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Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury
Jennifer C Munoz Pareja1, Juan Pablo de Rivero Vaccari2, Maria Mateo Chavez3
1Department of Pediatric Critical Care, University of Miami Miller School of Medicine, Miami, Florida, USA.
Insights
Elevated serum biomarkers like GFAP and NfL can help diagnose pediatric traumatic brain injury (TBI). These markers may also predict neurological outcomes, aiding early detection and prognosis in children.
Area of Science:
- Pediatric Neurology
- Neurotrauma
- Biomarker Discovery
Background:
- Pediatric traumatic brain injury (TBI) is a significant cause of death and disability.
- Accurate diagnosis of pediatric TBI is challenging due to a lack of standardized methods.
- Identifying reliable diagnostic and prognostic tools for pediatric TBI is crucial.
Purpose of the Study:
- To investigate the utility of serum neuronal injury biomarkers for diagnosing pediatric TBI.
- To assess the potential of these biomarkers in predicting neurological outcomes in pediatric TBI patients.
- To evaluate biomarker concentrations at various time points post-injury (0, 24, and 48 hours).
Main Methods:
- Prospective observational study involving 34 children (0-18 years) with TBI and 19 healthy controls.
- Serum concentrations of GFAP, NfL, UCH-L1, S-100B, tau, and p-tau181 were measured.
- Patients stratified by Glasgow Coma Scale (GCS) and outcomes assessed using Glasgow Outcome Scale-Extended (GOS-E) Peds.
Main Results:
- All measured biomarkers were elevated in TBI patients compared to healthy controls.
- Biomarkers GFAP, tau, S100B, and p-tau181 differentiated TBI severity at 0h.
- Specific biomarkers (p-tau181, UCH-L1, GFAP, NfL, tau, S100B) showed predictive value for unfavorable outcomes at various time points.
Conclusions:
- Serum levels of neuronal injury biomarkers increase within 0-48 hours post-TBI in children.
- A panel of biomarkers could assist in the early diagnosis of mild to moderate pediatric TBI.
- Biomarker analysis shows promise for predicting neurological outcomes across the pediatric TBI spectrum.
Abstract:
Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0-18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9-15) and severe (GCS 3-8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6-9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0-48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.
