Two research teams reported Monday that three patients paralyzed from the waist down were able to take steps again after weeks of rehabilitation and the implantation of a device that zaps the spinal cord in precise ways, fueling hopes that some sensory and motor function may be regained even when it appears they have been completely lost.
“The fact that at one time, it was thought there would be no motor or sensory function in these patients — what is returning is just extraordinary,” said Peter Wilderotter, CEO of the Christopher & Dana Reeve Foundation, which has previously funded some of the researchers involved in the new studies. “It signals that the old dogma is being reversed and perhaps this isn’t as intractable as it was once believed.”
Past research has shown that a combination of rehab and electrical stimulation can help some people paralyzed from spinal cord injuries intentionally move their legs while lying on their sides. But these patients — a 29-year-old man in one study out of the Mayo Clinic, and a 34-year-old man and 23-year-old woman in a study from the University of Louisville — achieved new milestones. They were able to control their legs and walk with only the help of walkers or crutches and some balance assistance.
Experts noted that these were just a small number of case reports — a sign of research progress but not a demonstration that such an approach will work for all patients. Stephen Estes, a spinal cord injury researcher at the Shepherd Center in Atlanta, who was not involved with the research, said he was greeting the results with “cautionary optimism.”
Before they could take steps, the patients had to undergo training sessions several times a week for months, and they could only walk when the device was stimulating the spinal cord, not when it was turned off. Two patients in the Louisville study, which was published in the New England Journal of Medicine, did not regain independent walking ability, even with the stimulation and intensive rehabilitation.
None of the three individuals who regained some motor control saw any improvements in sensation. While the two Louisville patients had some slight sensation before the study, the Mayo patient had none.
Whatever answers the studies may have provided are accompanied by at least as many questions. Researchers still haven’t determined how the pulsing of the spinal cord device enables signals from the brain to travel past the point of injury and trigger controlled leg movements. Without that understanding, they can’t be sure who else might be primed for this type of progress.
“We really want to understand how that occurred, why that occurred, and, potentially going into the future, find out who we could help with this research protocol,” said Kristin Zhao, a biomedical engineer at the Mayo Clinic and one of the senior authors of that study, which was published in Nature Medicine.
The researchers do have a hypothesis.
It’s been thought that a severe spinal cord injury prevents signals coming from the brain from turning on nerves below the site of the lesion; those nerves are then no longer able to be activated and, say, direct the quadriceps to contract. But researchers are finding more evidence that some connections remain intact, and maybe just need a jolt.
“Across neuroscience as a whole, there’s a greater understanding that the nervous system is a lot more plastic than previously thought,” Estes said.
He likened the implanted stimulator to an amplifier. If there are normally, say, 100 connections that telegraph a command from the brain along the spinal cord, a serious injury might mean there are only one or two remaining. Those might not be enough to convert a signal into movement, but perhaps the stimulation boosts the signals enough to trigger movement.
The neurons are able to once again “take in the information from the brain to allow for voluntary control over the legs,” said Dr. Kendall Lee, a Mayo Clinic neurosurgeon and a senior author of the study.
For the studies, researchers implanted the electrical stimulation devices, which are normally used to treat pain, on the covering of the spinal cord, called the epidural space. In the Mayo Clinic patient, who was paralyzed in a snowmobiling accident, the device was placed below the site of the injury, at the site of the nerves that are wired to the muscles in the legs.
As the patient went through rehabilitation, the researchers embarked on their own form of training. Because they controlled the electrical pulse — the voltage, the pattern, and the length of the stimulation — they had to figure out the precise instructions to send to the spinal cord.
They managed to deliver a sequence of pulses that excited the nervous tissue in such a way that the man was able to swing one leg and then the other — what they called “interleaved” stimulation programs.
The Mayo team has implanted a device in a second patient but has not reported results from that case yet. Among other questions is what kind of rehabilitation protocol might be best.
“It’s a very rigorous and intensive protocol,” Zhao said. “Going forward, just how much rehabilitation is needed? Can we look at other strategies to streamline the rehabilitation?”