Concepts and Strategies for Clinical Management of Blast-Induced Traumatic Brain Injury and Posttraumatic Stress Disorder

Non-impact, blast-induced brain injuries including traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) may result from parenchymal brain damage, which is caused by the primary blast effect in war fighters exposed to a blast overpressure wave itself, but who do not sustain penetrating and blunt-impact injuries that are caused by secondary and tertiary blast effects.¹ Non-impact, blast-induced TBI and PTSD have been considered as the signature injury of the wars in Iraq and Afghanistan.^2–5 It is estimated that more than 300,000 veterans returning from Iraq and Afghanistan have suffered a TBI or PTSD or both since 2000.^6–10 Blast-induced TBI is strongly associated with the development of PTSD. Many PTSD symptoms (such as depression, anxiety, memory and attention deficits, sleep problems, and emotional disturbances) overlap with symptoms of TBI.^11,12 Some studies indicate that approximately 80% of patients with blast-induced and non-blast TBI develop chronic PTSD.^13–15 Blast-induced TBI and PTSD seem to have similar pathogenesis.¹

 A recent study on blast shock-wave mitigation using hydraulic energy redirection and release technology suggested that a volumetric blood surge might be created when the kinetic energy of the blast shock-wave was transferred into hydraulic energy in the cardiovascular system to cause a rapid physical movement or displacement of blood.¹⁶ The volumetric blood surge has also been verified by both wound ballistics experiments in animals¹⁷ and finite-element simulation of blast loads on the torso.¹⁸ It has a strong destructive power, and can cause a non-contact, remote injury to distant organs and tissues. The volumetric blood surge can possibly be the major cause of non-impact, blast-induced brain injuries (TBI and PTSD).¹ It may move through blood vessels from the high-pressure ventral body cavity (thoracic cavity and abdominal cavity) to the low-pressure cranial cavity, thus acutely increasing cerebral perfusion pressure and causing damage to both tiny cerebral blood vessels and the blood–brain barrier (BBB) in the global brain.

Global cerebrovascular insults and the BBB damage caused by the volumetric blood surge may result in diffuse cerebral edema, hyperemia, vasospasm, and microhemorrhaging in the brain, thus further triggering secondary neuronal damage (Figure 1[A]).¹ The delayed neuronal damage includes excitotoxicity, inflammation, ionic imbalance, oxidative stress, apoptosis, diffuse axonal injury, and neurodegeneration. Secondary neuronal damage is an indirect consequence of initial injury (such as cerebrovascular insults and the BBB damage after exposure of the body to blast shock-wave) and a major contributor to the ultimate neuronal cell death and neural loss in the injured brain. Much of the damage done to the brain does not typically occur at the time of initial injury and does not result directly from the initial injury itself. A cascade of progressive neural injury and neuronal cell death is triggered by the initial injury and continues in the hours, days or weeks following the initial insult.^19,20 This delayed secondary neuronal damage has been considered to be largely responsible for serious neurological and psychiatric impairments, including memory loss, inability to concentrate, speech problems, motor and sensory deficits, and behavioral problems (Figure 1[A]).²¹ However, because blast-induced brain injuries activate the cascade of progressive neuronal damage, it is difficult to separate clinical outcomes of the initial damage to tiny cerebral blood vessels and the BBB from that of secondary neuronal damage, and to separate neuropathophysiologically-based symptoms from neuropsychiatrically-based problems.

Some disorders, such as PTSD and memory and cognitive impairments, are more likely to be a psychological consequence of secondary neuronal damage induced by physical trauma (such as blast-induced TBI, non-blast TBI, hemorrhagic stroke, ischemic stroke, nerve-agent poisoning, prolonged hypoxia, infection, and neurological illness).^22–27 These psychiatric disorders can also possibly be induced by emotional and psychological trauma. These emotional and psychological traumatic events include 1) serious accidents; war or terrorist attacks; car, train, or plane crashes; the sudden death of a loved one; captivity as a hostage; serious physical illness diagnosis, medical emergencies, etc.;^28–32 2) devastating natural disasters, such as flood, tornado, hurricane, volcanic eruption, earthquake, landslide, etc.;^33–35 3) violent attacks, such as rape, sexual abuse, physical and emotional abuse, bullying, domestic violence, indoctrination, etc.;^37–43 and 4) other psychosocial stressors, such as marital separation, divorce, family argument, dispute at work, loss of job, unemployment or underemployment, serious financial problems, poverty, retirement, socioeconomic deprivation, alcohol and drug use, etc.^44–49 The mechanisms underlying the psychiatric disorders induced by the emotional and psychological traumatic events may also involve a volumetric blood surge created by a sudden rise in cardiovascular pressure.

When exposed to an emotional and psychological traumatic event, the victim’s heart will beat faster and stronger than usual, and blood pressure will dramatically rise because of the increased cardiac output, which may create a volumetric blood surge in the cardiovascular system. The volumetric blood surge induced by a sudden increase in blood pressure will move quickly through blood vessels to organs and tissues (including the brain). Unlike the peripheral tissues (such as lung, liver, and stomach) that have good tolerance to volumetric blood surge, a sudden rush of blood to the brain will dramatically increase cerebral perfusion pressure, owing to the limited space inside blood vessels in the brain. The extremely rapid increase in cerebrovascular pressure may cause damage to both very small cerebral blood vessels and the BBB in the brain, because cerebral blood vessels and the BBB are vulnerable to sudden fluctuations in perfusion pressure. Therefore, psychiatric disorders induced by emotional and psychological trauma may potentially also be a result of secondary neuronal damage caused by volumetric blood surge in the brain (Figure 2).

