PAEDIATRIC OUTCOMES AND SERUM BIOMARKER PANEL IN ACUTE TRAUMATIC BRAIN INJURY /CONCUSSION TO SEVERE TRAUMATIC BRAIN INJURY

Abstract

Introduction Paediatric mild traumatic brain injury (mTBI) is increasingly recognised to have significant longer term neurocognitive effects. Childhood is a time of high risk for head injury. There were no national guidelines for management of children with mTBI. Consensus management is based on adult clinical data. Animal models describe pathways of persistent inflammation that may be mirrored in the human population, and that have modifiable targets which may direct future therapies and guide management. Understanding of the innate immune system may offer therapeutic targets to shorten the course of the disorder and restore daily function at a critical period of growth and learning. Methods Retrospectively attendances to three paediatric emergency departments (PEDs) over 24 months were examined to establish prevalence. Short teaching modules about mTBI were established within paediatric hospitals, deficiencies identified and guidelines drawn up. A systematic review of the literature was performed. Blood from children attending PED with symptomatic mTBI, and those with severe TBI in PICU were recruited alongside controls undergoing routine phlebotomy. Sports Concussion Assessment Tools and Post Concussive Symptom Inventories were applied along with sleep questionnaires and an extensive history and clinical exam. Flow Cytometry and PCR analysis of whole blood was performed alongside an extensive panel of neuronal and inflammatory cytokines on Enzyme-linked immunoassay. Results The incidence of mTBI presenting to Dublin EDs was established. National guidelines for paediatric mTBI were established. Glial Fibrillary Acidic Protein identified mTBI and was strongly associated with vomiting. Serum Tau predicts ongoing symptoms at two weeks from injury. The immune pathway involving neutrophils, monocytes and lymphocytes are demonstrably altered. The inflammasome complex is activated. Inflammatory biomarkers, specifically IL-6 predict the presence of mTBI. There is a hyper-responsiveness to immune challenge with endotoxin at the time of injury. and priming with hypo-responsiveness at two weeks. This demonstrates sustained changes in the systemic immune response. Sleep is subjectively disturbed and circadian rhythm genes are measurably dysregulated. Conclusion Mild traumatic brain injury represents a significant problem for 700 children approximately attending paediatric emergency departments. We demonstrate that GFAP discriminates mTBI. Interleukin-6 predicts mTBI.