Methylprednisolone and acute spinal cord injury: an update of the randomized evidence.

Department of Epidemiology, Yale University School of Medicine, 60 College Street, New Haven, Connecticut 06520, USA.
Spine (Impact Factor: 2.3). 01/2002; 26(24 Suppl):S47-54.
Source: PubMed


Randomized trials are widely recognized as providing the most reliable evidence for assessing efficacy and safety of therapeutic interventions. This evidence base is used to evaluate the current status of methylprednisolone (MPSS) in the early treatment of acute spinal cord injury.
Medline, CINAHL, and other specified databases were searched for MeSH headings "methylprednisolone and acute spinal cord injury." The Cochrane Library and an existing systematic review on the topic were also searched.
Five randomized controlled trials were identified that evaluated high-dose MPSS for acute spinal cord injury. Three trials by the NASCIS group were of high methodologic quality, and a Japanese and French trial of moderate to low, methodologic quality. Meta-analysis of the final result of three trials comparing 24-hour high-dose MPSS with placebo or no therapy indicates an average unilateral 4.1 motor function score improvement (95% confidence interval 0.6-7.6, P = 0.02) in patients treated with MPSS. This neurologic recovery is likely to be correlated with improved functional recovery in some patients. The safety of this regimen of MPSS is evident from the spinal cord injury trials and a systematic review of 51 surgical trials of high-dose MPSS.
High-dose MPSS given within 8 hours of acute spinal cord injury is a safe and modestly effective therapy that may result in important clinical recovery for some patients. Further trials are needed to identify superior pharmacologic therapies and to test drugs that may sequentially influence the postinjury cascade.

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    • "In addition, secondary neurodegeneration takes place in the surrounding tissue site due to inflammatory factors and modifies substantially the prognosis (Andrade et al., 2008). High dose corticosteroid injection within 48 h after damage is the only accepted clinical method to reduce consequences of spinal damages (Bracken, 2001). Cell therapy is an issue that has raised much hope in regeneration of CNS and PNS. "

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    • "Methylprednisolone remains the only option for therapeutic intervention in the emergency management of SCI (33), despite conflicting results both in laboratory experiments and clinical trials (34–36). Indeed, some researchers have questioned clinical trial results (37–39), while others have criticized such evaluations for focusing solely on statistical details and theoretical safety concerns (33, 40). A major concern is that the side effects of methylprednisolone outweigh its modest functional benefits. "
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    ABSTRACT: There is strong evidence indicating that the social environment triggers changes to the psychological stress response and glucocorticoid receptor function. Considerable literature links the subsequent changes in stress resiliency to physical health. Here, converging evidence for the modulatory role of chronic psychological stress in the recovery process following spinal cord injury (SCI) is presented. Despite the considerable advances in SCI research, we are still unable to identify the causes of variability in patients' recovery following injury. We propose that individuals' past and present life experiences (in the form of stress exposure) may significantly modulate patients' outcome post-SCI. We propose a theoretical model to explain the negative impact of chronic psychological stress on physical and psychological recovery. The stress experienced in life prior to SCI and also as a result of the traumatic injury, could compromise glucocorticoid receptor sensitivity and function, and contribute to high levels of inflammation and apoptosis post-SCI, decreasing the tissue remaining at the injury site and undermining recovery of function. Both stress-induced glucocorticoid resistance and stress-induced epigenetic changes to the glucocorticoid receptor can modulate the nuclear factor-kappa B regulated inflammatory pathways and the Bcl-2 regulated apoptosis pathways. This model not only contributes to the theoretical understanding of the recovery process following injury, but also provides concrete testable hypotheses for future studies.
    Frontiers in Neurology 04/2014; 5:44. DOI:10.3389/fneur.2014.00044
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    • "All of these problems have a negative effect on the physiological, psychological and social behavior of SCI patients. Current clinical approaches are limited and mainly based on the use of antiinflammatory agents, such as methylprednisolone [1]; however, its use is controversial as recent studies failed to reveal conclusive beneficial outcomes [2]. Some of the other strategies that have been tested clinically include: minocycline [3], anti-NogoA [4] and transplantation of oligodendrocyte precursor cells [5]. "
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    ABSTRACT: The regenerative capacity of injured adult central nervous system (CNS) tissue is very limited. Specifically, traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory functions below the site of injury, as well as other detrimental complications. A potential regenerative strategy is stem cell transplantation; however, cell survival is typically less than 1%. To improve cell survival, stem cells can be delivered in a biomaterial matrix that provides an environment conducive to survival after transplantation. One major challenge in this approach is to define the biomaterial and cell strategies in vitro. To this end, we investigated both peptide-modification of gellan gum and olfactory ensheathing glia (OEG) on neural stem/progenitor cell (NSPC) fate. To enhance cell adhesion, the gellan gum (GG) was modified using Diels-Alder click chemistry with a fibronectin-derived synthetic peptide (GRGDS). Amino acid analysis demonstrated that approximately 300 nmol of GRGDS was immobilized to each mg of GG. The GG-GRGDS had a profound effect on NSPC morphology and proliferation, distinct from that of NSPCs in GG alone, demonstrating the importance of GRGDS for cell-GG interaction. To further enhance NSPC survival and outgrowth, they were cultured with OEG. Here NSPCs interacted extensively with OEG, demonstrating significantly greater survival and proliferation relative to monocultures of NSPCs. These results suggest that this co-culture strategy of NSPCs with OEG may have therapeutic benefit for SCI repair.
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