Journal Club: High-dose methylprednisolone for acute traumatic spinal cord injury

Abstract

Methylprednisolone is a corticosteroid medication used in acute traumatic spinal cord injury (SCI) to tackle secondary injury cascades. Its use in acute SCI has been the subject of controversy for over 30 years. The second National Acute Spinal Cord Injury Study (NASCIS-2) demonstrated a small benefit of methylprednisolone, 1 though this conclusion was derived from a post hoc subgroup analysis. 2 Studies that followed did not reach the same conclusion and reported potential adverse effects of the drug. 3 However, the 2017 AOSpine guideline continues to recommend high-dose methylprednisolone within 8 hours postinjury, 4 based on a meta-analysis with rigid inclusion criteria. 5 This Journal Club article reports on a study from Liu et al., 6 who have attempted to resolve this controversy. The study provides an elegant example of meta-analytic methods and has important implications for neurologic clinical practice. Hypotheses and design Does acutely administered methylprednisolone improve neurologic recovery following traumatic SCI? To answer this important question, Liu et al. 6 performed a meta-analysis of clinical trials and observational studies. The use of a meta-analysis is important here as it synthesizes all available evidence and provides the highest possible strength of recommendation for its use in clinical management. Methods This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, which is an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses. 7 A comprehensive literature search was performed of PubMed and the Cochrane Library, and articles were further restricted to those published in journals included in the Science Citation Index. In addition to traditional database searches, manual searches of the reference lists of all of the relevant studies, review articles, and conference abstracts were also conducted. Searching multiple databases is recommended when conducting metaanalyses in order to identify all the relevant articles. For instance, the Cochrane Handbook suggests the use of MEDLINE (accessible through PubMed) and the Cochrane Central Register of Controlled Trials. 8 Other commonly used databases include the Web of Science and Google Scholar. 9

Efficacy of miRNA-modified mesenchymal stem cell extracellular vesicles in spinal cord injury: A systematic review of the literature and network meta-analysis

“…Thus, it is critical to develop effective drugs. Currently, melatonin (Zhang et al, 2018 ), riluzole (Fehlings et al, 2021a ), Rho inhibitors (Fehlings et al, 2021b ), and methylprednisolone (Liu et al, 2020 ) have been evaluated in clinical and preclinical trials. The efficacy of these drugs remains controversial.…”

Sex-Related Differences in Epidemiology, Treatment and Economic Burden of Traumatic Spinal Cord Injury in China (2013-2018)

“…§"Others" included "Injuries caused by others," "Work-related injuries," "sharp injuries," "Massage-related injuries," "Electric shock injuries," "Gunshot wounds," "Crush injuries," and "Iatrogenic injury. [59][60][61] In this study, the utilization rate of high-dose ( ≥ 500 mg) MPSS/MP was only 4.6% within eight hours, and there was no significant sex difference at the time of initiation.…”

“…However, AOSpine recommended a high dose of MPSS/MP within eight hours of ASCI as a treatment option in 2017 57 . Some surveys found that, despite the great controversy, most patients preferred MPSS/MP early in injury 59–61 . In this study, the utilization rate of high-dose (≥500 mg) MPSS/MP was only 4.6% within eight hours, and there was no significant sex difference at the time of initiation.…”

Biodegradable nanoparticles targeting circulating immune cells reduce central and peripheral sensitization to alleviate neuropathic pain following spinal cord injury

“…1,25,38,66 The corticosteroid methylprednisolone has also been applied to reduce secondary immunological injury after SCI, but its use is limited by controversy over the balance between its efficacy and potential consequences relating to induction of a broadly immunosuppressive state. 12–14,51,62,81 By contrast, PLG NPs have selectively reprogrammed monocytes and neutrophils, reducing excessive early immune responses that initiate further neurological damage. 67 Importantly, with treatment cessation after 7 days after injury, proregenerative cytokine-mediated signaling is allowed to proceed without interruption.…”

“…Methylprednisolone has been used to reduce neuropathic pain post-SCI, yet it remains controversial because of treatment-associated adverse effects. [12][13][14]51,62,81 Nanoparticles (NPs) can be used as drug delivery platforms to distribute anti-inflammatory factors that modulate peripheral neuropathic pain responses through selective immune reprogramming. 5,11,63 Alternatively, poly(lactide-co-glycolide) (PLG) NPs, which do not have any active pharmaceutical ingredient, target scavenger receptors on circulating monocytes and neutrophils because of their size and surface charge and reprogram peripheral immune cells through drug-independent mechanisms, ultimately reducing monocyte and neutrophil accumulation at the injury.…”