Accelerating Recovery Post Spinal Cord Injury
Please note that these are draft documents under
construction. They are posted so that we can get feedback.
This document was last updated July 9, 1996
1. Introduction
2. Sub-Category Index
3. Analysis
4. Projections
5. Human Trials Update
6. Projected Research Funding FY 1996
7. Key Researchers in this Field
1. Introduction
by Dr.Wise Young, January 18, 1996
Contrary to popular opinion, some recovery is the rule rather than the exception in spinal cord injury. In the United States, about 60% of spinal injury victims are admitted to hospital with some motor or sensory function below the injury level. These people with so-called "incomplete" spinal cord injuries, even with the slightest pinprick or ability to move a toe, tend to recover substantial function.
On average, such people recover 59% of what they had lost and 75% when treated with methylprednisolone. Even people with no preserved motor or sensory function tend to recover on average 8% of what they had lost and 22% when treated with methylprednisolone. Recovery, however, is very slow and may take many months or even years. Therapies that can accelerate recovery may prevent degeneration and atrophy of denervated neurons and muscles and therefore may not only increase the rate of recovery but improve the final extent of recovery.
One therapy that has the potential to accelerate recovery is monosialic ganglioside (GM1 or Sygen). This drug is a natural substance that is found in the central nervous system. Animal studies suggested that GM1 can accelerate regeneration in brain injury models. A preliminary clinical trial by involving 35 patients suggested GM1 given shortly within 48 hours after and continued for 4-6 weeks daily will improve motor recovery. This trial was too small to be convincing and thus a larger multicenter clinical trial involving 800 patients was started in 1993. In this trial all the patients receive the standard dose of methylprednisolone during the first 24 hours. Half then receive daily GM1 and the other half receive daily placebo injections. Over 500 patients have been randomized and the remainder by the end of next year. The results are expected in about a year's time... but the results probably will not be applicable to persons with spinal injuries reading this since the treatment protocol starts with therapy at 24 hours after injury.
Another potentially interesting therapy is a combination treatment involving lipopolysaccharide-indomethacin-pregnenolone (LIP). Lipopolysaccharide is a bacterial toxin that has a strong inflammatory effect. Indomethacin is an anti-inflammatory drug with effects similar to aspirin. Pregnenolone is a steroid that is made in the central nervous system and that affects GABA receptors, among other actions. Guth, et al. recently reported that LIP started shortly after injury and continued for 4 weeks significantly improved locomotor recovery in rats after severe crush injuries of the spinal cord. The mechanisms of LIP's beneficial effects in spinal cord injury are not well-understood. While inflammation may be deleterious during the first few hours after spinal cord injury, it may also stimulate tissue repair and recovery in the days and weeks that follow spinal cord injury. Indomethacin presumably helps blunt some of the systemic side-effects of lipopolysaccharide. In any case, LIP is an example of a "cocktail" approach to treating spinal cord injury. It is important to emphasize that Guth's results need to be confirmed by another laboratory before it can be seriously considered for clinical trial.
In summary, recovery is the rule rather than the exception in spinal cord injury. Treatments that accelerate recovery from spinal cord injury are usually started a day or so after injury and continued to weeks or months. Designed to stimulate repair, such treatment may prevent degeneration and atrophy of the spinal cord and muscles and thereby not only increase the rate but also the extent of recovery. In general, because such treatments must be started shortly after injury and be maintained during the recovery period, they may not be applicable to people who have chronic spinal cord injury, i.e. people who are no longer recovering.
5. Human Trials
With regard to treatments, GM1 is now in clinical trial; over 500 patients have been randomized and the results are expected in about a year's time... but the results probably will not be applicable to persons with spinal injuries reading this since the treatment protocol starts with therapy within 24 hours after injury.
It is hoped that GM1 accelerates recovery and perhaps improves the extent of recovery when started within 24 hours and then given for about 3 months. The clinical trial on GM1 will show whether or not early and continued GM1 therapy will accelerate recovery and increase the extent of recovery.
The study will not tell us whether it is useful for chronic spinal cord injury. I have talked to six patients who have taken the drug chronically... One (an orthopedic surgeon) felt that it did help him. The rest did not notice much of a difference.
None of the above information, nor any information provided at this site is intended to constitute medical advice. Funding for clinical trials for chronic injuries is still lacking.