Mayo Clinic has challenged its researchers to transform the practice of medicine with research that leverages multidisciplinary expertise, technology and therapeutic advances to address unmet clinical needs. This story describes how one team has risen to the challenge, elevated the level of teamwork across disciplines and achieved novel results using spinal stimulation to enable function after spinal cord injury. The story focuses on two team members — both alumni of Mayo Clinic College of Medicine and Science schools in different disciplines.

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The two first authors on a recent publication in Nature Medicine have personal connections to the groundbreaking research they reported in the manuscript. Peter Grahn, Ph.D., a senior engineer in the Department of Physical Medicine and Rehabilitation and alumnus of Mayo Clinic Graduate School of Biomedical Sciences; and Megan Gill, D.P.T.,, an alumna of Mayo Clinic School of Health Sciences who also has a doctorate in physical therapy, have worked on a team of researchers from Mayo Clinic, UCLA and Houston Methodist during the last four years. The team has studied an emerging research approach to restore function in people with paralysis due to spinal cord injury. From a personal perspective, Drs. Gill and Grahn have each had a health-related event that affected their mobility

The study

In 2014, a team of 15 Mayo Clinic scientists and clinicians from neuro-engineering, neurosurgery, and physical medicine and rehabilitation acquired internal funding to collaborate with V. Reggie Edgerton, Ph.D., of UCLA, to establish his team’s spinal neuromodulation approach at Mayo Clinic. The approach was developed in conjunction with Susan Harkema, Ph.D., from the University of Louisville. Building on Dr. Edgerton’s work, the Mayo team designed the clinical trial protocol and acquired Mayo Clinic Institutional Review Board approval and an Investigational Device Exemption from the Food and Drug Administration (FDA). Mayo Clinic received FDA permission to use an electrical stimulation device for research purposes to study a condition not covered by its approved label. Co-principal investigators were Kendall Lee, M.D., Ph.D., Department of Neurologic Surgery and director of Mayo Clinic’s Neural Engineering Laboratories; and Kristin Zhao, Ph.D., Department of Physical Medicine and Rehabilitation and director of Mayo Clinic’s Assistive and Restorative Technology Laboratory.

The Mayo Clinic team’s objective was to determine whether spinal cord circuitry could be modulated with electrical stimulation and rehabilitation to restore function lost to paralysis. Two patients with complete spinal cord injury were enrolled in the trial.

“Dr. Edgerton’s team showed us the ropes of how to program the epidural electrical stimulator so we could replicate what they’d achieved in their studies,” says Dr. Grahn. “During our initial programming session, the subject moved his leg using his own intent. When we observed this ability, everyone in the room gasped.”

The Mayo team replicated the UCLA team’s results within the first week of the study and continued to see what more they could achieve. They accomplished much more than basic leg movements.

Jered Chinnock, who injured his spinal cord at the thoracic vertebrae in the middle of his back in a snowmobile accident in 2013, was the first participant in the Mayo Clinic study. He had complete loss of function and feeling below the middle of his torso. Dr. Lee and his neurosurgery team had implanted an electrode array in the epidural space at a specific location below Chinnock’s injury. The electrodes were connected to a pulse generator that was implanted near the patient’s abdomen. The generator communicates wirelessly to an external controller.

Chinnock participated in 113 rehabilitation sessions in the lab over 43 weeks in 2016 and 2017. Team members programmed the stimulator and recorded electrophysiology and biomechanical data. Dr. Gill led the physical therapy team and provided expertise about how rehabilitation with the device should occur. They provided Chinnock with physical assistance and used a body-weight harness to help him stand and step. With electrical stimulation, he was able to stand, swing his legs and shift his weight to maintain his balance. Because he didn’t regain sensation in his legs, Chinnock initially used mirrors to view his leg movement while rehabilitation team members provided verbal and tactile cues to describe his leg position, movement and balance.

“ Seeing our research subjects’ accomplishments is exciting, We’re grateful for their phenomenal effort and contributions to our research.”

