Hot Topic - Epidural Stimulation

Epidural Electrical Stimulation (EES) is the application of electrical pulses to the lower part of the spinal cord below an injury. The stimulation is generated via a small chip that is implanted over the protective coating (dura mater) of the spinal cord. A remote control about the size of a smart phone controls the frequency and intensity of the electrical current. Although research on this approach has been ongoing for some time, this year was special because of new reports that some people who were previously thought to be completely paralyzed are able to voluntarily move their legs when the stimulator is on, and other subjects with some residual motor function but couldn’t walk, became able to walk overground with assistive devices.

These breakthrough reports are from long-term studies led by different Principal Investigators, two of whom are previous recipients of the Reeve-Irvine Research Medal (Reggie Edgerton at UCLA andSusan Harkema at the University of Louisville, Kentucky).

In a study published in 2018 in the prestigious New England Journal of Medicine, Dr. Susan (Suzy) Harkema and her group at the University of Louisville report enhanced brain-to-spinal cord connectivity in subjects with complete paralysis. Here, they tested effects of EES combined with intensive locomotor treadmill training with weight support in 4 patients 2.5 to 3.3 years after SCI. Two of the four research participants developed the ability to walk over ground with a walker with no assistance from a therapist. In addition, all four participants achieved independent standing and improved trunk stability while maintaining their mental focus, which is defined as purposefully wanting to pick up their foot or leg to take steps.

Although improved motor function is only seen when the stimulator is on, there were other positive benefits that persisted, including improved function of the autonomic nervous system (temperature regulation, enhancement in sexual function, increase in bladder control and overall improvement in sense of quality of life).

In the new study, the subject received additional “multi-modal rehabilitation (MMR)” for 43 weeks. Eventually, the subject recovered the ability to walkover ground while using a front-wheeled walker with trainers providing only sporadic assistance.

Then, another study came out in September 2018 in the prestigious journal Nature Medicine from Reggie Edgerton’s group at UCLA along with researchers from the Mayo Clinic. This paper reported new findings involving a subject with complete loss of function below the sixth thoracic spinal segment due to SCI that occurred3 years prior to study enrollment. The subject previously had 22 weeks of locomotor training before the implantation of the EES system. After the implantation of the EES device and training, the subject was able to stand and generate step-like leg movements when the EES was on. In the new study, the subject received additional “multi-modal rehabilitation (MMR)” for 43 weeks. In the MMR training sessions, the subject first worked on voluntarily moving the legs with the EES turned on and then on standing and stepping with trainer assistance and body-weight support as needed. Eventually, the subject recovered the ability to walk over ground while using a front-wheeled walker with trainers providing only sporadic assistance. Additionally, he was able to take bilateral steps on a treadmill.

Is EES alone enough to regain locomotion? The short answer is no. All the studies published have shown that pairing implantation of the EES chip with locomotor training is needed for the success of the treatment. The stimulator may excite the spinal cord, but rehabilitative training is required to achieve recovery.

This research is based on two distinct treatments: epidural stimulation of the spinal cord and locomotor training. Epidural stimulation is the application of electrical pulses at varying frequencies and intensities to specific locations on the lumbosacral spinal cord. This area of the spinal cord, controls movement of the hip, knees, ankles and toes. The locomotor training aims to retrain the spinal cord to achieve the pattern of walking by repetitively practicing standing and stepping. Combining both treatments will play a critical role in enabling stepping abilities.

Although this is very exciting, things are still at an early stage, and there are some limits and caveats.First, improved function requires many weeks of intense rehabilitative training paired with EES. Second, not all SCI subjects will benefit from the approach. For there to be any voluntary motor function, subjects must have some spared connections across the injury. In this regard, an important scientific discovery is that some subjects that were diagnosed as having no spared functional connections (termed “motor complete”) were nevertheless able to move with stimulation. Going forward, it will be important to find away to identify which subjects can benefit before asking the subject to invest all the time required for training.

Epidural stimulation has transformed our understanding of “complete” injuries and suggests that even people previously diagnosed as motor complete may no longer face a lifelong sentence of paralysis.Spinal neuromodulation in the presence of a task-specific training can enable functions that were once thought to be permanently lost following SCI. Right now more clinical research must be done with larger cohorts in order to translate the treatment to a larger population of SCI community.