Ten Frequently Asked Questions Concerning Cure of Spinal Cord Injury
By Wise Young, Ph.D., M.D., Rutgers University
W. M. Keck Center for Collaborative Neuroscience
Revised 20 December 2008 from 21 July 2004
Many questions recur repeatedly on CareCure every few days. On 21 July 2004, I posted a summary of answers to the ten most frequently asked questions on CareCure (Link) . That thread received over 450 responses and over 80,000 page-views. Here, I update some of responses to the questions and will expand each of the answers with sequential articles to follow.
1. 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” requires complete eradication of spinal cord injury, I think that it would unlikely in my lifetime. If a cure means complete restoration of all functions to pre-injury levels for all people with spinal cord injury, I think that this would also be unlikely. Not only are we unlikely to be able to reverse aging but we may not be able to reverse all changes in the body due to spinal cord injury. On the other hand, I believe that there will be therapies that will restore sufficient function to a person with severe spinal cord injury so that a casual third-party observer would not be able to tell that the person had spinal cord injury. This is a reasonably practical definition of a cure for me and I think that will happen.
2. When will a cure be available?
First generation therapies are already restoring function to people with spinal cord injury, including weight-supported treadmill ambulation training, decompression and untethering of a spinal cord, and Fampridine. Preliminary data suggest that olfactory ensheathing glia transplants may restore some sensory function but only modest motor function, perhaps because the cells are not HLA-matched and are immune-rejected after a few weeks. Second generation therapies are in or soon-to-be started clinical trial, including umbilical cord blood mononuclear cells, Schwann cells, and embryonic stem cells. Several therapies such as Nogo receptor blockers and Nogo antibodies, glial-derived neurotrophic factor, cethrin, and other treatments are already in or are close to clinical trial. Finally, third generation therapies include combination cell transplants, growth factors, and growth inhibitor blockers. These should be in clinical trial in the next few years. The timing of clinical trials depends on availability of funding for clinical trials. With sufficient funding, I think that one or more of these clinical trials will yield the first therapies that restore function in chronic spinal cord injury.
3. Will a cure work for chronic spinal cord injury?
I believe there will be effective restorative therapies for chronic spinal cord injury for the following reasons. First, much animal and human data indicate 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 circuitry necessary to execute and control these functions. Only 10% of the axons in the spinal cord are necessary and sufficient to restore locomotor and other functions. Second, axons continue to try to regrow for many years after injury. Treatments that provide a path for growth, that negate factors that inhibit growth, and that provide long-term stimulation of axonal growth can restore function. Third, many people recover function years after injury. These observations give me hope that there will be therapies that facilitate functional recovery in chronic spinal cord injury.
4. What can I do now to be ready for the cure?
People with spinal cord injury should work hard to take care of their body and to prevent muscle and bone atrophy that may prevent recovery of function. This includes disciplined exercise to maintain their muscle and bone. They must 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.
5. What can I do about spasticity, spasms, and neuropathic pain?
Many people suffer from spasticity (increased tone), spasms (spontaneous movements), and neuropathic pain (in areas below the injury site where there sensory loss). Neurons that have lost their inputs tend to become hyperexcitable. Spasticity is the most common manifestation of spinal motoneurons that have been disconnected from the brain. Several treatments reduce spasticity. The most commonly used anti-spasticity drug is baclofen (a drug that stimulates GABA-B receptors in the spinal cord). Oral doses (80-120 mg/day) of baclofen reduce spasticity. However, for some people such doses are not enough or have too many side effects. For these people, it may be useful to combine lower doses of baclofen with clonidine or tizanidine, which activate alpha-adrenergic receptors. While anti-spasticity drugs reduce spasticity, they also weaken muscles and may cause flaccidity and muscle atrophy. So, people should titrate the dose of anti-spasticity drugs so that they retain some muscle tone. Unless they are taken in doses high enough to cause flaccidity, anti-spasticity drugs usually do not prevent spasms. However, gabapentin (Neurontin) and other anti-epileptic drugs may reduce both spasms and neuropathic pain. Neuropathic pain results from increased excitability of sensory neurons that have been disconnected and may manifest in “burning”, “freezing”, or “pressure” pain. People accommodate to gabapentin and high doses of as much as 4000 mg/day may be necessary for pain relief. In some people, low doses (20 mg/day) of the tricyclic anti-depressant drug amitriptyline (Elavil) may provide relief from neuropathic pain. Intrathecal delivery of baclofen or morphine may be necessary.
6. How can I exercise and will it do any good?
Exercise is difficult for paralyzed people and specialized equipment may be necessary. First, most people should stand for an hour or two every day. This can be done with standing frames. A device called a Glider 6000 allows both standing and leg movements. Second, functional electrical stimulation (FES) can be used to activate muscles. Arms and legs can be stimulated to pedal exercise devices. Third, standing, walking, and swimming in a pool allows people to exercise in an environment where the water supports their weight. Fourth, weight-supported treadmill ambulation training improves walking recovery. Finally, people should think about setting aside a month or two every year where they would essentially engage in full-time training. During the rest of the year, they need to 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.
