A bridge to independence

Cleveland, OH--AN AUTO ACCIDENT LEAVES A 26-YEAR-OLD MOTHER PARALYZED FROM THE CHEST DOWN. A 23-YEAR-OLD MAN SUFFERS A SIMILAR FATE DIVING INTO AN ABOVE-GROUND SWIMMING POOL. A STAR COLLEGE HOCKEY PLAYER CRASHES THE BOARDS AND FALLS TO THE ICE, UNABLE TO MOVE HIS LIMBS.

More than 10 thousand times a year in the U.S. alone, accidents like these dramatically change people's lives in a split second. Moreover, the majority of the people who lose control of their limbs because of traumatic spinal cord injuries are between the ages of 15 and 30--with decades of life remaining. Most of these patients--particularly quadriplegics who have lost the use of both legs and hands--become increasingly dependent on others for their basic needs.

Nearly 30 years ago, when most people felt that little could be done to improve the lives of such patients, a Cleveland biomedical engineer named Hunter Peckham seized on the emerging field of functional electrical stimulation (FES). This new tool, he reasoned, could serve as a bridge across the damaged nervous system to allow quadriplegics to once again use their hands. In the years since, he conducted the basic research and spearheaded the design of the first FDA-approved neural prosthesis for hand function--called Freehand.

"Hunter Peckham has become the premier person in the world in applying FES to restore motor function,'' says Dr. Peter Gorman, a neurologist and chief of physical medicine and rehabilitation at the Baltimore VA Medical Center.

Adds Dr. Michael Keith, a Cleveland hand surgeon and a close collaborator with Peckham for many years: "Hunter has a dream for people with disabilities to become more independent, and he is motivated to recruit and convince all sorts of people to work with him on this project. He uses his professional leverage both nationally and internationally to create more opportunities for professionals in this field, with the ultimate goal of helping patients.''

Similar comments can be heard not only from Peckham's engineering and medical colleagues, but also from experts at government health agencies and medical device companies. Meanwhile, Cleveland has become arguably the foremost research center in the world in FES technology. In 1990, for example, Peckham helped to establish the Cleveland FES Center, a consortium that supports research at such institutions as the Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, and the MetroHealth Medical Center.

Pioneering device. What has captured the attention of many in the engineering and health care fields is Freehand, approved for commercial use by the Food and Drug Administration in August of 1997 and produced by NeuroControl Corp., a medical startup that Peckham helped establish in 1993. The result of more than two decades of work by Peckham and his team, the device basically consists of a pacemaker-like stimulator, implanted in the chest, that sends electrical impulses from an external controller/power source to electrodes placed in the muscles of the forearm and hands. This neuroprosthesis stimulates the muscles in a coordinated fashion to provide functional grasp patterns (see sidebar).

The system targets individuals whose spinal cord injuries occur at the fifth or sixth cervical root, leaving them paralyzed from the chest down. With little or no control over their paralyzed hands, such patients can no longer hold a fork, pencil, or shaver. Consequently, they often must depend on others for their most basic needs. In fact, of all the physical limitations that result from spinal cord injuries, studies show that quadriplegics overwhelmingly rank loss of arm and hand function highest--above the loss of leg, bladder, or sexual function.

"I have never met a patient who, after seeing the benefits that Freehand brings, doesn't want to have the procedure performed on the other hand as well," says Dr. Keith, who has trained surgeons all over the world to implant the device. Such bilateral systems are already being tested on an experimental basis.

Since the procedure was approved by the FDA, surgeons have implanted Freehand in about 200 patients at some 30 medical centers worldwide, with the potential for hundreds more in the next five years, according to Donna Richardson, president of NeuroControl. The numbers could climb to many thousands as Freehand and related devices reach people whose motor functions have been affected by stroke, MS, or cerebral palsy.

"The potential of FES technology is huge," notes J.B. Richey, senior vice president of Invacare, a billion-dollar medical device company.

To a great extent, experts in the field say, the momentum for the expansion of FES technology comes from Hunter Peckham, a 1966 mechanical engineering graduate of Clarkson University, Potsdam, NY. Encouraged to "do things with my hands" by his grandfather, a tool-and-die maker, Peckham grew up with erector sets and Lincoln Logs strewn across the living room and up the stairs. "I don't know that I would have tolerated that with my own kids," jokes the 55-year-old father of two.

