Significant Mitigation of Blast Overpressure Exposure During Training by Adjustment of Body Position as Demonstrated With Field Data.

INTRODUCTION: During training and deployment, service members (SMs) experience blast exposure, which may potentially negatively impact brain health in the short and long term. This article explores if blast exposure mitigation can be effectively achieved for four different weapon training scenarios that are being monitored as part of the CONQUER (COmbat and traiNing QUeryable Exposure/event Repository) program. The training scenarios considered here are a detonating cord linear (det linear) breaching charge, a water breaching charge, a shoulder-fired weapon, and a 120-mm mortar. MATERIALS AND METHODS: This article focuses on the efficacy of modification of position and standoff distance on SMs' exposure to blast overpressure. Blast overpressure exposures were measured using BlackBox Biometrics (B3) Blast Gauge System (BGS) sensors worn by SMs during normal training. The BGS involves the use of three gauges/sensors, which are worn on the head, chest, and nondominant shoulder to record surface pressures at multiple locations on the SM. For the breaching charges, we compared the level of exposure when the SMs were directly in front of the blast with a breaching blanket to a modified standoff position around a corner from the charge without a breaching blanket. For the shoulder-fired weapon training, the modified approach simply increased the standoff distance of the SM. Finally, for mortars, blast overpressure exposures were compared for different levels of their ducking height (body position) below the mortar tube at the time of firing. RESULTS: Modification of the position of SMs during training with the det linear breaching charge had the highest measured blast exposure percent reduction, at 79%. Both the water breaching charge and shoulder-fired weapon showed lowered peak overpressures on all gauges. The measured percent reduction for the 120-mm mortar was 35%. When the blast gauges did not trigger at the modified standoff distance, the percent reduction was calculated with the assumption that the new overpressures were below ∼3.4 kPa (0.5 psi) (the lowest trigger threshold for the gauges). A figure summarizes the percent reduction for each subject in the training scenarios. CONCLUSIONS: Results show that the modification of the SMs' position effectively mitigated blast exposures for all considered weapon scenarios. There was at least a 50% overpressure reduction from the initial to modified standoff distances and a 35% reduction from the change in SM body posture. Based on these observations, new locations and body positioning of SMs during training have been suggested for blast mitigation.

Dynamic monitoring of service members to quantify blast exposure levels during combat training using BlackBox Biometrics Blast Gauges: explosive breaching, shoulder-fired weapons, artillery, mortars, and 0.50 caliber guns.

CONQUER is a pilot blast monitoring program that monitors, quantifies, and reports to military units the training-related blast overpressure exposure of their service members. Overpressure exposure data are collected using the BlackBox Biometrics (B3) Blast Gauge System (BGS, generation 7) sensors mounted on the body during training. To date, the CONQUER program has recorded 450,000 gauge triggers on monitored service members. The subset of data presented here has been collected from 202 service members undergoing training with explosive breaching charges, shoulder-fired weapons, artillery, mortars, and 0.50 caliber guns. Over 12,000 waveforms were recorded by the sensors worn by these subjects. A maximum peak overpressure of 90.3 kPa (13.1 psi) was recorded during shoulder-fired weapon training. The largest overpressure impulse (a measure of blast energy) was 82.0 kPa-ms (11.9 psi-ms) and it was recorded during explosive breaching with a large wall charge. Operators of 0.50 caliber machine guns have the lowest peak overpressure impulse (as low as 0.62 kPa-ms or 0.09 psi-ms) of the blast sources considered. The data provides information on the accumulation of blast overpressure on service members over an extended period of time. The cumulative peak overpressure, peak overpressure impulse, or timing between exposures is all available in the exposure data.

Blood-Based Biomarkers of Repetitive, Subconcussive Blast Overpressure Exposure in the Training Environment: A Pilot Study.

