Ten years ago scientists scoffed at the thought that a paralyzed person could walk again; today they’re counting on it.
Four years after being paralyzed from the neck down in a riding accident, Christopher Reeve is preparing to walk again, a feat long assumed to be impossible for any quadriplegic, even Superman.
As scientists work to develop drugs to minimize acute spinal cord damage and hunt for new ways to spur regeneration even long afterwards, Reeve is trying to “meet the scientists halfway. . .”
Speaking openly, often eloquently, by phone from his Bedford, New York home, despite his reliance on a respirator to breathe, Reeve believes that, ultimately, “recovery will go to the fittest.”
So every day, he has an electrical device attached to his muscles to stimulate contractions. “I have no loss of tone whatsoever,” he says, adding that his calf muscles “are the exact same size as when I was injured.”
To prevent osteoporosis, which can be caused by a lack of weight-bearing exercise, he is strapped to a “tilt table” and raised to a vertical position to force his weight onto his feet.
He also “walks” on a treadmill — his weight suspended in a harness, his feet propelled by the moving belt. The theory is that spinal nerves can be retrained to make the legs move in a coordinated way, even though the messages that control voluntary leg movements can’t get from the brain down to the legs across the damaged area of the spinal cord.
Ten years ago, if anyone as badly injured as Reeve even dreamed of walking again, scientists would have scoffed. Reeve’s injury is not only high on his spinal cord, it’s “complete,” which means the nerve fibers are cut all the way across, not just partway, as in some cases.
Indeed, the dogma has long been that, while nerves in the arms and legs regenerate, those in the central nervous system do not — a grim fact of life for 10,000 Americans a year whose spinal cords are injured as a result of car crashes, sports accidents and violence, and for the quarter million more living with their injuries, most of whom with fewer resources than Reeve.
But thanks to an explosion of new research — some to be presented next month at a major neuroscience conference in Miami — that pessimism is cracking.
“It will be a long, arduous path, but I no longer think it’s impossible for people with severe, even high, spinal cord injuries, to walk again,” says Dr. Evan Snyder a neuroscientist at Children’s Hospital in Boston and one of the leaders in spinal cord regeneration research.
“There is tremendous new hope. The neat thing is that the central nervous system does have the capacity to regenerate — we just need to harness it. And we’re also getting better at using advances in electronics and surgery to maximize a person’s independence,” says Dr. John W. McDonald, director of the spinal cord injury program at Washington University in St. Louis.
Electronic devices can help paralyzed patients gain control over their bladders; a drug called NT-3 seems to help the bowel work on command; and early data suggest another drug called inosine helps healthy nerves grow toward the damaged area.
Surgeons can also do “tendon transfers” to restore limited movement to paralyzed muscles by hooking them to still-functioning tendons. Many primary care doctors don’t think to recommend this, McDonald says, but by re-jigging tendons so a patient can grasp things between the thumb and forefinger, a person may be able to feed himself.
Indeed, a half-dozen new therapies to repair damaged spinal cords, including cell transplants, are or soon will be in human trials, says Dr. Wise Young, a neuroscientist at Rutgers University in New Jersey. “The hope is that if we can get 10 to 15 therapies going in parallel, at least one of them will hit.”
None of the new approaches was “dreamt of 10 to 15 years ago,” adds Arlene Chiu, who runs the spinal cord injury program at the National Institute of Neurological Disorders and Stroke. “So on that basis, I’d say things are very promising,” even though, so far, most research is in animals, not people.
Still, the challenges are daunting, almost as if evolution had “decided” that a spinal cord injury was so devastating, it was not worth investing the resources it would take to heal it.
The spinal cord, which runs inside the backbone, is only as thick as a thumb, but it’s through this channel that the brain sends signals through descending nerves onward to muscles and organs and carries messages, such as pain signals, up through ascending, sensory nerves.
Deep in the center of the cord lie the nerve cell bodies called “gray matter;” branching out from these are tendrils called dendrites, which catch incoming electrical signals; also projecting out are filaments called axons through which nerves send outgoing signals.
Some axons are long, running the entire length of the cord. Because they are coated with a white insulating material called myelin, bundles of axons are called “white matter.” Both white and gray matter also contain supporting cells called glia, and oligodendrocytes, which make the myelin.
The organization of the cord means that below an injury, nerves (and the muscles and organs they control) don’t work well or at all, while above it they do. It also means that below certain injuries, a person can feel nothing — neither pain nor pleasure.
If you injure your cord in the neck region, you may not be able to breathe without a respirator because the nerves that control the diaphragm won’t work; if you injure your cord farther down, you may have control over breathing and arm movements, but not over your legs, bladder and bowel. If the cord is not severed all the way across, there may be some function below the injury because some nerves still work.
When the cord is injured, there is instant damage to the immediate area: the bony vertebrae crush axons, rendering them useless. But for days, weeks, even months later, the damage spreads up and down the cord.
Ruptured blood vessels no longer deliver oxygen, causing waves of cell death. Damaged cells pump out glutamate, which triggers a cascade of chemical events that is fatal to nerve cells, including the release of destructive oxygen molecules called free radicals.
The injured cord also pumps out chemical signals such as IN-1 that inhibit regeneration of nerves. Axons that survive the initial injury may also lose their myelin coating, without which they can’t transmit signals. Glial cells clump into scar tissue, making it even harder for nerves on both sides of an injury to hook up. And inflammation, including the influx of immune cells that destroy nerve cells, further fans the flames of destruction.
But in 1990, the picture began to brighten when Dr. Michael Bracken and his team from Yale University showed that a drug called methylprednisolone, injected in huge doses in the first eight hours after injury, prevented some of this damage by blocking free radicals.
