Associations between post-traumatic amnesia, blood biomarkers, and outcomes following traumatic brain injury (Glasgow Coma Scale 13-15)

Background and Objectives Post-traumatic amnesia (PTA) is a state of disorientation, memory loss, and behavioral dysfunction after traumatic brain injury (TBI). Despite PTA being associated with injury severity and recovery, the pathophysiology is unclear. This study evaluated the relationships between PTA status at Emergency Department admission and PTA duration and blood biomarkers and six-month outcomes in participants with a Glasgow Coma Scale (GCS) of 13-15 from CENTER-TBI, a prospective, longitudinal, observational study aimed at improving TBI characterization. Methods Participants were included in this analysis if they met the following criteria: GCS 13-15, non-intubated, and with PTA status, 1 blood biomarker sample, and 1 six-month outcome available. PTA status was categorized as ongoing, resolved, or no PTA. PTA duration was grouped into <1 hour, 1-24 hours, or >1 day. The maximum acute (<24 hours) and subacute (6-31 days) neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), S100 calcium-binding protein B (S100B), and total tau concentrations were log-transformed. The associations between PTA and blood biomarkers and cognitive outcomes were analyzed with mixed-effects models. The associations between PTA and six-month dichotomized functional & patient-reported outcomes were assessed using logistic mixed-effects models. Results 1,708 participants from CENTER-TBI (mean age: 50.89; 35% female; 41.2% CT-positive) were included. Ongoing PTA was associated with higher acute GFAP (estimated differences(β),0.757, SE=0.100), UCH-L1 (β,0.424, SE=0.076), tau (β,0.271, SE=0.060), S100B (β,0.238, SE=0.053) (all: p<0.001), and subacute NfL (β,0.754, SE=0.304, p=0.031) concentrations compared to no PTA. Similar results were seen with resolved PTA. Longer PTA duration was associated with higher acute biomarkers. Participants with resolved PTA had more favorable outcomes on the Short-Form 12-Item Survey v2 Physical Component Summary than those without PTA (OR:0.52, [95% CI: 0.35-0.78], p=0.005). There were no associations with cognitive outcomes. Discussion Acute PTA assessment is associated with a pathophysiological gradient of neuro-axonal and astro-glial injury in patients with GCS 13-15 but has limited association with six-month outcomes. These findings point to the potential importance of assessing PTA when defining injury severity and the need to further establish if PTA has prognostic utility in patients following TBI (GCS 13-15). Clinical Trials Registration NCT02210221