Prognostic and Diagnostic Utility of Serum Biomarkers in Pediatric Traumatic Brain Injury.

Shannon Faulkenberry, Kevin K Wang, W Dalton Dietrich, Robert W Keane, Kristine H O'Phelan, Chad Thorson, Heather McCrea, Juan Solano, Paula Karina Perez, Joslyn Gober, Jason E Blatt, Lance S Governale, Ricardo Loor-Torres, Nora Al Fakhri, Maria C Pareja Zabala, Jennifer C Munoz Pareja, Lauren A Lautenslager, Prashanth Shanmugham, Rajderkar Dhanashree, Suman Ghosh, K Leslie Avery, Firas Kobeissy, Jennifer Coto, Kathryn Swaby, Kourtney Guthrie, Charlene Pringle, Maria Kerrigan, Maria Mateo Chavez, Juan Pablo de Rivero Vaccari

Journal: Journal of neurotrauma 2024;41(1-2):106-122

PMID: 37646421

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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.

Address: Department of Pediatric Critical Care, University of Miami Miller School of Medicine, Miami, Florida, USA.; Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.; Knowledge and Research Evaluation Unit, Mayo Clinic, Rochester, Minnesota, USA.; Louisiana State University School of Medicine, New Orleans, Louisiana, USA.; Department of Pediatric Critical Care, University of Florida College of Medicine, Gainesville, Florida, USA.; Department of University of Miami Concussion Program, University of Miami Miller School of Medicine, Miami, Florida, USA.; Department of Emergency Medicine, Multiomics & Biomarkers (CNMB), Morehouse University, School of Medicine, Atlanta, Georgia, USA.; Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Morehouse University, School of Medicine, Atlanta, Georgia, USA.; Department of Pediatric Neurology, Downstate Health Science University, New York, New York, USA.; Department of Radiology, Division of Pediatric Radiology, University of Florida College of Medicine, Gainesville, Florida, USA.; Department of Pediatric Critical Care, UT Southwestern University, Dallas, Texas, USA.; Department of Plastic Surgery, Indiana University School of Medicine, Bloomington, Indiana, USA.; Department of Pediatric Critical Care, Orlando Regional Medical Center, Orlando, Florida, USA.; Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA.; Department of Pediatric Critical Care, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Pediatric Neurosurgery, University of Florida College of Medicine, Gainesville, Florida, USA.; Department of Pediatric Physical Medicine and Rehabilitation, University of Miami Miller School of Medicine, Miami, Florida, USA.; Department of Pediatrics, Mailman Center for Child Development, University of Miami Miller School of Medicine, Miami, Florida, USA.; Department of Pediatric Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA.; Department of Pediatric Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.; Department of Neurology and Neurocritical Care, University of Miami Miller School of Medicine, Miami, Florida, USA.; Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida, USA.

DOI: 10.1089/neu.2023.0039

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MeSH Terms: Humans, Child, Prognosis, Prospective Studies, Brain Injuries, Traumatic, Biomarkers, Brain Injuries, Ubiquitin Thiolesterase, Glial Fibrillary Acidic Protein