Pharmacological therapy of spinal cord injury during the acute phase

Abstract

Study design: Prospective, randomized clinical trial. Setting: France. Objectives: To evaluate the safety and e ect on neurological outcome of nimodipine, methylprednisolone, or both versus no medical treatment in spinal-cord injury during the acute phase. Method: One hundred and six patients who had spinal trauma (including 48 with paraplegia and 58 with tetraplegia) were randomly separated into four groups: M=methylprednisolone (30 mg×kg 71 over 1 h, followed by 5.4 mg×kg 71 ×h 71 for 23 h), N=nimodipine (0.015 mg×kg 71 ×h 71 for 2 h followed by 0.03 mg×kg 71 ×h 71 for 7 days), MN (both agents) or P (neither medication). Neurological assessment (ASIA score) was performed by a blinded senior neurologist before treatment and at 1-year follow-up. Early spinal decompression and stabilization was performed as soon as possible after injury. Results: One hundred patients were reassessed at 1 year. Neurological improvement was seen in each group (P50.0001), however no additional neurological bene®t from treatment was observed. Infectious complications occurred more often in patients treated with M. Early surgery (49 patients underwent surgery within 8 h of their accident) did not in¯uence the neurological outcome. The only predictor of the latter was the extent of the spinal injury (complete or incomplete lesion). Conclusion: The present study con®rms the absence of bene®t of pharmacological therapy in this indication. Because of the paucity of clinical studies that demonstrate the e cacy of pharmacological treatment in spinal injury during the acute phase, systematic use of pharmaceutical agents should be reconsidered. Spinal Cord (2000) 38, 71 ± 76

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

“…Steroids were also previously thought to be helpful for patients with clinically significant head injuries until the recent randomized CRASH trial with over 10,000 enrolled patients demonstrated increased mortality when using methylprednisolone (Roberts et al, 2004). Modification of inflammatory processes and the resulting inhibitory extracellular matrices following trauma are likely to be important for improving clinical outcomes, but it appears that steroid treatment alone is not sufficient to provide reproducible and meaningful clinical recovery in human patients for spinal cord or brain injury (George et al, 1995;Pointillart et al, 2000;Prendergast et al, 1994;Roberts, et al, 2004;Tsutsumi et al, 2006). Some other strategies for encouraging CNS neurons to regenerate are to increase local levels of growth factors in an effort to stimulate axonal growth.…”

Does early decompression improve neurological outcome of spinal cord injured patients? Appraisal of the literature using a meta-analytical approach

“…32,34,[40][41][42][43][44][45] Most studies reported on retrospective case series with historical controls (Class III evidence).…”

“…[11][12][13] The limit of 24 h has been used in this study for two practical reasons: (1) very few reports provide data on an earlier treatment; (2) less than 50% of patients can be currently admitted to spinal cord centres within 24 h. 57,58 Analysis of results and limitations of the study The meta-analytic procedure consisted of extraction, pooling and statistical analysis of data from parent studies. Since only one prospective randomized (Class I evidence) 39 and eight prospective nonrandomized case series (Class II evidence) 32,34,40,[41][42][43][44][45] were found from the literature search, the meta-analysis was based on studies reported on retrospective case series with historical controls (Class III evidence). The outcome of patients undergoing a decompressive procedure within 24 h was then compared with that of patients treated through delayed decompressive procedures and that of nonoperatively managed patients.…”

Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture

“…6,8,14,15 Several smaller studies attempted to replicate aspects of the NASCIS trials, producing equivocal or conflicting results. 16,17 At the same time, the safety of MP treatment was being challenged by the publication of a number of non-randomized case series reports, suggesting an association between treatment and immune system compromise, pneumonia, mechanical ventilation days, gastrointestinal complications and myopathy. [18][19][20][21] The Great Debate: the quality of NASCIS evidence While the debate over the validity of NASCIS 2 and 3 conclusions may have been motivated by many factors including timing of the public dissemination, and feelings that a far-reaching standard had been imposed without proper vetting, the substance of the argument revolved around the quality of the evidence.…”