Kailey Denny, PharmD, BCEMP, Barnes Jewish Hospital

Caitlyn Patton, PharmD, BCEMP, Barnes Jewish Hospital

Pathophysiology of Spinal Cord Injury and Rationale for Steroids

Spinal cord injury (SCI) is a neurological condition that can lead to lifelong disability. SCI often occurs from traumatic events such as motor vehicle crashes, falls, and penetrating injuries. This results in a direct impact on the spinal cord leading to damage of the axons, blood vessels, and cell membranes.¹ The primary injury often provokes secondary injuries driven primarily by inflammation. As a result, ischemia, hemorrhage, and edema can further exacerbate neurological deficits and extension of nerve injury.¹ Standard of care treatment includes surgical decompression, neurorehabilitation, and spine stabilization.² While there is currently no direct pharmacological therapy for SCI, there are agents to aid in maintaining hemodynamic stability which has been shown to improve neurologic outcomes. For example, vasopressors may be used to augment mean arterial pressure (MAP) to a goal of at least 75 to 80 mmHg to ensure adequate spinal cord perfusion and reduce ischemic damage to neural tissues.³ Additionally, immunomodulatory approaches such as corticosteroids have been investigated for their ability to reduce lipid peroxidation, leading to decreased membrane damage, and promoting functional recovery. However, their use remains controversial due to significant adverse events and minimal evidence.¹ This article reviews the literature and controversies surrounding the role of steroids in the management of SCI.

Trial Data, Timing, and National Trends of Corticosteroids Use in SCI

Despite evolving guidelines and national prescribing trends, the use of steroids in SCI remains highly controversial. The National Acute Spinal Cord Injury Study (NASCIS) group initiated the widespread study of methylprednisolone in SCI management from their landmark NASCIS I-III trials, which later became a source of controversy regarding their role in treatment. NASCIS II and III found motor and sensory improvements when administered within 8 hours; however, significant rates of complications such as sepsis and pneumonia were specifically observed in NASCIS III.^6,7 Although the NASCIS trials may have seen positive outcomes with steroids, these trials had significant methodological limitations such as lack of placebo controls, arbitrary timing windows, unilateral assessments, and inconsistent implementation in standard of care which cast doubt on the clinical relevance of their findings. Since NASCIS, no subsequent high-quality studies have shown meaningful benefit from steroid use in SCI, leaving their role uncertain and controversial in clinical practice.

Historically, guidelines have had conflicting recommendations for the use of methylprednisolone within 8 hours following a SCI, prompting continued controversy of whether high-dose steroids are truly beneficial. In 2002, an expert panel recommended administering methylprednisolone sodium succinate (MPSS) for 24 or 48 hours in patients with SCI, while emphasizing the evidence of harmful side effects being more consistent than any suggested clinical benefit. In contrast, the 2013 guidelines by the American Association of Neurological Surgeons (AANS) did not advocate for steroids in SCI, which was consistent with the 2008 Paralyzed Veterans of America (PVA) guidelines. However, the 2017 AO Spine guidelines recommend a 24-hour infusion of high-dose methylprednisolone in adult patients within 8 hours of an acute SCI as a treatment option.⁴ Although the 2017 guidelines recommend the use of steroids for SCI, the strength of this recommendation is considered weak, as it relies on a limited evidence of four randomized controlled trials (RTCs) and two prospective studies. Not only did the studies demonstrate modest benefits in neurological outcomes, but it also raised concerns about adverse effects, highlighting the need for careful clinical judgement and consideration before initiating steroid therapy in these patients. National trends in using steroids to treat SCI have reflected these shifting guidelines and evidence. Prior to 2010, the trend in utilizing steroids for SCI was high but since then has been a steady downhill decline due to lack of efficacy in recent trials.⁵

Recent evidence has continued to challenge the efficacy of methylprednisolone in the management of acute SCI. A 2020 meta-analysis by Sultan et al., including five RCTs and seven observational studies, found that methylprednisolone within the first 8 hours of acute SCI failed to yield statistically significant results in both short- and long-term motor and neurological outcomes. These findings support earlier guideline recommendations against the use of steroids, especially when accounting for potential adverse effects.⁸

Conclusion

Based on current literature showing no consistent benefit for steroid use in SCI, the 2022 guidelines by the American College of Surgeons do not recommend the administration of methylprednisolone within 8 hours of injury. The decision to use methylprednisolone must be evaluated on an individual basis through risk versus benefits discussions.² The evidence has highlighted that the potential risks of long-term corticosteroid use, including immunosuppression, gastrointestinal bleeding, sepsis, and pneumonia, often outweigh any uncertain benefits. As research continues to explore alternative therapeutic options, clinicians must rely on current evidence and patient-centered judgement in the therapeutic management of SCI.

References

1. Lee, B.J., & Jeong, J. H. (2022). Review: Steroid use in patients with acute spinal cord injury and guideline update. Korean Journal of Neurotrauma, 18(1), 22–30. https://doi.org/10.13004/kjnt.2022.18.e21
2. American College of Surgeons Committee on Trauma. (2022, March). Best Practice Guidelines: Spine Injury. American College of Surgeons. https://www.facs.org/media/k45gikqv/spine_injury_guidelines.pdf
   
3. Badhiwala, J. H., Witiw, C. D., Nassiri, F., et al. (2024). Clinical practice guideline for the management of patients with acute spinal cord injury: Recommendations on the use of hemodynamic management, steroids, and neuroprotective pharmacologic interventions.Journal of Neurotrauma, 41(1-2), 1–33.https://doi.org/10.1089/neu.2023.0544
4. Fehlings, M. G., Wilson, J. R., Tetreault, L. A., et al. (2017). A clinical practice guideline for the management of patients with acute spinal cord injury: Recommendations on the use of methylprednisolone sodium succinate. Global Spine Journal, 7(3 Suppl), 203S–211S. https://doi.org/10.1177/2192
5. Hejrati, N., Aarabi, B., Neal, C. J., et al. (2023). Trends in the use of corticosteroids in the management of acute spinal cord injury in North American Clinical Trials Network sites. Journal of Neurotrauma, 40(17–18), 1938–1947.
6. Bracken, M. B., Shepard, M. J., Collins, W. F., et al. (1990). A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal‑cord injury. New England Journal of Medicine, 322(20), 1405–1411. https://doi.org/10.1056/NEJM199005173222001
7. Bracken, M. B., Shepard, M. J., Holford, T. R., et al. (1997). Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: Results of the Third National Acute Spinal Cord Injury Study. JAMA, 277(20), 1597–1604.
8. Sultan, I., Lamba, N., Liew, A., et al. (2020). The safety and efficacy of steroid treatment for acute spinal cord injury: A systematic review and meta-analysis. Heliyon, 6(2), e03414. https://doi.org/10.1016/j.heliyon.2020.e03414

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