Dr. Wise Young, Spinal Cord Injury Project at Rutgers University
Will there be a cure for spinal cord injury?
The answer to this question depends on one’s definition of a cure. If a cure means eradication of spinal cord injury, I think that it is unlikely in my lifetime. If a cure means complete restoration of all function to “normal” or pre-injury levels for all people with spinal cord injury, I think that that this is also unlikely, because we probably will not have therapies that can completely reverse aging.
On the other hand, I believe that there will be effective therapies that will restore function to people with spinal cord injury, including touch and pain sensations, bladder and bowel function, erection and ejaculation, and motor control including long-distance walking.
Several years ago, I tried to get around the problem of the definition of “cure” by proposing that a person would be cured if a well-informed observer cannot tell that a person has had spinal cord injury. This does not necessarily mean that the person has been completely restored to pre-injury levels or all functions are normal.
When will a cure be available?
Some therapies are already restoring substantial function to some people. These are what I call the first generation therapies, which include weight-supported treadmill ambulation training, decompression and untethering of a spinal cord that is compressed. Preliminary data suggest that some cell transplants such as olfactory en-sheathing glial (OEG) transplants will restore 4-8 levels of sensory function and 1-2 levels of motor function. None of these therapies can be construed as a cure.
Second generation therapies are beginning to come into clinical trial and should be available in a few years. These include transplants of nasal mucosa olfactory en-sheathing glia, Schwann cells, bone marrow stem cells, and perhaps even embryonic stem cells. The last unfortunately has been mired in political debate and has been delayed. In addition, several therapies such as Nogo receptor blockers and Nogo antibodies, glial-derived neurotropic factor, chondroitinase, and other treatments are being developed and may be in clinical trial within a year or two. The timing depends on availability of funding for clinical trials. If sufficient funding were available, some of these treatments will be shown to be effective and will be available in four years.
Third generation therapies will be closer to what we might consider a “cure.” These include possible combination cell transplant therapies with growth factors and other factors that stimulate regeneration, stem cells that can deliver growth factors and replace moto-neurons. These combination therapies should produce substantial recovery in most people. For example, cell transplants combined with drugs such as glial-derived neurotropic factor, chondroitinase ABC, and cAMP/rolipram have been reported to produce significantly better regeneration in rats compared to individual treatments. The rate at which these treatments get into clinical trial depend on the amount of funding available for clinical trial. If funding were made available, I think that some of third generation therapies will be available as soon as eight years from now.
Will a cure work for chronic spinal cord injury?
Yes, I believe so for the following reasons:
- First, much animal and human data suggest that regeneration of relatively few axons can restore function such as walking, bladder function, and sexual function. This is because the spinal cord contains much of the neural circuitry necessary to execute and control these functions. Probably about 10% of the axons in the spinal cord are necessary and sufficient to restore substantial function including walking.
- Second, animal studies suggest that axons continue to try to regrow for long periods of time after injury. Treatments that provide a path for growth, that negate some of the factors that inhibit growth, and that stimulate axonal growth can restore function.
- Third, while chronic spinal cord injury studies in animals are still very limited, the fact that many people continue to recover some function years after injury provide hope that these therapies will also work in chronic spinal cord injury.
However, it is important to emphasize that there are many obstacles to recovery. Recovery may be limited by muscle atrophy and other changes in the body. Likewise, there is a phenomenon called “learned non-use” where neural circuits may turn off after prolonged periods of non-use. Intensive exercise and physical therapy will be necessary to reverse these changes.
What can I do now to be ready for the cure?
The first and foremost concern of people with spinal cord injury should be to take care of their body and try to prevent muscle and bone atrophy and other changes that may prevent recovery of function.
People need to engage in disciplined exercise that maintains their muscle and bone, take care of their skin, bladder, and bowels.
People should avoid procedures that cause irreversible loss of peripheral nerve and other functions. On the other hand, it is important to weigh the benefits of procedures such as tendon transfers, which can provide greater functionality and independence for people with weak hands. Likewise, certain procedures such as Mitrofanoff and bladder augmentation to reduce bladder spasticity may provide greater independence but may not be easily reversible.
