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Evaluation of serum neurofilament light chain as a diagnostic and prognostic biomarker in traumatic brain injury Gill, Jasmine


Background: Traumatic brain injury (TBI) is a leading cause of death and disability and can cause mild, moderate, or severe injury. TBI occurs mostly in youth and in seniors, demonstrating the importance of understanding how age at injury affects TBI diagnosis and prognosis. Although most TBI studies focus on youth, seniors have high TBI incidence mainly from falls. Considerable research has identified serum neurofilament light (NF-L) as a sensitive marker of axonal injury, however, little is known about its diagnostic and prognostic utility in geriatric TBI. This study was designed to evaluate the diagnostic potential of NF-L for mild TBI and the potential of NF-L to predict outcome at 12-months after injury across the lifespan, using the Glasgow Outcome Scale-Extended (GOS-E). Methods: Blood specimens from TBI subjects (N=244; median age=46y) and age-matched trauma controls (TC) (N=128; median age=40y) were collected within 24 hours of injury, with additional specimens collected on days 4, 7, 14 and 28 wherever possible. Serum NF-L was quantified using Quanterix single molecule array assays. Logistic regression analyses were performed for diagnostic and prognostic models. Receiver operating characteristic (ROC) curve analysis was performed to assess diagnostic utility. Multiple imputations were performed for GOS-E prior to assessing prognostic utility. Results: Acute median serum NF-L levels were significantly elevated in mild and moderate-severe TBI (11.3 pg/mL and 78.6 pg/mL; p<0.0001) and were also elevated in TCs (8.3 pg/mL; p=0.010). Serum NF-L demonstrated limited discriminatory ability between mild TBI and TCs with an area under the curve of 0.751. Serum NF-L correlated with TBI severity (rho=-0.591), injury severity score (rho=0.620) and age (rho=0.534), with higher levels in TBI patients >60y. Longitudinally, serum NF-L increased over time, peaking at 14 days, and remaining elevated at 28 days. Acute median serum NF-L correlated with GOS-E (rho=-0.476), with significantly higher levels in subjects predicted to have poor (GOS-E <7, 26.7 pg/mL) versus good (GOS-E ≥7, 10.5 pg/mL; p<0.0001) recovery. Conclusions: Acute serum NF-L did not clearly distinguish mild TBI from peripheral trauma seen in TCs, limiting its diagnostic utility. However, serum NF-L correlates with functional outcome, supporting further investigation as a prognostic biomarker.

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