Non-surgical recovery of function: Not a fantasy

“Improved voluntary hand function occurred within a single session in every subject tested.”

Dr. Reggie Edgerton, Director of UCLA Edgerton Lab, poses for a portrait in his lab on the campus in Los Angeles, California, March 16, 2016. Photo by Kendrick Brinson for Stat.

By Kate Willette, New Mobility July 2, 2018

That’s the killer sentence from a new study soon to be published in the Journal of Neurotrauma. The principal investigator is our old friend, Professor Reggie Edgerton, who has been looking for ways to help people with chronic spinal cord injury since the late 1960s. I’ve met him a number of times in my own efforts to get my head around the difficulty of restoring function. In the small, intense universe of SCI research, he’s a sort of godfather — having mentored and trained a great many of the students currently on the hunt for therapies.

Until the first epidural stimulators were implanted in volunteers back in 2009 and 2010, no substantial functional recovery was happening with chronic injuries. You got back what you got back in the first year or two post-injury, and then you lived with it. Even the breakthrough moments of trials involving different kinds of cells were questionable, because they were invariably aimed at people with very new injuries.

The epidural stimulation work that I covered in my last column originated in Edgerton’s lab, but his new study is about what his team has christened tEMC, short for transcutaneous enabled motor control, also called transcutaneous stimulation.

There is no surgery, nothing implanted, no wires snaking through the body to a device embedded under the flesh. Instead, there are a couple of electrodes taped right onto the skin, not unlike the functional electrical stimulation units a lot of people use to ride stim bikes. The difference is that FES units are designed to push current directly into targeted muscle groups, while tEMC units push current toward the spinal cord itself. In that way, tEMC is just like epistim, and like epistim, it seems to work — in the sense that people do regain volitional movement.

In the fall of 2016, Edgerton published a report based on this question: If putting a stimulator into the lower back epidural space results in voluntary movement of feet and legs, would putting one into the cervical area result in the same for hands and fingers? The report included this line: “Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function.”

Volitional hand function means successfully willing the hand to move. We went from reports of epistim working on the lower limbs to studies showing epistim worked on the hands, and now we have tEMC working on the hands. I got to see this for myself in May. One of Edgerton’s collaborators, Chet Moritz PhD, runs a lab for SCI research at the University of Washington. He invited me to visit during one person’s tEMC session.

What a tEMC Session Looks Like
The session participant, Joe, a 60-something C3-4 quad, was undergoing follow-up work from an earlier tEMC study he’d done with Moritz. It’s the first documentation of tEMC helping a person with limited hand function regain a measure of independence.

Joe was a genial person working with a small team of grad students engaged in setting him up, monitoring his blood pressure, helping him move from place to place, giving him specific tasks to perform and measuring every scrap of data associated with the process. The electrodes were placed in the center of the back of his neck a few inches apart, one above the other.

Transcutaneous stimulation in the Moritz Lab at the University of Washington. Matt Hagen

One of the grad students operated a tablet that controlled the amount and nature of the current being sent to his cervical cord. Joe said it did not hurt at all. Did it feel like those FES units from the stim bikes? He said it was nothing like that. “It doesn’t tingle on your skin. It’s like you can feel the current moving through your spine and all the way down your legs.”

The session lasted for about an hour and a half, with plenty of rests and adjustments. Joe seemed to enjoy it, though I could see that he was getting tired by the end. In a video of Moritz discussing the initial study with Joe, you can see that while he’s not in any sense “cured,” Joe is able to do things independently that were impossible before the study. And as it turned out, Joe wasn’t an anomaly.

Edgerton’s team recruited a total of eight people with SCIs ranging from C3-4 to C7 who were 13 months to 21 years post-injury. None were vent users. Their hand function covered the range from barely a trace to measurable, but weak. The study began with three sessions of testing designed to locate a baseline function for each person. That was followed by four weeks of intervention with the tEMC, twice a week for an hour or two at a time. By the end, two of the subjects had to drop out, both for reasons unrelated to the study.

During each session, with their wrists in neutral positions and arms stabilized to prevent compensating, the subjects worked on maximizing grip strength and rhythmically opening and closing their hands. Electrodes were attached to the appropriate forearm and bicep muscles to measure the exact amount of energy their efforts were generating. All of them got stronger immediately under the influence of the tEMC — and those gains stayed with them. With each new session, their baseline grip strength improved from the previous time. Because the strength was retained, the improvements from week to week were also cumulative.

Finger dexterity also improved. Some could pinch a debit card and get it into an ATM, use a cell phone or turn a key in a lock. One of them was able to twist the cap off a water bottle. Their average maximum grip strength had more than tripled by the end of the study, but also — just as in the epistim trials — they enjoyed improvements in other quality of life measures. Sensation was better. Trunk control was more reliable. They even made gains in bowel and bladder control.

