Circulating brain derived neurotrophic factor (BDNF) has diagnostic and prognostic value in traumatic brain injury
Korley FK, Diaz-Arrastia R, Wu A, Yue JK, Manley GT, Sair HI, Van Eyk J, Everett AD, Okonkwo DO, Valadka A, Gordon WA, Maas A, Mukherjee P, Yuh EL, Lingsma H, Puccio AM, Schnyer DM. J Neuotrauma 2015; ahead of print.
Take Home Message: A serum biomarker measured on the day of an injury could help diagnose a traumatic brain injury and differentiate mild injuries from more severe injuries.
Knowing the risk factors for prolonged recovery following a concussion injury is important since there is a chance of developing chronic or progressive concussion symptoms due to repeated concussions before the brain completely heals. There are not many prognostic tools to monitor the brain during the recovery process. One potential solution is to measure biochemical markers (biomarkers) in the blood, which could help us make objective decisions on whether the patient has a concussion and how long might his/her symptoms persist. Some potential candidate are brain derived neurotropic factor (BDNF) due to is importance for neuronal survival and regeneration, glial fibrillary acidic protein (GFAP), which functions in maintaining the blood brain barrier, and Ubiquitin C-terminal hydrolase (UCH-L1) that is required for normal cognition. BDNF decreases in the blood and GFAP and UCH-L1 increases in blood after an injury, but there is limited evidence for them to be used as potential markers for sports-related concussion. Therefore, the authors evaluated whether BDNF is a valid diagnostic and prognostic biomarker for concussion in two independent cohorts of traumatic brain injury (TBI) cases presenting to the emergency departments of John Hopkins Hospital (76 cases) and San Francisco General Hospital (76 cases). The authors also collected samples from a control group with no traumatic brain injury from John Hopkins Hospital (150 cases), and utilized TBI case samples from a Transforming Research and Clinical Knowledge in TBI multi-center (150 cases). The authors also investigated the association between BDNF, GFAP, UCH-L1, and incomplete recovery (post-concussive syndrome or a Glasgow Outcome Scale Extended score<8 at 6 months). The authors reported that day-of-injury BDNF concentrations were typically lower among TBI cases than in controls. One proposed cut-off for BDNF concentrations was fairly accurate with only 1 control person (out of 150) being misclassified with a possible TBI and only 37 cases with TBI (out of 159 cases) being misclassified as possibly not having a TBI. Among the multi-center TBI cases, typical BDNF concentrations were higher in mild than in moderate or severe TBI cases. In the multi-center TBI cohort, the 75 (71.4%) individuals with very low BDNF values were 4 times more likely to suffer from incomplete recovery than those without very low values. The accuracy for discriminating complete and incomplete recovery was poor for BDNF, GFAP, and UCH-L1. Addition of GFAP and UCH-L1 to BDNF did not improve outcome prediction.
The authors found that day-of-injury circulating BDNF is different between those with and without a TBI and may have prognostic ability for identifying patients that are likely to have persistent TBI-related problems at 6 months. Additionally, BDNF could differentiate mild TBI patients from those with moderate or severe TBI, which could help us identify concussed athletes that may need extra time before returning to play. However, the ability of the three biomarkers in providing a prognosis to predict who will have a complete and incomplete recovery was poor. The chances of discriminating between groups were not much higher than flipping a coin. Therefore, more research is necessary to test the prognostic benefits of these biomarkers however, this study is important because it illustrate the need for determining tools that may aid in TBI risk stratification.
Questions for Discussion: Would a prognostic tool be helpful in determining who is at risk for incomplete recovery? Do you think biomarkers will eventually be used for the diagnosis of concussion?
Written by: Jane McDevitt, PhD
Reviewed by: Jeff Driban