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Association Between Plasma Glial Fibrillary Acidic Protein, Ubiquitin Carboxy-Terminal Hydrolase-L1, S100B, and
Deena Godfrey1, Michael Bambrick2, Gillian Hotz3
1Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Pediatric traumatic brain injury (TBI) biomarkers like GFAP show promise in identifying intracranial findings on CT and MRI scans. These blood tests can help triage children needing further neuroimaging after injury.
Area of Science:
- Pediatric neurology
- Biomarker research
- Neurotrauma
Background:
- Blood-based biomarkers aid in diagnosing traumatic brain injury (TBI) in adults.
- Understanding these biomarkers in children, considering age and injury severity, is crucial but less understood.
- Associations between specific biomarkers and clinical/imaging findings in pediatric TBI require further characterization.
Purpose of the Study:
- To investigate associations between plasma biomarkers and clinical/imaging findings in pediatric TBI patients.
- To evaluate the utility of biomarkers such as GFAP, UCH-L1, S100B, NSE, and hsCRP in children.
- To determine if biomarkers can predict intracranial traumatic findings on CT and MRI in pediatric TBI.
Main Methods:
- Analysis of plasma biomarkers (GFAP, UCH-L1, S100B, NSE, hsCRP) from pediatric TBI patients in the TRACK-TBI study.
- Comparison of biomarker levels between patients with and without radiographical traumatic intracranial findings on CT and MRI.
- Statistical analysis including univariate and multivariable regression models to assess biomarker associations with clinical and imaging data.
Main Results:
- Plasma GFAP, UCH-L1, S100B, and hsCRP levels correlated with time since injury and CT findings.
- GFAP levels were associated with Glasgow Coma Scale (GCS) scores and MRI findings.
- GFAP emerged as the strongest predictor of imaging findings; S100B and NSE showed age-related differences.
Conclusions:
- Day-of-injury plasma biomarkers are associated with radiographical intracranial findings in children with acute TBI.
- GFAP is a strong predictor of neuroimaging results in pediatric TBI.
- These biomarkers may assist in triaging pediatric TBI patients for neuroimaging.
Abstract:
Blood-based biomarkers have shown utility in discriminating adult patients with and without traumatic brain injury (TBI). Biomarker levels vary with severity, time since injury, and imaging findings (computed tomography [CT] and magnetic resonance imaging [MRI]). However, the association of specific biomarkers with clinical and imaging findings in children across the age spectrum and with different injury severities and presentations is not fully understood. To better characterize biomarker and clinical associations, we studied pediatric blood biomarker patterns within the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (ClinicalTrials.gov #NCT02119182). TRACK-TBI is an observational multisite study that prospectively enrolled TBI patients across the lifespan and injury spectrum, from 2014 through 2018. Two centers enrolled children (ages 0-17 years). All participants underwent a head CT or MRI at the discretion of treating clinicians as part of acute clinical care, and the majority underwent a study MRI 2 weeks after injury. For this TRACK-TBI pediatric cohort, blood sampling was optional with informed consent provided by guardians. For the purposes of this study, only pediatric subjects with study-specific neuroimaging and plasma biomarkers were included. Plasma biomarkers assessed included glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and high-sensitivity C-reactive protein (hsCRP). Biomarker levels were compared between participants with and without radiographical traumatic intracranial findings (day-of-injury CT-positive versus CT-negative and 2-week study MRI-positive versus MRI-negative) and between participants with different clinical indices of injury. Of 158 pediatric participants, 75 consented to blood collection and underwent biomarker analysis. Of these, 65 had acute CT scans (within 24 h of injury) and 43 had standardized study-related MRI scans at 2 weeks (±3 days) from injury; thus, 70 subjects had biomarker levels and study-reviewed CTs and/or MRIs and are included in the present analysis. Univariate analyses showed significant differences in plasma GFAP, UCHL1, S100B, and hsCRP with respect to time since injury and CT findings. GFAP levels differed by Glasgow Coma Scale (GCS) severities and MRI findings; S100B levels differed by GCS and loss of consciousness. Multivariable linear regression models confirmed a significant association of GFAP, UCH-L1, and S100B levels with CT-positive findings and a significant association of GFAP with 2-week MRI-positive findings. Among the biomarkers evaluated in our study, GFAP was the strongest predictor of imaging findings using receiver operating characteristic analysis. Significant age effects were seen for S100B and NSE, with higher values in younger children. Multivariable associations were observed for specific day-of-injury plasma biomarkers and radiographical traumatic intracranial findings on CT and MRI in children with acute TBI. These biomarkers have potential utility to aid in TBI screening by helping to triage which patients are likely to have intracranial findings on neuroimaging.
