The Cost of War Includes at Least 253,330 Brain Injuries and 1,700 Amputations

Here are indications of the lingering costs of 11 years of warfare. Nearly 130,000 U.S. troops have been diagnosed with post-traumatic stress disorder, and vastly more have experienced brain injuries. Over 1,700 have undergone life-changing limb amputations. Over 50,000 have been wounded in action. As of Wednesday, 6,656 U.S. troops and Defense Department civilians have died.

That updated data (.pdf) comes from a new Congressional Research Service report into military casualty statistics that can sometimes be difficult to find — and even more difficult for American society to fully appreciate. It almost certainly understates the extent of the costs of war.

Start with post-traumatic stress disorder, or PTSD. Counting since 2001 across the U.S. military services, 129,731 U.S. troops have been diagnosed with the disorder since 2001. The vast majority of those, nearly 104,000, have come from deployed personnel.

But that’s the tip of the PTSD iceberg, since not all — and perhaps not even most — PTSD cases are diagnosed. The former vice chief of staff of the Army, retired Gen. Peter Chiarelli, has proposed dropping the “D” from PTSD so as not to stigmatize those who suffer from it — and, perhaps, encourage more veterans to seek diagnosis and treatment for it. (Not all veterans advocates agree with Chiarelli.)

The congressional study also brings to light the extent of one of the signature injuries of the post-9/11 wars, Traumatic Brain Injury (TBI), often suffered by survivors of explosions from homemade insurgent bombs. From 2000 (a pre-9/11 year probably chosen for inclusion for control purposes) to the end of 2012, some 253,330 troops have experienced TBI in some form. About 77 percent of those cases are classified by the Defense Department as “mild,” meaning a “confused or disoriented state lasting less than 24 hours; loss of consciousness for up to thirty minutes; memory loss lasting less than 24 hours; and structural brain imaging that yields normal results.”

More-severe TBI is measured along those metrics, lasting longer than a day. Nearly 6,500 of of those cases are “severe or penetrating TBI,” which include the effects of open head injuries, skull fractures, or projectiles lodged in the brain.

Like with PTSD, the TBI diagnoses scratch the surface. The military’s screening for TBI is notoriously bad: One former Army chief of staff described it as “basically a coin flip.” Worse, poor military medical technology, particularly in bandwidth-deprived areas like Iraq and Afghanistan, have made it uncertain that battlefield diagnoses of TBI actually transmit back to troops’ permanent medical files.

Amputations are a feature of any prolonged war. Almost 800 Iraq veterans have undergone “major limb” amputations, such as a leg, and another 194 have experienced partial foot, finger or other so-called “minor limb” losses. For Afghanistan veterans, those numbers are 696 and 28, respectively.

The Iraq war is over for all but a handful of U.S. troops and thousands of contractors. The Afghanistan war is in the process of a troop drawdown through 2014 of unknown speed and will feature a residual troop presence of unknown size. Even if the U.S. deaths and injuries in those wars may almost be over, the aftereffects of the wars on a huge number of veterans will not end.

Study Seeks Biomarkers for Invisible War Scars

Over the past decade, about half a million veterans have received diagnoses of post-traumatic stress disorder or traumatic brain injury. Thousands have received both. Yet underlying the growing numbers lies a disconcerting question: How many of those diagnoses are definitive? And how many more have been missed?

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Oxygen Chamber Can Boost Brain Repair

Stroke, traumatic injury, and metabolic disorder are major causes of brain damage and permanent disabilities, including motor dysfunction, psychological disorders, memory loss, and more. Current therapy and rehab programs aim to help patients heal, but they often have limited success.

Now Dr. Shai Efrati of Tel Aviv University’s Sackler Faculty of Medicine has found a way to restore a significant amount of neurological function in brain tissue thought to be chronically damaged — even years after initial injury. Theorizing that high levels of oxygen could reinvigorate dormant neurons, Dr. Efrati and his fellow researchers, including Prof. Eshel Ben-Jacob of TAU’s School of Physics and Astronomy and the Sagol School of Neuroscience, recruited post-stroke patients for hyperbaric oxygen therapy (HBOT) — sessions in high pressure chambers that contain oxygen-rich air — which increases oxygen levels in the body tenfold.

Analysis of brain imaging showed significantly increased neuronal activity after a two-month period of HBOT treatment compared to control periods of non-treatment, reported Dr. Efrati in PLoS ONE. Patients experienced improvements such as a reversal of paralysis, increased sensation, and renewed use of language. These changes can make a world of difference in daily life, helping patients recover their independence and complete tasks such as bathing, cooking, climbing stairs, or reading a book.

