Autopsy Data Reveal New Insights About Brain Swelling After Pediatric TBI

Bilateral brain swelling was more common in children than in adults who died after moderate or severe traumatic brain injury (TBI), an autopsy case series showed.

At autopsy, macroscopic evidence of brain swelling was more prevalent in children compared with adults (83% vs 65%, P=0.02). When brain swelling was present, it was more often bilateral in pediatric patients (83% vs 34%, P<0.001), reported William Stewart, MBChB, PhD, of Queen Elizabeth University Hospital in Glasgow, and co-authors.

Blood-brain barrier (BBB) disruption was very common in both groups. Patterns of BBB disruption varied, however: more pediatric patients had predominantly microvascular pathology than adults did (84.7% vs 31.2%, P<0.001), the researchers said in JAMA Network Open.

“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,” Stewart and colleagues wrote.

“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,” they continued. “This observation of distinct microvascular pathology in pediatric acute TBI requires further investigation.”

TBI is the leading cause of death and permanent disability in young children under age 4 and in adolescents ages 15-18, the researchers noted. “In the U.S. alone, pediatric TBI accounts for almost 500,000 emergency department visits and more than 7,000 fatalities each year,” they wrote.

Diffuse brain swelling has long been seen as a distinct feature of severe and moderate TBI in children, noted Patrick Kochanek, MD, of UPMC Children’s Hospital of Pittsburgh, and co-authors in an accompanying editorial.

“Many potential mechanisms contributing to diffuse cerebral swelling in infants and children have been suggested in preclinical and clinical studies and comprehensively reviewed. These include biomechanical differences related to unique mechanical properties of the skull in infants and young children,” they observed.

“Children, with a proportionally larger head-to-body ratio and less neck support may also be more susceptible to acceleration-deceleration forces, like those experienced in road traffic collisions, with subsequent development of diffuse axonal injury, which is characterized by scattered hemorrhages in the microvasculature on neuroimaging and neuropathology,” the editorialists suggested.

Studies performed in pediatric models of cardiopulmonary arrest (not TBI) suggested more BBB disruption in the developing brain, they added.

Stewart and co-authors conducted a retrospective case series study of 81 pediatric and 62 adult patients who died within 2 weeks of moderate or severe TBI. Samples came from the Glasgow TBI Archive and were acquired after autopsy was conducted from 1979 through 2006.

Pediatric patients had a mean age of about 12 years; adults had a mean age of about 39. In both groups, more than half were male.

The most common mechanism of head injury in pediatric cases was road traffic incidents (73%); 10% of injuries were caused by assault. Among adults, the most common causes of TBI were falls (44%), road traffic incidents (37%), and assault (18%). Children survived 57.8 hours, and adults survived 71.7 hours, on average.

“It is possible that biomechanical differences in injury mechanism contributed to the findings,” the editorialists suggested.

“The high prevalence of motor vehicle collisions in the pediatric patients vs falls in adults could differentially impact the shear forces imparted on the cerebral vasculature,” Kochanek and co-authors pointed out.

The role of ICU treatment effects also can’t be excluded, they added.

The case series has other limitations, the researchers noted. It used postmortem patient samples from the Glasgow TBI Archive, which primarily represents a Scottish white population. Diagnostic imaging data also were not available. The “largely historical nature of case acquisition” may not reflect current patient profiles, Stewart and colleagues said.

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