Neurofilament Light Protein: a marker for injury severity, clinical course and outcome following moderate-severe Traumatic Brain Injury

Background: Recent studies demonstrate increased Neurofilament Light (NfL) levels across all types of Traumatic Brain Injury (TBI). We aimed to evaluate the relationship between acute temporal NfL with ICU physiology and outcome. Methods: Stored serum from 97 patients with severe TBI were analyzed. Samples werecollected every 6h for the first 24h and then daily through day 10. Temporal NfL patterns were examined using group-based trajectory (TRAJ) modeling, and means were calculated over day 0, 1-5, 6-10 and 0-10. ICU injury burden scores were generated using ridge regression anchored to Glasgow Outcome Scale-Extended (GOSE) over the same time-bins. We used both univariable and multivariable regression to assess NfL TRAJ and means with respect to ICU injury burden, demographic data, clinical factors, and outcome. NfL TRAJ and day 0-10 ICU injury burden were added to a baseline model to evaluate outcome discrimination. Mediation analysis was applied to assess the mediation effect of ICU injury burden between NfL and GOSE. Results: Patients demonstrated increasing levels over the monitoring period. Sixty-three patients had low NfL temporal profile (low-TRAJ), and 34 patients had higher profile (high-TRAJ). Individuals in the high-TRAJ group had lower GCS (p=0.0009), more frequently required barbiturate coma (p=0.01) or decompressive surgery (p=0.02) and had worse 6-months outcome (p=0.001). NfL means and ICU injury burden both negatively correlated with GCS. Multivariate logistic regression showed a 2.24X increased odds of unfavorable GOSE per unit increase in ICU injury burden (p=0.0447). When modeled with ICU injury burden, the NfL high-TRAJ group relationship to outcome was attenuated, with ICU burden being a significant mediator of the NfL relationship to GOSE. Conclusion: Our results suggest that ICU injury burden contributes to serum NfL associations with GOSE. Temporal NfL profiles provide novel information about intracranial pathophysiology as a causal mediator of axonal injury burden following severe TBI.