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

• Published in: Neurocritical care Vol. 22; no. 1; pp. 52 - 64
• Main Authors: Papa, Linda, Robertson, Claudia S., Wang, Kevin K. W., Brophy, Gretchen M., Hannay, H. Julia, Heaton, Shelley, Schmalfuss, Ilona, Gabrielli, Andrea, Hayes, Ronald L., Robicsek, Steven A.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2015; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers - cerebrospinal fluid; Brain Injuries - cerebrospinal fluid; Brain Injuries - mortality; Critical Care Medicine; Female; Glasgow Coma Scale; Head injuries; Humans; Intensive; Internal Medicine; Male; Medicine; Medicine & Public Health; Microtubule-Associated Proteins - cerebrospinal fluid; Middle Aged; Models, Statistical; Mortality; Neurology; Original Article; Prognosis; Severity of Illness Index; Traumatic brain injury; Young Adult; Microtubual associated protein (MAP-2); Mortality; Biomarkers; Severe traumatic brain injury; S100B; Alpha-spectrin breakdown products (SBDPs); Ubiquitin C-terminal hydrolase (UCH-L1)
• ISSN: 1541-6933; 1556-0961; 1556-0961
• DOI: 10.1007/s12028-014-0028-2

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