Using Routine Inflammatory and Metabolic Blood Tests (Bedside Included) to Predict Brain Injury in Children After Minor Head Trauma

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.

Inclusion criteria

Patients aged 0 to 18 years old presenting to the ED with mild traumatic brain injury (with or without cervical injury):

• Mild TBI will be defined as GCS 14-15 or A (AVPU) upon admission
• Patients underwent head CT
• Routine blood biomarkers have been collected (complete blood count - CBC, biochemistry and/or (arterial) venos blood gases - (A)VBG).

Exclusion criteria

• Patients with moderate (GCS 13-9 or V) or severe (GCS 8-3 or P,U) head trauma
• Patients with associated trauma (limb/rib/pelvic fractures, organ injuries).