UCLA study first to image concussion-related abnormal brain proteins in retired NFL players

Now, for the first time, UCLA researchers have used a brain-imaging tool to identify the abnormal tau proteins associated with this type of repetitive injury in five retired National Football League players who are still living. Previously, confirmation of the presence of this protein, which is also associated with Alzheimer’s disease, could only be established by an autopsy.

The preliminary findings of the small study are reported Jan. 22 in the online issue of the American Journal of Geriatric Psychiatry, the official journal of the American Association for Geriatric Psychiatry.

Previous reports and studies have shown that professional athletes in contact sports who are exposed to repetitive mild traumatic brain injuries may develop ongoing impairment such as chronic traumatic encephalopathy (CTE), a degenerative condition caused by a build up of tau protein. CTE has been associated with memory loss, confusion, progressive dementia, depression, suicidal behavior, personality changes, abnormal gait and tremors.

"Early detection of tau proteins may help us to understand what is happening sooner in the brains of these injured athletes," said lead study author Dr. Gary Small, UCLA’s Parlow–Solomon Professor on Aging and a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA. "Our findings may also guide us in developing strategies and interventions to protect those with early symptoms, rather than try to repair damage once it becomes extensive."

Small notes that larger follow-up studies are needed to determine the impact and usefulness of detecting these tau proteins early, but given the large number of people at risk for mild traumatic brain injury — not only athletes but military personnel, auto accident victims and others — a means of testing what is happening in the brain during the early stages could potentially have a considerable impact on public health.

Research Reveals Exactly How the Human Brain Adapts to Injury

For the first time, scientists at Carnegie Mellon University’s Center for Cognitive Brain Imaging (CCBI) have used a new combination of neural imaging methods to discover exactly how the human brain adapts to injury. The research, published in Cerebral Cortex, shows that when one brain area loses functionality, a “back-up” team of secondary brain areas immediately activates, replacing not only the unavailable area but also its confederates.

“The human brain has a remarkable ability to adapt to various types of trauma, such as traumatic brain injury and stroke, making it possible for people to continue functioning after key brain areas have been damaged,” said Marcel Just, the D. O. Hebb Professor of Psychology at CMU and CCBI director. “It is now clear how the brain can naturally rebound from injuries and gives us indications of how individuals can train their brains to be prepared for easier recovery. The secret is to develop alternative thinking styles, the way a switch-hitter develops alternative batting styles. Then, if a muscle in one arm is injured, they can use the batting style that relies more on the uninjured arm.”

For the study, Just, Robert Mason, senior research psychologist at CMU, and Chantel Prat, assistant professor of psychology at the University of Washington, used functional magnetic resonance imaging (fMRI) to study precisely how the brains of 16 healthy adults adapted to the temporary incapacitation of the Wernicke area, the brain’s key region involved in language comprehension. They applied Transcranial Magnetic Stimulation (TMS) in the middle of the fMRI scan to temporarily disable the Wernicke area in the participants’ brains. The participants, while in the MRI scanner, were performing a sentence comprehension task before, during and after the TMS was applied. Normally, the Wernicke area is a major player in sentence comprehension.

The research team used the fMRI scans to measure how the brain activity changed immediately following stimulation to the Wernicke area. The results showed that as the brain function in the Wernicke area decreased following the application of TMS, a “back-up” team of secondary brain areas immediately became activated and coordinated, allowing the individual’s thought process to continue with no decrease in comprehension performance.

The brain’s back-up team consisted of three types of brain regions: (1) contralateral areas —areas that are in the mirror-image location of the brain; (2) areas that are right next to the impaired area; and (3) a frontal executive area.

“The first two types of back-up areas have similar brain capabilities as the impaired Wernicke area, although they are less efficient at the capability,” Just said. “The third area plays a strategic role as in responding to the initial impairment and recruiting back-up areas with similar capabilities.”

Additionally, the research showed that impairing the Wernicke area also negatively affected the cortical partners with which the Wernicke area had been working. “Thinking is a network function,” Just explained. “When a key node of a network is impaired, the network that is closely collaborating with the impaired node is also impaired. People do their thinking with groups of brain areas, not with single brain areas.”

