The latest news and information about what's going on with SCI science and research. Brought to you by Sam Maddox, author of the Christopher & Dana Reeve Foundation Paralysis Resource Guide.

Epidural Stimulation: Research Progressing

We reported last summer that several more young men with spinal cord injuries have been surgically implanted with electrical stimulator units. The devices, off-the-shelf products made for pain relief, are placed over the lower part of the spinal cord, in the lumbar area. The concept is this: the spinal cord contains an intricate weave of nerve fibers that, when properly activated, are able to control certain motor functions. This control occurs without any input from the brain; this means the spinal cord itself is, to a degree, able to remember and to execute. The cord is “smart.” In recent years research scientists have been able to exploit this smartness, using aggressive exercise protocols and, more recently, electrical impulses, to activate the lumbar circuitry.

The first four patients in the epidural stimulation experiments: Andrew Maes, Dustin Shillcox,
Kent Stephenson and Rob Summers.

Support the weight of an infant with his or her feet on the ground and the baby will begin taking alternating steps, left-right-left. How is this done? Not fully by brain input; that system has not fully formed. The stepping motions are organized in the spinal cord by way of what scientists call a central pattern generator (CPG). If the spinal cord receives the right information from the sensory system – e.g. weight bearing or perhaps in the form of weight bearing on a treadmill, or Locomotor Training (LT) – the CPG responds by initiating step patterns by itself.

Many animal experiments, and more recently, a limited number of human trials, have shown that activating the CPG can have important benefits. Some people have regained walking function; almost all participants in the LT program of the Reeve Foundation NeuroRecovery Network (NRN), have gained meaningful health benefits.

Two years ago an international team of researchers funded mainly by the Reeve Foundation raised the ante in boosting CPG response. A small electrical array was implanted over the dura of the lumbar cord. The first patient with the epidural stimulator had no motor function below his chest-level injury. When the lumbar cord was stimulated, however, he could stand on his own and take steps. To the surprise of the research team, the young man regained voluntary motor function when the stim was on. What was even more surprising, he regained bladder control and sexual function, even when the stim was off. Not only was the CPG reawakened, it seemed to remain awake. We’re talking, of course of Rob Summers, who is no stranger to readers of this website.

This epidural stimulation work – overseen at Frazier Rehab Institute in Kentucky by Susan Harkema, Ph.D., director of the NRN, and based to a large degree on the research of Reggie Edgerton, Ph.D., at UCLA – has continued. So far, four patients have been fitted with epidural stimulators. While the data have not yet been published, all four have shown similar patterns of recovery: they can step when the stim is on. They all gained muscle mass, improved cardiovascular function and were able stand with no assistance with the stimulator on.

Summers’s story was presented in a paper in the journal Lancet. It was, as you may recall, a big media story. So far only one additional paper has been published on the human epidural stimulation experiments, this one based on the first three patients, from the electrophysiology lab of Yury P Gerasimenko, from the Pavlov Institute of Physiology, St. Petersburg, Russia, and a close collaborator of Edgerton at UCLA, with Dimitry G Sayenko at the U of Louisville as lead author. We’ll look more at that set of experiments below. First, more on the epidural stim pioneers.

I interviewed each of the four patients for an article in the Reeve newsletter, Progress in Research. None of the four had the ability to move any muscles below the lesion level. With the stim on, all got meaningful recovery – not walking per se but autonomic improvement, including bowel, bladder, sexual function and for the one quad of the bunch, an important gain in temperature regulation. Herewith is that article, fresh off the press.

Two other pieces came out ahead of published data, one last year from New Mobility on patient #2 Kent Stephenson’s enthusiastic endorsement of the procedure.

Another piece, a nice long one, focused more closely on patient #4, Dustin Shillcox, and the engineering side of the stimulation experiments. This appeared a couple of months ago in Spectrum, a publication of IEEE (Institute of Electrical and Electronics Engineers). One major point of this piece: the equipment being used to stimulate the spinal cord is crude and inefficient; they’re working on better tools, but this is all we have now.

Now, to the aforementioned second paper, just out in December from the Journal of Neurophysiology, titled “Neuromodulation of evoked muscle potentials induced by epidural spinal cord stimulation in paralyzed individuals.” It doesn’t focus on recovery of function so much as the measurable vitality of the spinal cord circuits awakened by the stimulation. The response of the body to stimulation is map-able and tune-able, and works fine on people with chronic injuries.

From the paper:
The purpose of this study was to investigate the functional and topographic organization of compound evoked potentials induced by the [epidural] stimulation.
The components of neural pathways that can mediate motor evoked potentials were highly dependent on the stimulation parameters and sensory conditions, suggesting a weight-bearing induced reorganization of the spinal circuitries.
The scientists recorded EMG signals from the epidural stimulation in several locations in the legs, glutes, hamstrings etc. using surface electrodes. The team suggests they will need to study more subjects to fully map out the motor behaviors from the stimulation but that it may be possible at some point to selectively fine-tune responses, even long after initial spinal cord injury.
Here we show the feasibility of the method and provide the beginning of a comprehensive data base that can be used to compare primordial spinal circuitry properties across individuals with different injuries, as well as for repeated measures over time within the same individual.

The person data are consistent with the conclusion that the selective recruitment of the specific motor neuron pools can be titrated during localized stimulation of the spinal cord, particularly at lower stimulation intensities.

It has been recently suggested that individuals with SCI gradually lose some intrinsic properties of spinal circuitry as they progress from the acute to the chronic state, supporting that the loss of sensory and motor input leads to re-organization of the underlying spinal networks However, our findings showing that the state of excitability of lumbar cord networks can be effectively modulated during such functional task, as standing, look promising in light of the functional rehabilitation of individuals that can occur at the chronic stages after the injury.

So far so good. Let's hear it for more functional rehab. Four patients makes a case but doesn't lock it down enough to get it past regulatory hurdles. There's much more to learn.
Posted by Sam Maddox on Jan 17, 2014 9:40 PM America/New_York