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A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed, which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3,047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1,426 individuals with PTSD and 1,621 controls (2174 males/873 females) between ages 18–83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen’s d=−0.11, p=0.0055). The tapetum connects the left and right hippocampus, structures for which structure and function have been consistently implicated in PTSD. Results remained significant/similar after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Statins constitute a class of medications commonly used in the treatment of elevated cholesterol. However, in experimental studies, statins also have other non-cholesterol-mediated mechanisms of action, which may have neuroprotective effects. The aim of this study was to determine whether administration of atorvastatin for 7 days post-injury would improve neurological recovery in patients with mild traumatic brain injury (mTBI). The hypothesis was that atorvastatin administration would reduce post-concussion symptoms and also that atorvastatin administration for 1 week post-injury would be safe. One hundred forty patients with mTBI were planned to be enrolled and randomly assigned to receive atorvastatin 1 mg/kg (up to 80 mg/kg) per day or placebo for 7 days starting within 24 h of injury. Assessments of post-concussion syndrome, post-traumatic stress and depressive symptoms, cognition, memory, verbal fluency, functional, and work status were performed at baseline, 1 week, and 1 and 3 months. The result on the Rivermead Post-Concussion Symptoms Questionnaire at 3 months was the primary outcome. Enrollment in the trial was stopped early because of difficulty in recruiting sufficient numbers of subjects. Fifty-two patients with mTBI were enrolled; 28 patients received atorvastatin and 24 received placebo. The median Rivermead score was 2 for the atorvastatin group, compared to 3.5 for the placebo group, at 3 months post-injury (χ

To address controversy surrounding the most appropriate comparison group for mild traumatic brain injury (mTBI) research, mTBI patients 12–30 years of age were compared with an extracranial orthopedic injury (OI) patient group and an uninjured, typically developing (TD) participant group with comparable demographic backgrounds. Injured participants underwent subacute (within 96 h) and late (3 months) diffusion tensor imaging (DTI); TD controls underwent DTI once. Group differences in fractional anisotropy (FA) and mean diffusivity (MD) of commonly studied white matter tracts were assessed. For FA, subacute group differences occurred in the bilateral inferior frontal occipital fasciculus (IFOF) and right inferior longitudinal fasciculus (ILF), and for MD, differences were found in the total corpus callosum, right uncinate fasciculus, IFOF, ILF, and bilateral cingulum bundle (CB). In these analyses, differences (lower FA and higher MD) were generally observed between the mTBI and TD groups but not between the mTBI and OI groups. After a 3 month interval, groups significantly differed in left IFOF FA and in right IFOF and CB MD; the TD group had significantly higher FA and lower MD than both injury groups, which did not differ. There was one exception to this pattern, in which the OI group demonstrated significantly lower FA in the left ILF than the TD group, although neither group differed from the mTBI group. The mTBI and OI groups had generally similar longitudinal results. Findings suggest that different conclusions about group-level DTI analyses could be drawn, depending on the selected comparison group, highlighting the need for additional research in this area. Where possible, mTBI studies may benefit from the inclusion of both OI and TD controls.

Although most patients with mild traumatic brain injury (mTBI) recover within 3 months, a subgroup of patients experience persistent symptoms. Yet, the prevalence and predictors of persistent dysfunction in patients with mTBI remain poorly understood. In a longitudinal study, we evaluated predictors of symptomatic and cognitive dysfunction in adolescents and young adults with mTBI, compared with two control groups-patients with orthopedic injuries and healthy uninjured individuals. Outcomes were assessed at 3 months post-injury. Poor symptomatic outcome was defined as exhibiting a symptom score higher than 90% of the orthopedic control (OC) group, and poor cognitive outcome was defined as exhibiting cognitive performance poorer than 90% of the OC group. At 3 months post-injury, more than half of the patients with mTBI (52%) exhibited persistently elevated symptoms, and more than a third (36.4%) exhibited poor cognitive outcome. The rate of high symptom report in mTBI was markedly greater than that of typically developing (13%) and OC (17%) groups; the proportion of those with poor cognitive performance in the mTBI group exceeded that of typically developing controls (15.8%), but was similar to that of the OC group (34.9%). Older age at injury, female sex, and acute symptom report were predictors of poor symptomatic outcome at 3 months. Socioeconomic status was the only significant predictor of poor cognitive outcome at 3 months.

OBJECTIVE AND BACKGROUND: We examined sleep-related problems in adolescents and young adults after a mild traumatic brain injury (MTBI) or orthopedic injury. We extended the analysis of data from a study of early emotional and neuropsychological sequelae in these populations (McCauley et al. 2014. J Neurotrauma. 31:914). METHODS: We gave the Pittsburgh Sleep Quality Index to 77 participants with MTBI, 71 with orthopedic injury, and 43 non-injured controls. The age range was 12 to 30 years. We tested sleep quality within 96 hours of injury and at 1- and 3-month follow-up. Participants also completed measures of pain and fatigue, drug and alcohol use, and post-traumatic stress symptoms. RESULTS: Older participants (mean age=25 years) in the MTBI group exhibited a sharp increase in sleep-related symptoms between the baseline assessment and 1 month, and still had difficulties at 3 months. Younger participants with MTBI (mean age=15 years) and older participants with an orthopedic injury had modest increases in sleep difficulties between baseline and 1 month. The participants with MTBI also had more clinically significant sleep difficulties at all 3 assessments. At 3 months, Pittsburgh Sleep Quality Index scores in younger participants with MTBI and all participants with orthopedic injury did not differ significantly from the non-injured controls'. The controls had no significant change in their sleep symptoms during the 3 months. CONCLUSIONS: Sleep difficulties in young adults may persist for ≤3 months after MTBI and exceed those after orthopedic injury. Clinicians should seek and treat sleep-related problems after MTBI. Language: en

Although mild traumatic brain injury (mTBI) is now recognized as a major health issue, there have been relatively few studies of its acute effects. Previous studies of mTBI assessed at 1 week or less post-injury have produced inconsistent results, spanning reports of no ill effects to findings of robust dysfunction. These gross disparities reflect study differences such as the criteria for mTBI diagnosis and selection of comparison groups. In consideration of these issues, this study investigated outcome in the first 96 hours after injury in adolescents and adults ages 12-30 years with mTBI (n=73) compared with orthopedically injured (OI, n=65) and typically developing controls (TDC, n=40). The mTBI group reported significantly greater general psychological distress, post-concussion symptom severity, and post-traumatic stress severity than OI (all p

