Long-Paralyzed Patients Move Legs With Epidural Stimulation

Pauline Anderson

April 08, 2014

Researchers have developed what they describe as a "fundamentally new" treatment approach for paralysis: epidural stimulation.

In a new report, they describe how 4 men with chronic complete motor paralysis were able to recover some voluntary movement after receiving epidural stimulation from an implanted unit. The ability of these patients to move voluntarily improved over time with daily stimulation and training.

The study seems to indicate that electrical stimulation can reprogram damaged nerves in the spinal cord so they regain the ability to receive stimuli.

"After their injury, these patients are pretty much told that they're never going to be able to move again and are going to be wheelchair bound for the rest of their life," said lead author Claudia A. Angeli, PhD, senior researcher, Frazier Rehab Institute, Kentucky One Health, and Department of Neurological Surgery, Kentucky Spinal Cord Research Center, University of Louisville, Kentucky, told Medscape Medical News.

"So this is very significant, particularly for the individuals who were classified as motor and sensory complete."

Their findings are published online April 8 in Brain.

Lost Receptivity

The study included 4 men, average age 26.9 years, with a spinal cord injury incurred at least 2 years before the study. Their injuries ranged in neurologic level from C7 to T5. None were able to stand or walk independently or voluntarily move their lower extremities despite standard-of-care rehabilitation and additional intense locomotor training.

One of the 4 patients to undergo task-specific training with epidural  stimulation at the Human Locomotion Research Center laboratory, Frazier Rehab Institute, as part of the University of Louisville Kentucky Spinal Cord Injury Research Center.

Researchers implanted a stimulator into the abdomen of each patient. The stimulator was originally developed for use in pain but was refined for use as an epidural spinal cord stimulator.

The investigators also implanted a 16-electrode array over vertebrae T11 to T12, where the locomotor sensors are located, said Dr. Angeli. The electrodes were placed in the same location in all patients, regardless of the location of their injury.

Each patient had an individually programmed device that they simply placed over the abdomen to initiate stimulation. There was a separate program for the left and for the right leg.

With stimulation and with auditory and visual cues, the patients could execute intentional movements of the legs. Dr. Angeli emphasized that such movements required "very precise motor control."

Waiting for Feedback

The spinal cord has a resting state during which it's "waiting to receive feedback from the brain" on how to react, said Dr. Angeli. It's believed that after a spinal cord injury, receptivity to those stimuli is lost.

But the site of the injury is the only part of the spinal cord that is compromised, "so you have a lot of spinal cord still active and ready to perhaps relearn," said Dr. Angeli.

"With epidural stimulation, we are raising the excitability of the spinal cord, or raising the awareness of spinal cord, making it ready to listen, so when the intent to move comes from the brain, the spinal cord can receive that and take care of all the details of how that movement is going to take place," she said.

Study patients underwent step and stand training sessions with stimulation in the laboratory and later on their own. They were eventually training with stimulation for over 2 hours a day, said Dr. Angeli.

With this daily stimulation and training, the voluntary movements of the 4 men improved over time. This, said the authors, demonstrates the ability of the spinal networks to learn with task-specific training.

Now, with stimulation, these men "can move their legs, move their toes independently, and move their ankles," said Dr. Angeli.

Although the patients can stand and lift a leg, they can't walk, which requires more complex coordination between the left and right legs, the flexors and the extensors.

"That's a limitation of the technology," said Dr. Angeli. "We're using a stimulator that was developed for pain and we're pretty much pushing it to its functional limitation."

But new technology is being developed to "overcome that hurdle," she said.

This new research challenges current thinking surrounding the level of plasticity in the spinal cord and how much control the spinal cord has, commented Dr. Angeli. "There are a lot of individuals out there, especially physicians, who feel that after a spinal cord injury occurs, the spinal cord is done, that it has no potential," she said.

Dr. Claudia A. Angeli

But epidural stimulation will be only part of the rehabilitation equation in future, she added. It has to be accompanied by training and perhaps by a pharmacologic agent.

No Longer "Life-Long Sentence"

Reached for a comment on this new research direction, Roderic Pettigrew, PhD, MD, director, National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health, called it "exciting news" and "a milestone."

"It means that a spinal cord injury may no longer mean a life-long sentence of permanent paralysis," he told Medscape Medical News.

The stimulation doesn't cause muscles to contract but rather resets or reprograms the level of excitability of nerve cells, added Dr. Pettigrew. "This is not simply putting in electrodes, turning on a battery, and suddenly you can move again because the battery-powered electrical system is making you move."

When you see this kind of outcome in the first 4 subjects that you treat, where each of them has been completely paralyzed for over 2 years, this is substantial. Dr. Roderic Pettigrew

There are over 1.2 million people with paralysis secondary to a spinal cord injury in the United States alone, he said. "This is a devastating problem, and what this study indicates is that there is a new approach to treating patients with this kind of injury."

"When you see this kind of outcome in the first 4 subjects that you treat, where each of them has been completely paralyzed for over 2 years, this is substantial," said Dr. Pettigrew.

And the technology can only improve. Dr. Pettigrew's group is involved in developing next-generation technology that will stimulate nerves in a more precise way, and will be totally noninvasive.

"The current approach requires surgical implantation of electrodes to stimulate target nerves, but the new approach will utilize electrodes placed on the skin," he said.

Researchers are also testing the technology on patients with upper-limb paralysis, said Dr. Pettigrew.

Funding for the study came from the National Institutes of Health, Christopher and Dana Reeve Foundation, Leona M. and Harry B. Helmsley Charitable Trust, Kessler Foundation, University of Louisville Foundation, Jewish Hospital and St. Mary's Foundation, Frazier Rehab Institute, and University of Louisville Hospital.

Brain. Published online April 8, 2014. Abstract


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