Neurocritical Care

, Volume 22, Issue 1, pp 52–64 | Cite as

Biomarkers Improve Clinical Outcome Predictors of Mortality Following Non-Penetrating Severe Traumatic Brain Injury

  • Linda Papa
  • Claudia S. Robertson
  • Kevin K. W. Wang
  • Gretchen M. Brophy
  • H. Julia Hannay
  • Shelley Heaton
  • Ilona Schmalfuss
  • Andrea Gabrielli
  • Ronald L. Hayes
  • Steven A. Robicsek
Original Article



This study assessed whether early levels of biomarkers measured in CSF within 24-h of severe TBI would improve the clinical prediction of 6-months mortality.


This prospective study conducted at two Level 1 Trauma Centers enrolled adults with severe TBI (GCS ≤8) requiring a ventriculostomy as well as control subjects. Ventricular CSF was sampled within 24-h of injury and analyzed for seven candidate biomarkers (UCH-L1, MAP-2, SBDP150, SBDP145, SBDP120, MBP, and S100B). The International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) scores (Core, Extended, and Lab) were calculated for each patient to determine risk of 6-months mortality. The IMPACT models and biomarkers were assessed alone and in combination.


There were 152 patients enrolled, 131 TBI patients and 21 control patients. Thirty six (27 %) patients did not survive to 6 months. Biomarkers were all significantly elevated in TBI versus controls (p < 0.001). Peak levels of UCH-L1, SBDP145, MAP-2, and MBP were significantly higher in non-survivors (p < 0.05). Of the seven biomarkers measured at 12-h post-injury MAP-2 (p = 0.004), UCH-L1 (p = 0.024), and MBP (p = 0.037) had significant unadjusted hazard ratios. Of the seven biomarkers measured at the earliest time within 24-h, MAP-2 (p = 0.002), UCH-L1 (p = 0.016), MBP (p = 0.021), and SBDP145 (0.029) had the most significant elevations. When the IMPACT Extended Model was combined with the biomarkers, MAP-2 contributed most significantly to the survival models with sensitivities of 97–100 %.


These data suggest that early levels of MAP-2 in combination with clinical data provide enhanced prognostic capabilities for mortality at 6 months.


Biomarkers Severe traumatic brain injury Mortality Microtubual associated protein (MAP-2) S100B Alpha-spectrin breakdown products (SBDPs) Ubiquitin C-terminal hydrolase (UCH-L1) 


Conflict of interest

Drs. Gabrielli, Hannay, Heaton, Robertson, Robicsek, and Schmalfuss have no competing financial interests.


This study was funded by NIH RO1 NS052831 “Biochemical Markers of Severe Traumatic Brain Injury”. Drs. Brophy and Papa are consultants of Banyan Biomarkers, Inc. but receive no stocks or royalties from the company and will not benefit financially from this publication. Dr. Hayes and Wang own stock, receive royalties from Banyan Biomarkers Inc., and as such may benefit financially as a result of the outcomes of this research or work reported in this publication.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Linda Papa
    • 1
  • Claudia S. Robertson
    • 2
  • Kevin K. W. Wang
    • 3
  • Gretchen M. Brophy
    • 4
  • H. Julia Hannay
    • 5
  • Shelley Heaton
    • 6
  • Ilona Schmalfuss
    • 7
  • Andrea Gabrielli
    • 8
  • Ronald L. Hayes
    • 9
  • Steven A. Robicsek
    • 8
  1. 1.Department of Emergency MedicineOrlando Regional Medical CenterOrlandoUSA
  2. 2.Department of NeurosurgeryBaylor College of MedicineHoustonUSA
  3. 3.Department of PsychiatryUniversity of FloridaGainesvilleUSA
  4. 4.Department of Pharmacotherapy and Outcomes Science and NeurosurgeryVirginia Commonwealth UniversityRichmondUSA
  5. 5.Department of PsychologyUniversity of HoustonHoustonUSA
  6. 6.Department of Clinical and Health PsychologyUniversity of FloridaGainesvilleUSA
  7. 7.Department of RadiologyUniversity of Florida and NF/SG Veterans AdministrationGainesvilleUSA
  8. 8.Department of AnesthesiologyUniversity of FloridaGainesvilleUSA
  9. 9.Banyan LaboratoriesBanyan Biomarkers Inc.AlachuaUSA

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