Temporal Profile of Serum Neurofilament Light (NF-L) and Heavy (pNF-H) Level Associations With 6-Month Cognitive Performance in Patients With Moderate-Severe Traumatic Brain Injury

Erin Trifilio; Sarah Bottari; Leah E McQuillan; David J Barton; Damon G Lamb; Claudia Robertson; Richard Rubenstein; Kevin K Wang; Amy K Wagner; John B Williamson

doi:10.1097/HTR.0000000000000932

Temporal Profile of Serum Neurofilament Light (NF-L) and Heavy (pNF-H) Level Associations With 6-Month Cognitive Performance in Patients With Moderate-Severe Traumatic Brain Injury

J Head Trauma Rehabil. 2024 May 14. doi: 10.1097/HTR.0000000000000932. Online ahead of print.

Authors

Erin Trifilio¹, Sarah Bottari, Leah E McQuillan, David J Barton, Damon G Lamb, Claudia Robertson, Richard Rubenstein, Kevin K Wang, Amy K Wagner, John B Williamson

Affiliation

¹ Brain Rehabilitation Research Center (BRRC), Malcom Randall VAMC, Gainesville, Florida (Drs Trifilio, Lamb, Wang, and Williamson and Ms Bottari); Department of Clinical and Health Psychology (Drs Trifilio and Williamson and Ms Bottari), College of Public Health and Health Professions, and Departments of Emergency Medicine (Dr Wang) and Psychiatry (Drs Lamb and Williamson), College of Medicine, University of Florida, Gainesville; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (Dr Robertson); Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, New York (Dr Rubenstein); Department of Physical Medicine and Rehabilitation (Ms McQuillan and Dr Wagner), Department of Emergency Medicine (Dr Barton), Department of Neuroscience (Dr Wagner), Clinical and Translational Science Institute (Dr Wagner), and Safar Center for Resuscitation Research (Dr Wagner); University of Pittsburgh, Pittsburgh, Pennsylvania; and Department of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia (Dr Wang).

PMID: 38758056
DOI: 10.1097/HTR.0000000000000932

Abstract

Objective: Identification of biomarkers of cognitive recovery after traumatic brain injury (TBI) will inform care and improve outcomes. This study assessed the utility of neurofilament (NF-L and pNF-H), a marker of neuronal injury, informing cognitive performance following moderate-to-severe TBI (msTBI).

Setting: Level 1 trauma center and outpatient via postdischarge follow-up.

Participants: N = 94. Inclusion criteria: Glasgow Coma Scale score less than 13 or 13-15 with clinical evidence of moderate-to-severe injury traumatic brain injury on clinical imaging. Exclusion criteria: neurodegenerative condition, brain death within 3 days after injury.

Design: Prospective observational study. Blood samples were collected at several time points post-injury. Cognitive testing was completed at 6 months post-injury.

Main measures: Serum NF-L (Human Neurology 4-Plex B) pNF-H (SR-X) as measured by SIMOA Quanterix assay. Divided into 3 categorical time points at days post-injury (DPI): 0-15 DPI, 16-90 DPI, and >90 DPI. Cognitive composite comprised executive functioning measures derived from 3 standardized neuropsychological tests (eg, Delis-Kaplan Executive Function System: Verbal Fluency, California Verbal Learning Test, Second Edition, Wechsler Adult Intelligence Scale, Third Edition).

Results: pNF-H at 16-90 DPI was associated with cognitive outcomes including a cognitive-executive composite score at 6 months (β = -.430, t34 = -3.190, P = .003).

Conclusions: Results suggest that "subacute" elevation of serum pNF-H levels may be associated with protracted/poor cognitive recovery from msTBI and may be a target for intervention. Interpretation is limited by small sample size and including only those who were able to complete cognitive testing.