Methylprednisolone improved motor function after acute spinal cord injury
ACP J Club. 1992 May-June;116:79. doi:10.7326/ACPJC-1992-116-3-079
Bracken MB, Shepard MJ, Collins WF Jr, et al. Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. J Neurosurg. 1992 Jan;76:23-31.
To evaluate treatment with high-dose methylprednisolone or naloxone after spinal cord injury in the recovery of neurologic function after 1 year.
Randomized, double-blind, placebo-controlled trial.
10 university medical centers in the United States.
Participants ≥ 13 years of age were diagnosed with acute spinal cord injury by a standardized neurologic examination in the emergency department ≤ 12 hours after injury. Patients with spinal nerve root or cauda equina damage only; gunshot injury; other serious morbidity; pregnancy; addiction to narcotics; use of steroids; or patients who had received > 100 mg of methylprednisolone or > 1 mg of naloxone before admission were excluded. 487 patients were randomized, and 427 of the surviving patients (95%) were followed for 1 year.
Patients were assigned to methylprednisolone (administered as an intravenous bolus of 30 mg/kg and an infusion of 5.4 mg/kg per hour over 24 hours; n = 162); naloxone (5.4 mg/kg bolus and 4.0 mg/kg per hour infusion; n = 154); or placebo (n = 171). 208 patients received the intervention ≤ 8 hours after injury; 183 patients (88%) were re-evaluated after 1 year.
Main outcome measures
Change in motor function (scale 0 to 70); and pinprick and touch sensations (scales 29 to 87).
Neurologic status did not differ among groups at admission or after 1 year. The mean time from the injury to loading dose was 8 to 9 hours. After adjustment for severity of injury, patients who received the drug bolus ≤ 8 hours after injury had a greater mean improvement in motor status scores on the methylprednisolone regimen (21 to 38 points) than on placebo (24 to 36 points, P = 0.03); a trend toward greater improvement in sensation occurred with early use of methylprednisolone. Early administration of naloxone did not improve recovery significantly. 1-year survival was similar for the treatment groups (between 91% and 94%, P = 0.5). The groups did not differ in frequency and type of complications.
Administration of intravenous methylprednisolone within 8 hours of spinal cord injury was associated with a modest increase in recovery of motor function over 1 year. Intravenous naloxone did not affect recovery.
Sources of funding: National Institute of Neurological Disorders and Stroke; Upjohn Corporation and DuPont Corporation supplied drugs.
Address for article reprint: Dr. M.B. Bracken, 60 College Street, New Haven, CT 06510, USA.
The benefits of methylprednisolone for acute spinal cord injury reported in the original paper and confirmed in this 1-year follow-up report are, at best, modest. Although the follow-up data show no significant differences among the treatment groups for any of the potential complications of therapy noted, physicians who treat acute spinal cord injury still havesome doubts concerning efficacy. Some methodologic issues are pertinent: Quantifying neurologic function in patients with spinal cord injury in the chaos of the emergency room is extraordinarily difficult. The initial assessment of motor function (on a 0 to 5 scale) for 14 different muscles, plus the evaluations of pinprick and light-touch sensation, formed the basis for the scoring in this study. The training of research personnel is not specified, although standardization of examination technique is important for minimizing interobserver variability. Other factors that would affect the scores at the first or follow-up assessment are the statistical effect of the "recovery" of a single root (which often reflects the uncertainty of initial observations) and the type of injury. In the study by Bracken and colleagues, improvements in motor scores were significantly better in patients treated within 8 hours of injury. 25 patients, however, were lost to follow-up or were not re-evaluated; the estimate of efficacy might be different if these patients had been re-examined. The sample size of this study may be too small to recognize a small benefit in neurologic recovery of sensation through treatment with steroids or naloxone.
For the above reasons it is difficult to be certain how many patients have benefited from methylprednisolone. Even so, this report offers a ray of hope that has been embraced with some enthusiasm by neurosurgeons who treat these all-too-common neurologic catastrophes. One can offer these patients so little that a therapy with few complications and some possible benefits is certainly better than none.
S. J. Peerless, MD
University of MiamiMiami, Florida, USA
S. J. Peerless, MD
University of Miami
Miami, Florida, USA