Longitudinal Course of Traumatic Brain Injury Biomarkers for the Prediction of Clinical Outcomes: A Review

Protein biomarkers are often measured at hospital presentation to diagnose traumatic brain injury (TBI) and predict patient outcomes. However, a biomarker measurement at this single time point is no more accurate at predicting patient outcomes than less invasive and more cost-effective methods. Here, we review evidence that TBI biomarkers provide greater prognostic value when measured repeatedly over time, such that a trajectory of biomarker concentrations can be evaluated. PubMed, Google Scholar, and Cochrane Central Register were searched to identify studies from the last decade in which established TBI biomarkers had been measured at more than one time point following acute TBI, and which related their findings to patient outcomes. Twenty-two studies were identified, 18 of which focused on adults and 4 of which focused on children. Three general biomarker trajectories were identified: persistently high, persistently low, and reversal of decreasing concentrations. Downtrend reversal was highly specific to predicting poor patient outcomes. Four studies demonstrated that biomarker trajectories can be affected by therapeutic interventions. Additional studies demonstrated that biomarkers measured at a later time point offered superior prognostic value than a single measurement obtained at initial hospital presentation. Among other details, longitudinal biomarker trajectory assessments may identify ongoing injury and predict patient deterioration before clinical symptoms develop and thus help guide therapeutic interventions.