Traumatic brain injury (TBI) poses significant strains on the paediatric population, for which the possible side effects of diagnostic imagistics could induce life-altering conditions. Routine inflammatory and metabolic biomarkers (complete blood count, C reactive protein, glucose) are frequently sampled in the paediatric patients admited within emergency departments, including the low-resource settings. This study aims to retrospectively document whether such routine blood biomarkers could predict a positive head CT scan and subsequently contribute to a prediction score, ment to enable more accurate decision on which minor TBI paediatric patients should be submitted to diagnotic imagistics.
Epidemiology and Clinical Context Traumatic brain injury (TBI) is a significant global health concern, with an estimated paediatric global annual incidence of 226.4 cases per 100,000 children (1). The vast majority of these cases are categorized as non-severe, as up to 95% of head injuries in children are classified as minor or mild (mTBI) (1,2). Nevertheless, approximately one-third of paediatric patients experience persistent symptoms lasting beyond one month (3). The current diagnostic gold standard remains non-contrast head Computed Tomography (CT). However, CT utilization carries significant associated risks, including exposure to ionizing radiation, high institutional costs, and the frequent necessity for procedural sedation (4). To mitigate these risks, clinical decision rules such as PECARN, CATCH, and CHALICE were developed to identify children at high risk for intracranial lesions. Despite these tools, most CT scans are still performed in cases of mTBI where the diagnostic yield is remarkably low (5). As such, additional aiding tools have been investigated for refining the clinical decision rules regarding the paediatric mTBI patients in need of a CT scan. Brain-Specific Biomarkers (GFAP, UCH-L1, S100B) In 2018, the US FDA authorized the first biomarkers (GFAP and UCH-L1) for predicting the necessity of CT scans in patients with minor TBI, supported by the ALERT-TBI trial (6). These markers serve as critical tools for both diagnosis and prognosis in neurotrauma (7). GFAP (Glial Fibrillary Acidic Protein) is an astroglial protein that can predict positive CT findings in children with a sensitivity of 94% and a specificity of 47% (8). Its high sensitivity makes it an ideal "rule-out" marker. UCH-L1 (Ubiquitin C-terminal Hydrolase L1) is a neuronal marker released into the bloodstream following axonal injury (6). While extensively studied, S100B has shown limitations in paediatric emergency care. Research by Babcock et al. (2012) demonstrated it could not accurately predict positive CT findings in children with a normal GCS (9). Furthermore, its specificity is hindered by age-dependent baseline levels (10). Routine Hematological and Metabolic Markers Beyond brain-specific proteins, routine complete blood count (CBC) parameters and metabolic markers provide an immediate, cost-effective snapshot of the injury's systemic impact, additionally to being easily accessible even in low-resource environments. 1. Inflammatory Indexes (NLR, Delta NLR, SII) Paediatric TBI patients with intracranial lesions on imaging demonstrate a significantly higher absolute neutrophil count (11). Significant differences in the Neutrophil-to-Lymphocyte Ratio (NLR) are observed at 24 and 48 hours post-injury (12,13). Longitudinal changes (Delta NLR) are associated with poorer clinical outcomes in children (14). The Systemic Immune-Inflammation Index (SII) (Neutrophils × Platelets / Lymphocytes) is increasingly used to monitor the secondary inflammatory cascade (15). 2. Glucose as a Modifiable Risk Factor Metabolic distress, specifically hyperglycemia, is a critical factor in the acute phase of TBI. Admission glucose levels are a potentially modifiable risk factor in TBI; elevated glucose is closely linked to the severity of the primary injury (16) and the occurrence of coagulopathy in TBI patients, further complicating the clinical trajectory (17). Elevated blood glucose levels may aid clinicians in the decision-making process for ordering CT scans in cases of minor head trauma (18). Conclusion The integration of specialized biomarkers like GFAP and UCH-L1 offers high sensitivity for ruling out acute pathology, yet their availability remains limited in the setting of emergency care. As such, routine biomakers, such as glucose levels, CBC panel and its derived inflammatory indexes, could provide relevant prognostic data in a more cost-effective approach for the triage and monitoring of emergency department paediatric mTBI, whilst limiting the radiation exposure of paediatric patients. References 1. Baticulon RE, Sy JJ, Haizel-Cobbina J, et al. Global Epidemiology of Pediatric Traumatic Brain Injury: Systematic Review and Meta-Analysis. Neurosurgery. 