Pediatric Traumatic Brain Injury and Microvascular Blood-Brain Barrier Pathology

Abstract

Pediatric traumatic brain injury (TBI) is a major cause of morbidity and mortality, with an increased risk of catastrophic outcome compared with adult TBI, including diffuse brain swelling and so-called second impact syndrome. Nevertheless, the biological substrates driving adverse outcomes in pediatric TBI remain poorly described. To compare neuropathological evidence of brain swelling and blood-brain barrier (BBB) disruption after moderate or severe acute TBI in adult vs pediatric case material. In this retrospective case series, cases of pediatric (aged 3-18 years) and adult (aged ≥19 years) TBI were accrued from January 1, 1979, to December 31, 2005, and underwent laboratory-based assessment of autopsy material from the Glasgow TBI Archive. Data analysis was performed from January 2019 to January 2024. Single moderate or severe TBI. Evaluation of representative brain tissue sections stained for markers of endothelia (CD34) and BBB integrity (fibrinogen and immunoglobin G). Eighty-one pediatric patients (mean [SD] age, 12.1 [4.6] years; 50 [62%] male) and 62 adult patients (mean [SD] age, 38.7 [12.9] years; 35 [56%] male) were studied. At autopsy, when present, brain swelling was more often diffuse and bilateral among pediatric patients (64 of 81 cases [83%]) when compared with adult patients (21 of 62 [34%]) (P < .001). Histologic evidence of BBB disruption was common in material from both adult (57 of 62 [91%]) and pediatric (65 of 81 [80%]) (P = .06) patients. In pediatric patients, however, this was a predominantly microvascular, capillary-level pathology, which was a less common finding in adult case material (mean [SD], 84.7% [8.6%] vs 31.2% [7.7%]; P < .001). This autopsy case series of patients dying in the acute phase after single moderate or severe TBI provides neuropathological evidence of age-dependent differences in vascular pathology. Specifically, although BBB disruption in pediatric material was typically confined to microvascular, capillary-level vessels, in adult case material, BBB disruption more typically involved larger-diameter vessels. This observation of distinct microvascular pathology in pediatric acute TBI requires further investigation. In the meantime, this study presents an intriguing potential candidate pathology contributing to diffuse brain swelling in this age group.