and the Christopher and Dana Reeve Foundation.
Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, Ferreira C, Willhite A, Rejc E, Grossman RG, Edgerton VR. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. 2011 Jun 4;377(9781):1938-47.