“I thought, ‘He must be so sad! Both of his parents have died. What could I do to make him feel better?  If I cured spinal cord injuries, that would make him feel better, I bet,’” she recalled.

Thus was born her interest in spinal cord injury rehabilitation. After graduating from the University of Louisville School of Medicine this spring, Wilkins will follow that passion as a physical medicine and rehabilitation resident with Case Western Reserve University in Cleveland.

Before embarking on a path to becoming a physician, however, Wilkins earned an undergraduate degree in her other passion, theater and music, and she spent three years working as an actor and a singer in New York City.

“I’m a really people-oriented person, a love-oriented person. In theater you are trying to get people to feel things. You are bringing people into space that they might not feel comfortable or that they had forgotten about or just helping them understand their own experiences about life,” she said. “But when the curtain closes, I don’t actually get to see how they experienced it and ask them, ‘Do you feel better? Is there anything I can do to make you feel better?’ A way to do that would be in medicine.”

So, as she was navigating the bustling world of auditions and theater productions, she also was completing science requirements and applying to medical school.

“I had always loved science. I said, I’ll give it one shot and if I get in, that’s the path I’ll take. If I don’t, I’ll just continue to be an actress and it’ll be fine,” she said.

“I ended up getting in and I chose Louisville because of the work with spinal cord injury.”

Just a week after the wrap of her third New York production, in which she played one of the stepsisters in a production of “Into the Woods,” she moved to Louisville to start classes. But the dramatic life transition caused her to wonder if she was making the right choice.

“I had a big identity crisis,” she said. “Am I abandoning theater because I’m giving up? Am I truly excited and feel like I’m called to go do this other thing?”

The crisis resolved a few months into her first year of medical school when, with encouragement from her instructor, Jennifer Brueckner Collins, she joined a community theater group. The weekly classes with the Commonwealth Theater Company allowed her to stay connected with music and acting.

“I loved doing it! It was a great addition to my life here in Louisville.,” Wilkins said. “It just helped me kind of merge my two personalities. I was able to say, ‘OK, I can be both things. I can still consider myself an actress, too.’”

It also helped that she was able to connect with UofL’s spinal cord injury researchers, starting with Susan Harkema, who leads UofL’s groundbreaking research in epidural stimulation with the Kentucky Spinal Cord Injury Research Center.

“She met with me, she got me plugged in to a research position with Dr. Max Boakye’s lab and I met a bunch of people that way,” Wilkins said.

“I could not have gone to a more supportive place, a better place for what I’m interested in. I cannot say enough great things about the UofL School of Medicine and Frazier Rehab. They’re very inclusive and excited to get students involved.”

In her third year at UofL, however, Wilkins faced another personal challenge. She already was frustrated as the pandemic limited students’ clinical activities when her father was diagnosed with cancer. COVID restrictions meant she was unable to visit him in the hospital and he died just a few months later.

“It was very, very difficult. I was wondering if I should take a leave of absence, if I should go home to Atlanta,” she said.

But she persevered.

“My dad and my mom and all of the faculty and professors here were really integral to me deciding that I could stay, I could finish on time and match on time.”

On Match Day this year, with a photo of her dad in hand, she learned she would be spending her four-year residency at Case Western Reserve University and MetroHealth Medical Center in Cleveland, pursuing specialty training in physical medicine and rehabilitation.

“I’m so excited! I’m in PM&R for life now. I’m over the moon,” she said.

Wilkins plans to continue participating in music and theater, but as she pursues her goal to cure spinal cord injury, she appreciates the ability to have the more personal connections with the people she will treat as a physician.

“I’m still there with people in dark moments, but I actually get to hold their hand and be with them throughout the whole process.”

Instead, this tablet allows Smith, who has tetraplegia, more independent control of an implanted Medtronic Intellis neurostimulator, allowing him to better take advantage of the stimulator’s benefits for the disabling effects of a spinal cord injury.

Smith received the stimulator two years ago while participating in a study involving individuals paralyzed by spinal cord injuries at the University of Louisville’s (KSCIRC). The stimulator has provided Smith benefits such as voluntary movement, increased trunk control and improved blood pressure regulation.��

“The stimulator has restored my health in a big way. I don’t feel sick all the time anymore. I’m not passing out; I’m not dizzy,” he said. “I am enjoying my life again. It gives me something I can use to fight for my recovery.”