2025. doi: 10.1227/neu.0000000000003875. Epub ahead of print. PMID: 41384742. 2. Babl FE, Borland ML, Phillips N, et al. Accuracy of PECARN, CATCH, and CHALICE decisions rules for children with minor head injury: a prospective cohort study. Lancet. 2017;389(10087):2393-402. 3. Eisenberg MA, Andrea J, Meehan W, Mannix R . Time interval between concussions and symptom duration. Pediatrics. 2013;132(1):8-17. PMID: 23753087. DOI: 10.1542/peds.2013-0432. 4. Sheppard JP, Nguyen T, Alkhalid Y, et al. Risk of Brain Tumor Induction from Pediatric Head CT Procedures: A Systematic Literature Review. J Pediatr Surg. 2018;53(12):2450-2455. DOI:10.1016/j.jpedsurg.2018.04.032. 5. Marincowitz C, Lecky FE, Townend W, et al. The Risk of Deterioration in GCS13-15 Patients with Traumatic Brain Injury Identified by Computed Tomography Imaging: A Systematic Review and Meta-Analysis. J Neurotrauma. 2018; 35(5):703-718. PMID: 29324173. DOI: 10.1089/neu.2017.5259. 6. Bazarian JJ, Biberthaler P, Welch RD, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782-789. PMID: 30054151. Doi: 10.1016/S1474-4422(18)30231-X. 7. Wang KK, Yang Z, Zhu T, et al. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018;18(2):165-180. PMID: 29338452. DOI: 10.1080/14737159.2018.1428089. 8. Papa L, Brophy GM, Welch RD, et al. Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury. JAMA Neurol. 2016;73(5):551-60. PMID: 27018834. DOI: 10.1001/jamaneurol.2016.0039. 9. Babcock L, Byczkowski T, Mookerjee S, Bazarian JJ. Ability of S100B to predict severity and cranial CT results in children with TBI. Brain Inj. 2012;26(11):1372-80. PMID: 22725661. DOI: 10.3109/02699052.2012.694565. 10. Oris C, Pereira B, Durif J, et al. The Biomarker S100B and Mild Traumatic Brain Injury: A Meta-analysis. Pediatrics. 2018;141(6):e20180037. PMID: 29716980. DOi: 10.1542/peds.2018-0037. 11. Mukherjee S, Sivakumar G, Goodden JR, Tyagi AK, Chumas PD. Prognostic value of leukocytosis in pediatric traumatic brain injury. J Neurosurg Pediatr. 2020;27(3):335-345. PMID: 33361484. DOI: 10.3171/2020.7.PEDS19627.. 12. Siempis T, Georgalis PA, Lianos G, et al. Blood Biomarkers for Prediction of Positive CT Findings in Mild Traumatic Brain Injury in Paediatric Population. J Integr Neurosci. 2023;22(4):91. PMID: 37519178. DOI: 10.31083/j.jin2204091. 13. Kimball R, Shachar E, Eyerly-Webb S, Patel DM, Spader H. Using the neutrophil-to-lymphocyte ratio to predict outcomes in pediatric patients with traumatic brain injury. Clin Neurol Neurosurg. 2020;193:105772. PMID: 32155528. DOI: 10.1016/j.clineuro.2020.105772. 14. Melo JRT, Masini MHH, de Oliveira JG, Veiga JCE. Performance of the neutrophil-lymphocyte ratio as a predictor of severity and mortality in children and adolescents with traumatic brain injury. Childs Nerv Syst. 2024;40(12):4251-4257. PMID: 39080015. DOI: 10.1007/s00381-024-06556-9. 15. Parenrengi MA, Suryaningtyas W, Dariansyah AD, Utomo B, Taryana GO, Kusumo C, et al. 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Study Type
OBSERVATIONAL
Enrollment
800
Spitalul Clinic Judetean de Urgenta
Arad, Romania
Spitalul Judetean de Urgenta
Baia Mare, Romania
Spitalul Clinic Judetean de Urgenta
Bistriţa, Romania
Spitalul Judetean de Urgenta MAVROMATI
Botoșani, Romania
Spitalul Clinic de Urgenta penru Copii
Brasov, Romania
Spitalul Clinic de Urgenta pentru Copii
Cluj-Napoca, Romania
Spitalul Clinic Judetean de Urgenta
Craiova, Romania
Routine Biomarkers
1. CBC, the following items being mandatory: * WBC (white blood cells) and its subpopulations (NEU, LYM, MON) * NLR (neutrophiles-to-lymphocytes ratio) * PLR (platelets-to-lymphocyes ratio) * MLR (monocytes-to-lymphocytes ratio) * SII (systemic immune inflammation) index = NEU x PLT/ LYM * SIRI (systemic inflammatory response index) = NEU x MON/ LYM 2. C Reactive Protein 3. Glucose 4. (A)VBG - pH, lactate, base deficit, anion gap, bicarb
Time frame: Upon ED admission for mTBI
Epidemiological Data
Additionally, epidemological data will be collected (age, gender, trauma mechanism, associated lessions, risk factors for TBI classification, physical examination, need of procedural sedation, seniority of treating physician, disposition), alongside the results of the head (and cervical) CT scan.
Time frame: Upon ED admission for mTBI
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