Peter Grahn, Ph.D.

The results

By the end of the study, Chinnock no longer needed a harness and had only occasional help from the therapists. He learned to use his body to transfer weight, maintain balance, and propel forward on a treadmill while using his arms on the support bars to help with balance. He required minimal verbal cues and periodic glances at his legs. He progressed to using a front-wheeled walker to step with minimal assistance from the team.

“I was surprised by the amount of motor activity Jered was able to do with stimulation,” says Dr. Grahn. “Looking at past studies, we thought he may be able to stand without assistance and move his legs while lying down. No studies had shown that someone with complete paralysis could stand and take steps. With the stimulator off, the subject remains completely paralyzed below the level of his injury. These findings suggest that even the most severe cases of paralysis likely have some connections intact across the injury, and that neural networks below the spinal cord injury can be facilitated by epidural stimulation to restore functions such as standing and stepping. Altogether, these results support the concept that task-specific rehabilitation performed during spinal stimulation can enable functional reorganization of the spinal cord to recover functions lost due to spinal cord injury.”

Dr. Grahn says the results generated by the Mayo team could be attributed to factors such as the patient’s specific injury, some aspect of the rehabilitation or key changes made to stimulator settings. Certainly, their findings have sparked more questions to investigate.

The team is endeavoring to further explore the use of epidural electrical stimulation and other emerging spinal neuromodulation techniques, combined with intense physical therapy, to help paralyzed patients regain function. A subsequent trial will help answer some of the unknowns from the first — to gain a better understanding of how and why the epidural electrical stimulation enables these functional gains and which patients will respond to stimulation.

Now that Chinnock is home in Tomah, Wisconsin, he works on an exercise program the Mayo team specified. He has approval to use the device for standing with a walker and to improve his trunk strength and balance during daily activities in his wheelchair.

The personal connection

While it can’t be measured as part of the data, Dr.Gill and Dr. Grahn say their personal experiences had a significant impact on their perspectives and dedication to the project.

At age 18, Dr. Gill developed a systemic infection that required a year of rehabilitation and healing to allow normal use of her left leg. That experience led her to pursue a medical career and develop personal drive to help patients achieve their goals.

Dr. Grahn has had quadriplegia due to spinal cord injury since 2005 and uses a powered wheelchair for mobility. When he was 18, he dove off of a dock in central Minnesota and hit the shallow bottom of a lake, fracturing the fifth vertebrae in his neck. He was instantly paralyzed and spent almost a year in rehabilitation.

Dr. Grahn, whose injury has affected his motor functions more than the patient in the Mayo Clinic study, says he felt a strong sense of excitement as Chinnock’s abilities progressed during the study. “In the early stages of my own recovery, I admit there was a sense of jealousy when someone in the rehab gym with a similar prognosis as mine would recover to walk again. My point of view is different now. For the first couple of months after my accident, I thought if I worked hard enough at rehabilitation, I’d get better as I had with past sports-related injuries. Over time I realized my disability was permanent, and I experienced dark times during that period in my life. Eventually I realized that life is full of challenges, and learning to live with my disability was one of those challenges. I was also curious why the spinal cord doesn’t heal.

“Fast forward 13 years, and I’m in a unique position to contribute to making discoveries and generating information to advance the research fields of neuromodulation and spinal cord injury. It was exciting to see the potential of what our patient could do when we turned on the stimulator. Our work demonstrates that spinal cord injury severity is more of a spectrum. We may be able to improve function even in severely injured patients who are diagnosed with the worst category of injury.”

Dr. Gill says Dr. Grahn advocated for epidural stimulation research at Mayo Clinic. “Peter is a prime example of someone living to their greatest capacity. Never has his disability held him back. He has gained a deep understanding of the neuromodulation literature and has developed the skills to communicate this information to all team members regardless of the level of expertise in paralysis research. And, because he has a spinal cord injury, he has unique understanding of our research subjects’ situation.”

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