Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Children's Emergency Clinical Hospital Cluj-Napoca | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
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. 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). Nevertheless, approximately one-third of paediatric patients experience persistent symptoms lasting beyond one month.
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. 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.
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. These markers serve as critical tools for both diagnosis and prognosis in neurotrauma.
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%. 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.
While extensively studied, S100B has shown limitations in paediatric emergency care. Research demonstrated it could not accurately predict positive CT findings in children with a normal GCS. Furthermore, its specificity is hindered by age-dependent baseline levels.
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.
Inflammatory Indexes (NLR, Delta NLR, SII) Paediatric TBI patients with intracranial lesions on imaging demonstrate a significantly higher absolute neutrophil count.
Significant differences in the Neutrophil-to-Lymphocyte Ratio (NLR) are observed at 24 and 48 hours post-injury. Longitudinal changes (Delta NLR) are associated with poorer clinical outcomes in children.
The Systemic Immune-Inflammation Index (SII) (Neutrophils × Platelets / Lymphocytes) is increasingly used to monitor the secondary inflammatory cascade.
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 and the occurrence of coagulopathy in TBI patients, further complicating the clinical trajectory. Elevated blood glucose levels may aid clinicians in the decision-making process for ordering CT scans in cases of minor head trauma.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients aged 0 to 18, mild TBI (GCS 14-15 or A on AVPU) | Patients aged 0 to 18 years old presenting to the ED with mild traumatic brain injury (with or without cervical injury):
|
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Routine Biomarkers |
| Upon ED admission for mTBI |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Upon ED admission for mTBI |
| Measure | Description | Time Frame |
|---|---|---|
| TBI Registry | A TBI registry will be also filled in, registering all TBI patients who do not meet the study inclusion criteria (mTBI without CT scan, moderate and severe TBI). For these patients, the collected data are the following:
| Upon ED admission for mTBI |
Inclusion Criteria:
Patients aged 0 to 18 years old presenting to the ED with mild traumatic brain injury (with or without cervical injury):
Exclusion Criteria:
Not provided
Not provided
Not provided
Paediatric patients being admitted to ED for minor traumatic brain injuries, who are undergoing a head CT scan and routine blood tests.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eugenia M Lupan-Muresan, MD, PhD | Contact | +40748451098 | muresan.eugenia@umfcluj.ro | |
| Daniela M Mitrofan, MD | Contact | +40 751 110 065 | danamitro@yahoo.com |
| Name | Affiliation | Role |
|---|---|---|
| Eugenia M Lupan-Muresan, MD, PhD | Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca | Principal Investigator |
| Daniela M Mitrofan, MD | Children's Emergency County Hospital Cluj-Napoca | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spitalul Clinic Judetean de Urgenta | Arad | Romania |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31093304 | Background | Alexiou GA, Sotiropoulos A, Lianos GD, Zigouris A, Metaxas D, Nasios A, Michos E, Mitsis M, Pachatouridis D, Voulgaris S. Blood Glucose Levels May Aid the Decision for CT Scan in Minor Head Trauma. Dis Markers. 2019 Apr 9;2019:1065254. doi: 10.1155/2019/1065254. eCollection 2019. | |
| 24564221 | Background | Alexiou GA, Lianos G, Fotakopoulos G, Michos E, Pachatouridis D, Voulgaris S. Admission glucose and coagulopathy occurrence in patients with traumatic brain injury. Brain Inj. 2014;28(4):438-41. doi: 10.3109/02699052.2014.888769. Epub 2014 Feb 24. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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 |
|
| 27626493 | Background | Shi J, Dong B, Mao Y, Guan W, Cao J, Zhu R, Wang S. Review: Traumatic brain injury and hyperglycemia, a potentially modifiable risk factor. Oncotarget. 2016 Oct 25;7(43):71052-71061. doi: 10.18632/oncotarget.11958. |
