Use of Cerebral Biomarkers in Minor Traumatic Brain Injury in the Emergency Unit

Overview

The use of serum biomarkers in the setting of the emergency department (ED) has been well characterized over the years as an adjunctive tool for the clinician in the setting of complex decision making. In this regard, the serum dosage of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) has been evaluated in a series of successful multicenter prospective studies as a potentially useful marker of, respectively, glial and neuronal damage in the setting of mild traumatic brain injury (mTBI), which is defined as a brain injury (concussion) secondary to trauma with a GCS (Glasgow coma scale) score of 13-15. It seems that both markers are detectable in serum less than 1 hour after the traumatic event, with highest levels appearing at around 2 hours, and are capable of distinguishing between patients with traumatic brain injury from those without acute brain injury after trauma. Furthermore, they seem to possess a high negative predictive value for detection of intracranial injuries at head CT-scan as well as the need of neurosurgical intervention after head trauma. Mild traumatic brain injury is one of the most frequent chief-complaints for patients presenting to emergency departments worldwide. At present, head CT scan is the gold standard diagnostic test for the identification of potentially life-threatening intra-cranial injuries. Although effective in the identification of serious lesions which might require neurosurgical intervention or in-hospital prolonged observation, the extensive use of head CT scan in mTBI has been questioned due to the potential risks related to radiation exposure, as well as unnecessary deployment of ED resources and increased costs, considering that the prevalence of CT-detected intra-cranial injury in mTBI is around 5-10%. For this reason, a number of international clinical guidelines suggest several Clinical Decision Rules (CDR) and algorithms to guide the clinician in the correct management of these patients, in particular in the difficult feat of identifying those patients who don't need to perform neuroradiological evaluation (CT scan or MRI) in the setting of the ED, without the risk to overlook potentially fatal brain injuries. The adjunctive role of these biomarkers has been well characterized in the setting of mTBI. It seems they correlate well with neurological damage as well as with the presence of CT abnormalities, and it seems that they might perform better than clinical evaluation alone. Nonetheless, according to current international guidelines and several systematic reviews and meta-analysis, patients who present with mTBI and risk factors for bleeding and delayed bleeding (such as known coagulopathy, patients on blood thinners or advanced age), need to perform CT scan plus clinical observation or even serial CT scans when the risk of delayed bleeding is considered to be high according to clinical evaluation of the ED physician and according to local standard-of-care and clinical practice. The execution of serial CT scans can be time consuming, expensive for the health-care services, and might pose a significant radiological risk for patients; furthermore, this risk might be unjustified considering that the prevalence of development of late intra-cranial bleeding in patients with risk factors who perform a second head CT scan during observation in the ED is considered to be around 2%. Nonetheless, in this category of patients, clinical observation and the repetition of a second head CT scan is felt to be the safest course of action for patients in order not to overlook potentially fatal injuries. Ideally, a clinical decision algorithm which takes into consideration a serum biomarker with a high negative predictive value for brain injury might aid the clinician to reduce the number of useless CT scans, therefore reducing the observation time in the ED as well as the exposure to ionizing radiations for the patients, while not increasing the number of missed delayed bleedings. At present, the role of GFAP and UCH-L1 in the risk stratification of patients with risk factors for delayed cerebral bleeding after mTBI has not been evaluated yet.