Despite advances in both prevention and treatment, traumatic brain injury (TBI) remains one of the most burdensome diseases; 2% of the US population currently lives with disabilities resulting from TBI. Recent advances in the understanding of inflammation and its impact on the pathophysiology of trauma have increased the interest in inflammation as a possible mediator in TBI outcome.
The goal of this systematic review is to address the question: “What is the evidence in humans that inflammation is linked to secondary brain injury?” As the experimental evidence has been well described elsewhere, this review will focus on the clinical evidence for inflammation as a mechanism of secondary brain injury.
Medline database (1996-Week 1 June 2014), Pubmed and Google Scholar databases were queried for relevant studies.
Studies were eligible if participants were adults and/or children who sustained moderate or severe TBI in the acute phase of injury, published in English. Studies published in the last decade (since 2004) were preferentially included. Trials could be observational or interventional in nature.
To address the quality of the studies retrieved, we applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria to assess the limitations of the included studies.
Trauma initiates local central nervous system as well as systemic immune activation. Numerous observational studies describe elevation of pro-inflammatory cytokines that are associated with important clinical variables including neurologic outcome and mortality. A small number of clinical trials have included immunomodulating strategies, but no intervention to date has proven effective in improving outcomes after TBI.
Inclusion of studies not initially retrieved by the search terms may have biased our results. Additionally, some reports may have been inadvertently excluded due to use of non-search term key words. Conclusions and Implications of Key Findings Clinical evidence of inflammation causing secondary brain injury in humans is gaining momentum. While inflammation is certainly present, it is not clear from the literature at what juncture inflammation becomes maladaptive, promoting secondary injury rather than facilitating repairand identifying patients with maladaptive inflammation (neuro-inflammation, systemic, or both) after TBI remains elusive. Direct agonism/antagonism represents an exciting target for future study.
Systematic review, level III.
From the Departments of Neurology and Neurocritical Care (H.E.H.) and Surgery (S.R., M.S.), Oregon Health and Science University, Portland, Oregon.
Submitted: April 25, 2014, Revised: July 30, 2014, Accepted: August 1, 2014.
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.
Address for reprints: Holly E. Hinson, MD, Neurology and Neurocritical Care, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, CR-127, Portland, OR 97239; email: email@example.com.