Mason, the study’s lead author, noted that following the TMS, the impaired area and its partners gradually returned to their previous levels of coordinated activity, while the back-up team of brain areas was still in place. “This means, that for some period of time, there were two cortical teams operating simultaneously, explaining why performance is sometimes improved by TMS,” he said.

This research builds on Just’s previous research on brain resilience after stroke and brain training to remediate dyslexia. The studies are motivated by a computational theory, called 4CAPS, that provides an account of how autonomous brain systems dynamically self-organize themselves in response to changing circumstances, which the researchers believe to be the basis of fluid intelligence.

Is There a Period of Increased Vulnerability for Repeat Traumatic Brain Injury?

Repeat traumatic brain injury affects a subgroup of the 3.5 million people who suffer head trauma each year. Even a mild repeat TBI that occurs when the brain is still recovering from an initial injury can result in poorer outcomes, especially in children and young adults. A metabolic marker that could serve as the basis for new mild TBI vulnerability guidelines is described in an article in Journal of Neurotrauma, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Journal of Neurotrauma website.

In an Editorial, “The Window of Risk in Repeated Head Injury,” accompanying this article, John T. Povlishock, PhD, Editor-in-Chief of Journal of Neurotrauma and Professor, VCU Neuroscience Center, Medical College of Virginia, Richmond, states that recent studies of TBI in animal models have shown that while repeat injury can exacerbate structural, functional, metabolic, and behavioral responses, “these responses only occur when the injury is repeated within a specific time frame post-injury.”

"Specifically, this window of risk is greatest when the interval between injuries is short, hours to days, while any risk for increased damage is obviated when the intervals between injuries are elongated over days to weeks," says Dr. Povlishock. It is not yet clear if these time periods of increased risk are age- or gender-specific or depend on the intensity of the initial injury.

A consistent finding following TBI in both humans and animal models is a decrease in glucose uptake by the brain. Mayumi Prins, Daya Alexander, Christopher Giza, and David Hovda, The UCLA Brain Injury Research Center, Los Angeles, CA, simulated single and repeat (after 1 or 5 days) mild TBI in rats and measured cerebral glucose metabolism. They tested the hypothesis that the rats’ brains would be more vulnerable to the damaging effects of repeat TBI at 1 day post-injury, when glucose metabolism was still decreased, than at 5 days, when it had returned to normal levels.

In the article, “Repeat Mild Traumatic Brain Injury: Mechanisms of Cerebral Vulnerability,” the authors propose that the duration of metabolic slowdown in the brain could serve as a valuable biomarker for how long a child might be at increased risk of repeat TBI.

Cognitive deficits from concussions still present after two months

The ability to focus and switch tasks readily amid distractions was compromised for up to two months following brain concussions suffered by high school athletes, according to a study at the University of Oregon.

Research team members, in an interview, said the discovery suggests that some athletes may need longer recovery periods than current practices dictate to lower the risk of subsequent concussions. Conventional wisdom, said lead author David Howell, a graduate student in the UO Department of Human Physiology, says that typical recovery from concussion takes seven to 10 days.

"The differences we detected may be a matter of milliseconds between a concussed person and a control subject, but as far as brain time goes that difference for a linebacker returning to competition too soon could mean the difference between another injury or successfully preparing to safely tackle an oncoming running back," Howell said.

The findings are based on cognitive exercises used five times over the two months with a pair of sensitive computer-based measuring tools — the attentional network test and the task-switching test. The study focused on the effects of concussions to the frontal region of the brain, which is responsible for working, or short-term, memory and executive function, said Li-Shan Chou, professor of human physiology and director of the UO Motion Analysis Laboratory.

The study was published online ahead of print by Medicine & Science in Sports & Exercise, the official journal of the American College of Sports Medicine.

USF and VA researchers find long-term consequences for those suffering traumatic brain injury

Researchers from the University of South Florida and colleagues at the James A. Haley Veterans’ Hospital studying the long-term consequences of traumatic brain injury (TBI) using rat models, have found that, overtime, TBI results in progressive brain deterioration characterized by elevated inflammation and suppressed cell regeneration. However, therapeutic intervention, even in the chronic stage of TBI, may still help prevent cell death.

Their study is published in the current issue of the journal PLOS ONE.

“In the U.S., an estimated 1.7 million people suffer from traumatic brain injury,” said Dr. Cesar V. Borlongan, professor and vice chair of the department of Neurosurgery and Brain Repair at the University of South Florida (USF). “In addition, TBI is responsible for 52,000 early deaths, accounts for 30 percent of all injury-related deaths, and costs approximately $52 billion yearly to treat.”

