Dataset Information

Early Clinical Predictors of 5-Year Outcome After Concussive Blast Traumatic Brain Injury.

ABSTRACT: 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.

SUBMITTER: Mac Donald CL

PROVIDER: S-EPMC5732492 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Early Clinical Predictors of 5-Year Outcome After Concussive Blast Traumatic Brain Injury.

Mac Donald Christine L CL Barber Jason J Jordan Mary M Johnson Ann M AM Dikmen Sureyya S Fann Jesse R JR Temkin Nancy N

JAMA neurology 20170701 7

<h4>Importance</h4>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.<h4>Objectives</h4>To examine 5-year clinical outcomes leveraging existing clinical data collected at 1 year after injury in the same ...[more]

PMID: 28459953

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Project description:ImportanceAlthough previous work has examined clinical outcomes in combat-deployed veterans, questions remain regarding how symptoms evolve or resolve following mild blast traumatic brain injury (TBI) treated in theater and their association with long-term outcomes.ObjectiveTo characterize 5-year outcome in patients with nonmedically evacuated blast concussion compared with combat-deployed controls and understand what clinical measures collected acutely in theater are associated with 5-year outcome.Design, setting, and participantsA prospective, longitudinal cohort study including 45 service members with mild blast TBI within 7 days of injury (mean 4 days) and 45 combat deployed nonconcussed controls was carried out. Enrollment occurred in Afghanistan at the point of injury with evaluation of 5-year outcome in the United States. The enrollment occurred from March to September 2012 with 5-year follow up completed from April 2017 to May 2018. Data analysis was completed from June to July 2018.ExposuresConcussive blast TBI. All patients were treated in theater, and none required medical evacuation.Main outcomes and measuresClinical measures collected in theater included measures for concussion symptoms, posttraumatic stress disorder (PTSD) symptoms, depression symptoms, balance performance, combat exposure intensity, cognitive performance, and demographics. Five-year outcome evaluation included measures for global disability, neurobehavioral impairment, PTSD symptoms, depression symptoms, and 10 domains of cognitive function. Forward selection multivariate regression was used to determine predictors of 5-year outcome for global disability, neurobehavior impairment, PTSD, and cognitive function.ResultsNonmedically evacuated patients with concussive blast injury (n?=?45; 44 men, mean [SD] age, 31 [5] years) fared poorly at 5-year follow-up compared with combat-deployed controls (n?=?45; 35 men; mean [SD] age, 34 [7] years) on global disability, neurobehavioral impairment, and psychiatric symptoms, whereas cognitive changes were unremarkable. Acute predictors of 5-year outcome consistently identified TBI diagnosis with contribution from acute concussion and mental health symptoms and select measures of cognitive performance depending on the model for 5-year global disability (area under the curve following bootstrap validation [AUCBV]?=?0.79), neurobehavioral impairment (correlation following bootstrap validation [RBV]?=?0.60), PTSD severity (RBV?=?0.36), or cognitive performance (RBV?=?0.34).Conclusions and relevanceService members with concussive blast injuries fared poorly at 5-year outcome. The results support a more focused acute screening of mental health following TBI diagnosis as strong indicators of poor long-term outcome. This extends prior work examining outcome in patients with concussive blast injury to the larger nonmedically evacuated population.

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 traumatic brain injury is ubiquitous in modern military conflict with significant morbidity and mortality. Yet the mechanism by which blast overpressure waves cause specific intracranial injury in humans remains unclear. Reviewing of both the clinical experience of neurointensivists and neurosurgeons who treated service members exposed to blast have revealed a pattern of injury to cerebral blood vessels, manifested as subarachnoid hemorrhage, pseudoaneurysm, and early diffuse cerebral edema. Additionally, a seminal neuropathologic case series of victims of blast traumatic brain injury (TBI) showed unique astroglial scarring patterns at the following tissue interfaces: subpial glial plate, perivascular, periventricular, and cerebral gray-white interface. The uniting feature of both the clinical and neuropathologic findings in blast TBI is the co-location of injury to material interfaces, be it solid-fluid or solid-solid interface. This motivates the hypothesis that blast TBI is an injury at the intracranial mechanical interfaces. In order to investigate the intracranial interface dynamics, we performed a novel set of computational simulations using a model human head simplified but containing models of gyri, sulci, cerebrospinal fluid (CSF), ventricles, and vasculature with high spatial resolution of the mechanical interfaces. Simulations were performed within a hybrid Eulerian-Lagrangian simulation suite (CTH coupled via Zapotec to Sierra Mechanics). Because of the large computational meshes, simulations required high performance computing resources. Twenty simulations were performed across multiple exposure scenarios-overpressures of 150, 250, and 500 kPa with 1 ms overpressure durations-for multiple blast exposures (front blast, side blast, and wall blast) across large variations in material model parameters (brain shear properties, skull elastic moduli). All simulations predict fluid cavitation within CSF (where intracerebral vasculature reside) with cavitation occurring deep and diffusely into cerebral sulci. These cavitation events are adjacent to high interface strain rates at the subpial glial plate. Larger overpressure simulations (250 and 500kPa) demonstrated intraventricular cavitation-also associated with adjacent high periventricular strain rates. Additionally, models of embedded intraparenchymal vascular structures-with diameters as small as 0.6 mm-predicted intravascular cavitation with adjacent high perivascular strain rates. The co-location of local maxima of strain rates near several of the regions that appear to be preferentially damaged in blast TBI (vascular structures, subpial glial plate, perivascular regions, and periventricular regions) suggest that intracranial interface dynamics may be important in understanding how blast overpressures leads to intracranial injury.

Project description:ObjectiveProlonged post-concussive symptoms (PCS) affect a significant minority of patients withmild traumatic brain injury (mTBI). The aetiology is multifactorial depending on preinjury as well as peri-injury and postinjury factors. In this study, we examine outcome from an emotional reserve perspective.DesignProspective cohort study.SettingPatients were recruited from three emergency departments in major university hospitals in Stockholm, Sweden. Follow-up data were collected in an outpatient setting at one of the recruiting hospitals.Participants122 patients with a history of blunt head trauma (aged 15-65 years; admitted for mTBI within 24 hours after trauma (Glasgow Coma Scale score of 14-15, loss of consciousness <30 min and/or post-traumatic amnesia <24 hours). Exclusion criteria were other significant physical injury and other major neurological disorder, including previous significant head injury.ProcedureRecruitment in three emergency departments. Initial assessments were made within 1 week after the injury. Patients were mailed the follow-up questionnaires 1 year postinjury.Outcome measuresA psychiatric assessment was performed at 1 week post injury. The participants also completed a personality inventory, measures of psychological resilience, depression, anxiety and post-traumatic symptoms. One-year outcome was measured by the Rivermead Post Concussion Symptoms and the Rivermead Head Injury Follow-Up questionnaires.ResultsThe psychiatric assessment revealed more symptoms of anxiety, depression and post-traumatic symptoms in the acute stage for patients who later developed PCS.After 1 year, 94 participants were still in the programme (male/female 57/37) and 12% matched the extended criteria for PCS (≥3 symptoms and ≥2 disabilities). PCS patients reported more preinjury and concurrent psychiatric problems, lower level of functioning before the injury and experienced more stress. They showed higher somatic trait anxiety, embitterment, mistrust and lower level of psychological resilience than recovered participants.ConclusionIntrapersonal emotional reserve shape the emergence and persistence of PCS after mTBI.

Dataset Information

Early Clinical Predictors of 5-Year Outcome After Concussive Blast Traumatic Brain Injury.

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Early Clinical Predictors of 5-Year Outcome After Concussive Blast Traumatic Brain Injury.

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