Efficacy of Methylprednisolone in Acute Spinal Cord Injury

Abductor hallucis for monitoring lower-limb recovery after spinal cord injury in man

“…In this case, the AbH had the lowest probability of showing recruitment (29%; seven of 24 possible cases), whereas the probability of psoas recruitment was highest (92%) in this population for two-thirds of our subject population, 14 compared to values that did not exceed 45% in any of the three NASCIS trials. 6,17,18 The scope and breadth of research into animal-based SCI treatments continues to expand, leading to predictions that clinical trials of treatment strategies to optimize functional recovery are inevitable. [19][20][21][22][23] Success in such trials will necessitate optimal subject selection and the utilization of outcome measures both sensitive to and specific for the treatment effects.…”

“…24 Detailed neurologic testing will almost certainly be a cornerstone of these outcome measures, as it has been for pharmacological clinical trials after acute SCI. 6,17,18,25 At this time, such neurologic testing does not include the AbH muscle, or any of the intrinsic foot muscles. However, the present study shows that for persons with SCI at or rostral to T10, the AbH muscle: (1) has a higher probability of recovering from traumatic SCI compared to other lower-limb muscles; and (2) recovers from paralysis earlier than other lower-limb muscles.…”

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

“…The initial report of the NASCIS 1 trial, which enrolled 330 patients, was published in 1984. 10 Analysis of neurological recovery measures did not show significant difference of outcome between the treatment groups, the lack of a 'dose effect' posing a challenge to the presumed efficacy of steroids in acute SCI. Safety analyses showed an elevated early-case fatality rate, which while not statistically significant, was of sufficient concern in the context of lack of demonstrated efficacy, that it prompted patient accrual to be discontinued before the planned study termination.…”

“…[6][7][8][9] It could be justifiably claimed that the clinical trial era of SCI research began in February of 1979 with the enrollment of the first patient in a multicenter double-blind randomized control trial (RCT) of MP that was the first of three National Acute SCI Study (NASCIS) trials to be performed under the leadership of the NASCIS Group. 10 The NASCIS 1 trial, a test of 'high dose' (1000 mg bolus and daily thereafter for 10 days) vs 'standard dose' (100 mg bolus and daily thereafter for 10 days) MP began in an era when corticosteroid treatment of acute SCI was widespread and without firm clinical evidence basis (although the majority of pre-clinical laboratory studies had been supportive). It was also an era in which clinical research methodology and outcome measurement was in relatively uncharted territory.…”

Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design

“…This should be maintained throughout the conduct of the entire trial from determination of eligibility through evaluation of all endpoints, and requires full compliance of the subject. Double Blind design has been used in a number of pharmacological trials in SCI, including investigations of methylprednisolone and GM-1 ganglioside in acute injury [11][12][13][14][15] and 4-aminopyridine in chronic spinal injury, 16,17 and in more recent surgical trials for Parkinson's disease. 9,10 Randomization in the assignment of trial participants to the different study arms (groups), including a placebo (or standard of care) control group, is done to reduce bias, and introduces a deliberate element of chance into the assignment of treatments.…”