“This was the first time anything had been shown to work in spinal cord injury,” says Bracken, a neurologist. To this day, methylprednisolone is the only drug approved to treat either acute or chronic spinal cord injury.
But other ways to treat the cord in the immediate aftermath of injury are in the pipeline, including a drug called an AMPA antagonist that blocks glutamate receptors, likely to be studied in humans soon, and another called interleukin-10 that blocks inflammation, at least in rats.
Cooling the body after injury also slows damage in rats, says Naomi Kleitman, a neuroscientist at the Miami Project to Cure Paralysis.
The implications are compelling. The more doctors can limit the immediate injury, the more they can focus on the really tough part: restoring nerve function in people whose spinal cords were injured months or years earlier.
It’s a tall order, but Christopher Reeve is ready: “I expect full recovery — up to and including walking.” SIDEBAR 1: Getting a lift from new devices, wheelchairs
The holy grail of spinal cord research is to restore some or all nerve function, but even in the most optimistic scenarios, that’s still five years away. In the meantime, however, new devices and better medical care can improve the quality of life for the estimated 230,000 Americans living with spinal cord injuries, and for many others with mobility disorders as well.
Two years ago, the US Food and Drug Administration approved an electronic signalling device that allows some quadriplegics — people whose arms and legs are paralyzed — to regain partial use of one hand. In January, the agency approved another electronic device that restores some control over bladder, bowel and penile function.
And three months ago, Johnson & Johnson began human testing of a fancy, $20,000 wheelchair that can operate on two wheels or four and can climb stairs, go up hills and maneuver over curbs.
To be sure, even with better devices, learning to live with a spinal injury is a task that takes time “and a lot of work,” says Michael Ferriter, 47, a carpenter who was injured in a work accident 20 years ago.
But with every new device and improvement in basic care, the lives of paralyzed people get a bit better, though the amount of care necessary — and the cost, estimated to be $1.4 million over the life of a spinal injury patient — are huge.
That’s because a spinal cord injury can affect every organ and body function below the level of injury: muscles, bones, skin, blood vessels, internal organs and breathing, notes Dr. Daniel Lyons,, medical director of the spinal cord injury program at Health South/New England Rehabilitation Hospital in Woburn.
Without skin sensation, for instance, a person can’t tell when he’s getting sore from sitting too long in one position. This can lead to pressure sores and ulcers, which can lead to infections. The solution here is low tech: having someone monitor the skin, helping the patient change position often, and developing better cushions for wheelchairs.
Blood clots are another challenge. Because a paralyzed person can’t move, blood can pool in the legs and form clots that travel to the lungs. One solution is to take a blood thinner such as Lovenox.
Heart arrhythmias are a problem, too. In a healthy person, signals from the parasympathetic nerves, which tend to slow down heart rate, are coordinated with signals from the sympathetic nerves, which tend to speed it up.
But in many people with spinal injuries, this balance is thrown off. The parasympathetic nerves remain intact because they branch off high on the spinal cord, while the sympathetic nerves, which branch off lower, are damaged. The result is that the heart beats erratically because slow-down messages are not coordinated with speed-up ones. The body can compensate but if it can’t, implantable pacemakers can help.
Breathing, even just coughing, can be another huge problem. The solution is often to use a respirator, which literally pushes air into the lungs, though rehabilitation specialists try to wean people with some remaining nerve function off respirators and teach them to strengthen muscles in the diaphragm and neck to assist with breathing.
Depression is also a threat. Though many patients regain significant quality of life, says Lyons, getting to that point is difficult. “Everyone does it differently,” he says. “Well-educated business executives are often very devastated early on, then do very well as time goes by,” he says.
“Younger people who don’t have a lot of plans for their lives sometimes do well early on, then have more difficulty later as they realize that things will be tough.”
Mobility is an obvious challenge, too. At UCLA and the Miami Project to Cure Paralysis, researchers are trying to retrain damaged spinal cords by suspending a patient over a moving treadmill.
In some patients, the legs move involuntarily, and even do so in a coordinated — left foot, right foot — manner. Researchers theorize that even below the level of injury, there may be a neural “pattern generator” and “memory” in the cord that — without messages from the brain — may make walking possible.
German researchers have demonstrated improvements in mobility by putting such patients on a treadmill, says Reggie Edgerton, a UCLA physiologist pioneering the method. But so far, no one with a “complete” cord injury (one that cuts across the entire cord) has been able to regain the ability to walk.
Of more immediate benefit to many is the Freehand device, made by the NeuroControl Corp., to regain use of a hand.
The Freehand system uses a sensing device taped to the skin on the shoulder. Wires from the sensor run to an external control box and from there to a transmitting coil taped to the chest. Just under that coil is a stimulating device that is implanted surgically under the skin.
Leads from the implanted device run down the arm to electrodes on the fingers and thumb. When the shoulder is moved, signals travel down to the hand. So far, about 150 people worldwide are using the device.
The VOCARE system, distributed by NeuroControl and made in England, is similar. In this case, the implantable part of the system is surgically placed under the skin on the abdomen, with electrodes on nerves to the bladder, bowel and in men, the penis. The transmitter coil is held or taped to the skin over the implant and the unit is controlled externally by the patient if he has sufficient hand control, or by a helper. The device, which allows patients to urinate, defecate or get an erection, is now used by 1,500 people worldwide, most of them in Europe.
Michael Ferriter, the carpenter injured in a work accident, welcomes the new options for treatment of injuries like his. But he also has hard-won advice: “Live healthy — mentally, physically and spiritually until there’s a cure. Don’t wait for it. Live it now. . .You’ve got to do it. That’s what life is about.”