Serum GFAP and UCH-L1 Distinguish Brain Injury Caused by High Velocity Trauma versus Anoxia/Hypoxia, Spontaneous Hemorrhage, and Other Etiologies

• Published in: Neurosurgery Vol. 67; no. Supplement_1
• Main Authors: Rafter, Daniel J, Li, Zhuliu, Sterk, Brett, Kuang, Rui, Samadani, Uzma
• Format: Journal Article
• Language: English
• Published: Philadelphia Wolters Kluwer Health, Inc 01.12.2020
• Subjects: Brain surgery; Classification; Hemorrhage; Neurosurgery; Surgical techniques; Trauma; Traumatic brain injury; Velocity
• ISSN: 0148-396X; 1524-4040
• DOI: 10.1093/neuros/nyaa447_428

INTRODUCTION Objective classification of brain injuries based on etiology, particularly in the acute setting when limited information is available, is critical for prognostication and targeting of therapeutics. Our current ability to differentiate pathophysiology in brain injury patients is limited and relies on subjective accounts of the precipitating mechanistic injury. METHODS We prospectively recruited atraumatic and traumatic brain injury (TBI) subjects presenting to a level-1 trauma center within 32 hours of injury. Serum concentrations of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) were collected and compared between five cohorts; traumatic hemorrhage, spontaneous hemorrhage, oxygen deprivation injury (cardiopulmonary arrest), high-velocity CT negative TBI, and non-injured controls. Differences in GFAP and UCH-L1 concentrations were assessed using the t-test and Wilcoxon rank-sum test. Support vector machine learning was then utilized for the classification of the patient samples in our prediction tasks. Prediction accuracy was measured by the area under the curve (AUC), precision, recall, and F1 score. RESULTS 111 matched GFAP and UCH-L1 samples were analyzed; 36 traumatic hemorrhage, 10 spontaneous hemorrhage, 16 oxygen deprivation, 10 high-velocity CT negative TBI, and 39 healthy controls. GFAP concentrations were statistically different (P < .05) in all but one comparison, high-velocity CT negative TBI and oxygen deprivation injury, while UCH-L1 concentrations were only statistically different for comparisons with non-injured control subjects. When GFAP and UCH-L1 concentrations were combined for prediction classification, the AUC for comparisons were as follows; 0.90 spontaneous vs traumatic hemorrhage, 0.93 oxygen deprivation vs spontaneous hemorrhage, 0.84 oxygen deprivation vs traumatic hemorrhage, 0.94 CT negative TBI vs traumatic hemorrhage, 1.00 CT negative TBI vs spontaneous hemorrhage, and 0.96 CT negative TBI vs oxygen deprivation. The classification prediction using both biomarkers for healthy controls and high-velocity CT negative TBI demonstrated an AUC of 0.93, precision 0.9, recall 0.84, and F1 score of 0.87. CONCLUSION Serum concentrations of S100B and GFAP collected within 32 hours of injury have utility in classifying brain-injured subjects based on the etiology of their injuries which has implications for early targeted management and prognostication of brain injury.