After Clarkson, the emerging field of biomedical engineering drew him to Cleveland's Case Western Reserve University. "I remember being intrigued by an engineering journal piece on a ball cage valve used in cardiac replacement," he says. Now acknowledged to be one of the country's leading universities for biomedical engineering, Case Western at the time had an engineering design center devoted to biomedical. After an initial teaching assistantship, Peckham received a research fellowship. He was particularly attracted to the work being done by engineers in what was called the "Cybernetics Systems Group". "These engineers were looking for ways to animate the body to help people with paralysis,'' recalls Peckham.

Among his first projects in the early 1970s was to investigate alternatives to using electrodes on the skin's surface to provide stimulation for those with paralysis. Notes Peckham: "Very little was known at that time on how electrodes would survive under harsh conditions inside the body over many years--issues like corrosion and brittleness." The work involved both in vitro and animal studies.

Like other Case Western biomedical engineers, Peckham also spent a lot of time in hospitals, trying to understand the concerns of patients. Says Peckham: "It was essential to the development of FES technology to learn how patients with spinal cord injury were treated, such as the typical methods of rehabilitation."

Technical hurdles. From a materials standpoint, engineers had to design electrodes and lead wires that could withstand literally thousands of flexions over many years and be able to deliver the current without degrading. From a physiological standpoint, Peckham and his colleagues had to resolve such issues as getting isolation of the stimulus response to individual muscles, as well as achieving a gradation of force control. Finally, from a clinical standpoint, engineers needed to design a system that surgeons could implant--and patients could use--without great difficulty, including provision for component repair or replacement if necessary. Much of Peckham's early work revolved around the notion that the system wouldn't be able to generate enough muscle force and that the muscles would fatigue very quickly. "A lot of people left the field because they felt this problem could not be solved,'' observes Patrick Crago, an early research colleague of Peckham's and now the chairman of the Biomedical Engineering Department at Case Western.

Overcoming this obstacle required a great deal of understanding of both muscle physiology and the effects of exercise on muscles. Hunter's early experiments showed that you could electrically stimulate muscles and that this exercise provided an increase in muscle force and muscle endurance. In fact, even today patients who are candidates for the Freehand implant use a surface stimulator for several weeks prior to surgery to exercise and strengthen the muscles of their hands and forearms.

The first experimental FES systems for motor control were completely external devices, which relied on electrodes placed on the surface of the skin. This design often required great skill to locate the precise position to get the desired response. It was also difficult to activate specific muscles, and stimulation could at times generate painful sensations before sufficient activation of motor fibers could be achieved. Patients could also suffer burns if electrodes were dislodged.

From surface stimulation methods, Peckham and his colleagues shifted the research to subcutaneous stimulation. In its simplest form, the procedure involved using a hypodermic needle to inject electrodes in the desired locations. When the needle was withdrawn, the electrodes remained in the muscle tissue with the wire exiting through the skin for connection to the external stimulator. Such research proved invaluable to answering such questions as how many electrodes would be required for an effective hand control design. However, the obvious tangle of wires and other exterior components proved to be a hassle to both patients and clinicians participating in the research.

By 1986, however, research by Peckham and others had proceeded far enough to merit the very first implant on an experimental basis of what is now called Freehand. The recipient of the stimulator, which featured eight subcutaneous electrodes sutured to hand and forearm muscles, was Jim Jatich, a former Firestone design engineer who had suffered a cervical-level spinal cord injury in a diving accident. "My hands were everything to me,'' says Jatich, "and without Hunter Peckham I would not be using them today.'' Jatich remains an active and enthusiastic participant in the FES research programs in Cleveland (see sidebar, page 96).

From that first transplant, the device moved into clinical trials at multiple centers in the early 1990s, culminating in FDA approval in 1997. In all, estimates Peckham, the fundamental FES research leading up to Freehand consumed 25 years and cost nearly $60 million, about $10 million of it specifically for the Freehand device. NeuroControl, the company started to manufacture new FES technologies, spent about $5 million to meet FDA requirements.

