Assistant Professor of Neurology, Weill Cornell Medical College

Dr. Murthy reports no financial relationships relevant to this field of study.

SYNOPSIS: In a comprehensive review of published literature and meta-analysis of clinical trials of acute spinal cord injury treatment with high-dose steroids within eight hours of onset, the authors concluded that there is no benefit regarding neurological recovery and function and an increased risk of adverse side effects from gastrointestinal bleeding.

SOURCE: Liu Z, Yang Y, He L, et al. High-dose methylprednisolone for acute traumatic spinal cord injury. Neurology 2019;93:e841-e850.

Acute traumatic spinal cord injury (SCI) affects nearly half a million people every year globally, with the majority of patients being severely disabled. Given very few therapeutic options to improve outcomes after SCI, the use of high-dose steroids has been revisited. The authors of a landmark trial, the National Acute Spinal Cord Injury Study (NASCIS-2), showed that methylprednisolone did not result in improvement in functional recovery or mortality after SCI compared to placebo. However, prespecified post-hoc analyses suggested a modest benefit for recovery of motor and sensory function when methylprednisolone was administered within eight hours of injury. Large observational studies since then have failed to demonstrate improved outcomes after SCI with steroids. As a result, major guidelines either equivocate or recommend avoiding steroids in these patients. However, a recent guideline update has suggested a 24-hour infusion of high-dose methylprednisolone within eight hours of SCI, which has become a point of contention among clinicians.

In this study published in Neurology, Liu et al presented a systematic review and meta-analysis of published literature restricted to the use of high-dose steroids within eight hours of SCI. A total of 16 studies, including three randomized trials, were included. The main outcomes were motor and sensory recovery, incident adverse events, and cost of hospitalization. The authors concluded that there was no significant difference in motor or sensory recovery scores among SCI patients, regardless of steroid use. Furthermore, similar results were obtained when stratified by duration of follow-up. However, the use of high-dose methylprednisolone was associated with an increased risk of gastrointestinal hemorrhage and respiratory infections. Finally, there was no cost-benefit to using steroids after SCI.

COMMENTARY

These study investigators summarized the current evidence on use of high-dose steroids after SCI. Given the lack of improvement in functional status with administration of high-dose steroids, coupled with a higher risk of steroid-related complications, the risk-benefit profile would favor avoiding steroids after SCI. Recent AOSpine guidelines¹ advocating high-dose methylprednisolone for 24 hours were based on a meta-analysis, albeit a less comprehensive one that had rigid inclusion criteria compared to the current study. That said, one of the limitations of the current study is the significant heterogeneity between individual studies and the lack of a meta-regression to identify potential sources of heterogeneity. The overwhelming futility of steroids in SCI observed in multiple observational studies and two randomized trials likely will impact the feasibility of future clinical trials on the use of methylprednisolone in the first eight hours after injury. Comprehensive meta-analyses such as the current study may lend support to prevent harm by avoiding steroids in patients with SCI.

REFERENCE

1. Fehlings MG, Wilson JR, Tetreault LA, et al. A clinical practice guideline for the management of patients with acute spinal cord injury: Recommendations on the use of methylprednisolone sodium succinate. Global Spine J 2017;7(3 Suppl):203s-211s.