| 39777169 | Background | Parenrengi MA, Suryaningtyas W, Dariansyah AD, Utomo B, Taryana GO, Kusumo C, Brilliantika SP. Utility of systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio as a predictive biomarker in pediatric traumatic brain injury. Surg Neurol Int. 2024 Dec 6;15:456. doi: 10.25259/SNI_900_2024. eCollection 2024. |
| 39080015 | Background | 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 Dec;40(12):4251-4257. doi: 10.1007/s00381-024-06556-9. Epub 2024 Jul 30. |
| 33361484 | Background | Mukherjee S, Sivakumar G, Goodden JR, Tyagi AK, Chumas PD. Prognostic value of leukocytosis in pediatric traumatic brain injury. J Neurosurg Pediatr. 2020 Dec 25;27(3):335-345. doi: 10.3171/2020.7.PEDS19627. Print 2021 Mar 1. |
| 32155528 | Background | 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 Jun;193:105772. doi: 10.1016/j.clineuro.2020.105772. Epub 2020 Mar 3. |
| 37519178 | Background | Siempis T, Georgalis PA, Lianos G, Kafritsas G, Metaxas D, Alexiou ES, Zika J, Sotiropoulos A, Alexiou GA, Voulgaris S. Blood Biomarkers for Prediction of Positive CT Findings in Mild Traumatic Brain Injury in Paediatric Population. J Integr Neurosci. 2023 Jul 7;22(4):91. doi: 10.31083/j.jin2204091. |
| 29716980 | Background | Oris C, Pereira B, Durif J, Simon-Pimmel J, Castellani C, Manzano S, Sapin V, Bouvier D. The Biomarker S100B and Mild Traumatic Brain Injury: A Meta-analysis. Pediatrics. 2018 Jun;141(6):e20180037. doi: 10.1542/peds.2018-0037. Epub 2018 May 1. |
| 22725661 | Background | 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. doi: 10.3109/02699052.2012.694565. Epub 2012 Jun 22. |
| 27018834 | Background | Papa L, Brophy GM, Welch RD, Lewis LM, Braga CF, Tan CN, Ameli NJ, Lopez MA, Haeussler CA, Mendez Giordano DI, Silvestri S, Giordano P, Weber KD, Hill-Pryor C, Hack DC. 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 May 1;73(5):551-60. doi: 10.1001/jamaneurol.2016.0039. |
| 29338452 | Background | Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, Manley GT. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018 Feb;18(2):165-180. doi: 10.1080/14737159.2018.1428089. Epub 2018 Jan 23. |
| 30054151 | Background | Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P, Bogner-Flatz V, Gunnar Brolinson P, Buki A, Chen JY, Christenson RH, Hack D, Huff JS, Johar S, Jordan JD, Leidel BA, Lindner T, Ludington E, Okonkwo DO, Ornato J, Peacock WF, Schmidt K, Tyndall JA, Vossough A, Jagoda AS. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018 Sep;17(9):782-789. doi: 10.1016/S1474-4422(18)30231-X. Epub 2018 Jul 24. |
| 29324173 | Background | Marincowitz C, Lecky FE, Townend W, Borakati A, Fabbri A, Sheldon TA. 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 Mar 1;35(5):703-718. doi: 10.1089/neu.2017.5259. Epub 2018 Jan 11. |
| 29717567 | Background | Sheppard JP, Nguyen T, Alkhalid Y, Beckett JS, Salamon N, Yang I. Risk of Brain Tumor Induction from Pediatric Head CT Procedures: A Systematic Literature Review. Brain Tumor Res Treat. 2018 Apr;6(1):1-7. doi: 10.14791/btrt.2018.6.e4. |
| 23753087 | Background | Eisenberg MA, Andrea J, Meehan W, Mannix R. Time interval between concussions and symptom duration. Pediatrics. 2013 Jul;132(1):8-17. doi: 10.1542/peds.2013-0432. Epub 2013 Jun 10. |
| 28410792 | Background | Babl FE, Borland ML, Phillips N, Kochar A, Dalton S, McCaskill M, Cheek JA, Gilhotra Y, Furyk J, Neutze J, Lyttle MD, Bressan S, Donath S, Molesworth C, Jachno K, Ward B, Williams A, Baylis A, Crowe L, Oakley E, Dalziel SR; Paediatric Research in Emergency Departments International Collaborative (PREDICT). Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study. Lancet. 2017 Jun 17;389(10087):2393-2402. doi: 10.1016/S0140-6736(17)30555-X. Epub 2017 Apr 11. |
| 41384742 | Background | Baticulon RE, Sy JJ, Haizel-Cobbina J, Du L, Figueredo L, Hounjet C, Mitchell R, Shlobin NA, Dewan MC. Global Epidemiology of Pediatric Traumatic Brain Injury: Systematic Review and Meta-Analysis. Neurosurgery. 2025 Dec 12. doi: 10.1227/neu.0000000000003875. Online ahead of print. |
| ID | Term |
|---|---|
| D001924 | Brain Concussion |
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D016489 | Head Injuries, Closed |
| D014947 | Wounds and Injuries |
| D014949 | Wounds, Nonpenetrating |
Not provided
Not provided