Enlarge / Trial participant Sherown Campbell manipulating a Rubik's Cube. UP-LIFT Trial
With a zap of electricity from well-placed electrodes on the back of the neck, patients with tetraplegia can regain some modest yet potentially "life-changing" functioning of their hands and arms, according to data from a small clinical trial published Monday in Nature Medicine.
The relatively simple stimulation method—which requires no surgery—offers an accessible, more affordable, non-invasive means for those living with paralysis to regain some meaningful function, the researchers behind the trial say. However, the therapy's further potential remains limited given that scientists have yet to fully understand exactly why it works.
For the trial, 60 patients with tetraplegia underwent the stimulation therapy over at least 24 sessions during a two-month period. At the end, 72 percent (43 patients) saw clinically meaningful improvements in both strength and functional performance. Further, 90 percent (54 patients) saw improvement from at least one strength or functional outcome. There were no serious adverse events reported.
"The most exciting thing for us is that we're seeing effects that improve quality of life," Chet Moritz, a co-author of the study and co-director for the Center for Neurotechnology at the University of Washington, said in a press briefing. "And also, we believe that the stimulation may be causing neuroplasticity or, in a sense, healing part of the damage to the spinal cord injury, such that the benefits persist beyond stimulation."
Clinical video of a trial participant testing grip
The trial, which took place at 14 clinical sites across the US, Canada, and Europe, was a prospective study—not the gold-standard design of a randomized, double-blind placebo control trial. Moritz and his colleagues explained that there were a number of reasons for this. For one, they weren't sure if they could use a sham electrical stimulation for a placebo group. Patients can feel the real electrical stimulation, described as an internal "buzz," and efforts to re-create the feeling, but not the effects of a sham treatment, were uncertain. Also, there were ethical concerns about having people with tetraplegia repeatedly travel to clinical sites and be subjected to potentially uncomfortable treatments with no expected benefit.
Still, the researchers behind the study are confident that the gains they saw were not simply placebo effects. For one thing, all the trial participants spent two months in standard rehabilitation therapy before they underwent the stimulation therapy. And their progress in that first phase of the trial was compared to their progress in the second half, in which they received the therapy. The differences were "very dramatic for many of the measures," Edelle Field-Fote, a co-author and Director of Spinal Cord Injury Research at Shepherd Center in Georgia, said in the briefing.
Real improvements
Melanie Reid, a trial participant and journalist with The Times of London who spoke at the press briefing, was quick to report that she also believed the benefits seen were not from a placebo effect. Reid broke her neck 14 years ago in a fall from a horse. She was initially left with little function below her armpits but eventually regained some function of her right hand, while her left remained "useless." She said that with the stimulation therapy, she had regained function in her left hand, allowing her to release a seat belt buckle, scroll on touchscreen devices, and put her hair in a ponytail.
In response to a question about placebo effects, Reid recalled an instance during therapy in which she was holding a wide, weighted jar in her hand. With the stimulator on, "I was able to hold it quite comfortably," she said. But then, the stimulator was turned off, and the loss of the stimulation caused her to immediately drop the jar. "It was, to me, a real illustration of the increased power [from the therapy]," she said.
And that increased power can make a world of difference, she emphasized. "Everyone thinks that spinal injury, you know, all you want to do is be able to walk again, but if you're a tetraplegic or a quadriplegic, what matters most is working hands," she said. "There's no miracles in spinal injuries, but tiny gains can be life-changing."
Another trial participant, Sherown Campbell, echoed Reid's points at the briefing. Campbell broke his neck about 10 years ago during a wrestling match and was subsequently diagnosed with quadriplegia. During the stimulation therapy, he could see real improvements in grasping and pinching tests. But, he also saw improvements at home afterward, with no stimulation. He improved his ability to open jars, grip a steering wheel, and tie balloons. Campbell also reported that, after the therapy, he regained the ability to sweat below the level of his injury, which allows him to control his body temperature in hot weather and during exercise—a significant improvement in quality of life.
Unknowns
While the therapy is making improvements in patients' lives, the potential for it to move past these modest (though meaningful) gains is held back by a lack of understanding of how the therapy works. In the study, the researchers describe the stimulation therapy as being from two electrodes placed along the spine, with one below and one above the point of injury. The electrodes then produce a stimulation at "30 Hz with a 10-kHz carrier frequency overlay, which consisted of 10 pulses with a 10-kHz frequency and 100-μs pulse width." But it's unclear how this stimulation is improving muscle control and, potentially, spurring neuroplasticity.
The device is similar to external spinal cord stimulators that are already used to treat chronic pain. But, even with those, researchers are still debating why it helps. The initial idea for the stimulation stems from the "gate control theory" dating back to the 1960s. In this hypothesis, pain impulses from around the body travel to the spinal cord to send a message up to the brain. But, at the spinal cord, there's a gated entry for the signal to continue on. The pain impulses, which travel along smaller fibers, can open the gate. But, if signals from larger, sensory fibers are activated (such as by a stimulator), they can close the gate, blocking the pain signal from reaching the brain. This is why, the theory initially went, sensations of hot, cold, or skin rubbing can also disrupt the feeling of pain. But in the decades since the theory's origin, researchers have come to understand that pain perception is far more complex, potentially involving various types of cells in the central nervous system, immune cell activation, ion channel alterations, epigenetics, and chemical mediators.
The researchers behind the trial call for more studies into the mechanisms responsible for the improvements seen in their patients. In the meantime, a startup called Onward Medical is preparing the non-invasive stimulator for the commercial market, calling it the ARC-EX system. In April, Onward reported that it had submitted the device to the Food and Drug Administration for review. Researchers involved in the trial also said they were working on implantable devices that they hoped could achieve greater benefits.