Patient satisfaction. The FDA premarket approval application included 10 volumes of documentation, including information on the improved quality of life realized by 25 Freehand recipients. More recently, Dr. Peckham and several associates published a paper on the experiences of 34 individuals who had received the neuroprosthesis. The results: Nearly 90% reported that they were very satisfied with the device, felt it had made a positive impact on their lives, and said it was responsible for improvements in daily living activities. Most of them also reported that the device made them more independent.

Freehand recipients enthusiastically talk about the difference the device has made in their lives. Eric Schremp cites simple pleasures, like being able to grasp a ball to play a game of fetch with his golden retriever, while Katie Bates can now write and color with her children--or brush her daughter's hair.

"It's hard for us to imagine what it means to lose control of our muscles," says Rebecca Craik, a Philadelphia area physical therapist and member of the Scientific Advisory Board that monitors research activities at the Cleveland FES Center. "That is why it is astonishing to see how beautifully these FES devices work in restoring movement to patients."

"Ultimately, what we want to accomplish for quadriplegics is to improve their motor skills to the point where they can function on a comparable level with paraplegics, many of whom are doing very well in the workplace and throughout our society," says Dr. Michael Keith, the assistant chief of hand surgery at Cleveland's MetroHealth Medical Center, one of the main settings for Cleveland's FES research.

Without question, Dr. Peckham's engineering skills propelled many of the technical advances that are now improving the lives of quadriplegics. Yet those who have worked with him from his earliest years in FES research say that perhaps his greatest talents are in understanding what is needed technically for a particular device, then bringing together both the resources and skills to get the job done.

Says Dr. Gorman of the Baltimore VA Center: "You still might find him soldering wires in the lab, but his real skill is soldering people into teams."

A special atmosphere. Visit Cleveland, and you'll find what many consider to be the world's finest concentration of engineering and medical talent working on FES technology. Clearly, the environment is anything but engineering in isolation. Says Peckham: "As engineers working with medical professionals, our approach has to be: What can we do together to help your patients?"

Dr. Graham Creasey, who is both a researcher and a physician specializing in physical medicine and rehabilitation, says he relocated to Cleveland from Scotland largely because of Hunter Peckham's work and the " close cooperation that exists here between engineers and clinicians."

Creasey is investigating new systems that apply FES technology to control bladder and bowel function after spinal cord injury. Many patients with paralysis die from kidney infections because of poor bladder control. Now, the FDA has given NeuroControl approval to market Vocare, an FES-based bladder system originally developed in England.

Similarly, biomedical engineer Ronald Triolo, who did FES research in Cleveland in 1985 and moved on to Philadelphia Shriners Hospital to establish FES programs, came back to Cleveland in 1992. Now, he is developing an implanted FES system, scheduled for limited clinical trials in four locations, that will allow paralyzed individuals to stand and take short-distance steps. The device not only benefits patients, but also family and attendants, who often have great difficulty transferring paralyzed patients, say, from wheelchair to bed.

"As a researcher, I feel very lucky to be here,'' says Triolo. "The atmosphere is very special, and much of it is due to Dr. Peckham who is always removing roadblocks that keep people from working together."

Senior Engineer Jim Buckett, who manages the technical development laboratory at the Cleveland FES Center, calls Peckham a "visionary" and has worked alongside him for 22 years, helping to design the prototypes for several FES systems. The lab developed virtually all the hardware and software for Freehand, including: electrodes, leads, sensors, controllers, and the implanted receiver/stimulator.

Among the lab's many innovations: an application specific integrated circuit in the implanted stimulator that decodes the radio frequency signals from the external controllers and provides up to 32 independent channels of stimulation. The lab tests the system's components, and engineers and technicians fabricate and assemble the components for FES systems in a class 1000 clean room.

Still other Peckham proteges have moved out of the lab to join NeuroControl, the company charged with manufacturing FES systems in commercial quantities. Biomedical engineer Geoffrey Thrope, who worked at the FES Center, is now a NeuroControl vice president. Among his chief concerns: educating the medical community and insurance providers about FES technology. Typically, the full costs of the Freehand implant total about $50,000, and the willingness of insurance carriers to cover the cost is still spotty.

Says Thrope: "Hunter Peckham is a true hero to me. He has sacrificed more for the welfare of patients than anyone I know. When it comes to FES for motor control, he has no peer."

