Blood Biomarkers to Help Diagnose and Guide Appropriate Treatment in TBI

by Bianca Garilli, ND

 Traumatic brain injury (TBI) research has grown rapidly in the past decade as awareness of the high prevalence and its potential devastating consequences have become clearer.¹ TBI may result in varying degrees of paralysis, loss of consciousness, amnesia and even death. Death was the most common outcome for those diagnosed with moderate and severe TBI where severity of TBI was classified according to the Glasgow Coma Scale (GCS). The two most common causes of TBI globally are motor vehicle collision and falls.²

Not all TBI patients present for medical treatment immediately after the event, often making it difficult for providers to know the extent of the injury and appropriate subsequent interventional strategy to reduce risk of adverse outcomes.¹

Research has indicated the presence of two important biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1), which may help in distinguishing severity of TBI at various time points after injury.¹  

Current evidence indicates GFAP and UCH-L1:¹

• Can be detected in the serum in less than 1 hour after a mild TBI and aids in distinguishing between patients with mild TBI and other trauma patients without acute brain injury Levels are significantly elevated in patients with TBI with intracranial lesions on computed tomography (CT) and, in patients with mild TBI, can distinguish between those with a normal and an abnormal CT scan of the brain
• Are elevated in patients with mild TBI requiring neurosurgical intervention and can predict with high sensitivity which patients with mild TBI will require neurosurgery

GFAP on its own is helpful in detecting intracranial lesions in polytrauma patients with mild TBI who have substantial extracranial injuries and fractures and can detect axonal injury on magnetic resonance imaging 3 months after TBI.¹

A great deal of information exists on the importance of these biomarkers in assessing TBI severity and timing, however, less well understood is when to use these biomarkers for the clinical evaluation of the trauma patient with suspected mild TBI. A study published in JAMA Neurology evaluated the temporal profiles of the serum biomarkers GFAP and UCH-L1 in a large cohort of trauma patients.¹ These patients were seen at a level I trauma center in Orlando, Florida within 4 hours of injury.  The cohort included individuals both with and without mild to moderate TBI (MMTBI) in whom these two biomarkers were assessed for their diagnostic accuracy and performance over time for:¹

1. Detecting the presence of MMTBI and distinguishing trauma patients with MMTBI from those without MMTBI
2. Identifying traumatic intracranial lesions on CT scan
3. Having a neurosurgical intervention, where neurosurgical intervention was defined as either death within 7 days secondary to brain injury or the need for any of the following procedures within 7 days: craniotomy, elevation of skull fracture, intracranial pressure monitoring, or intubation for brain injury

Results were obtained by analyzing a total of 1831 blood samples drawn from the study’s 584 subjects over a period of 7 days. It was found that GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury followed by a slow decline over the next 72 hours. UCH-L1 rose rapidly as well and peaked at 8 hours after injury then quickly declined over the following 48 hours.  Over the course of this week long study, GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical interventions while UCH-L1 performed best in the early post-injury period.

 Why is this Clinically Relevant?

• Variations of severity and time from traumatic event in TBI may be predicted through the analysis of the biomarkers GFAP and UCH-L1
• The various levels of these biomarkers may indicate traumatic intracranial lesions which would be seen on CT scan
• GFAP and UCH-L1 may be helpful in predicting neurosurgical intervention in mild to moderate TBI
• Combining the findings of both GFAP and UCH-L1 may improve diagnosis of severity of TBI, timing after event of TBI if unknown and may help with predicting outcomes after MMTBI

Link to abstract

Citations

1. Papa L, Brophy G, Welch R, et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Nuerol. 2016;73(5):551-560.
2. Li M, Zhao Z, Yu G, Zhang J. . Epidemiology of traumatic brain injury over the world: a systematic review. Austin Neurol & Neurosci. 2016;1(2):1007.