The Atlanta Journal-Constitution

Help for stroke patients

Research suggests spinal cord stimulatio­n could eventually help some stroke victims who suffer weakness, paralysis in arms and hands regain movement.

- Pam Belluck |

The study’s authors said their continuing research is evaluating patients of varying stroke severity, age and other characteri­stics to determine who would benefit from their approach.

Heather Rendulic was 23 when she suffered a stroke that disabled her left side. Ten years later, her left arm and hand remain so impaired that she cannot tie her shoes, type with two hands or cut her own food.

But for an extraordin­ary month, while participat­ing in an innovative study, she suddenly was able to open a padlock with a key, draw a map of Italy, dip a chicken nugget in sauce and eat it with a fork — all with that left hand.

“It was like I actually had two arms, oh, my gosh!” Rendulic said recently.

Researcher­s from the University of Pittsburgh and Carnegie Mellon University implanted electrodes along her spinal cord, delivering electrical stimulatio­n while she tried different activities. With stimulatio­n, her left arm had greater mobility, her fingers had more dexterity, and she could make intentiona­l movements more quickly and fluidly.

Small study, first stimulatio­n success

The study, published Monday in the journal Nature Medicine, represents the first successful demonstrat­ion of spinal cord stimulatio­n to address weakness and paralysis in the arms and hands of stroke patients.

The study was small and preliminar­y, involving only Rendulic and another patient. Several scientists said many questions remain about the technique’s effectiven­ess and applicabil­ity but that the research suggested spinal cord stimulatio­n could eventually help some of the many people who experience strokes.

“I think there’s enormous implicatio­ns for improving quality of life,” said Dr. Lumy Sawaki-adams, the program director in the clinical research division of the National Institute of Neurologic­al Disorders and Stroke, who was not involved in the research. Still, she said, “we have to be cautious that we’re not offering hope to many people when I think we’re not there yet.”

Spinal cord stimulatio­n has been used for decades to treat chronic pain. More recently, experiment­s delivering stimulatio­n — either through surgically implanted electrodes or noninvasiv­ely through electrodes placed on the skin — have shown promise in helping patients with spinal cord injuries regain mobility in their legs and, in some cases, their arms and hands.

But the approach has been mostly unexplored for stroke, partly because of difference­s in the location and type of damage, neurologic­al experts said.

Because strokes occur in the brain, it had been assumed that applying stimulatio­n outside the brain would not provide “the same bang for the buck,” said Arun Jayaraman, the executive director of the technology and innovation hub at Shirley Ryan Abilitylab, a rehabilita­tion center in Chicago. He said the study, which he was not involved in, countered that assumption, instead suggesting that stimulatin­g the spine, the pathway from the brain to hand and arm muscles, may help impaired limbs.

Hope for millions affected

Each year, more than 12 million people worldwide and nearly 800,000 in the United States experience strokes, said Dr. Karen Furie, the vice chair of the American Stroke Associatio­n’s stroke brain health science subcommitt­ee.

Initially, patients typically receive about six months of physical, occupation­al and other therapies, she said, but then progress often plateaus.

“We have virtually nothing to offer people who are years out and have long-standing disabiliti­es,” said Furie, who is also the chair of neurology at Brown University’s Warren Alpert Medical School and was not involved in the study.

About three-quarters of stroke patients experience impairment, weakness or paralysis in their arms and hands, said Dr. Elliot Roth, an attending physician at Shirley Ryan Abilitylab’s Brain Innovation Center, who was not involved in the study. “For many people, it’s the toughest part of the stroke recovery process and tends to recover the slowest,” he said.

The patients who participat­ed in the study had experience­d different types of strokes and had varying degrees of impairment. Rendulic’s stroke was hemorrhagi­c, caused by bursting blood vessels. The other, more severely impaired patient, a 47-year-old woman whom researcher­s did not identify, experience­d an ischemic stroke, which is more common and involves blocked blood vessels.

Researcher­s implanted strands of eight electrodes in two locations, correspond­ing to where neurosenso­ry fibers from the arm and the hand enter the spinal cord.

Marco Capogrosso, an assistant professor of neurologic­al surgery at the University of Pittsburgh, said that the approach derived from the fact that with strokes, some neural areas remain undamaged.

“So if we can build this technology to amplify neural signals, maybe we have a chance to restore arm and hand movement,” said Capogrosso, who led the research with Elvira Pirondini, an assistant professor of physical medicine and rehabilita­tion at the University of Pittsburgh, and Douglas Weber, a professor of mechanical engineerin­g at Carnegie Mellon’s Neuroscien­ce Institute.

Promise that stirs emotions

Five days a week for four hours each day, researcher­s activated the stimulatio­n, calibrated it to determine optimal parameters for each patient and asked them to attempt various movements and tasks. Right away, the effect was noticeable.

“The very first day in the lab and the first time they turned it on, I was sitting in a chair, and they asked me to open and close my hand, and that’s something that’s really difficult for me,” Rendulic said. As her husband and mother watched, “I immediatel­y was opening and closing my hand,” she said. “We all broke down in tears.”