To fully take advantage of the stimulator’s benefits, the stimulator must be adjusted periodically throughout the day to regulate his blood pressure and other functions, each of which requires distinct stimulator settings. Smith, who has limited use of his hands due to a C4-level spinal cord injury, previously had to rely on a caregiver to change the settings due to the small size of the buttons on the standard stimulator controller device.

But now, thanks to the new tablet controller with a larger, touchscreen interface designed with his needs in mind, Smith can adjust settings himself.

“Previously, the remote was controlled by my caregiver. I couldn’t do it because I don’t have [full use of] my hands. Now that we have this new technology, I can control it on my own,” Smith said. “I am going to be able to use many more functions and be able to control it and adjust it in a much more significant manner on my own. It’s a big benefit to my life.”

In addition to a more accessible interface, the updated controller has the capacity to store more setting configurations for immediate use and provides smoother transitions between configurations that allow the person with spinal cord injury to change positions such as from sitting to standing.

Over the last few months, the new tablet controllers have been provided to 16 participants in the spinal cord epidural stimulation research program at UofL. Additional participants will receive the new tablet controllers in the coming months, as well as any new participants receiving epidural stimulators.��Participants receiving or eligible to receive the new tablets include those taking part in clinical trial, a partnership with the Christopher & Dana Reeve Foundation.

Epidural stimulation, an experimental therapy for spinal cord injury recovery, involves implanting an electrode on the lower spinal cord, along with a neurostimulator under the patient’s skin, which delivers mild electrical impulses to the spine. When electrical pulses are delivered in different configurations, research at UofL and other centers has shown they help paralyzed individuals like Smith achieve voluntary movement, blood pressure regulation, the ability to stand, improvements in bowel, bladder and sexual function and other benefits, particularly when combined with activity-based therapy. Some participants even have been able to take steps.

UofL first used Medtronic epidural stimulators for spinal cord injury research in 2009 under an FDA Investigational Device Exemption. The research, led by Susan Harkema, professor of neurological surgery and associate director for KSCIRC, has resulted in multiple health benefits and function recovery for paralyzed individuals. While epidural stimulators, also known as spinal cord stimulators, have been proven to provide effective relief for chronic pain and are commercially available for this application, their use for individuals with spinal cord injury remains experimental.

The new controller, known as Stim X Release 1, also offers added benefits for the researchers by precisely recording stimulation use by the participants outside the lab.

“This is Release 1 and we expect future releases to continue to improve the technology,” said Claudia Angeli, assistant professor of bioengineering at UofL’s and director of the Epidural Stimulation Program at KSCIRC. “Additional improvements are planned with feedback from the participants and the development of wireless sensors to monitor the user’s condition and adjust stimulator settings as needed. In a closed-loop or human-in-the-loop system, the controller could alert the user or adjust the stimulation based on a change in blood pressure, for example.”

UofL, Kessler Foundation, Medtronic, Johns Hopkins Applied Physics Laboratory and multiple funders are working together to fast-track technology improvements that allow individuals with spinal cord injury to realize the benefits of epidural stimulation in their homes and communities, not just in the research setting.

“This is the sort of innovation a Carnegie Research-1 university can and ought to be doing,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “This is innovation with real, human impact – work that advances health and helps people live lives that are healthier, more resilient and more fully empowered.”

This work is funded through the  by the National Institute of Neurological Disorders and Stroke, the National Institutes of Health SPARC Common Fund Program, Kessler Foundation and the University of Louisville.

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Despite these significant results, use of epidural stimulation outside a research lab setting to restore function for people with spinal cord injury thus far has been hampered by several limitations, including the use of a technology that was designed for patients with chronic, intractable pain – not those with spinal cord injury.

Applying this therapy for spinal cord injury is a big step closer to use outside the research lab thanks to a $7.8 million grant from the National Institute of Neurological Disorders and Stroke, one of the National Institutes of Health. The grant will fund work at UofL’s  in collaboration with medical device manufacturer Medtronic to develop and test software applications specifically designed for spinal cord injury that work in concert with Medtronic’s commercially-available device, Intellis, which is indicated as a spinal cord stimulator for chronic pain. The five-year project, funded through the , is focused on incorporating technology to improve control of locomotor and bladder function using epidural stimulation.

