The UCLA study of Predictors of Cognitive Functioning Following Moderate/Severe Pediatric Traumatic Brain Injury.

OBJECTIVES: Following pediatric moderate-to-severe traumatic brain injury (msTBI), few predictors have been identified that can reliably identify which individuals are at risk for long-term cognitive difficulties. This study sought to determine the relative contribution of detailed descriptors of injury severity as well as demographic and psychosocial factors to long-term cognitive outcomes after pediatric msTBI. METHODS: Participants included 8- to 19-year-olds, 46 with msTBI and 53 uninjured healthy controls (HC). Assessments were conducted in the post-acute and chronic stages of recovery. Medical record review provided details regarding acute injury severity. Parents also completed a measure of premorbid functioning and behavioral problems. The outcome of interest was four neurocognitive measures sensitive to msTBI combined to create an index of cognitive performance. RESULTS: Results indicated that none of the detailed descriptors of acute injury severity predicted cognitive performance. Only the occurrence of injury, parental education, and premorbid academic competence predicted post-acute cognitive functioning. Long-term cognitive outcomes were best predicted by post-acute cognitive functioning. DISCUSSION: The findings suggest that premorbid factors influence cognitive outcomes nearly as much as the occurrence of a msTBI. Furthermore, of youth with msTBI who initially recover to a level of moderate disability or better, a brief cognitive battery administered within several months after injury can best predict which individuals will experience poor long-term cognitive outcomes and require additional services.

The UCLA Study of Children with Moderate-to-Severe Traumatic Brain Injury: Event-Related Potential Measure of Interhemispheric Transfer Time.

Traumatic brain injury (TBI) frequently results in diffuse axonal injury and other white matter damage. The corpus callosum (CC) is particularly vulnerable to injury following TBI. Damage to this white matter tract has been associated with impaired neurocognitive functioning in children with TBI. Event-related potentials can identify stimulus-locked neural activity with high temporal resolution. They were used in this study to measure interhemispheric transfer time (IHTT) as an indicator of CC integrity in 44 children with moderate/severe TBI at 3-5 months post-injury, compared with 39 healthy control children. Neurocognitive performance also was examined in these groups. Nearly half of the children with TBI had IHTTs that were outside the range of the healthy control group children. This subgroup of TBI children with slow IHTT also had significantly poorer neurocognitive functioning than healthy controls-even after correction for premorbid intellectual functioning. We discuss alternative models for the relationship between IHTT and neurocognitive functioning following TBI. Slow IHTT may be a biomarker that identifies children at risk for poor cognitive functioning following moderate/severe TBI.

White matter disruption in moderate/severe pediatric traumatic brain injury: advanced tract-based analyses.

Traumatic brain injury (TBI) is the leading cause of death and disability in children and can lead to a wide range of impairments. Brain imaging methods such as DTI (diffusion tensor imaging) are uniquely sensitive to the white matter (WM) damage that is common in TBI. However, higher-level analyses using tractography are complicated by the damage and decreased FA (fractional anisotropy) characteristic of TBI, which can result in premature tract endings. We used the newly developed autoMATE (automated multi-atlas tract extraction) method to identify differences in WM integrity. 63 pediatric patients aged 8-19 years with moderate/severe TBI were examined with cross sectional scanning at one or two time points after injury: a post-acute assessment 1-5 months post-injury and a chronic assessment 13-19 months post-injury. A battery of cognitive function tests was performed in the same time periods. 56 children were examined in the first phase, 28 TBI patients and 28 healthy controls. In the second phase 34 children were studied, 17 TBI patients and 17 controls (27 participants completed both post-acute and chronic phases). We did not find any significant group differences in the post-acute phase. Chronically, we found extensive group differences, mainly for mean and radial diffusivity (MD and RD). In the chronic phase, we found higher MD and RD across a wide range of WM. Additionally, we found correlations between these WM integrity measures and cognitive deficits. This suggests a distributed pattern of WM disruption that continues over the first year following a TBI in children.

Neurocognitive profiles in children with epilepsy.

PURPOSE: The presence of specific neurocognitive deficits may help explain why school achievement and psychosocial functioning are often worse in children with epilepsy than would be predicted by their global intellectual functioning. This study compared children with two forms of epilepsy: localization-related epilepsy with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to determine whether they display distinct neurocognitive profiles. METHODS: Fifty-one children with CPS, 31 children with CAE, and 51 controls underwent neuropsychological testing assessing verbal memory, visual memory, and executive functioning. Groups were compared in these cognitive domains. Within-group analyses were also conducted to examine seizure-related factors that may be related to neuropsychological test performance. KEY FINDINGS: When compared to controls, children with CPS showed a mild generalized cognitive deficit, whereas children with CAE did not. When we controlled for intelligent quotient (IQ), both epilepsy groups showed poorer performance relative to controls in the domain of verbal memory. When the epilepsy groups were compared to one another, the CPS group performed significantly poorer than the CAE group on a test of generalized cognitive functioning. However, in the specific domains of executive functioning, verbal memory, and visual memory the epilepsy groups did not differ when compared to one another. SIGNIFICANCE: Neurocognitive deficits present in the context of grossly intact global intellectual functioning highlight the importance of neuropsychological screening in both children with CPS and children with CAE.

Metabolic levels in the corpus callosum and their structural and behavioral correlates after moderate to severe pediatric TBI.

Diffuse axonal injury (DAI) secondary to traumatic brain injury (TBI) contributes to long-term functional morbidity. The corpus callosum (CC) is particularly vulnerable to this type of injury. Magnetic resonance spectroscopy (MRS) was used to characterize the metabolic status of two CC regions of interest (ROIs) (anterior and posterior), and their structural (diffusion tensor imaging; DTI) and neurobehavioral (neurocognitive functioning, bimanual coordination, and interhemispheric transfer time [IHTT]) correlates. Two groups of moderate/severe TBI patients (ages 12-18 years) were studied: post-acute (5 months post-injury; n = 10), and chronic (14.7 months post-injury; n = 8), in addition to 10 age-matched healthy controls. Creatine (energy metabolism) did not differ between groups across both ROIs and time points. In the TBI group, choline (membrane degeneration/inflammation) was elevated for both ROIs at the post-acute but not chronic period. N-acetyl aspartate (NAA) (neuronal/axonal integrity) was reduced initially for both ROIs, with partial normalization at the chronic time point. Posterior, not anterior, NAA was positively correlated with DTI fractional anisotropy (FA) (r = 0.88), and most domains of neurocognition (r range 0.22-0.65), and negatively correlated with IHTT (r = -0.89). Inverse corerlations were noted between creatine and posterior FA (r = -0.76), neurocognition (r range -0.22 to -0.71), and IHTT (r = 0.76). Multimodal studies at distinct time points in specific brain structures are necessary to delineate the course of the degenerative and reparative processes following TBI, which allows for preliminary hypotheses about the nature and course of the neural mechanisms of subsequent functional morbidity. This will help guide the future development of targeted therapeutic agents.