Because chronic disability after brain damage is largely attributable to mental sequelae, rather than focal motor or sensory neurological deficits in humans,⁵⁰ psychiatric disorders should be the long-term prominent clinical manifestations of the victims of brain damage induced by either physical trauma or emotional and psychological trauma. These chronic psychiatric consequences are serious public health problems caused by various types of brain damage, which result in the loss of many years of productive life and incur large healthcare costs.

Blast-induced brain injuries (TBI and PTSD) are typically difficult to detect by using traditional neuroimaging techniques (i.e., computed tomography [CT], magnetic resonance imaging [MRI], and angiography), because the damage to tiny cerebral blood vessels and the BBB might be the initial injuries induced by blast shock-wave in the brain.¹ Much of neuronal damage can be seen only under a microscope. Changes in both cerebral blood vessels and cerebral blood flow and vasogenic cerebral edema should be the most common pathophysiological characteristics of cerebrovascular insults and BBB damage.^51–53 Focused clinical diagnostic techniques that are able to sensitively detect tiny cerebral blood vessels, blood flow, and edema may be helpful for diagnosis of blast-induced brain injuries.

Using single-photon emission computerized tomography (SPECT) that is able detect the level of perfusion or blood flow inside the brain, decreased levels of blood flow in the temporal lobes that contain the cortex and the limbic system (the amygdala, hippocampus, gyrus cinguli, thalamus, and kleinhirn) were detected in a soldier who was exposed to a blast in Afghanistan and was diagnosed with both mild TBI and PTSD.⁵⁴ Diffusion tensor imaging (DTI), an advanced form of MRI that produces in-vivo images of the white-matter brain tissues weighted with the local microstructural characteristics of water diffusion, is sensitive to measurement of the restricted diffusion of water in the brain. Using DTI, marked persistent abnormalities in the middle cerebellar peduncles, cingulum bundles, and the right orbitofrontal white matter were observed in 18 of the 63 U.S. military personnel with blast-induced mild TBI within 90 days after the injury. The persistent abnormalities in the brain may involve diffuse axonal injury.⁵⁵

Three medical imaging technologies that are currently used in the clinical diagnosis of diseases can be considered for use in diagnosis of blast-induced brain injuries (Figure 1[B]): 1) three-dimensional CT or MR cerebral angiography using nanosized contrast materials (dyes) can be useful for measuring damage to tiny cerebral blood vessels. Cerebral angiography is clinically helpful for detecting and diagnosing acute stroke.^56–58 It is used to image the blood vessels of the brain and the blood flowing through the blood vessels and to detect abnormalities in the brain's blood vessels, such as narrowing (vasospasm) or blockage (thrombosis); 2) SPECT may be an ideal diagnostic tool for detection of early changes in cerebral blood flow after blast-induced TBI because it can measure the blood perfusion level relative to the brain's current need.^59,60 A decrease in blood flow levels in a region of the brain may suggest an injury to that brain region; 3) diffusion MRI, such as diffusion tensor imaging (DTI) may be beneficial to detect cerebral edema since it measures diffusion rates of water molecules in the brain parenchyma.^55,61 A decreased apparent diffusion coefficient obtained by the diffusion MRI represents reduced water diffusion or mobility in the brain, which indicates that edema has formed and neuronal damage has occurred.

Brain injuries, to-date, are untreatable disorders, because no pharmacological treatment has currently been proven to prevent secondary damage processes.⁶² However, secondary damage process offers a potential therapeutic window of opportunity,⁶³ in which progressive neural injury and neuronal cell death may be prevented, and the extent of disability may be reduced during the first few hours after initial injury.⁶⁴ According to the AANS (American Association of Neurological Surgeons) recommendations, there is no medication or “miracle treatment” that can be given to prevent brain damage or promote neuronal healing after TBI. The primary goal in the acute management of the patient with TBI is to prevent any secondary damage to the brain.⁶⁵ Therefore, neuroprotective strategies intended to halt or mitigate secondary neuronal damage at early stage of injury (2–3 hours after injury) may help block or slow down the development of subsequent neurological and neuropsychiatric impairments (including PTSD, persistent memory and cognitive deficits, nonspecific mental and emotional symptoms, chronic motor deficits, Alzheimer-like dementia, and Parkinson’s disease).

Diffuse cerebral edema, hyperemia, vasospasm, and hemorrhaging are the initial pathophysiological changes in the brain after non-impact, blast-induced brain injuries.^66,67 Proper and prompt medical treatment aiming to attenuate these pathophysiological changes (Figure 1[C]) may improve clinical outcome of blast-induced brain injuries, thus leading to a significant decrease in both the direct cost for medical care and indirect cost of lost productivity resulting from blast-induced TBI and PTSD. When an effective treatment is discovered, it may be important to treat the victims exposed to blasts as soon as possible, preferably within 8 hours, and not later than 24 hours after exposure.

A volumetric blood surge may be created when the kinetic energy of a blast shock-wave is transferred into hydraulic energy in the cardiovascular system to cause a rapid physical movement or displacement of blood. It may move rapidly through blood vessels to the cranial cavity, causing damage to tiny cerebral blood vessels and the BBB and triggering a secondary cascade of neuronal damage in the brain. The volumetric blood surge may be a major contributor not only to blast-induced TBI and PTSD, but also to some psychiatric disorders induced by emotional and psychological trauma. Three-dimensional CT or MR cerebral angiography, SPECT and diffusion MRI may help detect tiny cerebrovascular insults, changes in blood flow, and cerebral edema in the brains of victims exposed to blasts. Neuroprotective strategies for victims exposed to blasts, which include but not limited to reducing cerebral edema and inflammatory reaction, attenuating hemorrhage, and preventing cerebral vasospasm, may need to be executed within 8 hours after exposure to blasts.

The authors thank Mr. Haoxing Chen for his valuable assistance in the preparation of this manuscript.

The authors report no conflicts of interest.