“We have seen excellent results with epidural stimulation in the lab, but these enhancements to the technology system will make it much easier to implement this therapy out in the community. Integrating multiple systems will allow people with chronic spinal cord injuries to benefit from stimulation on a daily basis by reducing the need to monitor and manually revise stimulation settings,” said Claudia Angeli, assistant professor of bioengineering in the UofL and director of the Epidural Stimulation Program at KSCIRC. Angeli and Maxwell Boakye, neurosurgeon and clinical director of KSCIRC, will lead the project.

Medtronic epidural stimulators first were used for spinal cord injury in 2009 under an Investigational Device Exemption with the FDA during research at UofL led by Susan Harkema, professor of neurological surgery and associate scientific director for KSCIRC. The epidural stimulation therapy involves implanting a neurostimulator under the patients’ skin and implanting electrodes in the epidural space of the lower spinal cord, which together deliver mild electrical impulses to the spine.��

While epidural stimulation has been proven to provide effective relief for chronic pain, there are limitations in functionality when treating individuals with spinal cord injury. For example, the stimulation settings that allow individuals with spinal cord injury to stand are different from settings that allow them to walk, while a third configuration is required to help with bladder function and so forth. The devices that researchers use today must be programmed manually for each individual function.

The goal of the new project is to develop integrated, closed-loop programming for multiple systems, specifically locomotion and bladder function, using wireless sensors to monitor the user’s condition and adjust stimulator settings as needed. Working with Medtronic, the UofL researchers will develop learning programs for the closed-loop system and integrate the programming with commercially available epidural stimulators, as an investigational use.

“This device will be customized for the needs of individuals with spinal cord injury, which will require less manual interaction and lead to more positive outcomes in both locomotion and bladder function, dramatically improving the future of neuromodulation for spinal cord injury,” said Boakye, chief of spinal neurosurgery at the , neurosurgeon with and lead neurosurgeon for implantation of the device.

During the first phase of the study, the researchers will develop learning algorithms and the closed-loop system, working with the Medtronic’s Intellis Spinal Cord Stimulation platform. This phase calls for eight individuals to receive implanted stimulators and either locomotor or bladder interventions to develop learning algorithms, which later will be integrated in closed-loop controls. Those data and technical tools then will be applied to a second group of eight individuals who have not received prior training.

“By monitoring multiple systems and enabling the controller to adjust stimulation without direct input from the user, these improvements will make this device a powerful tool for improving the lives of people with spinal cord injury,” said April Herrity, an investigator on the project.

The 2018 breakthrough was the result of years of research by the UofL team, which found that applying electrical stimulation to the lower spinal cord, combined with physical therapy, allows unexpected degrees of recovery in people with complete spinal cord injury. Research participants are able to move voluntarily, stand and take steps, in addition to experiencing improvements in blood pressure regulation, bowel and bladder function and other common health issues associated with spinal cord injury.

“One of the main obstacles to making this therapy available to patients has been the need for programming specific for spinal cord injury,” said Harkema, also an investigator on this project. “This new work will promote the safe, long-term use of the therapy in the home and community, allowing people with spinal cord injury to benefit from the discoveries we have made over the past two decades.”

“Medtronic is excited to be collaborating with the University of Louisville on research related to the use of spinal cord stimulation to improve function for individuals with spinal cord injury,” said Charlie Covert, vice president and general manager of Pain Therapies, part of the Neuromodulation Operating Unit at Medtronic. “Collaboration is vital to innovation in this space in order to meet the needs of this important patient population.”

The research, conducted at the at the University of Louisville, was published online early and will appear in the Sept. 27 issue of the .��

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This groundbreaking progress is the newest development in a string of outcomes at UofL, all pointing to the potential of technology in improving quality of life – and even recovery – following spinal cord injury. This latest study builds on initial research published in The Lancet in 2011 that documented the success of the first epidural stimulation participant, Rob Summers, who recovered a number of motor functions as a result of the intervention. Three years later, a study published in the medical journal Brain discussed how epidural stimulation of the spinal cord allowed Summers and three other young men who had been paralyzed for years to move their legs. Later research from UofL demonstrated this technology improved .

