Before, During, and After Mild Traumatic Brain Injury
1Emergency Department, Royal London Hospital, United Kingdom
Traumatic brain injury (TBI) is common, with an incidence of up to 500/100,000 people per year in the United States. At least 80% of TBI is classified as mild. Commonly reported outcomes following mild TBI include post-concussion symptoms (including a diagnosis of post-concussion syndrome); functional outcomes such as Glasgow Outcome Scale-Extended, the Rivermead Head Injury Follow-up Questionnaire and return to work; neuropsychological measures; and quality of life. Many outcomes are reported but a real-world pragmatic outcome is return to work or usual activities following mild TBI. Although more than 50% of adults that sustain mild TBI have probably returned to work or usual activities by a month after injury, as many as 10% may not have returned to work by a year. Outcomes are associated with factors present prior to, at the time of and following the injury. Pre-injury factors associated with outcomes following mild TBI include age, sex, level of education, prior mild TBIs, and pre-existing physical or mental health problems. Peri-injury factors associated with outcomes include loss of consciousness, amnesia, intoxication, presence of abnormality on computed tomography scan of the head (CT), and extracranial injuries. Early post-injury factors associated with outcomes include symptoms, cognitive tests, neuroimaging (including magnetic resonance imaging [MRI] techniques), and biomarkers.
Serum biomarkers are investigated and used for two outcomes. The first is to identify patients that are likely to have or not have acute intracranial abnormalities (including cerebral contusions or extra-dural, subdural, intra-parenchymal, or subarachnoid haemorrhage). The second is to identify patients that have persistent symptoms. Biomarkers can be detected in serum, cerebrospinal fluid and saliva but serum biomarkers are most useful in mild TBI prognostication. The most commonly investigated biomarkers are S100B, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurone specific enolase (NSE), and neurofilaments light, medium and heavy (NF-L, NF-M, and NF-H). S100B is a glial specific protein and is the most extensively investigated. It is used as a screen in many Emergency Departments to discriminate between patients that may or may not have intracranial injury. At a threshold of 0.1 µg/L it has a high sensitivity (low false negative rate) but low specificity for acute intracranial abnormality. It was first incorporated as part of the assessment strategy for patients with head injury in Scandinavian head injury guidance in 2013 and has since been adopted by multiple other countries. GFAP and UCH-L1 are marketed as a combined test, which at a threshold of 0.022 µg/L and 0.327 µg/L respectively has a sensitivity and negative predictive value approaching 100%, and is the only biomarker licensed by the FDA for use in mild TBI. No biomarkers have shown consistent or compelling value in predicting longer term outcomes such as post-concussion syndrome.