Because of their unknown long-term effects, repeated mild traumatic brain injuries (TBIs), including the low, subconcussive ones, represent a specific challenge to healthcare systems. It has been hypothesized that they can have a cumulative effect, and they may cause molecular changes that can lead to chronic degenerative processes. Military personnel are especially vulnerable to consequences of subconcussive TBIs because their training involves repeated exposures to mild explosive blasts. In this pilot study, we collected blood samples at baseline, 6 h, 24 h, 72 h, 2 weeks, and 3 months after heavy weapons training from students and instructors who were exposed to repeated subconcussive blasts. Samples were analyzed using the reverse and forward phase protein microarray platforms. We detected elevated serum levels of glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 (UCH-L1), nicotinic alpha 7 subunit (CHRNA7), occludin (OCLN), claudin-5 (CLDN5), matrix metalloprotease 9 (MMP9), and intereukin-6 (IL-6). Importantly, serum levels of most of the tested protein biomarkers were the highest at 3 months after exposures. We also detected elevated autoantibody titers of proteins related to vascular and neuroglia-specific proteins at 3 months after exposures as compared to baseline levels. These findings suggest that repeated exposures to subconcussive blasts can induce molecular changes indicating not only neuron and glia damage, but also vascular changes and inflammation that are detectable for at least 3 months after exposures whereas elevated titers of autoantibodies against vascular and neuroglia-specific proteins can indicate an autoimmune process.

Development of a Fast-Running Algorithm to Approximate Incident Blast Parameters Using Body-Mounted Sensor Measurements.

INTRODUCTION: The Office of Naval Research sponsored the Blast Load Assessment-Sense and Test program to develop a rapid, in-field solution that could be used by team leaders, commanders, and medical personnel to make science-based stand-down decisions for service members exposed to blast overpressure. However, a critical challenge to this goal was the reliable interpretation of surface pressure data collected by body-worn blast sensors in both combat and combat training scenarios. Without an appropriate standardized metric, exposures from different blast events cannot be compared and accumulated in a service member's unique blast exposure profile. In response to these challenges, we developed the Fast Automated Signal Transformation, or FAST, algorithm to automate the processing of large amounts of pressure-time data collected by blast sensors and provide a rapid, reliable approximation of the incident blast parameters without user intervention. This paper describes the performance of the FAST algorithms developed to approximate incident blast metrics from high-explosive sources using only data from body-mounted blast sensors. METHODS AND MATERIALS: Incident pressure was chosen as the standardized output metric because it provides a physiologically relevant estimate of the exposure to blast that can be compared across multiple events. In addition, incident pressure serves as an ideal metric because it is not directionally dependent or affected by the orientation of the operator. The FAST algorithms also preprocess data and automatically flag "not real" traces that might not be from blasts events (false positives). Elimination of any "not real" blast waveforms is essential to avoid skewing the results of subsequent analyses. To evaluate the performance of the FAST algorithms, the FAST results were compared to (1) experimentally measured pressures and (2) results from high-fidelity numerical simulations for three representative real-world events. RESULTS: The FAST results were in good agreement with both experimental data and high-fidelity simulations for the three case studies analyzed. The first case study evaluated the performance of FAST with respect to body shielding. The predicted incident pressure by FAST for a surrogate facing the charge, side on to charge, and facing away from the charge was examined. The second case study evaluated the performance of FAST with respect to an irregular charge compared to both pressure probes and results from high-fidelity simulations. The third case study demonstrated the utility of FAST for detonations inside structures where reflections from nearby surfaces can significantly alter the incident pressure. Overall, FAST predictions accounted for the reflections, providing a pressure estimate typically within 20% of the anticipated value. CONCLUSIONS: This paper presents a standardized approach-the FAST algorithms-to analyze body-mounted blast sensor data. FAST algorithms account for the effects of shock interactions with the body to produce an estimate of incident blast conditions, allowing for direct comparison of individual exposure from different blast events. The continuing development of FAST algorithms will include heavy weapons, providing a singular capability to rapidly interpret body-worn sensor data, and provide standard output for analysis of an individual's unique blast exposure profile.

Initial Biphasic Fractional Anisotropy Response to Blast-Induced Mild Traumatic Brain Injury in a Mouse Model.