“This research demonstrates that some brain-to-spine connectivity may be restored years after a spinal cord injury as these participants living with motor complete paralysis were able to walk, stand, regain trunk mobility and recover a number of motor functions without physical assistance when using the epidural stimulator and maintaining focus to take steps,” said Susan Harkema, PhD, the study’s author, professor and associate director of the . “We must expand this research – hopefully, with improved stimulator technology – to more participants to realize the full potential of the progress we’re seeing in the lab, as the potential this provides for the 1.2 million people living with paralysis from a spinal cord injury is tremendous.”

Progress for individuals living with paralysis

The American Spinal Injury Association Impairment Scale (AIS) was used to classify the spinal cord injuries of each of the four participants. When the four participants joined the study, they were at least 2.5 years post injury. They were unable to stand, walk or voluntarily move their legs.

Eight to nine weeks prior to the implantation of an epidural stimulator, they started daily locomotor training – manual facilitation of stepping on a treadmill – five days per week for two hours each day. Although there were no changes to their locomotor abilities prior to the implant, following the epidural stimulation participants were able to step when the stimulator was on and the individual intended to walk. Participants 3 and 4 were able to achieve walking over ground – in addition to on a treadmill – with assistive devices, such as a walker and horizontal poles for balance while the stimulator was on.

“Being a participant in this study truly changed my life, as it has provided me with a hope that I didn’t think was possible after my car accident,” said Kelly Thomas, a 23-year-old from Florida, also referred to as Participant 4. “The first day I took steps on my own was an emotional milestone in my recovery that I’ll never forget as one minute I was walking with the trainer’s assistance and, while they stopped, I continued walking on my own. It’s amazing what the human body can accomplish with help from research and technology.”

Jeff Marquis, a 35-year-old Wisconsin native who now lives in Louisville, was the first participant in this study to attain bilateral steps.

“The first steps after my mountain biking accident were such a surprise, and I am thrilled to have progressed by continuing to take more steps each day. In addition, my endurance has improved, as I’ve regained strength and the independence to do things I used to take for granted like cooking and cleaning,” said Marquis, who is participant 3 in New England Journal of Medicine study. “My main priority is to be a participant in this research and further the findings, as what the University of Louisville team does each day is instrumental for the millions of individuals living with paralysis from a spinal cord injury.”

“While more clinical research must be done with larger cohorts, these findings confirm that the spinal cord has the capacity to recover the ability to walk with the right combination of epidural stimulation, daily training and the intent to step independently with each footstep,” said Claudia Angeli, PhD, senior researcher, Human Locomotor Research Center at Frazier Rehab Institute, and assistant professor, University of Louisville’s Kentucky Spinal Cord Injury Research Center.

Advancements for spinal cord injury community

This research is based on two distinct treatments: epidural stimulation of the spinal cord and locomotor training.

• Epidural stimulation is the application of continuous electrical current at varying frequencies and intensities to specific locations on the lumbosacral spinal cord. This location corresponds to the dense neural networks that largely control movement of the hips, knees, ankles and toes.
• Locomotor training aims to ultimately retrain the spinal cord to “remember” the pattern of walking by repetitively practicing standing and stepping. In a locomotor training therapy session, the participant’s body weight is supported in a harness while specially trained staff move his or her legs to simulate walking while on a treadmill.

“We are seeing increasing interest in the use of neuromodulation procedures and technologies such as epidural stimulation in the treatment of spinal cord injury and restoration of locomotor, cardiovascular and urodynamic functions,” said Maxwell Boakye, MD, MPH, MBA, chief of spinal neurosurgery at UofL and clinical director of the Kentucky Spinal Cord Injury Research Center. “Epidural stimulation is likely to become a standard treatment with several improvements in design of the device to target more specific neurological circuits.”  

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust, University of Louisville Hospital and Medtronic plc.Fo

Left to right:  Kelly Thomas, Claudia Angeli, Ph.D., Jeff Marquis and Susan Harkema, Ph.D.

