Systematic Review of Clinical Research on Biomarkers for Pediatric Traumatic Brain Injury

Abstract

The objective was to systematically review the medical literature and comprehensively summarize clinical research performed on biomarkers for pediatric traumatic brain injury (TBI) and to summarize the studies that have assessed serum biomarkers acutely in determining intracranial lesions on CT in children with TBI. The search strategy included a literature search of PubMed,(®) MEDLINE,(®) and the Cochrane Database from 1966 to August 2011, as well as a review of reference lists of identified studies. Search terms used included pediatrics, children, traumatic brain injury, and biomarkers. Any article with biomarkers of traumatic brain injury as a primary focus and containing a pediatric population was included. The search initially identified 167 articles. Of these, 49 met inclusion and exclusion criteria and were critically reviewed. The median sample size was 58 (interquartile range 31-101). The majority of the articles exclusively studied children (36, 74%), and 13 (26%) were studies that included both children and adults in different proportions. There were 99 different biomarkers measured in these 49 studies, and the five most frequently examined biomarkers were S100B (27 studies), neuron-specific enolase (NSE) (15 studies), interleukin (IL)-6 (7 studies), myelin basic protein (MBP) (6 studies), and IL-8 (6 studies). There were six studies that assessed the relationship between serum markers and CT lesions. Two studies found that NSE levels ≥15 ng/mL within 24 h of TBI was associated with intracranial lesions. Four studies using serum S100B were conflicting: two studies found no association with intracranial lesions and two studies found a weak association. The flurry of research in the area over the last decade is encouraging but is limited by small sample sizes, variable practices in sample collection, inconsistent biomarker-related data elements, and disparate outcome measures. Future studies of biomarkers for pediatric TBI will require rigorous and more uniform research methodology, common data elements, and consistent performance measures.

Sports-related brain injuries: connecting pathology to diagnosis

“…111 Interest in biomarkers for mTBI has increased dramatically over the past 2 decades following the increased understanding of CTE and the intensifying need for early diagnostics of brain injury. 41,111,112 However, the development of biomarkers specifically for CTE has proved elusive. Numerous gaps remain in our understanding of the pathophysiological processes leading to the development of CTE.…”

Predicting Outcome after Traumatic Brain Injury: Development of Prognostic Scores Based on the IMPACT and the APACHE II

“…This may be achieved by including more TBI-specific intensive care variables, such as measures of intracranial pressure, cerebral perfusion pressure, partial brain tissue oxygenation, microdialysate monitoring, and different biomarkers. [39][40][41] Further, although the IMPACT models were introduced in 2008, they were developed upon studies conducted in 1984-1997. 42 Since then, advances in ICU and TBI treatment has been made, for example, the release of standardized international guidelines for the treatment of patients with TBI, cerebral perfusion pressure-targeted therapies, and advances in radiological techniques.…”

S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

“…3,4 One of the biochemical responses following glial activation induced by brain injury is increased circulating serum and cerebro-spinal fluid levels of the calcium-binding protein S100B, which is primarily expressed in the astrocytes and Schwann cells. 5 The mechanisms of action of S100B as an intracellular regulator are different from those as an extracellular factor. As an intracellular regulator, S100B stimulates cell proliferation and migration, inhibits apoptosis and differentiation, and activation of astrocytes, which may have implications for brain repair after central nervous system (CNS) injury.…”

“…13,14 In addition, recently an association between elevated circulating S100B levels and impaired neurologic outcomes has been observed after clinical brain injury. 5,15 Studies suggest that cellular signaling resulting from the interaction of S100B with AGER may be responsible for its proinflammatory effects. 16 AGER is a member of the immunoglobulin (Ig) family of cell surface molecules that recognizes multiple ligands, including AGE, amphoterin, amyloid-β-peptide and β-fibrils, and S100B.…”