Longitudinal white matter changes after traumatic axonal injury.

Diffusion tensor imaging (DTI) has been useful in showing compromise after traumatic axonal injury (TAI) at the chronic stage; however, white matter (WM) compromise from acute stage of TAI to chronic stage is not yet well understood. This study aims to examine changes in WM integrity following TAI by obtaining DTI, on average, 1 d post injury and again approximately seven months post-injury. Sixteen patients with complicated mild to severe brain injuries consistent with TAI were recruited in the intensive care unit of a Level I trauma center. Thirteen of these patients were studied longitudinally over the course of the first seven months post-injury. The first scan occurred, on average, 1 d after injury and the second an average of seven months post-injury. Ten healthy individuals, similar to the cohort of patients, were recruited as controls. Whole brain WM and voxel-based analyses of DTI data were conducted. DTI metrics of interest included: fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD). tract-based spatial statistics were used to examine DTI metrics spatially. Acutely, AD and RD increased and RD positively correlated with injury severity. Longitudinal analysis showed reduction in FA and AD (p<0.01), but no change in RD. Possible explanations for the microstructural changes observed over time are discussed.

The Community Integration Questionnaire: factor structure across racial/ethnic groups in persons with traumatic brain injury.

OBJECTIVE: To examine the factor structure and construct validity of the Community Integration Questionnaire, a widely used measure of community participation among individuals with traumatic brain injury (TBI), among 3 racial/ethnic groups. DESIGN: Prospective longitudinal cohort study. SETTING: Enrollment in acute inpatient TBI rehabilitation with follow-up at 1 year after injury. PARTICIPANTS: A total of 1756 persons with TBI enrolled in the Traumatic Brain Injury Model Systems (TBIMS) national Database. MAIN OUTCOME MEASURE: Community Integration Questionnaire at 1 year after injury. RESULTS: The goodness of fit for the factor structure of the Community Integration Questionnaire, separating items into Home Competency, Social Integration, and Productive Activity, was satisfactory for whites but not for blacks or Hispanics. CONCLUSIONS: Clinicians and researchers should take race/ethnicity into account when utilizing measures of community integration.

Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury.

OBJECTIVE: To examine the functional connectivity of hippocampal and selected frontal lobe circuits in patients with traumatic axonal injury (TAI). DESIGN: Observational study. SETTING: An inpatient traumatic brain injury unit. Imaging and neurocognitive assessments were conducted in an outpatient research facility. PARTICIPANTS: Twenty-five consecutive patients with brain injuries consistent with TAI and acute subcortical white matter abnormalities were studied as well as 16 healthy volunteers of similar age and sex. INTERVENTIONS: Echo-planar and high-resolution T1-weighted images were acquired using 3-T scanners. Regions of interest (ROI) were drawn bilaterally for the hippocampus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex and were used to extract time series data. Blood oxygenation level-dependent data from each ROI were used as reference functions for correlating with all other brain voxels. Interhemispheric functional connectivity was assessed for each participant by correlating homologous regions using a Pearson correlation coefficient. Patient functional and neurocognitive outcomes were assessed approximately 6 months after injury. MAIN OUTCOME MEASURES: Interhemispheric functional connectivity, spatial patterns of functional connectivity, and associations of connectivity measures with functional and neurocognitive outcomes. RESULTS: Patients showed significantly lower interhemispheric functional connectivity for the hippocampus and ACC. Controls demonstrated stronger and more focused functional connectivity for the hippocampi and ACC, and a more focused recruitment of the default mode network for the dorsolateral prefrontal cortex ROI. The interhemispheric functional connectivity for the hippocampus was correlated with delayed recall of verbal information. CONCLUSIONS: Traumatic axonal injury may affect interhemispheric neural activity, as patients with TAI show disrupted interhemispheric functional connectivity. More careful investigation of interhemispheric connectivity is warranted, as it demonstrated a modest association with outcome in chronic TBI.

Diffusion tensor imaging biomarkers for traumatic axonal injury: analysis of three analytic methods.

Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel-based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3 Tesla magnet. Patients were scanned approximately eight months postinjury, and underwent an outcomes assessment at that time. Histogram analysis of fractional anisotropy (FA) and mean diffusivity showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.

Diffusion tensor tractography of traumatic diffuse axonal injury.

BACKGROUND: Diffuse axonal injury is a common consequence of traumatic brain injury that frequently involves the parasagittal white matter, corpus callosum, and brainstem. OBJECTIVE: To examine the potential of diffusion tensor tractography in detecting diffuse axonal injury at the acute stage of injury and predicting long-term functional outcome. DESIGN: Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome. SETTING: Inpatient traumatic brain injury unit. PATIENTS: From 2005 to 2006, magnetic resonance images were acquired in 12 patients approximately 7 days after injury and in 12 age- and sex-matched controls. MAIN OUTCOME MEASURES: Six fiber variables of the corpus callosum, fornix, and peduncular projections were obtained. Glasgow Outcome Scale-Extended scores were assessed approximately 9 months after injury in 11 of the 12 patients. RESULTS: At least 1 fiber variable of each region showed diffuse axonal injury-associated alterations. At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale-Extended scores. The predicted outcome scores correlated significantly with actual scores in a mixed-effects model. CONCLUSION: Diffusion tensor tractography-based quantitative analysis at the acute stage of injury has the potential to serve as a valuable biomarker of diffuse axonal injury and predict long-term outcome.

Impact of age on long-term recovery from traumatic brain injury.

OBJECTIVE: To determine whether older persons are at increased risk for progressive functional decline after traumatic brain injury (TBI). DESIGN: Longitudinal cohort study. SETTING: Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers. PARTICIPANTS: Subjects enrolled in the TBIMS national dataset. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS), FIM instrument cognitive items, and the Glasgow Outcome Scale-Extended. RESULTS: Participants were separated into 3 age tertiles: youngest (16-26y), intermediate (27-39y), and oldest (> or =40y). DRS scores were comparable across age groups at admission to a rehabilitation center. The oldest group was slightly more disabled at discharge from rehabilitation despite having less severe acute injury severity than the younger groups. Although DRS scores for the 2 younger groups improved significantly from year 1 to year 5, the greatest magnitude of improvement in disability was seen among the youngest group. In addition, after dividing patients into groups according to whether their DRS scores improved (13%), declined (10%), or remained stable (77%) over time, the likelihood of decline was found to be greater for the 2 older groups than for the youngest group. A multiple regression model showed that age has a significant negative influence on DRS score 5 years post-TBI after accounting for the effects of covariates. CONCLUSIONS: This study supported our primary hypothesis that older patients show greater decline over the first 5 years after TBI than younger patients. In addition, the greatest amount of improvement in disability was observed among the youngest group of survivors. These results suggest that TBI survivors, especially older patients, may be candidates for neuroprotective therapies after TBI.

Racial differences in employment outcomes after traumatic brain injury.

OBJECTIVE: To examine racial differences in employment status and occupational status 1 year after a traumatic brain injury (TBI). DESIGN: Retrospective study. SETTING: Longitudinal dataset of the Traumatic Brain Injury Model Systems national database. PARTICIPANTS: Subjects with primarily moderate to severe TBI (3468 whites vs 1791 minorities) hospitalized between 1989 and 2005. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment status (competitively employed or unemployed) and occupational status (professional/managerial, skilled, or manual labor) at 1 year postinjury. RESULTS: Race and/or ethnicity has a significant effect on employment status at 1 year postinjury (chi(1)(2)=58.23, P<.001), after adjusting for preinjury employment status, sex, Disability Rating Scale at discharge, marital status, cause of injury, age, and education. The adjusted odds of being unemployed versus competitively employed are 2.17 times (95% confidence interval, 1.78-2.65) greater for minorities than for whites. Race and ethnicity does not have a significant effect on occupational status at 1 year postinjury. CONCLUSIONS: With this empirical evidence supporting racial differences in employment outcomes between minorities and whites at 1 year postinjury, priority should be given to tailoring interventions to maximize minority survivors' work-related productivity.