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Blood-based biomarkers suggest prolonged axonal Injury following pediatric mild traumatic brain injury
Andrew R Mayer1,2,3,4,5, Tracey V Wick6, Jessica R McQuaid6
1The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, 87106, USA. amayer@mrn.org.
Insights
Neurofilament light chain (NFL) protein levels remain elevated in youth up to four months after mild traumatic brain injury (mTBI). NFL shows promise as a biomarker for tracking recovery and injury severity in pediatric mTBI patients.
Area of Science:
- Neuroscience
- Pediatric Traumatology
- Biomarker Discovery
Background:
- Pediatric mild traumatic brain injury (pmTBI) is a common injury in youth, yet its pathophysiology and recovery timelines are poorly understood.
- Current diagnostic and prognostic tools for pmTBI lack sensitivity to capture the full spectrum of injury and recovery.
Purpose of the Study:
- To investigate longitudinal changes in blood-based protein biomarkers following pediatric mild traumatic brain injury (pmTBI).
- To assess the utility of biomarkers like NFL, GFAP, Tau, pTau181, and UCH-L1 in reflecting injury severity and recovery status.
- To compare the diagnostic accuracy of biomarkers against clinical assessments over time.
Main Methods:
- Plasma samples were collected from 59 pmTBI patients and 41 healthy controls (HC) at approximately 7 days and 4 months post-injury.
- Concentrations of GFAP, NFL, Tau, pTau181, and UCH-L1 proteins were measured using immunoassays.
- Clinical data, including post-concussive symptoms and mental status, were collected and correlated with biomarker levels.
Main Results:
- Neurofilament light chain (NFL) levels were significantly elevated in pmTBI patients compared to HC at both 7 days and 4 months post-injury.
- Elevated NFL levels correlated with altered mental status, such as post-traumatic amnesia, in pmTBI patients.
- While UCH-L1, GFAP, and pTau181 showed no group differences, they suggested faster clearance, and NFL demonstrated potential for differentiating injury severity.
Conclusions:
- Blood biomarker levels, particularly NFL, exhibit dynamic changes in the initial phase and persist up to 4 months post-pmTBI.
- NFL shows promise as a sensitive biomarker for assessing injury severity and monitoring recovery in pediatric mild traumatic brain injury.
- Longitudinal NFL measurements may offer valuable insights into the pathophysiology and recovery trajectory of pmTBI.
Abstract:
Pediatric mild traumatic brain injury (pmTBI) affects millions of youth annually but underlying pathophysiology and time for physiological recovery remains unknown. Non-fasting plasma samples were obtained in 59 pmTBI (28 females; age 14.9 ± 2.7) at approximately 7 days and 4 months post-injury and in 41 matched healthy controls (HC: 20 females; age 14.3 ± 2.8). Samples were analyzed for GFAP, NFL, Tau, pTau181 and UCH-L1 protein concentrations in conjunction with a clinical battery. Significant effects of diagnosis (pmTBI > HC) existed at ~ 7 days (p < 0.001; Cohen's d = 0.72) and ~ 4 months (p = 0.015; Cohen's d = 0.41) post-injury for NFL. NFL was also elevated in pmTBI with significant alterations to mental status (e.g., post-traumatic amnesia) relative to patients without (p = 0.014; Cohen's d = 0.77). UCH-L1, GFAP and pTau181 did not differ between groups, but demonstrated negative associations with days post-injury (small to medium effect sizes) suggestive of a more rapid release/clearance. Post-concussive symptoms had the best diagnostic classification accuracy at ~ 7 days, but NFL ranked higher at 4 months post-injury. Preliminary findings highlight dynamic fluctuations in blood-based biomarkers in the first week of pmTBI, with ongoing evidence of protein release (NFL) at 4 months. NFL demonstrated additional promise for delineating injury severity within the spectrum of pmTBI.
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