While TBI is generally considered an acute injury, secondary cell death caused by neuroinflammation and an impaired repair mechanism accompany the injury over time, said the authors. Long-term neurological deficits from TBI related to inflammation may cause more severe secondary injuries and predispose long-term survivors to age-related neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and post-traumatic dementia.

Since the U.S. military has been involved in conflicts in Iraq and Afghanistan, the incidence of traumatic brain injury suffered by troops has increased dramatically, primarily from improvised explosive devices (IEDs), according to Martin Steele, Lieutenant General, U.S. Marine Corps (retired), USF associate vice president for veterans research, and executive director of Military Partnerships. In response, the U.S. Veterans Administration has increasingly focused on TBI research and treatment.

“Progressive injury to hippocampal, cortical and thalamic regions contributes to long-term cognitive damage post-TBI,” said study co-author Dr. Paul R. Sanberg, USF senior vice president for research and innovation. “Both military and civilian patients have shown functional and cognitive deficits resulting from TBI.”

Because TBI involves both acute and chronic stages, the researchers noted that animal model research on the chronic stages of TBI could provide insight into identifying therapeutic targets for treatment in the post-acute stage.

“Using animal models of TBI, our study investigated the prolonged pathological outcomes of TBI in different parts of the brain, such as the dorsal striatum, thalamus, corpus callosum white matter, hippocampus and cerebral peduncle,” explained Borlongan, the study’s lead author. “We found that a massive neuroinflammation after TBI causes a second wave of cell death that impairs cell proliferation and impedes the brain’s regenerative capabilities.”

Upon examining the rat brains eight weeks post-trauma, the researchers found “a significant up-regulation of activated microglia cells, not only in the area of direct trauma, but also in adjacent as well as distant areas.” The location of inflammation correlated with the cell loss and impaired cell proliferation researchers observed.

Microglia cells act as the first and main form of immune defense in the central nervous system and make up 20 percent of the total glial cell population within the brain. They are distributed across large regions throughout the brain and spinal cord.

“Our study found that cell proliferation was significantly affected by a cascade of neuroinflammatory events in chronic TBI and we identified the susceptibility of newly formed cells within neurologic niches and suppression of neurological repair,” wrote the authors.

The researchers concluded that, while the progressive deterioration of the TBI-affected brain over time suppressed efforts of repair, intervention, even in the chronic stage of TBI injury, could help further deterioration.

Research offers new targets for stroke treatments

New research from the University of Georgia identifies the mechanisms responsible for regenerating blood vessels in the brain.

Looking for ways to improve outcomes for stroke patients, researchers led by the UGA College of Pharmacy assistant dean for clinical programs Susan Fagan used candesartan, a commonly prescribed medication for lowering blood pressure, to identify specific growth factors in the brain responsible for recovery after a stroke.

The results were published online Dec. 4 in the Journal of Pharmacology and Experimental Therapeutics

Although candesartan has been shown to protect the brain after a stroke, its use is generally avoided because lowering a person’s blood pressure quickly after a stroke can cause problems-like decreasing much-needed oxygen to the brain-during the critical period of time following a stroke.

"The really unique thing we found is that candesartan can increase the secretion of brain derived neurotrophic factor, and the effect is separate from the blood pressure lowering effect," said study coauthor Ahmed Alhusban, who is a doctoral candidate in the College of Pharmacy. "This will support a new area for treatments of stroke and other brain injury."

Alhusban and Fagan worked with Anna Kozak, a research scientist in the college, and Adviye Ergul, a professor and director of the physiology graduate program at Georgia Health Sciences University. They are the first to show that the positive effects of candesartan on brain blood vessel growth are caused by brain derived neurotrophic factor, or BDNF.

The research shows that when candesartan blocks the angiotensin II type 1 receptor, which lowers blood pressure, it stimulates the AT2 receptor and increases the secretion of BDNF, which encourages brain repair through the growth of new blood vessels.

"BDNF is a key player in learning and memory," said Fagan, the Albert W. Jowdy Professor. "A reduction of BDNF in the brain has been associated with Alzheimer’s disease and depression, so increasing this growth factor with a common medication is exciting."

AT2 is a brain receptor responsible for angiogenesis, or the growth of new blood vessels from pre-existing vessels. Angiogenesis is a normal and vital process in human growth and development-as well as in healing.

(Image: iStock)