Diffusion tensor imaging (DTI) is a recent imaging technique that assesses the microstructure of the cerebral white matter (WM) based on anisotropic diffusion (i.e., water molecules move faster in parallel to nerve fibers than perpendicular to them). Fractional anisotropy (FA), which ranges from 0 to 1.0, increases with myelination of WM tracts and is sensitive to diffuse axonal injury (DAI) in adults with traumatic brain injury (TBI). However, previous DTI studies of pediatric TBI were case reports without detailed outcome measures. Using mean FA derived from DTI fiber tractography, we compared DTI findings of the corpus callosum for 16 children who were at least 1 year (mean 3.1 years) post-severe TBI and individually matched, uninjured children. Interexaminer and intraexaminer reliability in measuring FA was satisfactory. FA was significantly lower in the patients for the genu, body, and splenium of the corpus callosum. Higher FA was related to increased cognitive processing speed and faster interference resolution on an inhibition task. In the TBI patients, higher FA was related to better functional outcome as measured by the dichotomized Glasgow Outcome Scale (GOS). FA also increased as a function of the area of specific regions of the corpus callosum such as the genu and splenium, and FA in the splenium was reduced with greater volume of lesions in this region. DTI may be useful in identifying biomarkers related to DAI and outcome of TBI in children.

To evaluate the effects of mild to moderate blast-related traumatic brain injury (TBI) on the microstructure of brain white matter (WM) and neurobehavioral outcomes, we studied 37 veterans and service members (mean age 31.5 years, SD = 7.2; post-injury interval 871.5 days; SD = 343.1), whose report of acute neurological status was consistent with sustaining mild to moderate TBI due to blast while serving in Iraq or Afghanistan. Fifteen veterans without a history of TBI or exposure to blast (mean age 31.4 years, SD = 5.4) served as a comparison group, including seven subjects with extracranial injury (post-injury interval 919.5 days, SD = 455.1), and eight who were uninjured. Magnetic resonance imaging disclosed focal lesions in five TBI participants. Post-concussion symptoms (Neurobehavioral Symptom Inventory), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist-Civilian), and global distress and depression (Brief Symptom Inventory) were worse in the TBI participants than the comparison group, but no group differences were found in perceived physical or mental functioning (SF-12). Verbal memory (Selective Reminding) was less efficient in the TBI group, but there were no group differences in nonverbal memory (Selective Reminding) or decision making (Iowa Gambling Task). Verbal memory in the TBI group was unrelated to PTSD severity. Diffusion tensor imaging (DTI) using tractography, standard single-slice region-of-interest measurement, and voxel-based analysis disclosed no group differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC). However, FA of the left and right posterior internal capsule and left corticospinal tract was positively correlated with total words consistently recalled, whereas ADC for the left and right uncinate fasciculi and left posterior internal capsule was negatively correlated with this measure of verbal memory. Correlations of DTI variables with symptom measures were non-significant and inconsistent. Our data do not show WM injury in mild to moderate blast-related TBI in veterans despite their residual symptoms and difficulty in verbal memory. Limitations of the study and implications for future research are also discussed.

In vivo MRI volumetric analysis enables investigators to evaluate the extent of tissue loss following traumatic brain injury (TBI). However, volumetric studies of pediatric TBI are sparse, and there have been no volumetric studies to date in children examining specific subregions of the prefrontal and temporal lobes. In this study, MRI volumetry was used to evaluate brain volume differences in the whole brain, and prefrontal, temporal, and posterior regions of children following moderate to severe TBI as compared to uninjured children of similar age and demographic characteristics. The TBI group had significantly reduced whole brain, and prefrontal and temporal regional tissue volumes as well as increased cerebrospinal fluid (CSF). Confidence interval testing further revealed group differences on gray matter (GM) and white matter (WM) in the superior medial and ventromedial prefrontal regions, WM in the lateral frontal region, and GM, WM, and CSF in the temporal region. Whole brain volume and total brain GM were reduced, and total ventricular volume, total CSF volume, and ventricle-to-brain ratio (VBR) were increased in the TBI group. Additional analyses comparing volumetric data from typically developing children and subgroups of TBI patients with and without regional focal lesions suggested that GM loss in the frontal areas was primarily attributable to focal injury, while WM loss in the frontal and temporal lobes was related to both diffuse and focal injury. Finally, volumetric measures of preserved frontotemporal tissue were related to functional recovery as measured by the Glasgow Outcome Scale (adapted for children) with greater tissue preservation predicting better recovery.

Fourteen cancer patients had evidence of persistent neurotoxicity of interferon-alpha therapy long after their treatment was discontinued. Although most of the cognitive symptoms were mild to moderate in severity, they were incapacitating to these individuals in their usual work. The neuropsychological test abnormalities were not attributable to subsequent therapy, disease status, or other medical problems. The pattern of deficits was consistent with frontal-subcortical dysfunction. Of the four patients who had follow-up assessment, two had improved and two had deteriorated. These findings suggest that in some cases interferon neurotoxicity is not reversible.