7. What is osteoporosis, its mechanisms and consequences, and ways to reverse it?
Osteoporosis is bone loss. It occurs after spinal cord injury, particularly in the pelvis and leg bones below the injury site. The mechanism is not well understood but appears to be related to loss of gravitational and other mechanical stresses on the bone. In acute spinal cord injury, bone begins to decalcify within days after spinal cord injury, with significant increases in urine calcium (hypercalciuria) within 10 days. The pattern of bone loss is 2-4 times greater than those associated with prolonged bed rest without spinal cord injury. Increased dietary calcium intake may slow down but does not prevent the bone loss. Parathyroid hormone level is usually low in the first year but may increase above normal after the first year. Substantial (25-43%) decreases in bone mineral densities occur in the leg bones within a year and may exceed 50% loss by 10 years. People with spasticity have less bone loss than those who are flaccid. Osteoporosis is associated with greater fracture rates. The Model Spinal Cord Injury System, for example, reported a 14% incidence of fracture by 5 years after injury, 28% and 39% by 10 and 15 years, usually in the most demineralized bone. People with complete spinal cord injury and paraplegia have ten times greater fracture rates than incomplete injury or tetraplegia. Weight bearing and bicycling with functional electrical stimulation may prevent osteoporosis. Bisphosphonates (Pamidronate) and parathyroid hormone (Teriparatide) can reduce osteoporosis and fracture rates in people with chronic spinal cord injury. Much research is underway to find effective therapies of osteoporosis.
8. What is autonomic dysreflexia, its mechanisms and consequences, and treatments?
Autonomic dysreflexia (AD) refers to increased activity of the sympathetic nervous system, associated with profuse sweating, rash, elevated blood pressure, and vasodilation above the injury level. AD usually causes a headache due to vasodilation of brain blood vessels. Heart rate falls and vision may be blurred. Nasal congestion may be present. Between 40-90% of people with spinal cord injury suffer from AD. It is more severe in people with spinal cord injury above T6. AD can be triggered by many potential causes, including bladder distension, urinary tract infection, and manipulation of the bowel and bladder system, pain or irritation, menstruation, labor and delivery, sexual intercourse, temperature changes, constrictive clothing, sunburns, and insect bites. When AD occurs, doctors usually catheterize the bladder to ensure adequate urinary drainage, check for fecal impaction manually using lidocaine jelly as a lubricant, and eliminate all other potential causes of irritation to the body. Treatment includes use of the calcium channel blocker Nifedipine (Procardia 10 mg capsule) to reduce blood pressure or adrenergic alpha-receptor blocking agent phenoxybenzamine (10 mg twice a day), mecamylamine (Inversine 2.5 mg orally), and Diazoxide (Hyperstat 1-3 mg/kg). Doctors in emergency room may not know how to handle AD crises in people with spinal cord injury and it may be useful for patients to carry a card that give treatment instructions.
9. What is syringomyelia, its mechanisms and consequences, and treatments?
Syringomyelia refers to the development a spinal cord cyst that results from enlargement of the central canal. The central canal is typically 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 and 5% may show symptoms of pain and loss of function associated with cyst enlargement, as early as one month and 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 may be aggravated by postural changes and Valsalva maneuver (that increase 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. Syringomyelic cysts can be observed with MRI scans. It is usually associated with scarring of meninges or arachnoid membranes of the spinal cord, observable with CT-scan with myelography. Surgical intervention is recommended when there is progressive neurological loss. Traditionally, syringomyelia has been treated with shunting of the cyst by placement of a catheter between the cyst and the subarachnoid space or pleural cavity. But shunting alone is frequently associated with shunt blockade within a year. More recent studies suggest that meticulous removal of adhesions with duroplasty (repairing the dura by grafting membrane) to re-establish subarachnoid cerebrospinal fluid flow is more effective and may eliminate the cyst in 80% of cases.
10. How does spinal cord injury affect sexual function and what can be done to improve such function?
Most people with spinal cord injury above the T10 will continue to have reflex erections associated with stimulation. Some people may have prolonged erections called priapism. A majority can have ejaculation although increased stimulation including vibration may be required. In many people, ejaculation may be retrograde, i.e. the ejaculate goes into the bladder rather comes out, because the external sphincter may be open. Retrograde ejaculation should not be harmful or cause urinary tract infections. A serious associated complication of sexual intercourse in both men and women is the occurrence of autonomic dysreflexia (AD) with orgasm, with associated headaches and other symptoms of AD. These can be treated with drugs to lower blood pressure (see answer to AD above). In addition, sexual intercourse may be associated with increased spasticity and spasms. People with injuries below T10 may have damage to the spinal cord centers responsible for erection and ejaculation. Many techniques are available to increase erection, including drugs such as Sildenafil (Viagra), vacuum pumps, cock rings, and penile prostheses. Several studies have reported that women with “complete” spinal cord injury can achieve orgasms, possibly through neural pathways outside of the spinal cord.