That respect also extends to government funding bodies, such as the National Institutes of Health, Food and Drug Administration, and the Dept. of Veterans Affairs, all of which Peckham has approached often over the years to gain support and funding for Cleveland's FES programs. "Dr. Peckham has pulled together and inspired an extraordinary, interdisciplinary team to develop a very complex device and see it through to commercialization,'' notes Dr. William Heetderks, who heads the Neural Prosthesis Program at the National Institutes of Health.

In 1998, the FDA presented Peckham with a special citation "for a career dedicated to restoring movement and independence to those who are paralyzed." Just recently, he received the Veteran Affairs Senior Research Career Scientist Award.

A time of hope. Peckham's contributions are being recognized at a time of renewed public interest in new methods to aid those paralyzed by spinal cord injury. The welfare of such individuals came sharply into national focus in May of 1995 when actor Christopher Reeve, famous for his "Superman" movies, took a spill while horseback riding, shattering his C-1 and C-2 vertebrae.

Paralyzed from the neck down and dependent on a ventilator for breathing, Reeve has nonetheless crusaded courageously to help those with spinal cord injury. Through his Christopher Reeve Paralysis Foundation, the actor has already raised millions of dollars for spinal cord research. Unlike FES technology, however, the goal of much of the research funded by the Reeve Foundation is to develop drugs and other chemical agents to limit degeneration of the spinal cord after trauma--or to actually grow new tissue in the damaged central nervous systems (see sidebar).

Simply put, many of those working in the regeneration area of the field are searching for a cure. Indeed, Christopher Reeve has stated time and again that the regeneration research will someday allow him to walk again.

While that hope is shared by thousands of individuals with spinal cord injuries, experts believe that an effective regimen for rebuilding severely damaged spinal cords and overcoming paralysis may still be many years away. Says Dr. Heetderks of NIH: "I don't think we are going to soon find the magic bullet--to the extent that we'll be able to say, 'Take this medication or implant this cell, and everything will be back to normal.' " Even so, he adds that there is a great deal of "hope and excitement" at NIH because of all the work going on in both FES and regeneration. "When you put it all together," says Heetderks, "there is the potential to restore a lot of function in those with paralysis."

If past history is any indication, Hunter Peckham and his team will be in the forefront of tomorrow's breakthroughs. The engineers and clinicians at the FES Center in Cleveland are working on designs that will be smaller, more user-friendly, and allow for a wider range of functions. In the future, one implanted stimulator might well control standing, movement in both hands, and bladder function.

The Cleveland researchers also are developing FES devices to benefit those whose injuries, like Christopher Reeve's, lie above the C5 cervical level and who must cope with more severe paralysis. These include a neural prosthesis to aid breathing in people dependent on respirators. In addition, work goes on to extend FES technology to a broader range of neurological disorders, such as systems to aid walking in individuals recovering from stroke or head injuries.

For his part, Peckham admits to frustration that research isn't moving as fast as he would like to help those in need. Still, he notes that it is the patients themselves who put things in perspective. "They tell me that these devices don't have to do everything," says Peckham. "They appreciate what FES can do for the quality of their lives now, and they accept the notion that more improvements are coming."