More about the research participants

Jeff Marquis, 35, Louisville

Jeff Marquis was living in Montana, working as a sous chef and enjoying an active life kayaking, mountain biking, skiing and snowboarding. However, in the fall of 2011 his life changed forever while biking on a mountain trail, as he missed a jump and landed on his head which left him unable to move.

He sustained a C 5-6, Asia B spinal cord injury and was a quadriplegic, paralyzed from the chest down. Marquis spent the next two years in rehab therapy, strengthening the muscles above his injury. He added his name to the research database at the University of Louisville’s Kentucky Spinal Cord Injury Research Center shortly after his injury and got the call to participate in 2014. As part of Marquis’s recovery process, he had an epidural stimulator surgically implanted in his spine and completed a rigorous schedule of daily activity-based step and stand therapy sessions at Frazier Rehab Institute. This technology and physical training, coupled with mental intention, allowed him to take voluntary steps on his own. In addition to being less fatigued, which was a significant problem prior to the implant, Jeff no longer needs daily in-home help and also now shops, cooks and bakes again— activities he was unable to do before the epidural stimulator.

Kelly Thomas, 23, Citrus County, Florida

Kelly Thomas grew up in Citrus County, Florida, riding horses, raising show cattle and helping her dad on the ranch. In 2014, a car accident left her a paraplegic with a C7, T1 incomplete spinal cord injury. She was paralyzed from the chest down, unable to use her legs.

Believing recovery was possible, Thomas learned about Harkema and applied to participate in research at the University of Louisville’s Kentucky Spinal Cord Injury Research Center. She was admitted to the research program in 2017 and had the epidural stimulator implanted that September. Thomas was committed to her training and achieved independent right leg stepping on the treadmill after just three therapy sessions. Among the many accomplishments in her journey towards recovery, she has achieved walking over ground with a walker, without contact assistance from trainers, when she has the mental intention to walk.

Thomas continues therapy training and has moved back to Florida to pursue a bachelor’s degree in criminal justice at the University of Central Florida. After graduating, she plans to attend law school.

“My whole life has opened up for me again!” Putnam said.

A C4 spinal cord injury in 2009 left Putnam paralyzed from the neck down and suffering from chronic low blood pressure. She relied on medication and tight corsets to maintain her blood pressure, but she still passed out five or six times a day.

Her new lease on life is the result of spinal cord epidural stimulation (scES) she received as a participant in research at the University of Louisville’s (KSCIRC) to aid recovery for individuals with spinal cord injury. Research published today in describes the improvements Putnam and three other research participants experienced in blood pressure and heart rate regulation during and after scES. All four participants had chronic, complete cervical spinal cord injury, persistent low resting blood pressure and blood pressure decrease when sitting up prior to receiving scES.

“From a quality of life perspective, orthostatic hypotension, or low blood pressure when sitting up, is truly life limiting,” said Glenn A. Hirsch, MD, a cardiologist with the UofL School of Medicine and co-author of the study.

Spinal cord epidural stimulation uses an implanted electrode array to deliver electrical signals to the lumbar spine. For this study, research participants received stimulation using specific configurations selected to target cardiovascular function, monitoring blood pressure and cardiovascular function throughout, for an average of 89 daily, two-hour sessions. Earlier research showed the benefits of scES in controlling cardiovascular function during stimulation, but this data reveals participants’ blood pressure and heart rate remained stabilized between sessions, showing an enduring effect.

“What was most surprising was that only having it on for a few hours a day, we were noticing participants having normal blood pressure through longer periods of each day,” Hirsch said. “We are noticing it now across the research participants who had that problem, that there is a prolonged stabilizing effect even after the stimulator is turned off.”

Since receiving scES for her cardiovascular symptoms, Putnam said she enjoys increased independence and alertness, and she no longer needs medication to increase her blood pressure.

“I am an active member in my own life instead of merely existing. I am really living! I can prepare and cook my own meals. I can feed myself and carry on a conversation. Without the disruption of passing out or gasping for breaths in the middle of a task or having to stop and be back in my chair for two hours at a time, I can accomplish so much more. Now I can live my best life with energy to focus on my future.” Putnam said.

Research at UofL using scES, led by Susan Harkema, PhD, associate director of KSCIRC and professor of neurosurgery at UofL, began with the goal of restoring motor function. However, researchers and participants soon noticed stimulation led to improvements in cardiovascular and autonomic systems as well.

