Researchers in UofL’s provided a combination therapy to five children with complete paralysis. The children, ages 7-12, took part in a clinical study in which they received external electrical stimulation over the spine, combined with activity-based therapy and encouragement to consciously intend to step. During the study, the children all gained the ability to take steps and experienced unexpected improvements in sensation, bladder function, transferring and other abilities. The study was published in the.

“We have found that electrical stimulation can “charge” the spinal cord, making it possible for a paralyzed individual to step voluntarily,” said Andrea Behrman, professor in the UofL Department of Neurological Surgery and director of the Center for Pediatric NeuroRecovery, who led the study. “This ability increases over time when the stimulation is combined with locomotor training and mental intent to step.”

Stimulation + activation + intent

In the study, children who were completely paralyzed for more than a year, unable to move below their level of spinal injury, participated in a series of 60 sessions that included noninvasive, transcutaneous (through the skin) electrical stimulation of the sensory nerves to the spinal cord and specialized physical therapy.

The electrical stimulation was applied with a specially designed technique for external electrical stimulation developed by Yury Gerasimenko, now gratis professor of the UofL Department of Physiology. The technique consisted of several small stimulators, about the size of a quarter, placed on the child’s skin over the sensory nerves of the spinal cord. During the sessions, electrical stimulation was applied through the pads while the children took part in physical therapy known as activity-based locomotor training.

This therapy consists of researchers and therapy technicians manually facilitating the child’s legs in stepping motions as they lay on their side on a table with their legs suspended and also during assisted walking with part of their body weight supported over a treadmill. In addition, the children were encouraged to consciously attempt to step.

Over the course of the study, the children were able to initiate and control the stepping themselves. After various numbers of sessions, they were able to take steps over ground, voluntarily initiating the steps both with and without the stimulation present. Three to six months after the sessions were completed, all of the children still were able to take steps with and without the stimulation.

“The results we see with this study confirm what I have learned more and more over the last two decades working with children with spinal cord injury,” Behrman said. “Your spinal cord is more than a conduit or a pipeline for nervous system messages. It processes information and is smart like your brain. The spinal cord can’t decide to go to Starbucks for coffee, but it can help you with more automatic movements such as sitting up better and taking steps. It also works somewhat like a battery and needs the right charge to help produce steps and respond to therapy.”  

For many years, the medical community as a whole has believed that after injury in which communication along the spinal cord was interrupted and the patient could not move on their own, that function below the injury could never be restored. As a result, treatment for most people with complete paralysis included helping them adapt to mobility with wheelchairs and other forms of assistance.

For the parents of children participating in Behrman’s studies and clinical care, even the small gains achieved through the sessions have a significant positive impact on their child’s quality of life and often, their health.

Kalyn MacIntyre, whose son Malcolm participated in the study, said that even three years after the study concluded, he retains many of the benefits he gained from his sessions.

“He can still step on the treadmill, he can kick a ball consistently. He can now feel when he needs to go to the restroom and his overall health has been good,” Kalyn said, adding that he also has sensory gains. “I don’t know what his future is as far as walking. I just want him to be functionally capable of doing things on his own – to have more independence – and I want him to be healthy. We have more of that here because of this study.”

The personal connection

One of the most challenging aspects of the research is motivating the children during long training sessions.

“We can have the most beautifully designed study, but if a child can’t get into it and you can’t help them be successful, it will not work,” Behrman said. “You can’t just come in and say, ‘Do this 50 times.’ For each child, you must figure out how to connect with who they are.”

To engage them in the activities, Behrman and the therapists working with the children have cultivated the art of motivation by incorporating their personal interests. One child in the study was a basketball player before he was injured, so Behrman used a whistle to encourage him to go faster or drive harder, similar to when he was running drills for basketball.

For Malcolm, the research staff devised a point system to reward him for every time he was able to kick a ball. Behrman recalled one session when she told him that instead of the 10 or 20 points he received for kicking the ball off the treadmill, she would award him 10,000 points if he could kick the ball to hit a target on the opposite wall.

On the next try, Malcolm’s kick sent the ball sailing across the room, squarely hitting the target.

