Object: In the second National Acute Spinal Cord Injury Study (NASCIS II) investigators evaluated several standard neurological parameters but not functional activity. This has led to questions concerning the clinical importance of the increase in neurological recovery observed following administration of methylprednisolone (MP) within 8 hours of acute spinal cord injury (SCI). The safety of the therapy has also been questioned.
Methods: Both neurological and functional recovery were assessed in NASCIS III, a trial that followed an almost identical protocol to NASCIS II. In the current analysis locally weighted scatterplot smoothing (LOESS) nonparametric regression is used to model the extent of recovery in the Functional Independence Measure (FIM) that is predicted by improvement in the NASCIS/American Spinal Cord Injury Association motor scores that were documented in NASCIS III 1 year after SCI, and the models are applied to the extent of motor recovery demonstrated in NASCIS II. The models predict improvement in FIM that would be expected from the motor function recovery observed in NASCIS II. Estimates are provided overall and for patients with complete and incomplete neurological loss at time of injury. The authors review recent evidence obtained from randomized studies documenting adverse effects that may result from high-dose MP therapy. The relationship between motor function and FIM is strongly nonlinear and dependent on initial level of injury and degree of injury severity. In the best statistical model, the expanded motor score could be used to explain 77.2% of the variability in the FIM. Based on the mean MP-related 3.6-unit improvement in the motor score for patients with complete injuries and 7.3 for those with incomplete injuries owed to MP in NASCIS II, 18.6% of patients would improve six or more FIM points and 9% nine or more points, respectively. In those with complete neurological injury, the mean motor improvement of 3.6 predicted that 63.9% of the patients would improve three or more FIM points and 12.1% six or more points to a maximum of eight points. Of those with incomplete neurological injury, a 7.3 mean improvement in motor function predicted that 27.4% would gain six or more FIM points and that 21% would gain nine or more points to a maximum of 15 points. Analysis of the current best evidence from SCI and other randomized surgical trials in which high-dose MP has been administered provides no grounds for concern about commonly studied adverse effects.
Conclusions: The extent of MP therapy-related motor function recovery observed in NASCIS II predicted clinically important recovery in the FIM. Reasons to be cautious with regard to this prediction include the lack of robustness in statistical modeling, some loss of validity in the FIM, and considerable heterogeneity in the SCI population. Whatever functional activity is ascribed to high-dose MP therapy, it is does not appear to be associated with risk of adverse outcomes.