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.