As noted in the recent special issue in Brain Imaging and Behavior (Tate et al. 2012), there has been a growing interest among researchers, clinicians, policy makers, patients and family members, and other consumers regarding mild traumatic brain injury (mTBI). This interest stems from several converging points of view including epidemiology data that indicates the significant prevalence and incidence of mTBI in the general population, associated legal issues (i.e., symptom validity), our growing understanding of the effects of concussive and subconcussive sports injuries (i.e., chronic traumatic encephalopathy), and an attentiveness to the relationship between TBI and dementia in a rapidly aging society. These interests combined with recent advances in cognitive sciences, improvement in the clinical management of mTBI, a growing number of treatment options, and acquisition and analysis of imaging data are propelling the effort toward identification of unique biomarkers that could improve diagnosis, prognosis, and guide/assess treatments. Not surprisingly, mTBI occurs in the context of a number of different situations. However, in addition to common means of head injury among civilians (i.e., motor vehicle accidents, falls, and other collision-related events), Military and Veteran populations have a number of additional deployment-related risk factors for head injury including combatant training, gunshot wounds, blast exposure, and assault. Brain-related injury in many Military and Veteran TBI patients is also complicated by additional comorbid conditions not typically experienced by civilian TBI patients including combat-related PTSD or depression, burns, hearing dysfunction, traumatic amputations and other injuries associated with combat. With the recent combat operations in support of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), Operation New Dawn (OND), and other conflicts, surveillance data from the Defense and Veterans Brain Injury Centers (DVBIC) have identified over 327,299 U.S. ServiceMembers and Veterans across the branches of service that sustained a TBI (https://dvbic.dcoe.mil/sites/default/files/DoD-TBI-WorldwideTotals%202000-2015Q1-May15-2015.pdf). These head injuries occur both during theatre operations and in garrison with the majority (>70 %) falling into the mild range of severity. The sheer numbers of Service Members and Veterans injured underscore the importance of advancing our understanding of the functional, clinical, and long-term consequences of mild TBI, especially in Military populations. Moreover, there is a growing interest in understanding the impact of mTBI on unit readiness, return to duty, safety of troop operations, troop retention, and long-term cognitive effects (i.e., chronic traumatic encephalopathy and possible links with dementia). Given these concerns, there has been a sudden and rapid growth in the number of investigators * David F. Tate David.Tate@mimh.edu

There is significant heterogeneity in outcomes following mild traumatic brain injury (mTBI). While several host factors (age, gender, and preinjury psychiatric history) have been investigated, the influence of preinjury psychological resilience and mood status in conjunction with mild TBI remains relatively unexplored. Euthymic mood and high resilience are potentially protective against anxiety and postconcussion symptoms, but their relative contributions are currently unknown. This prospective study obtained preinjury estimates of resilience and mood measures in addition to measures of anxiety (Acute Stress Disorder Scale and PTSD-Checklist-Civilian form) and postconcussion symptom severity (Rivermead Post Concussion Symptoms Questionnaire)24 hours (Baseline), 1 week, and 1 month postinjury in patients with either mTBI (n=46) or a comparison group with orthopedic injuries not involving the head (OI, n=29). The groups did not differ on preinjury resilience or mood status at baseline, but differed significantly on measures of anxiety and postconcussion symptom severity at each subsequent study occasion. Multivariate linear regression analyses were conducted to determine if preinjury resilience and mood were significant contributors to anxiety and postconcussion symptoms during the first month postinjury after accounting for other known host factors (e.g., age at injury, gender, and education). Injury group and preinjury mood status were significant predictors for all three dependent variables at each study occasion (all p0.007). Preinjury resilience showed a positive trend only for acute stress severity at baseline, but demonstrated significant prediction of all three dependent measures at one week and one month postinjury. These results suggest that preinjury depressed mood and resilience are significant contributors to the severity of postinjury anxiety and postconcussion symptoms, even after accounting for effects of other specific host factors.

Few studies have examined the trajectory of recovery of executive function (EF) after mild TBI (mTBI). Therefore, consensus has not been reached on the incidence and extent of EF impairment after mTBI. The present study investigated trajectory of change in executive memory over 3 months after mTBI on 59 right-handed participants with mTBI, as defined by Centers for Disease Control criteria, ages 14–30 years, recruited within 96 hours post-injury and tested

Patients (n = 8) with uncomplicated mild traumatic brain injury (mTBI) underwent serial assessments (4) with diffusion tensor imaging (DTI) and neuropsychological testing within the first 8 days post-injury. Using a multi-case study design, we examined changes in brain parenchyma (via DTI-derived fractional anisotropy [FA], apparent diffusion coefficient [ADC], axial diffusivity [AD] and radial diffusivity [RD] in the left cingulum bundle) and in memory performance (via Hopkins Verbal Learning Test-Revised). Qualitative inspection of the results indicated that memory performance was transiently affected in most participants over the course of the week, with performance most negatively impacted on the second assessment (days 3-4 or 97-144 h post-injury), and then returning to within normal limits by 8 days post-injury. Alternatively, FA and other DTI metrics showed a more complex pattern, with the trajectory of some participants changing more prominently than others. For example, FA transiently increased in some participants over the study period, but the pattern was heterogeneous. Memory performance appeared to mirror changes in FA in certain cases, supporting a pathophysiological basis to memory impairment following mTBI. However, the pattern and the degree of symmetry between FA and memory performance was complex and did not always correspond. Serial imaging over the semi-acute recovery period may be important in reconciling conflicting findings in mTBI utilizing memory and/or DTI. Serial use of imaging modalities including DTI may aid understanding of underlying pathophysiological changes in the semi-acute post-injury period. Should a consistent pattern emerge that allows identification of patients at-risk for acute and/or persistent symptoms, such knowledge could guide development of therapeutic targets in mTBI and in understanding the most effective administration time window for these agents.

Traumatic brain injury (TBI) is a leading cause of death and disability in children, yet little is known regarding the pattern of TBI-related microstructural change and its impact on subsequent development. Diffusion tensor imaging (DTI) was used to examine between-group differences at two time points (planned intervals of 3 months and 18 months post-injury) and within-group longitudinal change in a group of children and adolescents aged 7-17 years with moderate-to-severe TBI (n = 20) and a comparison group of children with orthopedic injury (OI) (n = 21). In the 3- and 18-month cross-sectional analyses, tract-based spatial statistics (TBSS) generally revealed decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) in the TBI group in regions of frontal, temporal, parietal, and occipital white matter as well as several deep subcortical structures, though areas of FA decrease were more prominent at the 3-month assessment, and areas of ADC increase were more prominent at the 18 month assessment, particularly in the frontal regions. In terms of the within-group changes over time, the OI group demonstrated primarily diffuse increases in FA over time, consistent with previous findings of DTI-measured white matter developmental change. The TBI group demonstrated primarily regions of FA decrease and ADC increase over time, consistent with presumed continued degenerative change, though regions of ADC decrease were also appreciated. These results suggest that TBI-related microstructural changes are dynamic in children and continue until at least 18 months post-injury. Understanding the course of these changes in DTI metrics may be important in TBI for facilitating advances in management and intervention.

The purpose of this study was to assess patterns of cortical development over time in children who had sustained traumatic brain injury (TBI) as compared to children with orthopedic injury (OI), and to examine how these patterns related to emotional control and behavioral dysregulation, two common post-TBI symptoms. Cortical thickness was measured at approximately 3 and 18 months post-injury in 20 children aged 8.2-17.5 years who had sustained moderate-to-severe closed head injury and 21 children aged 7.4-16.7 years who had sustained OI. At approximately 3 months post-injury, the TBI group evidenced decreased cortical thickness bilaterally in aspects of the superior frontal, dorsolateral frontal, orbital frontal, and anterior cingulate regions compared to the control cohort, areas of anticipated vulnerability to TBI-induced change. At 18 months post-injury, some of the regions previously evident at 3 months post-injury remained significantly decreased in the TBI group, including bilateral frontal, fusiform, and lingual regions. Additional regions of significant cortical thinning emerged at this time interval (bilateral frontal regions and fusiform gyrus and left parietal regions). However, differences in other regions appeared attenuated (no longer areas of significant cortical thinning) by 18 months post-injury including large bilateral regions of the medial aspects of the frontal lobes and anterior cingulate. Cortical thinning within the OI group was evident over time in dorsolateral frontal and temporal regions bilaterally and aspects of the left medial frontal and precuneus, and right inferior parietal regions. Longitudinal analyses within the TBI group revealed decreases in cortical thickness over time in numerous aspects throughout the right and left cortical surface, but with notable "sparing" of the right and left frontal and temporal poles, the medial aspects of both the frontal lobes, the left fusiform gyrus, and the cingulate bilaterally. An analysis of longitudinal changes in cortical thickness over time (18 months-3 months) in the TBI versus OI group demonstrated regions of relative cortical thinning in the TBI group in bilateral superior parietal and right paracentral regions, but relative cortical thickness increases in aspects of the medial orbital frontal lobes and bilateral cingulate and in the right lateral orbital frontal lobe. Finally, findings from analyses correlating the longitudinal cortical thickness changes in TBI with symptom report on the Emotional Control subscale of the Behavior Rating Inventory of Executive Function (BRIEF) demonstrated a region of significant correlation in the right medial frontal and right anterior cingulate gyrus. A region of significant correlation between the longitudinal cortical thickness changes in the TBI group and symptom report on the Behavioral Regulation Index was also seen in the medial aspect of the left frontal lobe. Longitudinal analyses of cortical thickness highlight an important deviation from the expected pattern of developmental change in children and adolescents with TBI, particularly in the medial frontal lobes, where typical patterns of thinning fail to occur over time. Regions which fail to undergo expected cortical thinning in the medial aspects of the frontal lobes correlate with difficulties in emotional control and behavioral regulation, common problems for youth with TBI. Examination of post-TBI brain development in children may be critical to identification of children that may be at risk for persistent problems with executive functioning deficits and the development of interventions to address these issues.

Based on the importance of the perforant pathway (PP) for normal hippocampal function, the vulnerability of temporal structures, and significant memory impairment in patients with traumatic brain injury (TBI), we investigated in vivo changes in the PP zone, hippocampus, and temporal lobe white and gray matter using diffusion tensor imaging (DTI) and volumetric analysis, and any specific relations with memory performance (Verbal Selective Reminding Test, Rey-Osterrieth Complex Figure Test), in 14 patients with severe TBI. Compared to a demographically-similar control group, our patients had significantly decreased fractional anisotropy (FA) and higher apparent diffusion coefficient (ADC) for the PP zone bilaterally, and higher ADC bilaterally in the hippocampus. Volumetric analysis revealed significantly decreased volumes in both hippocampi and temporal gray matter bilaterally. Consistent long-term retrieval (CLTR) and delayed recall were significantly related to (1) right and left PP zone ADC, (2) left hippocampus ADC, and (3) left hippocampal volume. Nonverbal memory (immediate and delayed recall) was significantly associated with (1) right and left PP zone ADC, (2) left hippocampal volume, and (3) gray (immediate recall) and white (immediate recall, bilaterally; delayed recall, left) matter temporal volumes. Advanced neuroimaging analysis can detect in vivo changes in the PP zone and temporal structures in patients with severe TBI, with these changes being highly associated with memory impairment.

Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative risk [RR] 1·08, 95% CI 0·76–1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58–2·52; p=0·52). Interpretation This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury. Funding National Institute of Neurological Disorders and Stroke.

The integrity of the fornix using diffusion tensor imaging (DTI) in adolescent participants with acute mild traumatic brain injury (mTBI) compared to a demographically matched control group was examined. Fractional anisotropy (FA) in the fornix was elevated in the mild traumatic brain injured group. Performance on the Automated Neuropsychological Assessment Metrics (ANAM) was lower in the group with mTBI. A relation was found between lower performance on cognitive tasks and higher FA. The potential role of fornix injury as a basis of memory and processing speed deficits in mTBI is discussed.

The temporal stem (TS) of the temporal lobe is a major white matter (WM) region containing several major pathways that connect the temporal lobe with the rest of the brain. Because of its location, it may be particularly vulnerable to shear-strain effects resulting from traumatic brain injury (TBI). A case vignette is presented in a patient with severe brain injury and focal TS pathology. Also, 12 severe TBI subjects unselected for TS pathology were compared to demographically matched, neurologically-intact controls using diffusion tensor imaging (DTI) to examine white matter tracts associated with the TS, including the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), arcuate fasciculus (AF), cingulum bundle (CB) and the uncinate fasciculus (UF). For each tract, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and compared between the two groups and also examined in relationship to memory performance in the TBI subjects. Significant FA and ADC differences were observed in all tracts in the TBI patients compared to controls, with several relationships with memory outcome noted in the IFOF, ILF and AF. Based on these preliminary findings, the potential role of TBI-induced WM disconnection involving the TS is discussed as well as the relationship of TS damage to neurobehavioral outcome. The need for future studies specifically examining the role of TS injury in TBI is emphasized.

A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9) ≤18 months (mean = 3.1, SD = 3.2) following moderate (n = 8) to severe (n = 42) TBI, internal consistency of the NOS-TBI was high (Cronbach's alpha = 0.942). Test-retest reliability also was high (ρ = 0.97, p

The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure adapted from the National Institutes of Health Stroke Scale (NIHSS), and is intended to capture essential neurological deficits impacting individuals with traumatic brain injury (TBI) (see Wilde et al., 2010). In the present study we evaluate the measure's construct validity via comparison with a quantified neurological examination performed by a neurologist. Spearman rank-order correlation between the NOS-TBI and the neurological examination was ρ = 0.76, p

While event-based prospective memory (EB-PM) tasks are a familiar part of daily life for children, currently no data exists concerning the relation between EB-PM performance and brain volumetrics after traumatic brain injury (TBI). This study investigated EB-PM in children (7 to 17 years) with moderate to severe TBI or orthopedic injuries. Participants performed an EB-PM task and concurrently underwent neuroimaging at three months postinjury. Surface reconstruction and cortical thickness analysis were performed using FreeSurfer software. Cortical thickness was significantly correlated with EB-PM (adjusting for age). Significant thinning in the left (dorsolateral and inferior prefrontal cortex, anterior and posterior cingulate, temporal lobe, fusiform, and parahippocampal gyri), and right hemispheres (dorsolateral, inferior, and medial prefrontal cortex, cingulate, and temporal lobe) correlated positively and significantly with EB-PM performance; findings are comparable to those of functional neuroimaging and lesion studies of EB-PM.

This investigation had two main objectives: 1) to assess the comparability of volumes determined by operator-controlled image quantification with automated image analysis in evaluating atrophic brain changes related to traumatic brain injury (TBI) in children, and 2) to assess the extent of diffuse structural changes throughout the brain as determined by reduced volume of a brain structure or region of interest (ROI). Operator-controlled methods used ANALYZE software for segmentation and tracing routines of pre-defined brain structures and ROIs. For automated image analyses, the open-access FreeSurfer program was used. Sixteen children with moderate-to-severe TBI were compared to individually matched, typically developing control children and the volumes of 18 brain structures and/or ROIs were compared between the two methods. Both methods detected atrophic changes but differed in the magnitude of the atrophic effect with the best agreement in subcortical structures. The volumes of all brain structures/ROIs were smaller in the TBI group regardless of method used; overall effect size differences were minimal for caudate and putamen but moderate to large for all other measures. This is reflective of the diffuse nature of TBI and its widespread impact on structural brain integrity, indicating that both FreeSurfer and operator-controlled methods can reliably assess cross-sectional volumetric changes in pediatric TBI.

Compromised memory functioning is one of the commonly reported cognitive sequelae seen following mild traumatic brain injury (mTBI). Diffusion tensor imaging (DTI) has been shown to be sufficiently sensitive at detecting early microstructural pathological alterations after mTBI. Given its location and shape, the cingulate, which is comprised of the cingulate gyrus (gray matter) and cingulum bundles (white matter), is selectively vulnerable to mTBI. In this study we examined the integrity of cingulum bundles using DTI, and the relationship between cingulum bundles and memory functioning. Twelve adolescents with mTBI and 11 demographically-matched healthy controls were studied. All participants with mTBI had a Glasgow Coma Scale score of 15, and were without intracranial findings on CT scan. Brain scans were performed on average 2.92 days post-injury, and all participants were administered the Verbal Selective Reminding Test (VSRT), an episodic verbal learning and memory task. Participants with mTBI had a significantly lower apparent diffusion coefficient (ADC) bilaterally than controls (p

Prospective memory (PM) is the formation of an intention and remembering to perform this intention at a future time or in response to specific cues. PM tasks are a ubiquitous part of daily life. Currently, there is a paucity of information regarding PM impairments in children with traumatic brain injury (TBI) and less empirical evidence regarding effective remediation strategies to mitigate these impairments. The present study employed two levels of a motivational enhancement (i.e., a monetary incentive) to determine whether event-based PM could be improved in children with severe TBI. In a crossover design, children with orthopedic injuries and mild or severe TBI were compared on two levels of incentive (dollars vs. pennies) given in response to accurate performance. All three groups performed significantly better under the high- versus low-motivation conditions. However, the severe TBI group's high-motivation condition performance remained significantly below the low-motivation condition performance of the orthopedic injury group. PM scores were positively and significantly related to age-at-test, but there were no age-at-injury or time-postinjury effects. Overall, these results suggest that event-based PM can be significantly improved in children with severe TBI.

Traumatic brain injury (TBI) in children has received increasing attention in recent years among parents, educators, clinicians and service providers, researchers and policymakers owing to the incidence and financial burden associated with injury during infancy, childhood or adolescence. Understanding the ways in which the immature brain may exhibit specific vulnerabilities to injury, how injury at a young age may interact with subsequent development, and anticipating the likely cognitive and functional consequences of child TBI is critical in detection of injury, monitoring recovery, and designing and evaluating rehabilitation strategies that may enhance recovery.

Previous studies of postconcussional disorder (PCD) have utilized a dimensional approach (i.e., number and/or severity ratings of symptoms) to study postconcussional symptoms. This study used a syndromal approach (modified form of the DSM-IV criteria) for investigating risk factors for developing PCD, 3-months postinjury. The head trauma requirement was waived in order to determine specificity of symptoms to traumatic brain injury. Preliminary results from this ongoing study indicated significant risk factors including female gender, poor social support, and elevated self-reported depressive symptoms at 1-month postinjury. Comorbidities included concurrent diagnosis of major depressive disorder and/or posttraumatic stress disorder. Hispanics were significantly less likely to develop PCD than other racial/ethnic groups. PCD resulted more frequently from motor vehicle accidents and assaults. Screening tests for PCD risk factors/comorbidities performed shortly after injury (i.e., during routine follow-up clinic appointments) coupled with appropriate referrals for psychoeducational interventions and support groups may avoid prolonged loss of productivity and poor perceived quality of life in these patients.

Objective: To study the factor structure, internal consistency, concurrent validity, and sensitivity to detect change in patient report of problems of a structured interview in relationship with accepted outcome measures. Design: Outcome status of patients with severe traumatic brain injury participating in a randomized, phase III, multicenter clinical trial was assessed at 6 mo postinjury using the Glasgow Outcome Scale, the Disability Rating Scale, and the Severe Traumatic Brain Injury Outcome Interview. Results: Exploratory factor analysis of the Severe Traumatic Brain Injury Outcome Interview produced a meaningful five-factor model: (1) activities of daily living; (2) cognitive; (3) affective; (4) behavioral; and (5) instrumental activities of daily living. The internal consistency of the factors ranged from moderate (0.61 instrumental activities of daily living) to high (0.94 activities of daily living); the interfactor correlations were moderate. The summed factor scores were significantly correlated with measures of global outcome: the Glasgow Outcome Scale (r = 0.66; P < 0.0001) and the Disability Rating Scale (r = 0.61; P < 0.0001). Patient report of cognitive problems correlated moderately with the neuropsychological tests. The summed factor scores were sensitive to change over time. Conclusions: Overall, the interview assessed the major important features of outcome pertinent to traumatic brain injury and demonstrated greater sensitivity to subtle changes over time than the unidimensional approaches, such as the Glasgow Outcome Scale and Disability Rating Scale.

Generalized whole brain volume loss has been well documented in moderate-to-severe traumatic brain injury (TBI), as has diffuse cerebral atrophy based on magnetic resonance imaging (MRI) volumetric methods where white matter may be more selectively affected than gray matter. However, specific regional differences in gray matter thickness of the cortical mantle have not been previously examined. As such, cortical thickness was assessed using FreeSurfer® software to identify regions of significant gray matter cortical thinning in MRI scans of 16 young TBI subjects (age range, 9–16 years) compared to 16 demographically matched controls. Significant cortical thinning was observed globally in the TBI group compared to the cohort of typically developing children. Reduced cortical thickness was related to reported deficits in working memory. TBI-induced cortical thickness reductions are probably due to a combination of focal and diffuse effects and have implications for the neurobehavioral sequelae of TBI.

Although mild traumatic brain injury (mTBI), or concussion, is not typically associated with abnormalities on computed tomography (CT), it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at-risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved alphaII-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI) and normal uninjured controls (age range 12-30 years), and compared them with findings from diffusion tensor magnetic resonance imaging (DTI) and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the uninjured controls. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI.

The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16–45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the Glasgow Outcome Scale (GOS), GOS-Extended (GOS-E), Disability Rating Scale (DRS), and Neurobehavioral Rating Scale-Revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p

Objectives: This study investigated white matter alterations in the corpus callosum (CC) and centrum semiovale (CSO), using diffusion tensor imaging and magnetization transfer imaging, in participants with severe traumatic brain injury (TBI) and related these changes to processing speed measures. Participants and Methods: Fourteen adult participants with severe TBI underwent neuroimaging and assessment, using the Symbol Digit Modalities Test and Trail-Making Test, Part B, at approximately 6 months postinjury. Thirteen demographically similar, neurologically intact adults were imaged for comparison. Results: The TBI group demonstrated lower fractional anisotropy (FA) for the right CSO and higher apparent diffusion coefficient (ADC) for the CSO bilaterally than the control group. Lower FA and higher ADC were noted in all CC regions. Magnetization transfer imaging revealed smaller magnetization transfer ratios (MTRs) in the right and left CSO and CC genu and splenium. Written Symbol Digit Modalities Test performance was related to right CSO FA, bilateral CSO ADC, CC FA, and right CSO MTR, whereas oral Symbol Digit Modalities Test was related to right CSO FA, ADC, and MTR. Trail-Making Test, Part B, was related to right CSO FA and MTR. Conclusions: Advanced neuroimaging modalities such as diffusion tensor imaging and magnetization transfer imaging demonstrate significant alterations in white matter, which are related to processing speed. These techniques may be useful in quantifying the extent of injury even in normal appearing white matter after TBI. Key words: centrum semiovale, corpus callosum, diffusion tensor imaging, magnetization transfer imaging, processing speed, traumatic axonal injury, traumatic brain injury

The aim was to determine if there are changes in the integrity and volume of the ventral striatum following severe traumatic brain injury (TBI) and if these changes relate to executive functioning.This study recruited 14 participants with severe TBI (mean age: 22 years) and 15 demographically-matched controls. All participants underwent magnetic resonance imaging with diffusion tensor imaging (DTI) and volumetric analysis at 6 months post-injury. Participants with TBI underwent neuropsychological testing and the relation between imaging data and cognitive performance was examined.Differences in DTI parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) were found between participants with TBI and controls. Correlations between right and left ventral striatum ADC and the executive functioning factor of the Neurobehavioural Rating Scale-Revised (NRS-R) were found. Correlations between right ventral striatum FA and the Controlled Oral Word Association Test, Trails Making Test Part B (TMT-B) time and NRS-R executive functioning factor were also found. Volumetric analysis showed a difference only in left nucleus accumbens between TBI and control groups.The integrity of the ventral striatum is affected following severe TBI. Decreases in executive functioning are related to damage to the ventral striatum and its associated structures.

This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.

Information regarding the remediation of event-based prospective memory (EB-PM) impairments following pediatric traumatic brain injury (TBI) is scarce. Addressing this, two levels of monetary incentives were used to improve EB-PM in children ages 7 to 16 years with orthopedic injuries (OI, n = 51), or moderate (n = 25) and severe (n = 39) TBI at approximately 3 months postinjury. The EB-PM task consisted of the child giving a specific verbal response to a verbal cue from the examiner while performing a battery of neuropsychological measures (ongoing task). Significant effects were found for age-at-test, motivation condition, period, and group. Within-group analyses indicated that OI and moderate TBI groups performed significantly better under the high- than under the low-incentive condition, but the severe TBI group demonstrated no significant improvement. These results indicate that EB-PM can be significantly improved at 3 months postinjury in children with moderate, but not severe, TBI.

Few studies exist investigating the brain-behavior relations of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, children with moderate-to-severe TBI performed an EB-PM test with two motivational enhancement conditions and underwent concurrent diffusion tensor imaging (DTI) at 3 months post-injury. Children with orthopedic injuries (OI; n = 37) or moderate-to-severe TBI (n = 40) were contrasted. Significant group differences were found for fractional anisotropy (FA) and apparent diffusion coefficient for orbitofrontal white matter (WM), cingulum bundles, and uncinate fasciculi. The FA of these WM structures in children with TBI significantly correlated with EB-PM performance in the high, but not the low motivation condition. Regression analyses within the TBI group indicated that the FA of the left cingulum bundle (p = 0.003), left orbitofrontal WM (p

Structural damage to the prefrontal-cingulate network has been implicated in cognitive and neurobehavioral deficits associated with traumatic brain injury (TBI). Forty-six children who had sustained moderate-to-severe TBI and 43 children with extracranial injury were imaged using diffusion tensor imaging (DTI). Decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) values were found in the cingulum bundles bilaterally in the TBI group. Cingulum ADC was related to frontal lesion volume, injury severity, and injury mechanism. Finally, cingulum DTI parameters were related to cognitive control measures. DTI detects TBI-related injury to the cingulum, which may facilitate advances in assessment and treatment.

Background: Atrophy of the corpus callosum (CC) is a documented consequence of moderate-to-severe traumatic brain injury (TBI), which has been expressed as volume loss using quantitative magnetic resonance imaging (MRI). Other advanced imaging modalities such as diffusion tensor imaging (DTI) have also detected white matter microstructural alteration following TBI in the CC. The manner and degree to which macrostructural changes such as volume and microstructural changes develop over time following pediatric TBI, and their relation to a measure of processing speed is the focus of this longitudinal investigation. As such, DTI and volumetric changes in the CC in participants with TBI and a comparison group at approximately 3 and 18 months after injury as well as their relation to processing speed were determined. Methods: Forty-eight children and adolescents aged 7–17 years who sustained either complicated mild or moderate-to-severe TBI (n = 23) or orthopedic injury (OI; n = 25) were studied. The participants underwent brain MRI and were administered the Eriksen flanker task at both time points. Results: At 3 months after injury, there were significant group differences in DTI metrics in the total CC and its subregions (genu/anterior, body/central and splenium/posterior), with the TBI group demonstrating significantly lower fractional anisotropy (FA) and a higher apparent diffusion coefficient (ADC) in comparison to the OI group. These group differences were also present at 18 months after injury in all CC subregions, with lower FA and a higher ADC in the TBI group. In terms of longitudinal changes in DTI, despite the group difference in mean FA, both groups generally demonstrated a modest increase in FA over time though this increase was only significant in the splenium/posterior subregion. Interestingly, the TBI group also generally demonstrated ADC increases from 3 to 18 months though the OI group demonstrated ADC decreases over time. Volumetrically, the group differences at 3 months were marginal for the midanterior and body/central subregions and total CC. However, by 18 months, the TBI group demonstrated a significantly decreased volume in all subregions except the splenium/posterior area relative to the OI group. Unlike the OI group, which showed a significant volume increase in subregions of the CC over time, the TBI group demonstrated a significant and consistent volume decrease. Performance on a measure of processing speed did not differentiate the groups at either visit, and only the OI group showed significantly improved performance over time. Processing speed was related to FA in the splenium/posterior and total CC only in the TBI group on both occasions, with a stronger relation at 18 months. Conclusion: In response to TBI, macrostructural volume loss in the CC occurred over time; yet, at the microstructural level, DTI demonstrated both indicators of continued maturation and development even in the damaged CC, as well as evidence of potential degenerative change. Unlike volumetrics, which likely reflects the degree of overall neuronal loss and axonal damage, DTI may reflect some aspects of postinjury maturation and adaptation in white matter following TBI. Multimodality imaging studies may be important to further understand the long-term consequences of pediatric TBI.

This study examined the use of diffusion tensor imaging in detecting white matter changes in the frontal lobes following pediatric traumatic brain injury. A total of 46 children (ages 8-16 years) with moderate to severe traumatic brain injury and 47 children with orthopedic injury underwent 1.5 Tesla magnetic resonance imaging (MRI) at 3 months postinjury. Conventional MRI studies were obtained along with diffusion tensor imaging. Diffusion tensor imaging metrics, including fractional anisotropy, apparent diffusion coefficient, and radial diffusivity, were compared between the groups. Significant group differences were identified, implicating frontal white matter alterations in the injury group that were predictive of later Glasgow Outcome Scale ratings; however, focal lesions were not related to the Glasgow Outcome Scale ratings. Injury severity was also significantly associated with diffusion tensor imaging metrics. Diffusion tensor imaging holds great promise as an index of white matter integrity in traumatic brain injury and as a potential biomarker reflective of outcome.

BACKGROUND AND PURPOSE: DTI of normal-appearing WM as evaluated by conventional MR imaging in mTBI has the potential to identify important regional abnormalities that relate to PCS. VBA was used to examine WM changes in acute mTBI. MATERIALS AND METHODS: WM was assessed between 1 and 6 days postinjury with voxel-based DTI analyses in 10 adolescent patients with mTBI and 10 age-matched control participants. In addition to the voxel-based group, analysis used to identify brain pathology across all patients with mTBI, 2 voxel-based linear regressions were performed. These analyses investigated the relation between 1) the ADC and PCS severity scores, and 2) ADC and scores on the BSI of emotional symptoms associated with mTBI. We hypothesized that frontotemporal WM changes would relate to symptoms associated with PCS and endorsed on the BSI. RESULTS: Patients with mTBI demonstrated significant reductions in ADC in several WM regions and in the left thalamus. As expected, no increases in ADC were found in any region of interest. All injury-affected regions showed decreased radial diffusivity, unchanged AD, and increased FA, which is consistent with axonal cytotoxic edema, reflective of acute injury. CONCLUSIONS: Whole-brain WM DTI measures can detect abnormalities in acute mTBI associated with PCS symptoms in adolescents.

There are very few studies investigating remediation of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, we used 2 levels of motivational enhancement (dollarsvs.pennies) to improve EB-PM in children with moderate to severe TBI in the subacute recovery phase. Children with orthopedic injuries (OI;n= 61), moderate (n= 28), or severe (n= 30) TBI were compared. Significant effects included Group × Motivation Condition (F(2, 115) = 3.73,p< .03). The OI (p< .002) and moderate TBI (p< .03) groups performed significantly better under the high-versuslow-incentive condition; however, the severe TBI group failed to demonstrate improvement (p= .38). EB-PM performance was better in adolescents compared to younger children (p< .02). These results suggest that EB-PM can be significantly improved in the subacute phase with this level ofmonetaryincentives in children with moderate, but not severe, TBI. Other strategies to improve EB-PM in these children at a similar point in recovery remain to be identified and evaluated. (JINS, 2010,16, 335–341.)

Controversy surrounding the causation of symptom complaints after mild traumatic brain injury (MTBI) is reflected by the existence of alternative diagnostic criteria for postconcussional syndrome (PCS) in the International Classification of Diseases (ICD) and postconcussional disorder (PCD) in the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV). Previous studies of persisting symptoms have employed various symptom checklists rather than uniform criteria-based diagnoses. This is the first prospective study of persisting symptom complaints using the formal diagnostic criteria for PCD and PCS and comparing these criteria sets in terms of prevalence, relationship to potential compensation, and emotional/functional status. In this prospective study, an unselected series of adults with uncomplicated MTBI (N = 139) was assessed at 6 months postinjury with a brief neuropsychological battery and measures of psychiatric symptoms/disorders, social support/community integration, health-related quality of life, and global outcome. In parallel analyses, participants with PCD/PCS were compared to those without the disorder. Potential compensation was an equally significant factor in both criteria sets. Persistent PCS criteria were met 3.1 times more frequently than persistent PCD criteria. Significant racial differences in fulfilling PCD/PCS criteria were found. No differences in emotional/functional status patterns or global outcome were found between the criteria sets except for minor dissimilarities in the social/community integration domain. The results demonstrate that despite large differences in the frequency of patients meeting the two diagnostic criteria sets, a clear basis for preferring either the PCD or PCS criteria remains to be determined.

Primary objective: The Center for Epidemiologic Studies Depression scale (CES-D) is a frequently-used self-report measure of depressive symptom severity. Brief depression screening measures can be important in the identification and prediction of depression following traumatic brain injury. The objective of this study was to investigate the validity of the CES-D in measuring depressive symptoms in patients with mild-to-moderate TBI as it has been rarely used in neurologically compromised populations.Research design: Inception cohort.Methods and procedures: The CES-D was administered to 340 participants with mild-to-moderate TBI at 3-months post-injury.Main outcomes and results: Confirmatory factor analysis of the CES-D indicated that the data are a reasonable fit similar to that of Radloff 's original 4-factor model.Conclusions: These findings suggest that the CES-D may be appropriate for use in patients with mild-to-moderate TBI.

This study evaluated the prevalence and specificity of diagnostic criteria for postconcussional syndrome (PCS) in 178 adults with mild to moderate traumatic brain injury (TBI) and 104 with extracranial trauma. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and International Classification of Diseases (ICD-10) criteria for PCS were evaluated 3 months after injury. The results showed that prevalence of PCS was higher using ICD-10 (64%) than DSM-IV criteria (11%). Specificity to TBI was limited because PCS criteria were often fulfilled by patients with extracranial trauma. The authors conclude that further refinement of the DSM-IV and ICD-10 criteria for PCS is needed before these criteria are routinely employed.

Little is known about the characteristics and outcomes of patients diagnosed with postconcussional disorder (PCD) under the provisionally proposed criteria in the DSM-IV and how they differ from patients diagnosed with postconcussional syndrome (PCS) under the International Classification of Diseases, 10th edition clinical (ICD-10) criteria. This study investigated differences in outcome based on a diagnosis of PCD (DSM-IV) versus PCS (ICD-10 clinical criteria) as to which criteria set might be preferred for clinical practice. A consecutive series of adult patients with mild (N = 319) to moderate (N = 21) traumatic brain injury was assessed at 3 months postinjury with a brief neuropsychological battery and measures of specific outcome domains. In two separate series of analyses, patients with PCD were compared with those without PCD, and those with PCS were compared with those without PCS. Although the two criteria sets resulted in markedly different incidence rates, there was no substantial pattern of differences between the DSM-IV and ICD-10 in the outcome domains of psychiatric symptoms and disorders, social and community integration, health-related quality of life, or global outcome as measured by the Glasgow Outcome Scale-Extended. In spite of significant differences between the two diagnostic criteria sets and different incidence rates for PCD/PCS, outcome in all measured domains was very similar at 3 months postinjury. There is no compelling evidence, based on these outcome domains, to suggest which of the two diagnostic criteria sets should be clinically preferred.

Context Minimizing negative consequences of major depression following traumatic brain injury is an important public health objective. Identifying high-risk patients and referring them for treatment could reduce morbidity and loss of productivity. Objective To develop a model for early screening of patients at risk for major depressive episode at 3 months after traumatic brain injury. Design Prediction model using receiver operating characteristic curve. Setting Level I trauma center in a major metropolitan area. Participants Prospective cohort of 129 adults with mild traumatic brain injury. Main Outcome Measures Center for Epidemiologic Studies Depression Scale score and current major depressive episode module of the Structured Clinical Interview for the DSM-IV . Results A prediction model including higher 1-week Center for Epidemiologic Studies Depression Scale score, older age, and computed tomographic scans of intracranial lesions yielded 93% sensitivity and 62% specificity. Conclusion This study supports the feasibility of identifying patients with mild traumatic brain injury who are at high risk for developing major depressive episode by 3 months’ postinjury, which could facilitate selective referral for potential treatment and reduction of negative outcomes.

OBJECTIVE: Lost productivity after mild traumatic brain injury (TBI) is a large component of the economic costs of brain trauma in the United States. This is the first prospective study of employment after mild TBI to include patients not admitted to a hospital. METHODS: Concurrent inception cohorts of 210 working-age adults with mild to moderate TBI and 122 patients who sustained general trauma not involving the brain were recruited at a trauma center and followed up to 6 months later. Outcomes were time from injury until first day worked and problems reported after resuming work. RESULTS: Most patients who worked after their injury remained employed 6 months later in a similar capacity as before the injury. No consistent differences were demonstrated between employment outcomes of patients with mild TBI and those with general trauma. The majority of nonhospitalized patients with mild TBI did not work for at least 1 month and did not begin working until 1 to 3 months after injury. Most patients with moderate TBI remained unemployed at 6 months postinjury. Patients with lower preinjury occupational status tended to have longer work absences. CONCLUSION: Lost productive work time after nonhospitalized TBI may cause significant economic costs because these injuries are frequent. Contrary to the theory that brain injury is more disabling to patients in cognitively demanding occupations, patients with higher job status tended to begin work earlier. A technique is needed to screen patients with mild TBI for risk of employment problems. Rehabilitation after moderate TBI may help to minimize lost productivity.

Prospective memory (PM) performance was investigated in a preliminary study of children and adolescents ages 10-19 in 3 groups: individuals with orthopedic injuries (not involving the head) requiring hospitalization (Ortho, N = 15), mild traumatic brain injury (TBI, N = 17), and severe TBI (N = 15). All participants with TBI were at least 5 years postinjury and participants in the Ortho group were at least 3 years postinjury. The PM task involved reporting words presented in blue during a category decision task in which words were presented in several different colors and participants were to determine which of two categories the word belonged. Participants were asked to make their choices as quickly as possible. After a 10- to 15-min intervening computer task in which all words were presented in black letters, a large proportion of participants with mild or severe TBI failed to indicate any blue words when they appeared. After a reminder to perform the PM task was given to all at the same point in the task, PM performance increased in the Ortho and Mild TBI groups, but remained comparably impaired in the Severe TBI group. Reaction time (RT) data indicated that mean RT was slower with increasing TBI severity. Further, there was a significant cost in RT for performing the PM task during the ongoing category decision task for all groups. The cost in terms of slowed RT increased with greater TBI severity.

To investigate the frequency and risk factors of major depressive disorder (MDD) after mild to moderate traumatic brain injury (TBI), 69 TBI and 52 general trauma (GT) patients were prospectively recruited and studied at 3-months postinjury. There was a nonsignificant difference in the proportion of MDD patients in the TBI and GT groups. Therefore, a composite MDD group (TBI and GT patients) was compared to patients who were nondepressed. Female gender was related to MDD, but no other risk factors were identified. MDD was associated with disability (Glasgow Outcome Scale, Community Integration Questionnaire) and cognitive impairment. MDD was comorbid with posttraumatic stress disorder. Implications for postacute management of mild to moderate TBI are discussed.

Using a structured outcome interview, this study addressed the validity and sensitivity to change of the Glasgow Outcome Scale (GOS) and the Extended GOS (GOSE) in a prospective study of patients who sustained mild (n = 30) to moderate (n = 13) traumatic brain injury (TBI) or general trauma (n = 44). The patients were recruited from the emergency center or inpatient units of Ben Taub General Hospital and invited to participate in follow-up examinations at 3 and 6 months. Using a series of functional outcome measures, assessment of affective status, and neuropsychological tests as criteria, the validity of the GOSE generally exceeded the GOS. Analysis of the outcome data for the patients who completed both the 3-month and 6-month assessments disclosed that the GOSE was more sensitive to change than the GOS. Comparison of the 3-month outcome data disclosed that the GOSE and GOS scores did not differ for the TBI and general trauma groups. These findings lend further support for utilization of the GOSE in clinical trials when it is based on a structured interview.

Objective: The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure designed to assess neurological functioning in traumatic brain injury (TBI) across the spectrum of recovery. We hypothesized the NOS-TBI would demonstrate predictive validity and be more sensitive to change than other well-established measures. Background Clinical trials in TBI frequently rely on a single global outcome measure. Available tools do not provide an assessment of neurological functioning, per se. We recently developed a measure of neurological functioning in TBI, the NOS-TBI. While the NOS-TBI has been validated in patients with TBI undergoing rehabilitation up to 18 months post-injury, its performance in TBI-related clinical trials and its sensitivity to change over time are unknown. Design/Methods: We analyzed data from the National Acute Brain Injury Study: Hypothermia-II (NABIS:H-II) clinical trial. Patients were 16-45 years with severe TBI, assessed at 3, 6, and 12 months post-injury. A subset was assessed at 1 month. For analysis of criterion-related validity, Spearman correlations were performed comparing the NOS-TBI to Glasgow Outcome Scale (GOS), GOS-Extended (GOS-E), Disability Rating Scale (DRS), and Marshall CT classification. Sensitivity to change was analyzed using the Wilcoxon signed-rank sum test. Results: Significant correlation was observed between the NOS-TBI and the GOS, GOS-E, DRS, and NRS-R total scores, demonstrating the concurrent validity of these tools. The GCS, Marshall CT classification, and lesion volume demonstrated overall limited ability to predict outcome at 3, 6, and 12 months post-injury. In contrast, the NOS-TBI total score at both 1 and 3-months post-injury demonstrated a significant ability to predict outcome at 3, 6, and 12 months post-injury. Trial subjects whose recovery appeared to have stabilized based on GOS and GOS-E scores, demonstrated significant changes in their level of neurologic recovery using the NOS-TBI. Conclusions: The NOS-TBI demonstrated significantly better outcome prediction and sensitivity to change compared with well-established outcome measures. Supported by: In part by grant NS 43353 from the NIH/NINDS, Guy L. Clifton, Principal Investigator. Disclosure: Dr. Moretti has nothing to disclose. Dr. McCauley has nothing to disclose. Dr. Wilde has nothing to disclose. Dr. Levin has nothing to disclose. Dr. Clifton has nothing to disclose.