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Epidural Spinal Cord Stimulation in a Paraplegic Human

Frequently Asked Questions (Originally published in May 2011)

What is this new research? What has been discovered?
A team of scientists from several universities completed the first research study involving a person with a chronic spinal cord injury (paraplegic) and a promising treatment intervention consisting of epidural spinal cord stimulation and simultaneous Locomotor Training.

What were the results?
The individual, a young man who has no muscle control below his chest, was able to reach a standing position while his spinal cord was being stimulated electrically. Supplying the muscular push himself, he was able to stand independently, bearing full weight, for up to four minutes at a time without assistance. He could remain on his feet for up to an hour with periodic help when he weakened.

When stimulated and suspended on a treadmill, the individual was able to initiate robust, rhythmic stepping movements, with assistance in placing his feet. Prior to using the epidural stimulator, the subject underwent 170 Locomotor Training (LT) sessions over a period of 26 months, with no measurable effect; the treadmill therapy alone did not affect his function.

After seven months, he could also voluntarily move his toes, ankles, knees and hips. The research team was surprised by this. They speculate that this voluntary recovery of function may have been caused by the epidural stimulation awakening residual but weak spinal nerves. The recovery may also have been the result of nerve regeneration or sprouting as a result of repetitive activity-based training. There were also observations that may indicate some improvements in bladder control and regulation of temperature. However, more studies are needed to understand this further.

What is epidural spinal cord stimulation?
In this case, epidural stimulation is the application of a continuous electrical current, at varying frequencies and intensities, to specific locations on the lower part (lumbosacral) of the spinal cord. An epidural spinal cord stimulator with 16-electrodes was implanted over the spinal cord at T11-L1. This location corresponds to dense neural bundles that control movement of the hips, knees, ankles and feet.

Hasn't electrical stimulation been used for many years to help people move paralyzed muscles?
Yes, functional electrical stimulation is not uncommon in people with spinal cord injuries. But this study is not about stimulating muscle. In this case, epidural stimulation activated nerve circuits that exist in the spinal cord, with the intent of substituting for nerve signals that would normally have come from the brain to modulate these spinal networks. Stimulation of the spinal circuitry itself activates what scientists call a central pattern generator – a network of nerves that are able to initiate stepping function without input from the brain.

What is this central pattern generator all about?
The spinal cord used to be thought of as a passive nerve cable connecting the brain to the muscles in the body. It turns out the spinal cord is, to some degree, "smart." If certain sensory information is provided, the spinal cord can recognize this information and respond by generating a stepping pattern of muscle activity. This activity can be enhanced with repetition and training.

Animal experiments have shown that this patterning and stepping activity can be triggered by guided stepping on a treadmill (Locomotor Training). The spinal cord retains a level of automatic function; the spinal cord already knows what to do, it just needs to be reminded what to do, which is what happens with the sensory information that comes from treadmill stepping. Motor function can be improved if nerves in the lumbar spinal cord are made more receptive to sensory information. This is what electrical stimulation does: it sensitizes the cord. In animals, it has been shown that certain drugs also increase the cord's sensitivity and further improve the outcome of Locomotor Training. No such drugs exist yet for human trial. This human experiment confirms that the sensory system can actually control the stepping.

What is Locomotor Training?
Locomotor Training is a rehabilitation protocol based on the concept that sensory input triggers the spinal cord to activate stepping patterns. LT has been commonly used for about a decade and is the basis of the Reeve Foundation's NeuroRecovery Network. It has been shown that LT has health benefits for almost all participants; some incompletely injured individuals regain walking function.

In the current research, the individual's legs were repeatedly manipulated on a treadmill by therapists, reproducing a normal stepping pattern in real time as the appropriate spinal circuitry was being electrically stimulated.

Why did the treadmill training work with stimulation, and not by itself?
The epidural stimulation appears to alter the functional state of the spinal cord circuitry. It makes the cord more excitable, more sensitive. In animal experiments stimulation was augmented by use of a drug to further excite the lumbar spinal cord. Researchers are not yet to the point of using such a drug in humans.

What is the implication of this research for paralysis patients?
The researchers envision a day when at least some individuals with complete spinal cord injuries will be able to use a portable stimulation unit and, perhaps with the assistance of a walker, stand independently, maintain balance and execute some effective stepping.

Because secondary complications associated with spinal cord injury -- including impairment or loss of bladder control, sphincter control and sexual response – may also be alleviated, epidural stimulation could help improve the quality of life of individuals with spinal cord injury.

What's next? When will this treatment be available to the general public?
Although theoretical and animal research has been going on for many years, investigators are just beginning to develop an effective treatment for human spinal cord injury. Before this intervention can move into the public area its safety and efficacy must be established in many patients. Approval by the Food and Drug Administration is also required.

In addition, more sophisticated stimulation equipment needs to be developed. Scientists are also hoping to find the right pharmacological agents to boost the treatment's effectiveness.

While proof of concept for this epidural stimulation treatment has been demonstrated, further progress depends on time and available financial resources.

Is this intervention effective in patients with complete or incomplete spinal cord injury? What about acute (new) versus chronic (old) injuries?
The investigators believe this treatment has potential for patients with both complete and incomplete spinal cord injuries, but again, further testing is required. The current study suggests that this therapy works on patients with chronic injuries; it has not yet been tested on an acutely injured patient.

Is it possible for me to qualify as a subject for this research?
It's too soon to consider enrolling in a clinical trial. Once experiments expand to include more people, researchers will set forth the qualifying criteria. When trials do occur, information will be made public. To learn more about the ongoing studies, contact the University of Louisville/Frazier Rehab Institute at www.spinalcordmedicine.com or call 1-866-540-7719. Specific questions can be emailed to: info@spinalcordmedicine.com.

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Continue Christopher Reeve's LegacyPhoto by Timothy Greenfield-Sanders