Review articleBlood biomarkers in paediatric mild traumatic brain injury: a systematic review
Introduction
Traumatic brain injury (TBI) is defined as “an alteration in brain function, or other evidence of brain pathology, caused by an external force” (Menon et al., 2010). As the name suggests, mild traumatic brain injury (mTBI) is the mildest and yet arguably most common form of TBI (Crowe et al., 2009; Meehan and Mannix, 2010). The American Congress of Rehabilitation Medicine (ACRM) defines mTBI as a blow to the head resulting in at least one of the following immediate symptoms: a period of loss of consciousness ≤30 min, post-traumatic amnesia ≤24 h, any alteration in mental state at the time of the accident, focal neurological deficits (transient/not transient) or a Glasgow Coma Scale (GCS - providing an objective measure of the conscious state of a person) score of 13–15 (Kay et al., 1993; Saatman et al., 2008). One out of every 220 (0.5%) paediatric patients admitted to the emergency department within the United States is diagnosed with a mTBI, totalling approximately 144,000 patients per year on a national level and 18% of all paediatric head injury patients (Meehan and Mannix, 2010).
An audit of children who attended the Royal Children’s Hospital (RCH), Melbourne, Australia in 2004 for a HI found that 90% of the patients were classified as having a mTBI (Crowe et al., 2009). In fact, in Australia, 20% of 10 year olds (approximately 51,000 children annually) will have suffered at least one head injury requiring medical treatment (Harmon et al., 2013). As these studies do not account for individuals who did not receive medical care, it can be assumed that in reality the occurrence of mTBI is much higher. While most children improve within 1 week following a mTBI, there is growing consensus that post-mTBI symptoms can persist for up to a month in approximately 30% of patients (Barlow et al., 2010; Eisenberg et al., 2014). These prolonged symptoms, which may include headaches, dizziness, difficulties concentrating, irritability, cognitive/emotional impairments, and behavioural difficulties, have been termed persistent (Zemek et al., 2013) or Post Concussion Symptoms (PCS). If left unchecked, these predominantly non-specific symptoms have the potential to develop into significant cognitive, academic and emotional-behavioural difficulties that may impact a child’s overall quality of life.
Little is known about the predictive factors and mechanism of PCS in children. This systematic review aims to summarize the studies that have assessed blood biomarkers within the setting of paediatric mTBI and to determine the potential of blood biomarkers as a diagnostic, prognostic and/or monitoring tool.
Section snippets
Methods
The terms “concussion” and “mild traumatic brain injury” are often used synonymously. Various diagnostic criteria overlap significantly (e.g., the Concussion in Sport Group consensus statement versus the American Congress of Rehabilitation Medicine criteria for mild traumatic brain injury), which leads to inconsistent terminology and methodological heterogeneity. With that in mind, for the purpose of this review, the terms “concussion” and “mild traumatic brain injury” will be used
Results
From the excluded studies, 12 studies (27.3%) had no separate results for children, despite including children within their sample. A total of 21 studies were identified for inclusion in this review. These studies focused on blood biomarkers assessed in paediatric mTBI, in accordance with the ACRM criteria. Of the 21 studies, 19 (90.5%) included children aged less than 18 years and two (9.5%) included children up to 21 years. The biomarker S100 calcium-binding protein B (S100B) was assessed in
Discussion
This systematic review included 21 papers, reporting on a total of 14 different biomarkers. The biomarkers that were studied most frequently were S100B, GFAP, and UCH-L1. S100B is a small calcium-binding protein involved in a range of cellular processes with particular abundance in glial and neural cells of the central nervous system (CNS). S100B has been shown to be elevated in several neurological conditions and is a general marker of brain injury (Olsson et al., 2011). GFAP is an
Conclusion
Despite the fact that mTBI in children involves small biological changes, research focusing on more severe brain injuries and on adults suggests that there is great potential for blood biomarkers to be used in assessing paediatric mTBI, especially for prognostic and monitoring purposes. We recommend that research within this field focus on discovering and validating new biomarker associations. Specifically, future studies should strive to present results in a way that discriminates between TBI
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