By Dale Greer

March 25, 2006, was supposed to be a relaxing Saturday for Louisville businessman Mark Plummer.

It began with breakfast at a Middletown clubhouse less than two blocks from Plummer's home, after which he and a group of friends were scheduled to tee off for a round of golf. But halfway through breakfast, Plummer began to feel a sharp pain in the back of his head. Within minutes, it became so acute that golf was out of the question.

"I was able to drive myself home," Plummer recalls, "but by the time I got there the pain was just terrible. Fortunately, my wife was home and called EMS. If she hadn't done that I'd probably have laid down on the bed and died."

With the help of X-rays and MRIs, doctors soon learned that Plummer had suffered a spontaneous hematoma at the top of his spine.

"The bleeding formed a ball of blood that was compressing against my spine," Plummer explains.

Surgeons at Norton Hospital were able to operate, but a substantial amount of spinal cord damage had already occurred cutting off communication between brain and body. As Plummer lay in a recovery room following surgery, all he could do was blink his eyes. Thirteen hours earlier he was looking forward to a morning on the links. Now he was a quadriplegic who needed a ventilator to stay alive.

Plummer spent the next four weeks in the hospital, followed by another four weeks of in-patient care at Frazier Rehab Institute, a unit of Jewish Hospital and St. Mary's Healthcare, where physical therapists worked with him daily.

By the time he returned home in May of 2006, he was no longer on a ventilator and had regained limited use of his right arm. That progress was noteworthy (Plummer could now at least feed himself) but he still had no useful movement in his legs and simple tasks like sending e-mail were an exhausting chore.

Wheelchair-bound and dependent on others for almost everything, Plummer worked hard to maintain a positive mindset. "My wife and I decided early on that we were going to beat this thing," he says. So the 56-year-old president of a tractor-trailer brokerage continued at-home physical therapy while researching other options.

One of those options was the Locomotor Training Program at Frazier Rehab. Under the direction of Dr. Susan Harkema, the University of Louisville's Owsley Brown Frazier Chair in Neurological Rehabilitation, the experimental program uses novel techniques that help patients stand or walk again by "re-educating" their spinal cords, often with remarkable results.

Plummer's case is one such example. He was accepted into the program in November 2006 and was able to take a few tentative steps within just a couple of weeks of beginning therapy. Today, nine months later, he can climb stairs with assistance and walk up to 200 steps at a time before resting.

"It's just amazing," Plummer says of his progress. "In the beginning, it seemed like there was some new development almost every day. And things have just rapidly improved from there. I've still got a long, long way to go, but I can now stand and walk using a walker, and I recently graduated to canes.

"What it has done for my life is hard to describe. I may never play golf again, but I think my recovery has been incredible. And I don't think I'm anywhere near the end of my improvement.

"I can't thank Dr. Harkema and her team enough for what they've done."

Training the Spinal Cord

Harkema is one of the world's leading experts on locomotor training, a technique she pioneered with other scientists at UCLA in the late 1990s. Under the right conditions, it allows physical therapists to restore a paralyzed patient's ability to walk or stand—even when the patient has little or no sensation in his or her legs. It does this by taking advantage of several characteristics of the human nervous system.

First, specific muscles can be made to flex or contract at will if therapists manipulate tendons in the right way, much like a leg swings forward when a doctor hits a patient's knee with a reflex hammer.

Second, much of the body's motor control—like coordination between the legs when walking—is handled not by the brain but by spinal-cord tissue. This means that complex physical activities can, with the right physical therapy, still occur even if most of the connections between the brain and lower body have been severed by injury.

Third, spinal-cord neurons have the ability to learn or re-learn tasks simply by exposing the body to the right physical movements.

"The way you re-teach the nervous system is by providing appropriate sensory cues," Harkema says.

"We think about learning in a top-down sort of way: If I want to swing a bat, I'll think about swinging a bat. But the real learning takes place by doing something correctly over and over again. The information from your arms, muscle and skin goes back to your nervous system, to the spinal cord, where individual neurons form networks that have memory. It's those networks that remember and execute the details of movement."

Locomotor training applies these same ideas to standing and stepping after a spinal-cord injury.

Patients first are placed in a harness and suspended over a treadmill so their feet touch the mat. Physical therapists then assist the patient in standing and stepping by manipulating tendons and muscle reactions.

"We know that when we stretch a certain tendon there will be a particular response," Harkema says. "So if we want extensors to fire, we push on one tendon. And if we want flexors to fire, we push on another one."

In effect, therapists "show" the body how to walk, and the neural networks learn by undergoing the process again and again.

The whole thing appears deceptively simple, but therapists must be careful not to elicit the wrong kinds of movements, which could easily confuse the neural networks. It's so complex, in fact, that therapists use a 150-page protocol to guide treatment at Frazier Rehab and the six other centers around the country that are members of the NeuroRecovery Network.

