Corpus Callosum and Inferior Forebrain White Matter Microstructure Are Related to Functional Outcome from Raised Intracranial Pressure in Child Traumatic Brain Injury

Abstract

In severe paediatric traumatic brain injury (TBI), a common focus of treatment is raised intracranial pressure (ICP). We have previously reported frontal cerebral vulnerability with executive deficits from raised ICP in paediatric TBI. Now, using diffusion tensor imaging (DTI) in a different population, we have examined fractional anisotropy (FA), and mean, axial and radial diffusivity (MD, AD, RD) in 4 regions of the corpus callosum (CC) and in both inferior frontal regions. Our aim was to examine during the chronic phase of TBI whether the CC cross-sectional area correlated with regional DTI metrics of white matter microstructure, with global outcome ratings of function (Functional Independence Measure and Multiattribute Health Status Classification) and with performance in the Rey-Osterrieth Complex Figure (ROCF) test. We examined 33 paediatric TBI cases who were followed, on average, 4.9 years after severe injury. All cases had received mechanical ventilation during their acute treatment and, a priori, they were assigned to a non-ICP or a raised ICP group. Twenty-two participants had mainly right-sided injury at the time of acute ictus. The findings confirm that severe TBI in childhood, complicated by intracranial hypertension, results in CC vulnerability. In the chronic phase of recovery, it is reduced in the cross-sectional area, it is more compact and thinned, and the anterior region is disproportionately small. Late after raised ICP, we have also found that individuals exhibit regional microstructural abnormality with combined reduced FA and increased MD, AD and RD. Smaller size and such microstructural changes in the anterior CC were associated with similar right-sided (rather than left-sided) frontal microstructural changes in the ICP group. Taken together, this evidence points to an interaction between raised ICP-related brain tissue perturbation and focal frontal extracallosal injury, leading to anterior CC regional vulnerability, most likely wallerian degeneration. At long-term follow-up, this lack of white matter integrity in the anterior CC is correlated with functional outcome, particularly in aspects of social interaction and the copy component of the ROCF test, which suggests that the CC-to-forebrain function warrants further study in chronic TBI.

A Decade of DTI in Traumatic Brain Injury: 10 Years and 100 Articles Later

“…All except 8 articles reported sex breakdown; 65% of reported subjects were male. 6,30,41,46,52,77,81,83 Most commonly, abnormalities on DTI are defined on the basis of comparison with a control group because universal thresholds for abnormality have not yet been established. All studies, except 5, compared subjects with TBI with a control group.…”

“…43,55,90 The average number of control subjects per study was 18 (range, 6 -47). Several articles, in addition to comparing patients with TBI with controls by using DTI, looked at subgroups of patients with TBI, including patients with TBI with major depressive disorders, 53,99 with raised intracranial pressures, 81 with spinal cord injuries, 86 or veterans with blast injuries. 41,49,53,79,99 An important consideration in the selection of control subjects, particularly when studying symptom endorsement, is that comparison of subjects with TBI with healthy controls fails to eliminate the potential confound of morbidity due to the experience of trauma itself, rather than adverse outcomes specifically due to physical injury to the brain.…”

“…Children were studied exclusively in 29 of 72 articles. 4,5,[11][12][13][14]17,[19][20][21][22]25,27,42,43,55,66,75,81,[87][88][89][90][91][92][93][94]96,98 The total number of children studied across all 29 articles was 564. In addition, 20 studies included adults and children (younger than 19 years).…”

“…Seventy-two of 100 articles examined outcomes associated with TBI in addition to the imaging findings, 4-9,11,13,14,16-23,25,27,30,33, 36-43,45-47,49-59,61,62,64-68,70, 71,[74][75][76]78,[80][81][82]84,[87][88][89][90][91][92][93][94]96,98,101,102 and almost all of these 72 articles reported specifically on the association of DTI findings with the outcomes. Most surprising however, 3 articles, though they reported outcomes, did not report analysis of the relationship between the outcome measures and DTI.…”

Predicting outcome after childhood brain injury: Figure 1:

“…The outcome for many encephalopathies, including trauma and meningitis, may be determined by a combination of the severity of the primary injury, including the degree of damage to white matter; 58,59 the contribution of secondary factors, such as venous 60 and arterial focal ischemia, 61 the onset of status epilepticus 62 and the development of intracranial hypertension; 63 and multiple genetic determinants of the response to injury.…”