Brain volume abnormalities and clinical outcomes following paediatric traumatic brain injury

Long-term outcomes are difficult to predict after paediatric traumatic brain injury. The presence or absence of focal brain injuries often do not explain cognitive, emotional and behavioural disabilities that are common and disabling. In adults, traumatic brain injury produces progressive brain atrophy that can be accurately measured and is associated with cognitive decline. However, the effect of paediatric traumatic brain injury on brain volumes is more challenging to measure because of its interaction with normal brain development. Here we report a robust approach to the individualized estimation of brain volume following paediatric traumatic brain injury and investigate its relationship to clinical outcomes. We first used a large healthy control dataset (n > 1200, age 8-22) to describe the healthy development of white and grey matter regions through adolescence. Individual estimates of grey and white matter regional volume were then generated for a group of moderate/severe traumatic brain injury patients injured in childhood (n = 39, mean age 13.53 ± 1.76, median time since injury = 14 months, range 4-168 months) by comparing brain volumes in patients to age-matched controls. Patients were individually classified as having low or normal brain volume. Neuropsychological and neuropsychiatric outcomes were assessed using standardized testing and parent/carer assessments. Relative to head size, grey matter regions decreased in volume during normal adolescence development whereas white matter tracts increased in volume. Traumatic brain injury disrupted healthy brain development, producing reductions in both grey and white matter brain volumes after correcting for age. Of the 39 patients investigated, 11 (28%) had at least one white matter tract with reduced volume and seven (18%) at least one area of grey matter with reduced volume. Those classified as having low brain volume had slower processing speed compared to healthy controls, emotional impairments, higher levels of apathy, increased anger and learning difficulties. In contrast, the presence of focal brain injury and microbleeds were not associated with an increased risk of these clinical impairments. In summary, we show how brain volume abnormalities after paediatric traumatic brain injury can be robustly calculated from individual T1 MRI using a large normative dataset that allows the effects of healthy brain development to be controlled for. Using this approach, we show that volumetric abnormalities are common after moderate/severe traumatic brain injury in both grey and white matter regions, and are associated with higher levels of cognitive, emotional and behavioural abnormalities that are common after paediatric traumatic brain injury.