GFAP potential candidate biomarker for mild TBI in children

In a study published online in the journal Academic Emergency Medicine, researchers from the Departments of Emergency Medicine at Orlando Regional Medical, Arnold Palmer Hospital for Children ,Orlando, The Children’s Hospital of Philadelphia and the Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania , Philadelphia examined the performance of serum glial fibrillary acidic protein (GFAP) in detecting traumatic intracranial lesions on computed tomography (CT) scan in children and youth with mild and moderate traumatic brain injury (TBI) and assessed its performance in trauma control patients without head trauma.

They studied 257 children and serum samples were taken within 6 hours of injury. 197 had blunt head trauma and 60 were trauma controls. All children had GCS 13-15 consistent with a categorisation of mild head injury. 18 (11%) of the children had traumatic intracranial lesions on CT scan.

Serum median GFAP levels were significantly higher in those with intracranial lesions than those without. Moreover, the study showed that the blood test detected symptoms of concussions, even when brain injuries were not visible on CT scan.

In addition the serum GFAP levels seemed to correspond to the severity of injury. Levels of the biomarker were lower in mild cases, and were much more elevated in severe case. Performance for detecting intracranial lesions at a GFAP cut off level of 0.15 ng/mL yielded a sensitivity of 94%, a specificity of 47%, and a negative predictive value of 98%.

The area under the receiver operating characteristic curve (AUC) for GFAP in detecting children and youth with traumatic intracranial lesions on CT was 0.82 (95%confidence interval [CI] = 0.71 to 0.93). In those presenting with GCS scores of 15, the AUC for detecting lesions was 0.80 (95% CI = 0.68 to 0.92). Similarly, in children under 5 years old the AUC was 0.83 (95%CI = 0.56 to 1.00).

Glial fibrillary acidic protein (GFAP) is found in glial cells and is released following injury. They can pass the blood-brain-barrier and enter the bloodstream making them amenable to detection. The availability of a biomarker will enable physicians to diagnose concussion more accurately and also minimize the need for CT scans which are associated with radiation exposure, besides the expenses involved.

A number of recent studies have shown glial fibrillary acidic protein (GFAP) to be a promising brain-specific biomarker for mild and moderate TBI (Papa et al., 2012 & 2014; Metting et al., 2012; Diaz-Arrastia et al., 2014). The same researchers (Papa et al., 2012 & 2014) had recently found that Serum GFAP distinguished mild TBI in adults from trauma patients without TBI and detected intracranial lesions on CT with a sensitivity of 97% to 100%. GFAP has also been shown to be better than S100b in the setting of multiple trauma when extracranial fractures were present (Papa et al., 2014 & 2015).

Although this study did not look at the half-life or optimal timing after injury of GFAP in children and youth and had a relatively small number of children and young adolescents with traumatic brain lesions on CT (11%) suggested by the wide CIs, it points to the utility of GFAP as a valuable candidate biomarker for detecting traumatic intracranial lesions on CT in children and young adults with head injury. Larger multicentre studies would be necessary to validate these findings before applying them clinically.

It's estimated nearly a quarter of a million children a year are treated in hospitals for traumatic brain injuries like concussions, which occur while playing sports. That's approximately 700 children every day. Concussion is a clinical diagnosis at present and are often indicated by the clinical symptoms including vomiting, headaches, blurred vision or generally unwell, which does not give an objective indication of the severity of injury.

References

• Papa L, Lewis LM, Falk JL, et al. Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann Emerg Med 2012;59:471–83.
• Metting Z, Wilczak N, Rodiger LA, Schaaf JM, vander Naalt J. GFAP and S100B in the acute phase of mild traumatic brain injury. Neurology 2012;78:1428–33.
• Diaz-Arrastia R, Wang KK, Papa L, et al. Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. JNeurotrauma 2014;31:19 –25.
• Papa L, Lewis LM, Falk JL, et al. Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann Emerg Med2012;59:471–83.
• Papa L, Silvestri S, Brophy GM, et al. GFAP out- performs S100beta in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions. J Neurotrauma 2014;31:1815–22.
• Papa L, Silvestri S, Brophy GM, et al. GFAP out-performs S100beta in detecting traumatic intracra-nial lesions on computed tomography in traumapatients with mild traumatic brain injury and those with extracranial lesions. J Neurotrauma2014;31:1815–22.
• Papa L, Mittal MK, Ramirez J, et al. In children and youth with mild and moderate traumatic braininjury GFAP out-performs S100beta in detecting traumatic intracranial lesions on computed tomog-raphy. J Neurotrauma 2015;. doi:10.1089/neu.2015.3869