A real helping hand Freehand, the first implanted commercial functional electrical stimulation (FES) device for motor control, allows people with quadriplegia to perform tasks that most of us take for granted. Says Eric Schremp, 31, injured in a diving accident at age 23: "The Freehand system helps me to shave, work at my computer, take notes for class, and play with my dog." Manufactured by Cleveland-based NeuroControl Corp., Freehand consists of both external and implanted components. During the operation, which takes from five to seven hours, the surgeon implants a pacemaker-like device in the patient's chest. Called the implanted stimulator/telemeter (IST), it is composed of a microelectronic circuit hermetically sealed in a titanium capsule with feedthroughs. Branching out from the IST are eight lead wires, made of multifilament stainless steel enclosed in silicone elastomer. The leads connect to electrodes smaller than a dime. Seven of the electrodes are sutured to muscles in the forearm and hand that control motion of the fingers and thumb. The eighth electrode is placed in the supraclavicular region and provides sensory feedback. In most cases, the Freehand operation also involves ancillary surgery to further improve hand function, such as tendon transfers. In this procedure, the surgeon disconnects tendons from paralyzed forearm muscles linked to the bones of the hand and reattaches them to functioning arm muscles regulated by parts of the spine above the injury. Patients must keep their arm in a cast for up to four weeks after surgery to protect the tendon transfers and implants during healing. After the cast is removed, physical or occupational therapists work with the patients, teaching them to use the system. When the Freehand device is turned on, electrical signals cause the muscles to contract, allowing the hand to open and close, as if brain signals were still being received. An external joystick-position sensor device, worn on the opposite shoulder, controls hand grasp patterns by sending a signal to a battery-powered controller, usually located on the wheelchair. This controller processes the information into RF signals to power and control the implanted stimulator through a transmitting coil taped to the chest. The force output of each muscle is determined by modulating the stimulus delivered to the muscle. Stimulus parameters, programmed into the external control unit, are customized for each patient. David Purdy, president of BioControl Corp., Indiana, PA, a pacemaker manufacturer that helped the Peckham team develop the first implantable system, notes that the system is far more complex than a heart pacemaker. Freehand requires more electrodes, greater stimulation energy, and more sophisticated programming. Says Purdy: "Dr. Peckham attempted something that others thought was impossible." Potential recipients. Kevin Kilgore, a biomedical engineer who helps screen potential Freehand candidates at Cleveland's MetroHealth Medical Central, says most of the people inquiring about the device sustained spinal cord injuries at the cervical 5 or 6 level. They typically can move their shoulders, upper arms, and elbows--but not their hands. Those interested in the procedure must wait at least a year following their injury to allow doctors to fully evaluate the long-term damage to their nervous systems. "Patients are very excited about this device,'' says Kilgore, "and most become excellent users. It is the first time that many have been told that they will actually gain motor function." Kilgore and other engineers working with Hunter Peckham are already working on refinements to the system, which they hope will allow a wider range of movements and more transparent controls. For example, as an alternative to Freehand's external shoulder-control device, which can be cumbersome, engineers have developed an implantable joint-angle transducer (IJAT) for the wrist. In this system, the surgeon implants a titanium encapsulated array of Hall effect sensors and support circuitry on one bone and an encapsulated permanent magnet in an opposite bone, across a joint. The IJAT, while still in the research stage, provides consistent, high-quality signals for control of hand grasp movements. It contains two more stimulus channels than Freehand. This allows the option of stimulating the triceps, allowing patients to raise their arms and reach for objects, or stimulating finger intrinsic muscles for finer control. In search of a cure Break an arm. Cut a finger. Puncture a lung. Damage virtually any part of the peripheral nervous system, and if you are an otherwise healthy person, the injury will heal in a surprisingly short period of time. Not so with the brain and spinal column, which make up the body's central nervous system. Once the spinal cord is severed, the body's communication's highway no longer carries signals to and from the brain. Not only does the damaged tissue fail to heal over a time, but cell death actually accelerates in the hours and days immediately following spinal cord injuries. In recent years, however, a flurry of new research, funded by government health agencies and such private sources as actor Christopher Reeve's Paralysis Foundation, is raising hope that ways can be found to regenerate spinal cord tissue and restore more function to paralyzed patients. Among the many projects now underway at research centers, as reported by the American Paralysis Association: In Miami, John R. Bethea is focusing on a potent natural anti-inflammatory agent, interleukin-10, to see if it can limit secondary nerve damage and protect neurons that survive the initial trauma. At Vanderbilt University Medical School, Bruce Carter is studying the molecular mechanisms that endow Schwann cells, found in peripheral nerves, with regenerative powers. Pamela Diener of the University of Maryland, using animal studies, is