Steroid Use in Adult Patients With Incomplete Spinal Cord Injuries.

Acute spinal cord injuries (SCIs) are devastating and life-altering events. Although relatively few pharmacologic options exist, methylprednisolone (MP) has been the most extensively studied for acute SCI over the past several decades with the preponderance of data suggesting only limited efficacy with notable morbidity. Therefore, clinicians must weigh the risks of systemic complications against potential neurological benefits of administering pharmacologic agents, such as MP. We present the argument that steroids should NOT be used in adults with an incomplete SCI, as a critical analysis of the existing literature suggests that there is no clinical benefit of MP, and there is clear evidence that the administration of MP is associated with an increased risk of complications. The precedent for MP use was established by Bracken et al with the 3 National Acute Spinal Cord Injury Study (NASCIS) trials. These 3 randomized control studies involving hundreds of patients represent the highest quality research conducted on the topic, whereas all are considered level I evidence. However, we believe that the statistical interpretation of the NASCIS data suffers from multiple methodological flaws and significantly weakens the impact of their conclusions. The NASCIS II study by Bracken et al2 is the most relevant for discussing efficacy of MP, as authors reviewed the effects of MP and naloxone therapy compared with controls through enrolling and randomizing 487 patients with acute SCI injuries. The authors found no difference in a priori outcome measures. It was only after using arbitrary, post hoc, subgroup analysis (administration within 8 h of injury) that the authors concluded that MP treatment resulted in a 5-point (out of 70 possible) motor score improvement at 6 months with continued statistically significant motor score improvement at 1 year (P=0.03). The utility of post hoc subgroup analysis in prospective randomized controlled trials (RCTs) is controversial. As such, there have been several critical reviews of the NASCIS data published in the past decade. A primary criticism revolves around the fact that the 8-hour timepoint was arbitrary, poorly described, and effectively removed 291 patients (56% of the study group) given MP after the 8-hour timepoint from the analysis. This treatment of reporting subgroup analyses as significant without accounting for the number of subgroups analyzed leads to false-positive conclusions without using a Bonferroni correction. More importantly, the NASCIS trials failed to account for the time from the injury to decompression, and this is one of the only variables that has been clearly demonstrated in the literature to affect neurological recovery. Finally, the clinical relevance of a statistically significant 5-point motor score improvement is unclear, as functional outcomes were not subsequently described. Subsequent studies on MP use for the treatment of acute SCI have largely been underpowered observational trials, suffering from nonuniform MP administration, selection bias, and various outcome measures. Reviewing the compendium of available evidence, the most recent 2015 AANS/CNS recommendations are against the routine administration of MP for acute SCI (level 1). 5 Consistent with 2013 recommendations, the authors cite insufficient available high-level evidence for MP-mediated improvement of clinical outcomes with known increases in complications. Although multiple level 2 and 3 studies have been conducted subsequent to the NASCIS trials, the majority of these fail to show meaningful clinical benefit from MP use. Ito and colleagues reviewed a consecutive series of acute SCI patients (38 MP, 41 controls), noting similar rates of improvements by Z1 ASIA grades (45% with MP, 63% with control, P=NS) and no discernible benefit when stratified by complete versus incomplete injuries. Overall complications were found in 68% of MP patients versus 44% of control group (P=0.028). 6 Furthermore, Pollard reviewed 412 cases of incomplete cervical SCIs to determine what patient or treatment variables improved clinical outcomes. Central cord or Brown-Sequard lesions (P=0.019) and younger patients Received for publication January 6, 2016; accepted January 29, 2016. From the *Cleveland Clinic Center for Spine Health, Cleveland, OH; and wCenter for Sports Medicine and Orthopedics, Chattanooga, TN. The authors declare no conflict of interest. Reprints: Jason W. Savage, MD, Cleveland Clinic Center for Spine Health, 9500 Euclid Ave, S4-488, Cleveland, OH 44195 (e-mail: savagej2@ccf.org); and Jason C. Eck, DO, MS, Center for Sports Medicine and Orthopedics, 2415 McCallie Avenue, Chattanooga, TN 37404 (e-mail: jasoneck71@gmail.com). Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved. CONTROVERSIES IN SPINE SURGERY