Harkema serves as director of the network, which is funded through a grant/cooperative agreement between the Christopher and Dana Reeve Foundation and the Centers for Disease Control and Prevention (CDC), to provide standardized, activity-based therapy for victims of spinal cord injury. (She credits the late Christopher Reeve, the famous actor of Superman fame who was paralyzed following a horseback riding accident in 1995, with driving the creation of the network so all spinal-cord injury victims can receive leading-edge care regardless of their ability to pay for it.)

Plummer said the experience was exhilarating, even on his first attempt.

"It looks crazy, but I have to tell you: When you've been confined to a wheelchair and hospital bed for seven to eight months, and then you get on your feet and—with the help of three therapists—actually walk, it's the greatest feeling in the world. It's just sensational."

More than 120 patients have undergone treatment at NeuroRecovery Network centers since the program's inception in 2004, and the results have been encouraging, Harkema says. Some patients show little to no recovery, but others develop a range of control over standing and stepping, including full functionality.

Harkema's 20-member UofL research team is working to understand why patients with apparently similar damage experience such divergent outcomes, but one thing is clear: People with spinal cord injuries now have more hope for recovery than ever before.

The results are especially rewarding, Harkema says, because few clinicians took this approach seriously in the 1990s despite the fact that some animals had long demonstrated the ability to walk again even after their spinal cords were completely severed.

"I can remember giving talks about this area of study, and people would just roll their eyes," Harkema says. "Even 10 years ago the medical community didn't feel there was much hope after spinal cord injury. What functionality the patient had initially was all he was going to have. But I think we've now learned a lot that tells us that's not the case."

Breaking New Ground

Harkema first became interested in spinal cord damage during a post-doctoral fellowship at UCLA in 1995. She took the job only to gain some necessary clinical experience and planned to study muscle biochemistry for the rest of her career. But she had the good fortune to work with Dr. Reggie Edgerton, whose lab was then breaking new ground in spinal cord injury research.

Edgerton was the first researcher to show that adult animals have adaptable neural networks, which control walking independently of the brain.

"It was such a brand new area of research that I was able to play a significant role in developing the project to test humans," Harkema recalls. "Then I ended up getting a major NIH grant and was hired full-time by UCLA. So what was supposed to be a small human clinical research project became my career."

Harkema continued to study neural networks' plasticity—their potential for change and development—at UCLA over the next decade, trying in part to determine why patients with the most severe kind of spinal cord damage can't recover as fully as those with more moderate trauma.

"Individuals with complete injuries—in other words, the spinal cord is completely severed—can take independent steps in a controlled environment, but we've not been able to get them to translate that into steps over ground."

Harkema suspects that while the spinal cord is able to coordinate motor control in the legs without input from the brain, some faint connection is still needed between the brain and spinal cord to keep the neural network active.

"It's as if you were to start your car, and it sputters a bit before dying," Harkema says. "The system just doesn't seem excitable enough to sustain activity without some input from the brain. Patients take a few steps and then they just stop."

Harkema is continuing to probe this area of study at UofL, where she relocated in 2005 to join the faculty in the Department of Neurological Surgery and serve as rehabilitation director at the university's Kentucky Spinal Cord Injury Research Center (KSCIRC), a multifaceted program dedicated to expanding the boundaries of spinal-cord injury research and treatment. She also is director of research at Frazier Rehab.

One possible approach involves electrical stimulation of the spinal cord, Harkema says. Preliminary research shows that such a technique could jump-start neural networks in patients with the most severe spinal cord injuries, keeping those networks excitable enough to maintain motor activity. In other words, no sputtering.

Harkema's team, which includes two UCLA transplants, also is studying the effects of spinal-cord injury on the body's autonomic nervous system, including pulmonary and cardiovascular functions.

Her research currently is funded through eight grants from a variety of sources. Those include two NIH-backed projects that nicely augment KSCIRC's existing work in basic-science research and clinical care, says Dr. Chris Shields, the center's clinical director.

"We are so pleased to have recruited Dr. Harkema, whose groundbreaking clinical rehabilitation research is a superb addition to the portfolio of expertise we are developing at KSCIRC," he says.

Harkema, whose endowed university chair was created with a $1 million gift from the Kentucky Spinal Cord and Head Injury Research Trust, a $500,000 gift from Jewish Hospital and matching funds from the state's "Buck for Brains" program, is equally pleased with UofL.

"I came here because I was convinced that Louisville has the potential to do what major centers internationally are struggling with—to become a top center for recovery from spinal cord injury," she says.

"Louisville has everything that's needed—the basic-science component, the clinical component and the administrative component. There is a real commitment here that crosses a lot of worlds, and it's very difficult to do that."

She also praises Frazier Rehab for offering patients access to state-of-the-art technology.

"We have knowledge here right now that can help people, and there is so much more we're learning every day. I see a time when having a spinal-cord injury no longer means that people have to be confined to wheelchairs, even for quadriplegics.

"If we had more financial resources, there is no reason we couldn't solve this problem very, very quickly. I think it's very well within our reach. And we definitely have all the right pieces in place here in Louisville to make it happen."