Over four weeks, she was given increasing­ly challengin­g tasks, like gripping and moving a soup can. With stimulatio­n, her left hand moved 14 small blocks over a barrier in a box, compared with six blocks without stimulatio­n.

Typically, when Rendulic, 33, who works at home for a company’s human resources department, tries to make her left hand do something like grasp a pen, her arm feels like “it’s made of rock,” almost disconnect­ed from her brain, she said. With stimulatio­n, “it was like my brain was able to find my left arm so much easier.”

The other patient, who was given simpler tasks because her left hand was almost completely paralyzed, improved in skills like reaching.

Researcher­s also tested a “sham” stimulatio­n, activating electrodes randomly to see if patients responded to a kind of placebo effect rather than stimulatio­n targeted specifical­ly to their arms and hands. Both performed better with targeted stimulatio­n.

The patients sensed the stimulatio­n, but it didn’t cause pain, rigidity or safety problems, researcher­s reported.

The approved study protocol required removing the electrodes after 29 days. But one month later, the patients retained some improved abilities, surprising researcher­s. “We thought it was not possible” after only four weeks of stimulatio­n, Pirondini said.

It is unclear exactly why the benefit can persist, Capogrosso said, but he hypothesiz­ed that “the same neural processes that allow these people to use this stimulatio­n method also lead to a recovery of movement when the stimulatio­n is off.” He added, “We’re not creating new fibers, but we’re definitely restrength­ening what there is.”

Several experts noted that this pilot study was not designed to answer the most relevant question for patients: Can the improvemen­ts in laboratory tasks translate into skills that matter in daily life?

“It’s a first step among hundreds,” said Dr. Daniel Lu, a professor and vice chair of neurosurge­ry at UCLA, who co-authored a 2016 study that showed that spinal stimulatio­n from implanted electrodes improved hand strength and control in two spinal cord injury patients.

Questions still remain

Lu said he believes stimulatio­n is promising but that its impact in the new study was difficult to evaluate because there was no comparison group and patients were not given the same regimen of intensive activities before stimulatio­n — activities that might themselves have therapeuti­c benefit.

“Is it possible that you’re just exercising the patient, and the patient without the stimulatio­n would have gotten the same effect?” he asked.

Another question neuroscien­tists raise is whether — or in what circumstan­ces — it is better to surgically implant electrodes or place them on the skin, a less expensive method called transcutan­eous stimulatio­n. The new study’s authors consider surgical implantati­on superior because it is “much more specific,” said Weber, allowing it to “target the muscles that control the wrist and the hand.”

Others, like Chet Moritz, a professor of neurotechn­ology at the University of Washington, have reported improvemen­ts in spinal cord injury patients using electrodes on the skin, including benefits lasting months after stimulatio­n ends. “It’s true we can’t tune the shoulder to this degree and the elbow to this degree and the wrist to that degree, but the nervous system seems to take care of that for us,” he said.

Several neurologic­al experts predicted that both methods could eventually be helpful and appropriat­e for different patients, depending on their health and other factors. All the experts, including the study authors, said stimulatio­n would be more effective if accompanie­d by rehabilita­tion therapies.

The study’s authors said their continuing research is evaluating patients of varying stroke severity, age and other characteri­stics to determine who would benefit from their approach. They have formed a company and said they envision that, as with similar technology for chronic pain, patients could adjust their stimulatio­n via app or remote control.

If stimulatio­n becomes regularly available to stroke patients, Rendulic would welcome it. “I did threaten to not show up to the surgery to get it removed,” she said. “I just wanted it all the time.”

While she has devised onehanded ways to do activities like driving and typing, everyday frustratio­ns rankle, like needing her husband Mark, whom she calls “my left-hand man,” to slice steak for her.

“In the trial, I did get to cut up a steak, which was awesome,” she said. Then, fork in her left hand, she speared a piece and lifted it to her mouth — one previously impossible movement at a time.

 ?? PHOTOS BY KRISTIAN THACKER/THE NEW YORK TIMES ?? Heather Rendulic, shown Friday in Pittsburgh, had a stroke at age 23, disabling her left arm and hand. When she received spinal cord stimulatio­n in a scientific study, she could maneuver that arm more easily. The study involved Rendulic and one other person.
PHOTOS BY KRISTIAN THACKER/THE NEW YORK TIMES Heather Rendulic, shown Friday in Pittsburgh, had a stroke at age 23, disabling her left arm and hand. When she received spinal cord stimulatio­n in a scientific study, she could maneuver that arm more easily. The study involved Rendulic and one other person.
 ?? ?? During the stimulatio­n study, Rendulic was able to use her left hand to cut a strawberry. “It was like my brain was able to find my left arm so much easier,” she said.
During the stimulatio­n study, Rendulic was able to use her left hand to cut a strawberry. “It was like my brain was able to find my left arm so much easier,” she said.

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