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

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

by: Jane McDevitt, PhD
by: Jeff Driban


Korley FK, Diaz-Arrastia R, Wu AH, Yue JK, Manley GT M D Ph D, 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 (2015). Circulating Brain Derived Neurotrophic Factor (BDNF) Has Diagnostic and Prognostic Value in Traumatic Brain Injury. Journal of Neurotrauma PMID: 26159676f