Finally, many studies have shown that people with the highest levels of education after injury are more likely to have better quality of life and health. It is important that people do not neglect their brain, the most important part of their body.
How can I exercise and will it do any good?
Exercise is difficult for paralyzed people and specialized equipment may be useful for exercising muscles.
- First, most people use standing frames to stand for an hour or two every day.
- Second, others use functional electrical stimulation (FES) to stimulate their leg muscles to pedal exercise bicycles.
- Third, standing and walking in a swimming pool is possibly most cost-effective way for a person to stand and walk.
- Fourth, weight-supported treadmill ambulation training has been shown to improve walking recovery.
I believe that people set aside a month or two every year where they would essentially engage in intensive training. During the rest of the year, they can maintain the gains that they have achieved by spending an hour or so per day on exercising. Although there have been few formal studies of the subject, many people with spinal cord injury have reported significant increases in the girth of their legs when they use FES regularly. Also, it improves cardiovascular function and may reduce spasticity.
What is osteoporosis, its mechanisms and consequences, and ways to reverse it?
Osteoporosis is loss of bone calcium that occurs after spinal cord injury, particularly in the pelvis and legs below the injury site. The mechanism is not well understood but appears to be related to disuse and the loss of gravitational and other stresses on the bone, as well as hormonal changes.
Bone begins to lose calcium within days after spinal cord injury. The bone loss is 2-4 times greater than the bone loss seen in people on prolonged bed rest without spinal cord injury, similar to the bone loss seen in postmenopausal women. The loss of bone is not effectively reversed by increased dietary calcium intake alone. Parathyroid hormone level is generally low in the first year but increases above normal after the first year.
Substantial (25-43%) losses of bone mineral density occur within a year and may exceed 50% loss by 10 years. Bone density may increase in the arms after 4 months in paraplegic patients, as opposed to tetraplegics who will have bone loss in their arms as well. People with spasticity may have less bone loss than those who are flaccid.
Decalcification weakens bones. The Model Spinal Cord Injury System, for example, reported a 14% incidence of bone fracture by 5 years after spinal cord injury, 28% and 39% by 10 and 15 years. People with complete spinal cord injury and paraplegia have 10 times greater fracture rates than those with incomplete injury. Weight-bearing and bicycling with functional electrical stimulation will reverse osteoporosis when started within 6 weeks after injury.
However, such programs are less effective in people with chronic spinal cord injury. Some preliminary studies suggest that treatment with bisphosphonates (Pamidronate) and parathyroid hormone (Teriparatide) can prevent or reduce osteoporosis and fracture rates in people with chronic spinal cord injury.
What is syringomyelia, its mechanisms and consequences, and treatments?
Syringomyelia refers to a cyst in the spinal cord, resulting from enlargement of the central canal. The central canal is normally tiny and not visible on magnetic resonance images (MRI) of the spinal cord. As many as 15% of people develop a syringomyelic cyst in their spinal cords with perhaps 5% showing symptoms of pain and loss of function associated with cyst enlargement, beginning as early as one month to as late as 45 years after injury.
Pain is the most commonly reported symptom associated with syringomyelia. Other symptoms include increased weakness, loss of sensation, greater spasticity, and increased sweating. The symptoms can be aggravated by postural changes, Valsalva manuever (increasing pressure in the chest). It may also be associated with changes in bladder reflexes, autonomic dysreflexia, painless joint deformity or swelling, increased spasticity, dissociation of sensation and temperature, respiratory impairment.
The cyst can be observed with MRI scans. A cyst often forms when there is scarring of the meninges or arachnoid membranes and obstruction of cerebrospinal fluid flow. Surgical intervention is recommended when there is progressive neurological loss.
Traditionally, syringomyelia has been treated with shunting of the cyst by placing a catheter between the cyst and subarachnoid space or pleural cavity. But the shunt usually blocks within a few months to years. Some recent studies suggest that meticulous removal of adhesions with duroplasty (increasing the dura by grafting membrane) to re-establish subarachnoid cerebrospinal fluid flow is more effective and may result in elimination of the cyst in 80% of cases. One study has shown that transplantation of fetal tissues into the cyst can eliminate the cyst.