Drug Treatments For New Injuries
NOTE: It is important to realize these drugs are not a cure for chronic (long-term) spinal cord injuries. It is heart-ening to note, however, that treatments finally are available to lessen the severity of some acute injuries.
Research has shown that all damage in SCI does not occur instantaneously. Mechanical disruption of nerves and nerve fibers occurs at the time of injury. Within 30 minutes, hemorrhaging is observed in the damaged area of the spinal cord and this may expand over the next few hours. By several hours, inflammatory cells enter the area of spinal cord injury and their secretions cause chemical changes that can further damage nervous tissue. Cellular content of nerve cells killed by the injury contribute to this harmful chemical Environment. This process may go on for days or even weeks.
Hope lies, therefore, in treatments that could prevent these stages of progressive damage. Drugs that protect nerve cells following injury are now available to lessen the severity of some injuries. Other drugs and combinations of drugs are currently being tested in both animal and clinical trials.
Few treatment approaches have raised as much hope as the announcement by the National Institute of Health that the steroid, methylprednisolone, reduces the degree of paralysis if administered shortly after spinal cord injury.
In clinical trials, an extremely high dosage of methylprednisolone was used in a double-blind study (neither patients nor doctors knew who was getting the exper-i-mental drug). The improvement in some patients was so remark-able that the National Institutes of Health felt it was important to “break the code” (i.e., determine who was getting the drug and who was not) so more patients could potentially be helped.
Overall, the trial showed that while the methylprednisolone treated group retained significantly more function than the placebo group, subjects in both groups experienced chronic loss of function due to their injuries.
Methylprednisolone is effective only if used in high doses within eight hours of acute injury. It is hypothesized that this drug reduces damage caused by the inflammation of the injured spinal cord and the bursting open of the damaged cells. The contents of the damaged cells are believed to adversely affect adjacent cells. High doses of methylprednisolone can lead to side effects, such as suppression of the immune system, but no serious problems have been reported when it is used over a short term as in this study.
Because the success of the methylprednisolone trial had changed the “standard of care” in the United States, subsequent drug trials are now testing the effectiveness of other drugs in combination with methylprednisolone administration. Thus, to demonstrate significant effectiveness, new treatments will have to surpass the Functional sparing effects seen with methylprednisolone alone.
Simultaneously, researchers are cooperating to conduct a large multi-center animal study to test the effect of other drugs with or without methylprednisolone.
Similar positive results to those of methylprednisolone have been achieved in animal studies using another steroid, tirilizade mesylate (Freedox®). This drug, which acts like methylprednisolone, also appears to be effective only if administered within a few hours after injury. From initial animal studies, it appears that this drug may cause less side effects than methylprednisolone. Clinical trials are ongoing.
A large clinical trial with humans is currently underway comparing 48 hour treatment of methylprednisolone with or without added tirilizade. Study results are anticipated to be available in late 1995.
Once again, the announcement of a new treatment approach has raised interest and hope in the SCI community. In a small study, the experimental drug Sygen®, or GM-1 Ganglioside, was given within 72 hours of injury and then continued for up to 32 days. Neurological assessments were conducted up to one year after the treatment. Individuals who received Sygen®showed significantly more functional recovery than those who received a placebo.
Currently, a large scale multi-center clinical trial of GM-1 is ongoing with a targeted completion date of 1996-1997. In the current study, all patients receive the “standard” does of methylprednisolone. In earlier studies, a standard dose of methylprednisolone was not given.
There are two theories about how GM-1 Ganglioside may act on spinal cord tissue. The first is that it performs some type of damage control by reducing the toxicity of amino acids released after spinal cord tissue is injured. The “excitatory” amino acids cause cells to die and increase the damage caused by the initial injury. The second theory suggests there may be a neurotrophic effect, somehow encouraging the growth of injured neurons. Neither of these theories have been scientifically proven yet.
Sygen®has not yet been approved for clinical use in this country by the Food and Drug Administration (FDA). It has only been used in a limited number of experiments. Sygen®was provided recently to injured football player Dennis Byrd and approximately 65 other patients through an open-label protocol. Although this protocol is no longer in effect, the large double-blind, multi-center trial in acute SCI mentioned above is well underway.
Clinical studies are being conducted by surgeons to determine the optimum time for surgery to relieve pressure on the spinal cord after spinal cord injury. Additionally, the use of delayed decompressive surgery is being investigated in cases of chronic SCI.
Preventing new injuries during spinal surgery
Intraoperative monitoring techniques have been developed to protect healthy nerve roots during spinal stabilization procedures. Scientists tested, first on animals then on humans, a technique that assists surgeons in the placement of metallic hardware for stabilization of the spine. The technique which utilizes nerve stimulation and muscle responses has been shown to effectively predict and allow the prevention of nerve damage during surgery in the lumbosacral spinal column.
TREATMENTS FOR CHRONIC SPINAL CORD INJURY
AND ITS COMPLICATIONS
Functional Electrical Stimulation
FES uses implanted or external electrodes to stimulate paralyzed nerves so that arms and legs can be used for improved function. Over the past decade, three primary applications for FES have been developed: FES for exercise; FES for upper extremity (hand/arm) function; and FES for lower extremity (leg function.) FES is discussed in detail in Fact Sheet No. 9, Functional Electrical Stimulation: Clinical Applications.
One controversial treatment for SCI is Omentum Transposition. The omentum is a band of tissue in the abdomen of mammals which provides circulation to the intestines.
A surgical procedure is used to partially detach the omentum, tunnel it under the skin and suture it in place at the injury site. The omentum tissue, which is rich in blood vessels, may supply the damaged nerve cells with vital oxygen. It is believed that the omentum tissue may also secrete chemicals that stimulate nerve growth, as well as have the ability to soak up fluids to reduce pressure which can damage nerve cells.
Initial animal trials seem to show some functional improvement if the operation is completed within 3 hours of injury. Little or no improvement is shown when the procedure is done 6-8 hours post injury. This research, however, has never been scientifically documented.
The on-going clinical trial for people who have had a SCI for months or years has recently been cancelled. Many scientists believe it is premature for human trials, since the results of the earlier research have not been sufficiently documented.
Scientists in the field of biomedical engineering developed mechanical devices that use today’s computer technology to assist individuals in activities of daily life. Examples of the types of devices under research and development are environmental control devices, electronic had grip device, and walking devices.
The complications of spasticity and pain are common in spinal cord injury. Spasticity that is severe enough to cause problems with mobility and self care, that contributes to Skin Breakdown, and that causes pain is reported in a number of cases of SCI.
Studies in the treatment of spasticity are investigating pharmacological agents, Intrathecal Baclofen, and spinal cord stimulation. In addition to drugs that have been available for some time (baclofen, valium, dantrium) the use of tizanidine has recently been explored. FDA approval of tizanidine is expected in late 1995.
The problem of pain occurs in approximately 50% of all cases of SCI. Five to thirty percent characterize the pain as disabling. Pharmacologic agents as well as surgical interventions such as the DREZ (Dorsal Root entry zone) procedure, cordotomy and cordectomy are under investigation for the treatment of severe causes of pain from SCI.