Understanding How It Works
It turns out the spinal cord is not just a collection of individual neurons all wired to other individual neurons; it’s more like a collection of wired-together collections. In my imagination, these collections of neurons that function all together — called neural networks — are sort of like the clumps of jigsaw puzzle pieces you put together off to the side when you’re building a big puzzle. They lock on to one another, and they form part of the picture, but until you find at least one place where your small clump connects to the larger puzzle, they’re just floating, useless.

The neural networks are intact in the undamaged parts of the cord below the injury, but they’re useless without a sufficient connection to the brain. The tEMC and the epistim units light them up in such a way that whatever slender link exists becomes enough.

But what if there’s no link at all? Isn’t that exactly what we mean by “complete injury?” When I was writing Don’t Call It a Miracle in 2014, I asked Lyn Jakeman PhD, about this. As program director, Repair and Plasticity, at the National Institute of Neurological Disorders and Stroke, NINDS, her job is to oversee research funded by the National Institutes of Health that’s aimed at finding therapies for us. She told me that it’s possible the conventional wisdom is wrong — that there’s no such thing as a complete injury. There seems to exist in every cord, no matter how badly damaged, a way to restore some connection.

I call that good news. As Edgerton’s paper puts it: “The increasing number of examples of regained/improved supraspinal control after ‘complete’ paralysis suggest that the basic biology of a spinal lesion that is presently clinically defined to be motor complete must, at least, be challenged.”

What’s even better is these gains were not only quick, they were lasting. Combined with a few months of therapy, stimulator-enabled changes didn’t go away once the study was over. We’re entering a time, at long last, when there is reason to think that even years after injury, some recovery is possible. As Edgerton said, “We have no evidence that the intervention here has been developed to its optimal potential.”

The next task is to work out what that optimal potential might be. It is too early to know for certain. It will take time and a lot of dedicated effort, but we are definitely going to be hearing a lot more about transcutaneous stimulation.

About Kate Willette
Kate Willette’s most recent book, Don’t Call It a Miracle, was commissioned by the Christopher and Dana Reeve Foundation. Since her husband’s C6 injury in 2001, she has become a lively voice informing a worldwide community of people living with paralysis about the state of SCI research. When Willette isn’t roaming around Seattle’s Capitol Hill neighborhood with her dog, Utah, she’s usually at her desk, spinning new plans to comfort the disturbed and disturb the comfortable.

Source New Mobility

Noninvasive activation of cervical spinal networks after severe paralysis, Gad P, Lee S, Terrafranca N, Zhong H, Turner A, Gerasimenko Y, Edgerton VR. J Neurotrauma. 2018 Apr 13. doi: 10.1089/neu.2017.5461. [Epub ahead of print]

Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients, Lu DC, Edgerton VR, Modaber M, AuYong N, Morikawa E, Zdunowski S, Sarino ME, Sarrafzadeh M, Nuwer MR, Roy RR, Gerasimenko Y. Neurorehabilitation and Neural Repair. 2016 Nov;30(10):951-962. Epub 2016 May 18. PMID 27198185 DOI: 10.1177/1545968316644344

Transcutaneous Electrical Spinal Stimulation Promotes Long-Term Recovery of Upper Extremity Function in Chronic Tetraplegia, Inanici F, Samejima S, Gad P, Edgerton VR, Hofstetter CP, Moritz CT. IEEE transactions on neural systems and rehabilitation engineering: a publication of the IEEE Engineering in Medicine and Biology Society. 2018 Jun; 26 6: 1272-1278

Now is the Critical Time for Engineered Neuroplasticity, Moritz CT. Neurotherapeutics. 2018 Jun 11. doi: 10.1007/s13311-018-0637-0. [Epub ahead of print]

And yet it moves: Recovery of volitional control after spinal cord injury, Taccola G, Sayenko D, Gad P, Gerasimenko Y, Edgerton VR. Prog Neurobiol. 2018 Jan;160:64-81. doi: 10.1016/j.pneurobio.2017.10.004. Epub 2017 Nov 2.

A Proof-of-Concept Study of Transcutaneous Magnetic Spinal Cord Stimulation for Neurogenic Bladder, Tianyi Niu, Carol J. Bennett, Tina L. Keller, J.C. Leiter & Daniel C. Lu. Scientific Reports. volume 8, Article number: 12549 (2018)

Also see
The Promise of Epidural Stimulation in New Mobility
Spinal Cord Stimulation Helps Paralyzed People Move Hands in Neuroscience News
UCLA scientists awarded $6 million to study new ways to restore hand movement after paralysis in UCLA
Paralyzed Mice with Spinal Cord Injury Made to Walk Again in Science Daily

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