Groundbreaking NIH study spurs hope for those with spinal cord injury
Flex a muscle, any muscle? Certainly, it's second nature. But not if you're paralyzed.
Now, thanks to a novel combination of electrical stimulation of their spinal cords and long-term physical therapy, four young people, each paralyzed for more than two years, can voluntarily flex their toes, ankles, and knees. They participated in a groundbreaking research study supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the National Institute of General Medical Sciences (NIGMS), the Christopher & Dana Reeve Foundation, and others.
"The evidence suggests that a large number of people with little realistic hope of any meaningful recovery from spinal cord injury may benefit from this intervention," says NIBIB Director Dr. Roderic Pettigrew.
The new findings build upon a 2009 pilot trial that tested whether spinal stimulation, in conjunction with daily treadmill training, could help patients with paralysis regain some movement. In the pilot, Rob Summers, a young man paralyzed from the chest down, had a 16-electrode array implanted on his spinal cord. It delivered electrical pulses just below his injury while he underwent daily training, suspended from a harness over a treadmill. During training, researchers supported his legs, helping him to stand and walk.
Although not strong enough alone to activate muscles, the researchers believed the electrical stimulation combined with the sensory input from walking could lead to movement. The goal was to increase the sensitivity of the spinal cord's local circuits controlling basic motor functions such as the knee jerk from stepping on a tack, or even more complex patterned movements like stepping.
With the electrical stimulation turned on, Summers gradually could bear his own weight and stand as long as four minutes without assistance. Eventually, he realized that he had even regained some voluntary leg control in the presence of stimulation. Amazingly, intentional movement like this requires that information travel from the brain to the lower spinal cord, a path that was blocked in Summers. Also, other impairments from his injury began to improve, including bladder and blood pressure control, body temperature regulation, and sexual function, even with the stimulator turned off.
Three additional paralyzed patients joined Summers in the new study, which was conducted by Claudia Angeli, Ph.D., a senior researcher at the Human Locomotion Research Center at Frazier Rehab Institute and assistant professor at the University of Louisville's Kentucky Spinal Cord Injury Research Center, and colleagues. Two patients had complete motor and sensory paralysis. Because of this, one of them was meant to serve as the baseline patient. The third, like Summers, had complete motor paralysis but some sensation below his injury. Researchers had assumed at least some of the sensory pathway needed to be intact for their therapy to have worked. Surprisingly, all three regained some voluntary muscle control just a few days after starting stimulation.
"What was astounding about our 'baseline' patient was that not only was there voluntary movement, but we saw it in the first week of stimulation. We then saw it in the next two patients," recalls Susan Harkema, Ph.D., director of rehabilitation research at the Kentucky Spinal Cord Injury Research Center. Although much remains to be done, she believes these results provide enough evidence to challenge the current prognosis of patients with severe spinal cord injuries.
According to V. Reggie Edgerton, Ph.D, a UCLA distinguished professor of integrative biology and physiology who originated the new approach, the speed at which each patient regained voluntary control may mean that there are dormant connections in patients with complete motor paralysis. "The spinal stimulation could be reawakening these connections," he says.
In a further landmark, all four participants were able to synchronize leg, ankle, and toe movements in unison with the rise and fall of a wave on a computer screen, and three out of the four were able to change the force at which they flexed their leg.
By the end of the study, which lasted several months and included home-based training, some of the patients were able to make voluntary movements with greater force and under reduced stimulation. Others had enhanced movement accuracy. Whether these improvements were due to the training or to the cumulative effects of the stimulation is unclear and await further study.
With support from NIBIB, Edgerton is leading development of a new high-density, 27-electrode array that may provide finer, more robust motor control. "For a given type of movement, we want to be able to select exactly where and how to stimulate the spinal cord," he explains. He and others also are exploring ways to help patients with upper-limb paralysis, and working to develop a new technology that can deliver spinal stimulation through the skin, bypassing the need for surgical implantation.
"This is a wake-up call for how we see motor complete spinal cord injury," said Edgerton. "We don't have to necessarily rely on regrowth of nerves in order to regain function. The fact that we've observed this in all four patients suggests that this is actually a common phenomenon in those with complete paralysis."
Dr. Pettigrew says the results from this study represent a medical milestone. "It means that a spinal cord injury may no longer mean a lifelong sentence of permanent paralysis."