“In our motor system studies, we observed that we could actually regulate blood pressure without activating the motor system. That launched us into another area of research,” Harkema said. “Many people don’t realize that walking in many cases is not really the aspect that makes their daily lives most difficult because they have cardiovascular dysfunction and problems with respiratory, bowel, bladder, and sexual function. All of those things are disrupted so every day is incredibly difficult for people with spinal cord injury.”

In ongoing research to explore further the life-enhancing effects of epidural stimulation, the UofL researchers are conducting a six-year study with 36 participants with chronic, complete spinal cord injuries.

Today’s published research, “Epidural Spinal Cord Stimulation Training and Sustained Recovery of Cardiovascular Function in Individuals with Chronic Cervical Spinal Cord Injury,” was supported by the Craig H. Neilsen Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, University of Louisville Hospital, Christopher & Dana Reeve Foundation and Medtronic Plc.

Check out Stefanie’s story in her own words here: 

“People with severe spinal cord injury – especially when it occurs in a higher level in the spine – have problems with blood pressure regulation to the point that it becomes the main factor affecting quality of life for them,” said Glenn Hirsch, MD, professor of cardiology at the University of Louisville. “Some cannot even sit up without passing out. They are forced to use medications, compression stockings or abdominal binders to maintain an adequate blood pressure.”

Working with human research participants, Hirsch and researchers at the  at UofL, have found that spinal cord epidural stimulation can safely and effectively elevate blood pressure in individuals with SCI along with chronic hypotension. The research was reported this month in Frontiers in Human Neuroscience ().

Led by Susan Harkema, PhD, associate director of KSCIRC and professor of neurosurgery, the research included four research participants with chronic, motor complete, cervical SCI who suffered from persistent low resting blood pressure. The participants were implanted with an electrode array for epidural stimulation, and individual configurations for stimulation were identified for each participant. During five two-hour sessions, the participants’ blood pressure was elevated to normal ranges. Their blood pressure returned to low levels when stimulation ceased, and was again elevated to normal ranges with stimulation.

Stefanie Putnam was one of the research participants. Following a severe spinal cord injury in 2009, Putnam’s blood pressure was so low she was unable to engage in the simplest of activities without losing consciousness.

“It prevented me from participating in activities, from talking on the phone, from sitting at a table and eating food. I had trouble breathing, trouble swallowing, trouble carrying on a conversation,” Putnam said. “I was passing out periodically – six or more times a day. Then I would have to tilt back in the chair for two hours.”

To help sustain her blood pressure, Putnam took medication, wore an extremely tight corset and drank a large amount of caffeine.

“I would still pass out,” she said.

With epidural stimulation, Putnam said she immediately felt the effects.

“I went from feeling like I was glued to the floor to elevated – as though gravity was not weighing me down. I feel alive,” she said.

Because of the undesirable side effects of pharmaceutical and non-pharmaceutical interventions, Hirsch said epidural stimulation for chronic low blood pressure in SCI could have significant benefits.

“People with severe SCI who have problems with resting hypotension have limited options. This intervention appears to reliably and reproducibly maintain blood pressure,” Hirsch said.

This work builds on previous research at KSCIRC showing benefits of spinal cord epidural stimulation, along with activity-based training, in which individuals with SCI have achieved voluntary movement, standing and stepping, and improved bladder, bowel and sexual function.

Harkema, the publication’s first author, said the blood pressure research is promising, but must be tested over time and with a larger cohort of study participants.

“We need to see if it will have an impact over months or years,” Harkema said. “It will be very important to determine if these results are sustainable.”

To that end, UofL is screening participants for a six-year study that will further explore the life-enhancing effects of epidural stimulation on people with spinal cord injury. That study will measure the extent to which epidural stimulation will improve cardiovascular function as well as facilitate the ability to stand and voluntarily control leg movements below the injury level in 36 participants with chronic, complete spinal cord injuries. Individuals interested in being considered for this study can add their information to the university’s Victory Over Paralysis database, which is available online.  

The published research is supported by the Craig H. Neilsen Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, University of Louisville Hospital, Christopher & Dana Reeve Foundation and Medtronic Plc.

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: