Diffusion tensor imaging findings and neuropsychological performance in adults with TBI across the spectrum of severity in the chronic-phase.

PRIMARY OBJECTIVE: To examine associations between neuroimaging indicators of cerebral tract integrity and neurocognitive functioning in traumatic brain injury (TBI). RESEARCH DESIGN: Between-Groups design with two TBI groups and controls. METHOD AND PROCEDURES: Forty-four participants with TBI and 27 matched controls completed diffusion tensor imaging and neuropsychological measures of processing speed, attention, memory, and executive function. Multivariate analyses were conducted to examine group differences in white matter integrity (fractional anisotropy) for 11 regions of interest and cognitive performance among adult males with chronic phase, mild, moderate, or severe TBI. Correlational analyses investigated associations between white matter integrity, brain injury severity, and cognitive status. MAIN OUTCOMES AND RESULTS: Participants with moderate or severe TBI exhibited reduced white matter integrity in 8 of 11 ROIs and worse performance on most cognitive measures, relative to control participants. Persons with mild TBI did not differ from controls on white matter integrity values and differed on one measure of processing speed. Significant correlations were found between injury severity ratings and 10 ROIs, most notably between ROIs and measures of processing speed or memory. CONCLUSIONS: These findings provide nuanced information regarding white matter connectivity as it relates to neurocognitive abilities across the TBI severity spectrum.

Safety and feasibility of minocycline in treatment of acute traumatic brain injury.

BACKGROUND: Minocycline is a pleomorphic neuroprotective agent well studied in animal models of traumatic brain injury (TBI) and brain ischemia. METHODS: To test the hypothesis that administration of minocycline in moderate to severe TBI (Glasgow Coma Score 3-12). Fifteen patients were enrolled in a two-dose escalation study of minocycline to evaluate the safety of twice the recommended antibiotic dosage; tier 1 n = 7 at a loading dose of 800 mg followed by 200 mg twice a day (BID) for 7 days; tier 2 n = 8 at a loading dose of 800 mg followed by 400 mg BID for 7 days. RESULTS: The mean initial GCS was 5.6 for Tier 1 patients and 5.4 for Tier 2. The Disability Rating Scale (DRS) had a trend towards improvement with the higher dose 12.5 SD ± 7.7 (N = 5) for Tier 1 at 4 weeks and 8.5 SD ± 9.9 at week 12 (N = 5), whereas for Tier 2 it was 9.7 ± 6.9 (N = 6) for week 4 and 6.0 SD ± 6.1 (N = 7) for week 12 (p = .251 repeated measures ANOVA). Liver function tests increased but resolved after the first week and there were no infections. CONCLUSIONS: Minocycline was safe for moderate to severe TBI at a dose twice that as recommended for treatment of infection. The higher dose did trend towards an improved outcome.

Impact of psychiatric symptomatology on neuropsychological assessment performance in persons with TBI: A comparison of OEF/OIF veteran and civilian samples.

OBJECTIVE: To assess whether increased incidence of post-traumatic stress disorder and depressive symptomatology in veterans with combat-related traumatic brain injury might help account for neurocognitive impairment relative to civilians with traumatic brain injury. PARTICIPANTS: Neuropsychological assessment data of 53 Operation Enduring Freedom/Operation Iraqi Freedom veterans and 48 civilians with positive history of traumatic brain injury were analyzed to assess differences with respect to cognitive performance. DESIGN: Retrospective analysis of data including neurocognitive test performance and self-reported symptoms of post-traumatic stress disorder and depression. RESULTS: Results showed worse neurocognitive performance (i.e. RBANS Total Index score) in the veteran sample relative to the civilian sample [F(1,99) = 3.92, p = .05, ƞ2 = .04], particularly on tasks measuring attentional capabilities [F(1,99) = 9.18, p = .003, ƞ2 = .09]. Additional analyses found that after controlling for post-traumatic stress disorder symptomatology, differences were no longer significant. Broad correlations between measures also showcased attenuated relationships after controlling for both post-traumatic stress disorder and depressive symptomatology using partial correlations Conclusion: Findings suggest that the presence of post-traumatic stress disorder and depressive symptomatology negatively impacts cognitive performance across neuropsychological assessment above and beyond deficits related to traumatic brain injury.

The Clinical Utility of the Conners' Continuous Performance Test-II in Traumatic Brain Injury.

OBJECTIVE: The Conners' Continuous Performance Test Second Edition (CPT-II) is a measure commonly used in persons with suspected attentional deficits. Our study examined the utility of the CPT-II as a measure of attention in adults with traumatic brain injury (TBI) of varying severity. METHOD: As part of a larger investigation, several measures of cognitive functioning, including the CPT-II, were administered to 30 healthy control participants (HCP), 30 mild TBI participants (M-TBI), and 30 moderate to severe TBI participants (MS-TBI). Multivariate and correlational analyses compared group performances and examined convergent and divergent relationships between the CPT-II and various measures, including other tests of attention and neuropsychological function. RESULTS: Group differences were found for four of six CPT-II variables, with the MS-TBI group exhibiting greater impairment, relative to M-TBI and HCP. In addition, the CPT-II commission and detectability variables were found to correlate significantly with TBI severity. The CPT-II variables also demonstrated correlations of varying magnitude between commonly used neuropsychological measures. CONCLUSIONS: These findings support the utility of the CPT-II for assessing attentional abilities in persons with TBI of varying severity, particularly those with moderate to severe status. Moreover, the current study also demonstrates relationships that are consistent with convergent validity but inconsistent findings with regard to divergent validity. As a result, the CPT-II measures components of attention that is unique to other commonly used neuropsychological measures of attentive functioning. Further research examining CPT-II performance in TBI populations is recommended.

Evaluation of Cortical Thickness after Traumatic Brain Injury in Military Veterans.

Military service members frequently sustain traumatic brain injuries (TBI) while on active duty, a majority of which are related to explosive blasts and are mild in severity. Studies evaluating the cortical gray matter in persons with injuries of this nature remain scarce. The purpose of this study was to assess cortical thickness in a sample of military veterans with chronic blast-related TBI. Thirty-eight veterans with mild TBI and 17 veterans with moderate TBI were compared with 58 demographically matched healthy civilians. All veterans with TBI sustained injuries related to a blast and were between 5 and 120 months post-injury (M = 62.08). Measures of post-traumatic stress disorder (PTSD) and depression were administered, along with a battery of neuropsychological tests to assess cognition. The Freesurfer software package was used to calculate cortical thickness of the participants. Results demonstrated significant clusters of cortical thinning in the right hemispheric insula and inferior portions of the temporal and frontal lobe in both mild and moderate TBI participants. The TBI sample from this study demonstrated a high incidence of comorbid PTSD and depression symptoms, which is consistent with the previous literature. Cortical thickness values correlated with measures of PTSD, depression, and post-concussive symptoms. This study provides evidence of cortical thinning in the context of chronic blast-related mild and moderate TBI in military veterans who have comorbid psychiatric symptoms. Our findings provide important insight into the natural progression of long-term cortical change in this population and may have implications for future clinical evaluation and treatment.

Cognitive and self-reported psychological outcomes of blast-induced mild traumatic brain injury in veterans: a preliminary study.

The increased use of explosives in combat has resulted in a large number of returning veterans suffering from blast-related mild traumatic brain injury (mTBI) and self-reported complications. It remains unclear whether this increase in self-reported difficulties is unique to the blast mechanism or stressful preinjury environment and whether cognitive-functioning deficits correspond with these difficulties in the postacute phase. This study examined the relationship between cognitive performance and self-reported psychological and somatic symptoms of blast-related mTBI compared with civilian mTBI, independent of comorbid posttraumatic stress disorder (PTSD) symptoms. Twelve veterans with blast-related mTBI were compared to 18 individuals with civilian mTBI on cognitive tests and self-report questionnaires. Univariate analyses failed to reveal differences on any individual cognitive test. Further, veterans reported more psychological and somatic complaints. These self-reported difficulties were not significantly correlated with neuropsychological performance. Overall, preliminary results suggest that in the postacute phase, subjective complaints related to blast-related mTBI do not covary with objective cognitive performance. Additionally, cognitive outcomes from blast-related mTBI were similar to those of civilian forms of mTBI. Future studies should identify the cognitive and self-reported sequelae of blast-related mTBI independent of comorbid PTSD in a larger sample of veterans.

A comparison of insufficient effort rates, neuropsychological functioning, and neuropsychiatric symptom reporting in military veterans and civilians with chronic traumatic brain injury.

Neuropsychological evaluation of persons with chronic traumatic brain injury (TBI) symptoms is complicated by multiple factors. The authors explored the impact of mechanism of injury, effort testing performance, and neuropsychiatric status in a sample of military veterans (V-TBI) and civilians (C-TBI) with chronic TBI. V-TBI (n = 74), C-TBI (n = 67), and healthy civilian control (C-HC) participants (n = 66), completed a battery of neuropsychological, effort, and self-report neuropsychiatric measures. Results indicated that C-HC and C-TBI participants exhibited comparably low failure rates on effort tests (6% and 3%, respectively). V-TBI participants exhibited significantly higher rates of failure (18%). Subgroups (n = 20) of effort-screened participants matched for demographics and disability level were compared regarding neuropsychological performance and neuropsychiatric self-report. Both TBI groups exhibited limited neuropsychological impairment, relative to the C-HC participants. The V-TBI group exhibited pronounced neuropsychiatric symptomology compared with the other participant groups. The implications of these findings are discussed for evaluation in the context of disability and litigation.