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Functional status after blast-plus-impact complex concussive traumatic brain injury in evacuated United States military personnel.

ABSTRACT: Fundamental questions remain unanswered about the longitudinal impact of blast-plus-impact complex traumatic brain injuries (TBI) from wars in Iraq and Afghanistan. This prospective, observational study investigated measures of clinical outcome in US military personnel evacuated to Landstuhl Regional Medical Center (LRMC) in Germany after such "blast-plus" concussive TBIs. Glasgow Outcome Scale-Extended assessments completed 6-12 months after injury indicated a moderate overall disability in 41/47 (87%) blast-plus TBI subjects and a substantial but smaller number (11/18, 61%, p=0.018) of demographically similar US military controls without TBI evacuated for other medical reasons. Cognitive function assessed with a neuropsychological test battery was not different between blast-plus TBI subjects and controls; performance of both groups was generally in the normal range. No subject was found to have focal neurological deficits. However, 29/47 (57%) of blast-plus subjects with TBI met all criteria for post-traumatic stress disorder (PTSD) versus 5/18 (28%) of controls (p=0.014). PTSD was highly associated with overall disability; 31/34 patients with PTSD versus 19/31 patients who did not meet full PTSD criteria had moderate to severe disability (p=0.0003). Symptoms of depression were also more severe in the TBI group (p=0.05), and highly correlated with PTSD severity (r=0.86, p<0.0001). Thus, in summary, high rates of PTSD and depression but not cognitive impairment or focal neurological deficits were observed 6-12 months after concussive blast-plus-impact complex TBI. Overall disability was substantially greater than typically reported in civilian non-blast concussive ("mild") patients with TBI, even with polytrauma. The relationship between these clinical outcomes and specific blast-related aspects of brain injuries versus other combat-related factors remains unknown.

SUBMITTER: MacDonald CL

PROVIDER: S-EPMC4012688 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Functional status after blast-plus-impact complex concussive traumatic brain injury in evacuated United States military personnel.

MacDonald Christine L CL Johnson Ann M AM Nelson Elliot C EC Werner Nicole J NJ Fang Raymond R Flaherty Stephen F SF Brody David L DL

Journal of neurotrauma 20140210 10

Fundamental questions remain unanswered about the longitudinal impact of blast-plus-impact complex traumatic brain injuries (TBI) from wars in Iraq and Afghanistan. This prospective, observational study investigated measures of clinical outcome in US military personnel evacuated to Landstuhl Regional Medical Center (LRMC) in Germany after such "blast-plus" concussive TBIs. Glasgow Outcome Scale-Extended assessments completed 6-12 months after injury indicated a moderate overall disability in 41/ ...[more]

PMID: 24367929

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Project description:Blast-related traumatic brain injury (TBI) has been one of the "signature injuries" of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive 'mild' blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20min of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90days post-injury and 65 subjects underwent a follow-up scan 6 to 12months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI served as a validation dataset. The second independent cohort underwent an initial scan within 30days post-injury. 75% of the scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in the participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in the participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p<0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p=0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p=0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p=0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required.

Project description:Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered.We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury.Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectable intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P=0.002), and in the right orbitofrontal white matter (P=0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries.DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.).

Project description:Importance:The long-term clinical effects of wartime traumatic brain injuries (TBIs), most of which are mild, remain incompletely described. Current medical disability cost estimates from world conflicts continually surpass projections. Additional information regarding long-term functional trajectory is needed to reduce this extensive public health burden. Objectives:To examine 5-year clinical outcomes leveraging existing clinical data collected at 1 year after injury in the same patients and to identify early risk factors for long-term disability. Design, Setting, and Participants:This prospective, longitudinal study enrolled active-duty US military after concussive blast injury (n?=?50) in the acute to subacute stage and combat-deployed control individuals (n?=?44) in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. One- and 5-year clinical evaluations were completed in the United States. All concussive blast injuries met the Department of Defense definition of mild, uncomplicated TBI. In-person clinical evaluations included standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden that were essentially identical to the evaluations completed at 1-year follow-up. Data were analyzed from October 1 through November 30, 2016. Main Outcomes and Measures:Changes in the in-person standardized evaluations for neurobehavior, neuropsychological performance, and mental health burden from the 1- to 5-year follow-up. Predictive modeling was used to identify early risk factors for long-term disability. Results:Among the 94 participants (87 men [93%] and 7 women [7%]; mean [SD] age, 34 [8] years), global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the 5-year evaluation. Logistic regression on the dichotomized Extended Glasgow Outcome Scale (GOS-E) at 5 years as a measure of overall disability identified brain injury diagnosis, preinjury intelligence, motor strength, verbal fluency, and neurobehavioral symptom severity at 1 year as risk factors for a poor outcome at 5 years, with an area under the curve of 0.92 indicating excellent prediction strength. Thirty-six of 50 patients with concussive blast TBI (72%) had a decline in the GOS-E from the 1- to 5-year evaluations, in contrast with only 5 of 44 combat-deployed controls (11%). Worsening of symptoms in concussive blast TBI was also observed on measures of posttraumatic stress disorder and depression. Service members with concussive blast TBI experienced evolution, not resolution, of symptoms from the 1- to 5-year outcomes. Conclusions and Relevance:Considerable decline was observed in military service members with concussive blast TBI when comparing 1- and 5-year clinical outcomes. These results advocate for new treatment strategies to combat the long-term and extremely costly effect of these wartime injuries.

Project description:Mortality and CKD risk have not been described in military casualties with post-traumatic AKI requiring RRT suffered in the Iraq and Afghanistan wars.This is a retrospective case series of post-traumatic AKI requiring RRT in 51 military health care beneficiaries (October 7, 2001-December 1, 2013), evacuated to the National Capital Region, documenting in-hospital mortality and subsequent CKD. Participants were identified using electronic medical and procedure records.Age at injury was 26±6 years; of the participants, 50 were men, 16% were black, 67% were white, and 88% of injuries were caused by blast or projectiles. Presumed AKI cause was acute tubular necrosis in 98%, with rhabdomyolysis in 72%. Sixty-day all-cause mortality was 22% (95% confidence interval [95% CI], 12% to 35%), significantly less than the 50% predicted historical mortality (P<0.001). The VA/NIH Acute Renal Failure Trial Network AKI integer score predicted 60-day mortality risk was 33% (range, 6%-96%) (n=49). Of these, nine died (mortality, 18%; 95% CI, 10% to 32%), with predicted risks significantly miscalibrated (P<0.001). The area under the receiver operator characteristic curve for the AKI integer score was 0.72 (95% CI, 0.56 to 0.88), not significantly different than the AKI integer score model cohort (P=0.27). Of the 40 survivors, one had ESRD caused by cortical necrosis. Of the remaining 39, median time to last follow-up serum creatinine was 1158 days (range, 99-3316 days), serum creatinine was 0.85±0.24 mg/dl, and eGFR was 118±23 ml/min per 1.73 m(2). No eGFR was <60 ml/min per 1.73 m(2), but it may be overestimated because of large/medium amputations in 54%. Twenty-five percent (n=36) had proteinuria; one was diagnosed with CKD stage 2.Despite severe injuries, participants had better in-hospital survival than predicted historically and by AKI integer score. No patient who recovered renal function had an eGFR<60 ml/min per 1.73 m(2) at last follow-up, but 23% had proteinuria, suggesting CKD burden.

Project description:In the military, explosive blasts are a significant cause of mild traumatic brain injuries (mTBIs). The symptoms associated with blast mTBIs causes significant economic burdens and a diminished quality of life for many service members. At present, the distinction of the injury mechanism (blast versus non-blast) may not influence TBI diagnosis. However, using noninvasive imaging, this study reveals significant distinctions between the blast and non-blast TBI mechanisms. A cortical whole-brain thickness analysis was performed using structural high-resolution T1-weighted MRI to identify the effects of blasts in persistent mTBI (pmTBI) subjects. A total of 41 blast pmTBI subjects were individually age- and gender-matched to 41 non-blast pmTBI subjects. Using FreeSurfer, cortical thickness was quantified for the blast group, relative to the non-blast group. Cortical thinning was identified within the blast mTBI group, in two clusters bilaterally. In the left hemisphere, the cluster overlapped with the lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, superior frontal, rostral anterior cingulate and frontal pole cortices (p < 0.02, two-tailed, size = 1680 mm2). In the right hemisphere, the cluster overlapped with the lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, pars orbitalis, pars triangularis and insula cortices (p < 0.002, two-tailed, cluster size = 2453 mm2). Self-report assessments suggest significant differences in the Post-Traumatic Stress Disorder Checklist-Civilian Version (p < 0.05, Bonferroni-corrected) and the Neurobehavioral Symptom Inventory (p < 0.01, uncorrected) between the blast and non-blast mTBI groups. These results suggest that blast may cause a unique injury pattern related to a reduction in cortical thickness within specific brain regions which could affect symptoms. No other study has found cortical thickness difference between blast and non-blast mTBI groups and further replication is needed to confirm these initial observations.

Project description:OBJECTIVE: Approximately one-quarter of military personnel who deployed to combat stations sustained one or more blast-related, closed-head injuries. Blast injuries result from the detonation of an explosive device. The mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI), and place military personnel at high risk for chronic symptoms of post-concussive disorder (PCD), post-traumatic stress disorder (PTSD), and depression are not elucidated. METHODS: To investigate the mechanisms of persistent blast-related symptoms, we examined expression profiles of transcripts across the genome to determine the role of gene activity in chronic symptoms following blast-TBI. Active duty military personnel with (1) a medical record of a blast-TBI that occurred during deployment (n = 19) were compared to control participants without TBI (n = 17). Controls were matched to cases on demographic factors including age, gender, and race, and also in diagnoses of sleep disturbance, and symptoms of PTSD and depression. Due to the high number of PCD symptoms in the TBI+ group, we did not match on this variable. Using expression profiles of transcripts in microarray platform in peripheral samples of whole blood, significantly differentially expressed gene lists were generated. Statistical threshold is based on criteria of 1.5 magnitude fold-change (up or down) and p-values with multiple test correction (false discovery rate <0.05). RESULTS: There were 34 transcripts in 29 genes that were differentially regulated in blast-TBI participants compared to controls. Up-regulated genes included epithelial cell transforming sequence and zinc finger proteins, which are necessary for astrocyte differentiation following injury. Tensin-1, which has been implicated in neuronal recovery in pre-clinical TBI models, was down-regulated in blast-TBI participants. Protein ubiquitination genes, such as epidermal growth factor receptor, were also down-regulated and identified as the central regulators in the gene network determined by interaction pathway analysis. CONCLUSION: In this study, we identified a gene-expression pathway of delayed neuronal recovery in military personnel a blast-TBI and chronic symptoms. Future work is needed to determine if therapeutic agents that regulate these pathways may provide novel treatments for chronic blast-TBI-related symptoms.

Project description:Background:Diarrhea remains a major public health problem for both civilian and military populations. This study describes the prevalence of acute diarrheal illness etiological agents, their antibiotic resistance distribution patterns, the resulting impact upon military force health protection, and potential prevention and treatment strategies. Results:Forty-eight acute diarrhea stool samples from US military personnel deployed to Thailand from 2013-2017 were screened for enteric pathogens using ELISA, the TaqMan Array Card (TAC), and conventional microbiological methods. These isolates were also evaluated using antimicrobial susceptibility testing (AST) against ampicillin (AMP), azithromycin (AZM), ceftriaxone (CRO), ciprofloxacin (CIP), nalidixic acid (NA), erythromycin (ERY), and trimethoprim-sulfamethoxazole (SXT) using commercial methodology. Susceptibility results were interpreted following the CLSI and NARM guidelines. Questionnaire data obtained from 47/48 volunteers indicated that 89.4% (42/47) reported eating local food and the most common clinical symptoms were nausea and abdominal pain (51%; 24/47). Multiple bacterial species were identified from the 48 stool samples with diarrhea etiological agents being detected in 79% (38/48) of the samples distributed as follows: 43.8% (21/48) Campylobacter jejuni and Campylobacter species, 42% (20/48) diarrheagenic Escherichia coli, and 23% (11/48) Salmonella. Co-infections were detected in 46% (22/48) of the samples. All C. jejuni isolates were resistant to CIP and NA. One C. jejuni isolate exhibited resistance to both AZM and ERY. Lastly, an association between exposure to poultry and subsequent detection of the diarrhea-associated pathogens E. coli and P. shigelloides was significant (p?<?0.05). Conclusion:The detection of Campylobacter isolates with CIP, AZM and ERY resistance has critical force health protection and public health implications, as these data should guide effective Campylobacteriosis treatment options for deployed military members and travelers to Southeast Asia. Additional research efforts are recommended to determine the association of pathogen co-infections and/or other contributing factors towards diarrheal disease in military and traveler populations. Ongoing surveillance and AST profiling of potential disease-causing bacteria is required for effective disease prevention efforts and treatment strategies.

Dataset Information

Functional status after blast-plus-impact complex concussive traumatic brain injury in evacuated United States military personnel.

Publications

Functional status after blast-plus-impact complex concussive traumatic brain injury in evacuated United States military personnel.

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