investigating whether enriched sensory environment, such as exercise, can enhance connections between neurons and the brain after spinal cord injury. At the University of Saskatchewan, Ronald Doucette is working to pinpoint the cellular and molecular interactions that control the production of myelin, the protective material surrounding axons that carry signals from cell to cell. Corey Goodman at the University of California, Berkeley, is looking for ways to thwart growth inhibitors that prevent the regeneration of axons. Major breakthrough. Writing in the September issue of Scientific American, John McDonald, a physician and researcher at Washington University Medical School in St. Louis, noted that this surge in research has accelerated since 1990, when a steroid called methylprednisolone was discovered. Now approved as a drug by the FDA, the substance can restore some motor and sensory function if administered in large doses within a few hours of a spinal cord injury. In a December lecture for engineers, clinicians, and scientists at Case Western, Dr. McDonald, a member of the Research Consortium of the Christopher Reeve Foundation, conceded that no one really knows when such research will evolve into real therapies for patients with long-term spinal cord damage. However, he noted the important role of new functional electrical stimulation devices, such as Hunter Peckham's Freehand, both to restore motor function and prevent muscle atrophy. He added that electrical fields could potentially be used to stimulate remyelination in damaged cells, as well as enhance the survival and migration of "progenitor cells" essential for growing new tissue. In short, there's increasing evidence that advances in both FES and in cellular research will work together to enhance the quality of life for those with spinal cord injury. For more information, visit the FES Center at http://www.fesc.org. The patient as designer When Firestone Design Engineer Jim Jatich sustained a cervical-level spinal cord injury in 1977, he didn't realize that he was about to embark on the most important work of his career. For it was shortly after that paralyzing injury that Jatich, now 50, met a young biomedical engineer named Hunter Peckham. Since then, Jatich has worked closely with Peckham in virtually every stage of the development work for Freehand and other systems being researched by the Cleveland FES team. In the process, the two have become best friends. "He's like my brother," says Jatich. On this particular December day, Jatich sits patiently in his wheelchair in a small lab at Cleveland's MetroHealth Medical Center. "After this, you're going to have a bad hair day," jokes researcher Rich Lauer, pointing to the odd-looking cloth cap covering Jatich's head. The cap, on which are mounted 64 electrodes, is the latest in a long line of control devices that Peckham and his team are testing for future FES systems. The ultimate goal of this particular research: Determine if the brain's own cortical signals, recorded by an electroencephalogram and then amplified, can be used effectively to control a neuroprosthesis. Such a system, which would eventually feature an array of implanted electrodes, could be very attractive to patients because it would allow a more natural operation of the hand by restoring the link between the brain and hand movements. "I think the word 'down' to close my hand and 'up' to open it," observes Jatich, as he grasps and moves small weights and other objects. Twenty years ago, Jatich sat in a similar lab with Hunter Peckham, as the engineer tested the first percutaneous systems, which involved injecting electrodes through the skin, leaving exterior wires that were connected to an external stimulator. "The only time I could use my hands was when I was in the lab with Hunter," recalls Jatich. System pioneer. Peckham listened closely to Jatich's suggestions in developing the first implanted neuroprosthesis for hand movement, which Jatich received in 1986. "If these systems aren't easy for patients to put on and operate, they will not use them," says Jatich. Since then, he has had a newer version of the system, still in the experimental stage, implanted to control his other hand. Together, the two devices allow Jim to tend to most of his daily needs, including using a computer. He has eliminated virtually all attendant care during his work day. Jim jokes that he has contributed to "about 20 Ph.D.s" over the years, as engineers and other researchers study his experiences with various FES systems. He also has counseled many others with spinal cord injury who are considering FES implants. "Some people hesitate because they think a cure is coming soon. Well, I heard that same talk 20 years ago. But if I hadn't received the implant, I would have gone all these years without the use of my hands. I have no regrets." The facts on spinal cord injury An estimated 250,000 spinal cord injured (SCI) individuals live in the United States. On average, 11,000 new injuries occur each year. Paraplegia (losses of movement and sensation in the lower body) affects 55% of the SCI population, and 44% are affected by quadriplegia (losses of movement and sensation in both the arms and legs). The chief causes of spinal cord injuries: 40% from car accidents, 25% from violence, 21% from falls, and 10% from diving accidents. About 60% of the SCI population were injured between the ages of 16 and 30, and 70% are male. And most (90%) live near-normal life spans. Initial hospitalization, adaptive equipment, and home modification costs following injury average $140,000. Additional lifetime costs incurred by SCI individuals average $600,000 and can reach as high as $1.35 million, depending on the severity of injury and the age at which injury occurred. Sources: American Paralysis Association, The University of Alabama National Spinal Cord Injury Statistical Center.