New Research on Epidural Electrical Stimulation in Spinal Cord Injury

Two research articles were recently published on the use of epidural electrical stimulation (EES) to help paralyzed individuals recover motor function. The first study was conducted by the Frazier Rehabilitation Institute and the Kentucky Spinal Cord Injury Research Center at the University of Louisville. It included four participants who had motor complete spinal cord injuries, meaning no motor function below the level of injury. Two of the participants had lost all sensation below their level of injury in the spinal cord, which is classified as AIS grade A, and the other two participants had retained partial sensory function below their level of injury, which is classified as AIS grade B. This grading system, The American Spinal Injury Association Impairment Scale (AIS), is used to describe and measure the severity and characteristics of a spinal cord injury. The second study was conducted by the Mayo Clinic Rehabilitation Medicine Research Center in Rochester, MN and included one participant who had a motor complete spinal cord injury and had lost all motor function below their level of injury.

In both studies, participants had received clinical rehabilitation after their spinal cord injury and were 2.5 to 3.3 years from when their injury was sustained. All participants received locomotor training at the start of each study, which lasted 8 to 22 weeks depending on the participant. The participants were then implanted with the EES system during a surgical procedure in which a 16-electrode array was implanted on the spinal cord and a spinal cord stimulator was implanted on the abdomen. After participants rested approximately three weeks, the EES system was tested to identify muscle groups in the legs using electromyographic (EMG) recording.

Next, participants in these studies received locomotor training with the aid of electrical stimulation. The participants practiced stepping on a treadmill, stepping over ground, and standing over ground. Participants used a body-weight support system (BWS), trainer assistance, and a walker when needed. They adjusted to not using these aids if progress was shown over the course of the training.

In the Frazier Rehabilitation Institute and the Kentucky Spinal Cord Injury Research Center study, the two AIS grade B participants were able to walk over ground while using assistive devices. The two AIS grade A participants were able to achieve some aspects of stepping on the treadmill with body-weight support, but they were unable to walk over ground. The participant in the Mayo Clinic Rehabilitation Medicine Research Center study was able to achieve stepping on a treadmill, independent standing, and stepping over ground while using a front-wheeled walker and occasional trainer assistance. All four participants were only able to perform these motor functions while the EES system was turned on and when they had the intention to move.

The results of these studies suggest that motor functions may be able to be restored in individuals with spinal cord injury with the use of electrical stimulation. The researchers at the Frazier Rehabilitation Institute and the Kentucky Spinal Cord Injury Research Center noted that the difference in outcomes between the two participants who were able to walk over ground and the two participants who were not able to walk over ground may be due to their sensory level below their injury or other factors. The researchers in both studies recommend a follow-up study be conducted with a larger number of participants.

Dr. Cristina Sadowsky, Clinical Director of the International Center for Spinal Cord Injury (ICSCI) at the Kennedy Krieger Institute, shared with us about how the results of these studies may be applicable to those with rare neuroimmune disorders.

“The epidural stimulation case reports prove that some brain-spinal cord connections are dormant post injury and can be activated by ‘raising the excitability level’ of the neurons in the ‘gait center’ in the lumbar spine using the epidural spinal cord stimulator. The stimulator appears to work better in people with (sensory) incomplete injuries, which makes sense, as the number of tracts that connect the brain to the lumbar spine is probably higher than those with motor complete injuries. The stimulation does not work in everyone.

While the case series reports on results in individuals with traumatic spinal cord injury, the results of epidural stimulation could potentially be applied to paralysis related to non-traumatic conditions, like transverse myelitis (TM), neuromyelitis optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis (ADEM), etc., as long as the injury spares the nerves leaving the cord and supplying the muscles in the legs. One way to determine that is to inquire about muscle spasms and reflexes – if they are present, the nerves to the legs are most likely intact.

What would the next steps be to advance this significant research discovery?

1. Making someone’s gait more energy efficient, which would allow for smoother, longer distance ambulation. You would do that by working towards a more “normal” gait, including reducing assistance from other people to stabilize the pelvis, etc.
2. Figuring out the best candidates for the procedure; establishing criteria that would preclude a person from getting the stimulator.
3. Making the process of figuring out the best electrode parameters that give the optimal gait response easier by making this process short, reliable, and clinician friendly.
4. Getting the smallest, safest, most reliable, customizable epidural stimulator.

There are also some concerns:

1. Implanting a stimulator/foreign object leads to the possibility of technological failure.
2. The implant might make it impossible to have an MRI study.
3. The stimulator assisted gait is not independent and certainly not normal/efficient (yet).
4. The hype it creates makes everyone think that they can walk if a stimulator is implanted.
5. It’s still far away from actual use in clinical care. It takes a long time to program, programing is very personalized and requires a lot of knowledge. Dr. Susie Harkema and Dr. Reggie Edgerton, the senior scientists on each paper, have been working in the gait training field for many years!

The case reports are more relevant for the fact that now there is a method to allow for meaningful remaining brain-spinal cord connections to be uncovered and used, and it points out to the absolute NEED to undergo extensive, well designed, meaningful activity based rehabilitative interventions.”

Angeli CA, Boakye M, Morton RA et al. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med. 2018;379(13):1244-1250.

Gill ML, Grahn PJ, Calvert JS et al. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018 Sep 24.