Previous success

Previously, researchers at UofL achieved remarkable success in restoring function to adults with spinal cord injury in studies using surgically implanted electrical spinal cord stimulators. In one study, adults who were completely paralyzed were able to take steps over ground with stimulation after a series of intensive physical therapy sessions and mental intent to take steps.

This new study shows that similar results can be achieved without the invasive procedure. In addition, the adults could only step when the stimulator was on, whereas the children in Behrman’s study were able to step long after the stimulation sessions had ceased.

For additional photos and video clips, visit . All images courtesy University of Louisville. The images with “study image” in the name were captured during the study sessions, 2021-2023.

Research participants receiving activity-based training conducted by KSCIRC at Frazier Rehab Institute initially reported improvements in bladder, bowel and sexual function anecdotally. Charles Hubscher, PhD, professor and researcher at KSCIRC, has documented those changes in .

For individuals with severe spinal cord injury, bladder and bowel dysfunction are among the most detrimental factors to their quality of life, even more than the loss of independent mobility.

“Patients with spinal cord injury say they are most concerned by the problems associated with bladder function,” Hubscher said. “These issues contribute heavily to a decline in their quality of life and impacts overall health.”

Bladder dysfunction associated with SCI results in numerous health complications, requiring lifelong management and urological care in the form of catheterization, drug and surgical interventions, peripheral electrical stimulation and urethral stents. All of these therapies bring with them serious side effects and none substantially improves the basic functions.

To document changes in bladder, bowel and sexual function resulting from activity-based therapy, Hubscher and his colleagues performed urological testing (urodynamics) and asked research participants with severe spinal cord injury to complete surveys about their bladder and other functions. Eight of the participants received activity-based training, which includes locomotor training, stepping on a treadmill with their body weight supported, and stand training in a specially-designed frame. Four participants did not receive training.

The active participants’ functions following training were compared with their own condition prior to training and with individuals not receiving training. Following 80 daily sessions of locomotor training with or without stand training, the active individuals were found to store significantly more urine at safer pressures, reported fewer incidents of nighttime voiding and reduced general incontinence, as well as improved bowel functioning and increased sexual desire.

“Today’s published research indicates that activity-based training strengthens the neural circuits that control urogenital and bowel functions,” Hubscher said. “We hope to further validate those findings by determining if the improvements can lead to elimination of related medications and/or long-term reduction in the number of daily catheterizations. In addition, we are evaluating the effects of spinal cord epidural stimulation on those circuitries.”

Susan Harkema, PhD, professor and associate director of KSCIRC and an author of the study, said the publication highlights the value of the research collaborations at UofL.

“This work showcases the exceptional environment for research at UofL, with basic scientists working in parallel with clinicians in rehabilitation and neurosurgery,” Harkema said. “There are relatively few researchers addressing bladder, bowel and sexual function both in animals and humans in chronic spinal cord injury. Dr. Hubscher’s work adds a unique and valuable aspect to our research.”

Epidural Stimulation Research

Researchers at KSCIRC are investigating the use of spinal cord epidural stimulation (scES) to facilitate the ability of SCI patients to stand, voluntarily control leg movements, and improve other functions. Spinal cord epidural stimulation involves the delivery of electrical signals to motor neurons in the spine by an implanted device.

In concert with this research, Hubscher is investigating the effects of scES on bladder, bowel and sexual function in SCI patients. Funded by a $3.5 million grant from the National Institutes of Health, Hubscher has begun work to map the lumbosacral spinal cord for multiple aspects of bladder function. This work will identify locations on the spine and device configurations for using scES to improve bladder storage and voiding efficiency.

The funding is through the NIH Common Fund program which aims to increase the understanding of nerve-organ interactions and neuromodulation to advance treatment of diseases and conditions for which conventional therapies fall short.

Hubscher’s SPARC project has a three-year timeline and includes concurrent investigations in both animals and humans. His team will enlist six human research participants who have received scES devices and have completed the initial epidural stimulation study to assist with the development of device parameters, then test those parameters at home.

For the estimated 1,275,000 people in the United States who live with paralysis from SCI, therapies resulting from this research have the potential to increase their quality of life as well as reduce health-care costs.

