METHYLPREDNISOLONE THERAPY IN ACUTE SPINAL CORD INJURIES
Abstract
Spinal cord injuries represent a major challenge in terms of current concepts of treatment. This condition is frequently associated with long term therapy in addition to a greater incidence of early and late complications. The goal of treatment is to alleviate pressure on the spinal cord caused by hematomas or bone fragments, in the shortest time possible. Hence, surgical decompression of the spinal cord is the first line of treatment, in cases where this approach is indicated. Apart from invasive methods, treatment also consists of the use of various pharmacological agents, whose therapeutic goal is to decrease edema and inflammation, especially in the first several days following injury. One of the most commonly administered drugs in such cases is methylprednisolone, however, controversy with regards to the timing of its administration and proper dosing, still exists. This drug has been in use for decades in the treatment of spinal cord injuries with various protocols having been introduced and revised overtime. The aim of this article is to showcase the current understanding of the use of corticosteroids in acute spinal cord injuries. The most significant protocols in use today for the administration of methylprednisolone (National Acute Spinal Cord Injury Studies-NASCIS I, II and III), along with a brief overview of pertinent literature, are discussed in this paper. Analysis of the available data suggests that the use of methylprednisolone in spinal cord injuries is still highly controversial due to the inconclusive relationship between the therapeutic benefits and the risk of side effects. The current understanding is that the use of the drug is justified in the first eight hours following injury, especially in cases involving incomplete neurological deficits, more specifically quadriparesis and paraparesis.
References
Spinal cord injury [Internet]. Who.int. 2020 [cited 9 July 2020]. Available from: https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury
Fehlings M, Wilson J, Harrop J, Kwon B, Tetreault L, Arnold P et al. Efficacy and Safety of Methylprednisolone Sodium Succinate in Acute Spinal Cord Injury: A Systematic Review. Global Spine Journal. 2017;7(3_suppl):116S-137S.
Burns C. The History of Cortisone Discovery and Development. Rheumatic Disease Clinics of North America. 2016;42(1):1-14.
Chen C, Cheung V, Hoshide R, Bansal V, Kasper E. Methylprednisolone in the management of spinal cord injuries: Lessons from randomized, controlled trials. Surgical Neurology International. 2015;6(1):142.
Hadley M, Walters B. The case for the future role of evidence-based medicine in the management of cervical spine injuries, with or without fractures. Journal of Neurosurgery: Spine. 2019;31(4):457-463.
Liu Z, Yang Y, He L, Pang M, Luo C, Liu B et al. High-dose methylprednisolone for acute traumatic spinal cord injury. Neurology. 2019;93(9):e841-e850
Hayta E, Elden H. Acute spinal cord injury: A review of pathophysiology and potential of non-steroidal anti-inflammatory drugs for pharmacological intervention. Journal of Chemical Neuroanatomy. 2018;87:25-31.
Anderson K, Tetreault L, Shamji M, Singh A, Vukas R, Harrop J et al. Optimal Timing of Surgical Decompression for Acute Traumatic Central Cord Syndrome. Neurosurgery. 2015;77:S15-S32.
Piazza M, Schuster J. Timing of Surgery After Spinal Cord Injury. Neurosurgery Clinics of North America. 2017;28(1):31-39.
Evaniew N, Noonan V, Fallah N, Kwon B, Rivers C, Ahn H et al. Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Propensity Score-Matched Cohort Study from a Canadian Multi-Center Spinal Cord Injury Registry. Journal of Neurotrauma. 2015;32(21):1674-1683.
Bracken M. 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 Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA: The Journal of the American Medical Association. 1997;277(20):1597-1604.
Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H. Early Complications of High-Dose Methylprednisolone Sodium Succinate Treatment in the Follow-Up of Acute Cervical Spinal Cord Injury. Spine. 2001;26(4):426-430.
Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury—outcomes at 6 months. The Lancet. 2005;365(9475):1957-1959.
Eck J, Nachtigall D, Humphreys S, Hodges S. Questionnaire Survey of Spine Surgeons on the Use of Methylprednisolone for Acute Spinal Cord Injury. Spine. 2006;31(9):E250-E253.
Hall ED, Braughler J. Glucocorticoid mechanisms in acute spinal cord injury: A review and therapeutic rationale. Surgical Neurology. 1982;18(5):320–7.
Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, Silten RM, Hellenbrand KG, Ransohoff J, Hunt WE, Perot PL Jr, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA. 1984 Jan 6;251(1):45-52. PMID: 6361287
Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med. 1990 May 17;322(20):1405-11. doi: 10.1056/NEJM199005173222001. PMID: 2278545.
Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W. 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 Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA. 1997 May 28;277(20):1597-604. PMID: 9168289.
Fehlings MG, Tetreault LA, Wilson JR, Kwon BK, Burns AS, Martin AR, et al. A Clinical Practice Guideline for the Management of Acute Spinal Cord Injury: Introduction, Rationale, and Scope. Global Spine Journal. 2017;7(3_suppl).
Hurlbert RJ, Hadley MN, Walters BC, Aarabi B, Dhall SS, Gelb DE, et al. Pharmacological Therapy for Acute Spinal Cord Injury. Neurosurgery. 2013;72(suppl_3):93–105.
Bowers C, Kundu B, Hawryluk G. Methylprednisolone for acute spinal cord injury: An increasingly philosophical debate. Neural Regeneration Research. 2016;11(6).
Bracken MB. Steroids for acute spinal cord injury. Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD001046. DOI: 10.1002/14651858.CD001046.pub2
Fehlings MG, Vaccaro A, Wilson JR, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS One 2012;7(2):e32037. Epub 2012 Feb 23. The Spine Journal. 2012;12(6):540.
Cabrera-Aldana EE, Ruelas F, Aranda C, Rincon-Heredia R, Martínez-Cruz A, Reyes-Sánchez A, et al. Methylprednisolone Administration Following Spinal Cord Injury Reduces Aquaporin 4 Expression and Exacerbates Edema. Mediators of Inflammation. 2017;2017:1–7.