INTRODUCTION: Blast-induced mild traumatic brain injury was generated in a mouse model using a shock tube to investigate recovery and axonal injury from single blast. METHODS: A supersonic helium wave hit the head of anesthetized male young adult mice with a reflected pressure of 69 psi for 0.2 ms on Day 1. Subsequently, the mice were cardioperfused on Days 2, 5, or 12. The isolated brains were subjected to diffusion tensor imaging. Reduced fractional anisotropy (FA) indicated axonal injury. RESULTS: After single blast, FA showed a biphasic response in the corpus callosum with decrease on Days 2 and 12 and increase on Day 5. CONCLUSIONS: Blast-induced mild traumatic brain injury in a mouse model follows a biphasic FA response within 12 days after a single blast similar to that reported for human subjects.

Effects on Neurons and Hippocampal Slices by Single and Multiple Primary Blast Pressure Waves From Detonating Spherical Cyclotrimethylenetrinitramine (RDX) Explosive Charges.

Threshold shock-impulse levels required to induce cellular injury and cumulative effects upon single and/or multiple exposures are not well characterized. Currently, there are few in vitro experimental models with blast pressure waves generated by using real explosives in the laboratory for investigating the effects of primary blast-induced traumatic brain injury. An in vitro indoor experimental platform is developed using real military explosive charges to accurately represent battlefield blast exposure and to probe the effects of primary explosive blast on dissociated neurons and tissue slices. Preliminary results indicate that physical insults altered membrane permeability, impacted cellular viability, created axonal beadings, and led to synaptic protein loss in hippocampal slice cultures. Injuries from blast under the conditions that were examined did not appear to cause immediate or sustained damage to the cells. Three consecutive primary blasts failed to disrupt the overall cellular integrity in the hippocampal slice cultures and produced a unique type of pathology comprised with distinct reduction in synaptic proteins before cellular deterioration set in. These observed changes might add to the challenges in regard to enhancing our understanding of the complex biochemical and molecular mechanisms caused by primary blast-induced injury.

Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.

Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.

Clinical and imaging assessment of acute combat mild traumatic brain injury in Afghanistan.

OBJECTIVE: To evaluate whether diffusion tensor imaging (DTI) will noninvasively reveal white matter changes not present on conventional MRI in acute blast-related mild traumatic brain injury (mTBI) and to determine correlations with clinical measures and recovery. METHODS: Prospective observational study of 95 US military service members with mTBI enrolled within 7 days from injury in Afghanistan and 101 healthy controls. Assessments included Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Post-Traumatic Stress Disorder Checklist Military (PCLM), Beck Depression Inventory (BDI), Balance Error Scoring System (BESS), Automated Neuropsychological Assessment Metrics (ANAM), conventional MRI, and DTI. RESULTS: Significantly greater impairment was observed in participants with mTBI vs controls: RPCSQ (19.7 ± 12.9 vs 3.6 ± 7.1, p < 0.001), PCLM (32 ± 13.2 vs 20.9 ± 7.1, p < 0.001), BDI (7.4 ± 6.8 vs 2.5 ± 4.9, p < 0.001), and BESS (18.2 ± 8.4 vs 15.1 ± 8.3, p = 0.01). The largest effect size in ANAM performance decline was in simple reaction time (mTBI 74.5 ± 148.4 vs control -11 ± 46.6 milliseconds, p < 0.001). Fractional anisotropy was significantly reduced in mTBI compared with controls in the right superior longitudinal fasciculus (0.393 ± 0.022 vs 0.405 ± 0.023, p < 0.001). No abnormalities were detected with conventional MRI. Time to return to duty correlated with RPCSQ (r = 0.53, p < 0.001), ANAM simple reaction time decline (r = 0.49, p < 0.0001), PCLM (r = 0.47, p < 0.0001), and BDI (r = 0.36 p = 0.0005). CONCLUSIONS: Somatic, behavioral, and cognitive symptoms and performance deficits are substantially elevated in acute blast-related mTBI. Postconcussive symptoms and performance on measures of posttraumatic stress disorder, depression, and neurocognitive performance at initial presentation correlate with return-to-duty time. Although changes in fractional anisotropy are uncommon and subtle, DTI is more sensitive than conventional MRI in imaging white matter integrity in blast-related mTBI acutely.