A study published today in describes the recovery of motor function in a research participant who previously had received long-term activity-based training along with spinal cord epidural stimulation (scES). In the article, senior author Susan Harkema, PhD, professor and associate director of the  at the University of Louisville, and her colleagues report that over the course of 34.5 months following the original training, the participant recovered substantial voluntary lower-limb motor control and the ability to stand independently without the use of scES.

“Activity-dependent plasticity can re-establish voluntary control of movement and standing after complete paralysis in humans even years after injury,” Harkema said. “This should open up new opportunities for recovery-based rehabilitation as an agent for recovery, not just learning how to function with compensatory strategies, even for those with the most severe injuries.”

Previous research at KSCIRC involving four participants with chronic clinically motor-complete spinal cord injury found that activity-based training with the use of scES – electrical signals delivered to motor neurons in the spine by an implanted device – allowed the participants to stand and to perform relatively fine voluntary lower limb movements when the scES device was activated. Andrew Meas was one of the four participants in that study.

The original training protocol included daily, one-hour, activity-based training sessions with the aid of epidural stimulation. During these sessions, the participant trained on standing activity for several months, followed by several months of training on stepping.

After completing a nine-month training program in the lab, Meas continued activity-based stand training at home. After a year of independent training, he returned to the lab to train for three months in a revised activity-based training schedule. The revised training called for two, daily one-hour training sessions and included both stand and step training each day, all with the aid of epidural stimulation.

After that training, Meas was able to voluntarily extend his knees and his hip flexion was improved. In addition, using his upper body and minimal additional assistance to reach a standing position, he was able to remain in a standing position without assistance, and even stand on one leg, without the use of epidural stimulation.

“We observed that in participants we have worked with so far, eight months of activity-based training with stimulation did not lead to any improvement without stimulation,” said Enrico Rejc, PhD, assistant professor in the UofL Department of Neurological Surgery and the article’s first author. “This participant kept training at home and, after several months, he came back to the lab and we tried a different training protocol. After a couple of months of training with the new protocol, we surprisingly observed that he was able to stand without any stimulation – with two legs and with one leg – using only his hands for balance control.”

The authors suggest that several mechanisms may be responsible for Meas’ recovery of mobility, including the sprouting of axons from above the point of injury into areas below the lesion. Another possible explanation may be that the activity-based training with scES promoted remodeling of connections among neurons in the spinal cord.

In addition, they suggest that the participant’s own effort at voluntary movement may have been a factor in the recovery. During the revised training, Meas was attentive and focused on the trained motor task, actively attempting to contribute to the motor output.

“The voluntary component of him trying constantly with spinal stimulation on and while performing motor tasks can lead to unexpected recovery,” Rejc said.

“The human nervous system can recover from severe spinal cord injury even years after injury. In this case, he was implanted with the stimulator four years after his injury. We saw motor recovery two years later — so six years after injury,” Rejc said. “It is commonly believed that one year from injury, you are classified as chronic and it’s likely that you will not improve any more. This data is proof of principle that the human nervous system has much greater recovery capabilities than expected.”

Funding for the research in Harkema’s lab is supported by the Christopher & Dana Reeve Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, Medtronic and the National Institutes of Health.

“We are enormously excited about this development in Dr. Harkema’s work, as it not only validates the promise of effective treatments for spinal cord injury, but further demonstrates the spinal cord’s ability to recover after severe trauma,” said Peter Wilderotter, president and CEO of the Christopher & Dana Reeve Foundation. “As we continue to support and fund Dr. Harkema’s research, it is awe-inspiring to see another breakthrough on the path to cures for paralysis, and how much this particular treatment has improved quality of life and health for Drew.”

Video files are available for download, including: 

.��The research participant with chronic motor complete spinal cord injury attempts to flex his right hip and subsequently his right knee voluntarily without epidural stimulation. He previously received long-term activity-based training with spinal cord epidural stimulation. Copyright, University of Louisville.

.��The first segment of the video shows the research participant prior to receiving the revised activity-based training, in which he is assisted to a standing position and was unable to stand independently. In the second segment of the video, taken after the intensified training, he is assisted to a standing position and is able to stand while holding the frame for balance without assistance and without epidural stimulation. He also is able to stand on one leg without epidural stimulation. The participant has chronic motor complete paraplegia and previously received long-term activity-based training with spinal cord epidural stimulation. Copyright, University of Louisville.

Check out footage from today’s press conference: