AANS/CNS, 2002c). The Christopher Reeve Paralysis Foundation is in the process of developing an international clinical trials network (see Chapter 6) and is examining the feasibility of performing a clinical trial to examine the optimal timing for spinal cord decompression.
Several human clinical trials of potential neuroprotective therapies after spinal cord injury were conducted in the 1980s and 1990s (Mirza and Chapman, 2001); however, none of these conclusively demonstrated a benefit for increasing function after a spinal cord injury. The most high profile clinical trials were of the medications methylprednisolone and the ganglioside GM-1. After careful review of the results by two separate panels, neither of the two medications received endorsement as a standard of care (Fehlings and Spine Focus Panel, 2001; AANS/CNS, 2002c).
The three clinical trials of methylprednisolone, a corticosteroid, were sponsored by the National Acute Spinal Cord Injury Study (NASCIS) (Bracken et al., 1984, 1990, 1997). The trials were launched after it was reported that methylprednisolone preserved neurological function in animal models by inhibiting ischemia, axon degeneration, and inflammation, among other effects. The first human clinical trial in the early 1980s compared high- versus low-dose methylprednisolone (Bracken et al., 1984); the second clinical trial compared the effects of methylprednisolone with those of another agent and a placebo (Bracken et al., 1990); and the third clinical trial compared the timing of methylprednisolone treatment (Bracken et al., 1997). Concerns have been raised about the robustness of the statistical analyses and the heterogeneity of the populations with spinal cord injuries used in the studies, which made it difficult to compare due to differences in the baseline characteristics of the study populations (Bracken and Holford, 2002) (see Chapter 6 and Appendix E). Consequently, it has been stated that the data describing improved recovery from methylprednisolone treatment are weak and that the improvements observed may represent random events (Hurlbert, 2000). In some cases the trials documented serious side effects, the most prominent of which were higher infection rates, respiratory complications, and gastrointestinal hemorrhage.
Another pharmacological therapy, the ganglioside GM-1, a lipid that is abundant in mammalian central nervous system membranes, was also reported to show improvement in animal models but has not been found to be useful in humans. Its potential therapeutic value was suggested by its ability to prevent apoptosis and to induce neuronal sprouting in animal models. However, the findings from a large-scale clinical trial were negative when the results for the treated group were compared with individuals who received placebo (AANS/CNS, 2002c).