Neuroanatomical predictors of awakening in acutely comatose patients.

OBJECTIVE: Lateral brain displacement has been associated with loss of consciousness and poor outcome in a range of acute neurologic disorders. We studied the association between lateral brain displacement and awakening from acute coma. METHODS: This prospective observational study included all new onset coma patients admitted to the Neurosciences Critical Care Unit (NCCU) over 12 consecutive months. Head computed tomography (CT) scans were analyzed independently at coma onset, after awakening, and at follow-up. Primary outcome measure was awakening, defined as the ability to follow commands before hospital discharge. Secondary outcome measures were discharge Glasgow Coma Scale (GCS), modified Rankin Scale, Glasgow Outcome Scale, and hospital and NCCU lengths of stay. RESULTS: Of the 85 patients studied, the mean age was 58 ± 16 years, 51% were female, and 78% had cerebrovascular etiology of coma. Fifty-one percent of patients had midline shift on head CT at coma onset and 43 (51%) patients awakened. In a multivariate analysis, independent predictors of awakening were younger age (odds ratio [OR] = 1.039, 95% confidence interval [CI] = 1.002-1.079, p = 0.040), higher GCS score at coma onset (OR = 1.455, 95% CI = 1.157-1.831, p = 0.001), nontraumatic coma etiology (OR = 4.464, 95% CI = 1.011-19.608, p = 0.048), lesser pineal shift on follow-up CT (OR = 1.316, 95% CI = 1.073-1.615, p = 0.009), and reduction or no increase in pineal shift on follow-up CT (OR = 11.628, 95% CI = 2.207-62.500, p = 0.004). INTERPRETATION: Reversal and/or limitation of lateral brain displacement are associated with acute awakening in comatose patients. These findings suggest objective parameters to guide prognosis and treatment in patients with acute onset of coma.

Functional recovery after moderate/severe traumatic brain injury: a role for cognitive reserve?

OBJECTIVE: To evaluate the hypothesis that educational attainment, a marker of cognitive reserve, is a predictor of disability-free recovery (DFR) after moderate to severe traumatic brain injury (TBI). METHODS: Retrospective study of the TBI Model Systems Database, a prospective multicenter cohort funded by the National Institute on Disability and Rehabilitation Research. Patients were included if they were admitted for rehabilitation after moderate to severe TBI, were aged 23 years or older, and had at least 1 year of follow-up. The main outcome measure was DFR 1 year postinjury, defined as a Disability Rating Scale score of zero. RESULTS: Of 769 patients included, 214 (27.8%) achieved DFR at 1 year. In total, 185 patients (24.1%) had <12 years of education, while 390 (50.7%) and 194 patients (25.2%) had 12 to 15 years and ≥16 years of education, respectively. DFR was achieved by 18 patients (9.7%) with <12 years, 120 (30.8%) with 12 to 15 years, and 76 (39.2%) with ≥16 years of education (p < 0.001). In a logistic regression model controlling for age, sex, and injury- and rehabilitation-specific factors, duration of education of ≥12 years was independently associated with DFR (odds ratio 4.74, 95% confidence interval 2.70-8.32 for 12-15 years; odds ratio 7.24, 95% confidence interval 3.96-13.23 for ≥16 years). CONCLUSION: Educational attainment was a robust independent predictor of 1-year DFR even when adjusting for other prognostic factors. A dose-response relationship was noted, with longer educational exposure associated with increased odds of DFR. This suggests that cognitive reserve could be a factor driving neural adaptation during recovery from TBI.

Management of seizure disorders in the deployed environment: a treatment guide for the non-neurologist in theater.

Patients with seizures can present a common and challenging problem for medical providers in the deployed environment. Unfortunately, there is a paucity of controlled clinical trial data that can be used to formulate evidence-based guidelines for management. In an attempt to aid the non-neurologist deployed provider in the care of patients presenting with seizures, the authors describe two cases illustrative of common presentations. Thereafter, the authors address many facets of the management questions commonly raised by such cases and offer suggestions regarding such issues as initial pharmacologic management, the need for admission and evacuation, seizure precautions, differentiation from syncope and nonepileptic seizures, addressing patient and command concerns regarding evaluation and duty restrictions, and obtaining online management assistance.

Pathophysiology of battlefield associated traumatic brain injury.

As more data is accumulated from Operation Iraqi Freedom and Operation Enduring Freedom (OEF in Afghanistan), it is becoming increasing evident that traumatic brain injury (TBI) is a serious and highly prevalent battle related injury. Although traditional TBIs such as closed head and penetrating occur in the modern battle space, the most common cause of modern battle related TBI is exposure to explosive blast. Many believe that explosive blast TBI is unique from the other forms of TBI. This is because the physical forces responsible for explosive blast TBI are different than those for closed head TBI and penetrating TBI. The unique force associated with explosive blast is the blast shock pressure wave. This shock wave occurs over a very short period, milliseconds, and has a specific profile known as the Freidlander curve. This pressure-time curve is characterized by an initial very rapid up-rise followed by a longer decay that reaches a negative inflection point before returning to baseline. This is important as the effect of this shock pressure on brain parenchyma is distinct. The diffuse interaction of the pressure wave with the brain leads to a complex cascade of events that affects neurons, axons, glia cells, and vasculature. It is only by properly studying this disease will meaningful therapies be realized.

Emergency neurological life support: intracranial hypertension and herniation.

Sustained intracranial hypertension and acute brain herniation are "brain codes," signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, evidence supports the organized implementation of a stepwise management algorithm. Because there are multiple etiologies and many treatments that can potentially reverse cerebral herniation, intracranial hypertension and herniation was chosen as an Emergency Neurological Life Support (ENLS) protocol.

Confusion and SIRPIDs regress with parenteral lorazepam.

Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) are EEG epileptiform periodic discharges (PD) induced by arousal. SIRPIDs lie along an ictal-interictal continuum with debate regarding urgency of treatment. In a patient with SIRPIDs, aphasia and confusion, i.v. lorazepam during EEG resulted in improved level of consciousness, return of verbal interaction and regression of SIRPIDs. This suggests that some forms of SIRPIDs may be associated with an ictal confusional state.

Imaging brain trauma.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) is a leading cause of death and long-term cognitive and behavioral dysfunction in children and young adults, yet effective treatments are lacking, in part because critical aspects of TBI neurobiology and natural history are not understood. We review recent advances in neuroimaging and discuss how they are helping to address these fundamental gaps. RECENT FINDINGS: Novel imaging methods provide detailed information on how TBI affects anatomical integrity (diffusion tensor imaging; voxel-based morphometry; susceptibility-weighted imaging, magnetization transfer imaging), metabolic activity (magnetic resonance spectroscopy), perfusion (positron emission tomography, perfusion computed tomography, perfusion magnetic resonance), and patterns of functional activation (functional magnetic resonance imaging). Individually and collectively, these methods can significantly enhance TBI diagnosis and outcome prediction. SUMMARY: Refinements in neuroimaging offer a window into the complex neuroanatomical and neurophysiological disturbances induced by TBI. Research is needed to understand how these alterations evolve with time and in response to therapeutic interventions.

Infant heart transplantation at Stanford: growth and neurodevelopmental outcome.

OBJECTIVE: To evaluate the growth and neurodevelopmental outcome of 18 surviving Stanford patients who received heart transplantations before their second birthday. METHODS: We compared the growth and neurodevelopmental outcome of these 18 patients with a second group of age-matched comparison patients who underwent other heart surgery requiring cardiopulmonary bypass. RESULTS: Difficulties with growth and development were more common in the transplant group as were neurologic abnormalities. Speech and language delays as well as hearing problems were also more common in the transplant group. CONCLUSION: Multicenter prospective longitudinal neurodevelopmental outcome studies of infant heart transplant patients should be conducted to provide a more efficient basis for evaluating management protocols and assessment of long-term outcomes and of the need for early intervention services.