Dr. Vassilis Koliatsos and colleagues in neuropathology recently published a study on traumatic brain injury (TBI) findings in veterans with histories of blast exposure in Iraq. Their research suggests that a unique microscopic damage signature may be associated with IEDs. Articles from JHU and the Washington Post discussing this research are found below.
JHU – Combat Veterans’ Brains Reveal Hidden Damage from IED Blasts
FAST FACTS:
- Autopsies of combat veterans who survived IEDs and later died of other causes reveal a unique pattern of injuries in parts of the brain involved in decision making, memory, reasoning and other executive functions.
- The honeycomb pattern of IED survivors’ brain injury is different than the effects of motor vehicle crashes, opiate overdoses or punch-drunk syndrome.
- The Johns Hopkins-led research team may have found the signature of “shell shock,” or blast neurotrauma, a mysterious ailment that has afflicted soldiers since World War I.
The brains of some Iraq and Afghanistan combat veterans who survived blasts from improvised explosive devices (IEDs) and died later of other causes show a distinctive honeycomb pattern of broken and swollen nerve fibers throughout critical brain regions, including those that control executive function. The pattern is different from brain damage caused by car crashes, drug overdoses or collision sports, and may be the never-before-reported signature of blast injuries suffered by soldiers as far back as World War I.
Vassilis Koliatsos, M.D., professor of pathology, neurology, and psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, recently published a study in Acta Neuropathologica Communications that found survivable blasts may cause hidden brain injuries that play a role in the psychological and social problems some veterans face after coming home.
“This is the first time the tools of modern pathology have been used to look at a 100-year-old problem: the lingering effect of blasts on the brain,” says Koliatsos, senior author of the study that used molecular probes to reveal details in the brains of veterans who died months or years after an IED blast. “We identified a pattern of tiny wounds, or lesions, that we think may be the signature of blast injury. The location and extent of these lesions may help explain why some veterans who survive IED attacks have problems putting their lives back together.”
Soldiers have struggled with bomb-induced brain damage since 1914, when German and Allied forces tried to blast one another out of entrenched positions with monthslong bombardments. Many World War I fighters survived the barrage outwardly unscarred, but with an array of cognitive and psychological difficulties known as shell shock. After World War I, mass bombardments of troops were rare, and shell shock became uncommon. Now renamed blast neurotrauma or blast injury to brain, it has re-emerged due to insurgent forces’ widespread use of IEDs in Iraq and Afghanistan.
To understand this puzzling ailment, a team of eight researchers examined the brains of five male United States military veterans who survived IED attacks but later died. The remains were donated to the Armed Forces Institute of Pathology. Three died of methadone overdoses that could have been accidental, Koliatsos says, since the drug is commonly prescribed to treat soldiers’ chronic pain. One died of a gunshot wound to the head, and one died of multiple organ failure. The researchers compared the veterans’ brains to those of 24 people who died of a range of causes, including motor vehicle crashes, opiate overdoses and heart attacks.
The researchers used a molecular marker to track a protein called APP that normally travels from one nerve cell to another via a long nerve fiber, or axon. When axons are broken by an injury, APP and other proteins accumulate at the breaks, causing swelling. In the brains of people killed in car accidents, the swellings are large and bulb-shaped. In cases of methadone overdose, these axonal swellings are small.
In the brains of four of the five veterans who survived wartime blast injuries, the axonal bulbs were medium-sized and usually arrayed in a honeycomb pattern near blood vessels. “We did not see that pattern in other types of brain injury,” says Koliatsos.
The veterans’ brains did not show signs of the neurodegenerative disease known as punch-drunk syndrome, which is caused by multiple concussions. But near the damaged axons, a second molecular probe revealed specialized cells, called microglia, that are involved in brain inflammation.
“In brains that had been exposed to blasts, we see microglial cells right next to these unusual axonal abnormalities,” Koliatsos says. Brain inflammation develops slowly, so microglia don’t normally appear in drug overdose cases. Their presence suggests the veterans who overdosed had pre-existing brain injuries.
The researchers found these distinctive lesions in a number of places in veterans’ brains, including in the frontal lobes, which control decision making, memory, reasoning and other executive functions. The lesions may be fragments of nerve fibers that broke at the time of the blast and slowly deteriorated, or they may have been weakened by the blast and broken by some later insult like a concussion or drug overdose.
“When you look at a brain, you are looking at the life history of an individual, who may have a history of blasts, fighting, substance abuse or all of those,” Koliatsos says. “If researchers could study survivors’ brains at different times after a blast — a week, a month, six months, one year, three years —that would be a significant step forward in figuring out what actually happens over time after a blast.”
A century after the first reported cases of shell shock, the struggle to overcome this invisible injury continues. Doctors treating IED survivors “often see depression, anxiety, post-traumatic stress, and substance abuse or adjustment disorders. Life is very difficult for some of these veterans,” says Koliatsos. “It’s important to understand that at least a portion of these difficulties may have a neurological foundation.”
This research was funded by the Johns Hopkins Alzheimer’s Disease Research Center (Grant RFA AG-09-001) and gifts from the Kate Sidran Family Foundation and the Sam and Sheila Geller family.
Other authors on the paper are Jiwon Ryu, Leyan Xu, Olga Pletnikova, Francesco Leri, Charles Eberhart and Juan C. Troncoso of the Johns Hopkins University School of Medicine and Iren Horkayne-Szakaly of the Veterans Administration Medical Center in Washington, D.C.
Washington Post
By Amy Ellis Nutt January 19 at 2:26 PM
Scientists have discovered what a traumatic brain injury, or TBI, suffered by a quarter-million combat veterans of Iraq and Afghanistan looks like, and it’s unlike anything they’ve seen before: a honeycomb pattern of broken connections, primarily in the frontal lobes, our emotional control center and the seat of our personality.
“In some ways it’s a 100-year-old problem,” said Vassilis Koliatsos, a Johns Hopkins pathologist and neuropsychiatrist. He was referring to the shell-shock victims of World War I, tens of thousands of soldiers who returned home physically sound but mentally wounded, haunted by their experiences and unable to fully resume their lives.
“When we started shelling each other on the Western Front of World War I, it created a lot of sick people . . . . [In a way,] we’ve gone back to the Western Front and created veterans who come back and do poorly, and we’re back to the Battle of the Somme,” he said. “They have mood changes, commit suicide, substance abuse, just like in World War I, and they really do poorly and can’t function. It’s a huge problem.”
Many of the lingering symptoms of shell shock, or what today is known as neurotrauma, are the same as they were a century ago. Only the nature of the blast has changed, from artillery to improvised explosive devices.
Koliatsos and colleagues, who published their findings in the journal Acta Neuropathologica Communications in November, examined the brains of five recent U.S. combat veterans, all of whom suffered a traumatic brain injury from an IED but died of unrelated causes back home. Their controls included the brains of people with a history of auto accidents and of those with no history of auto accidents or TBI. Koliatsos says he was prompted to do this study because he is both a pathologist and a neuropsychiatrist, and he sees many TBI cases, both in veterans and in young people with sports concussions.
“Their attention is off, mood is off, personality is off. They’re impulsive, aggressive, do poorly in school. . . . I wanted to help my patients by trying to understand what is going on in their brains.”
What he found surprised him. The “neural signature” for blast victims was distinctly different from those who suffer TBIs in car accidents.
“We saw a type of disease in the brain not seen before,” he said. “We didn’t even know if we’d see any sign of disease.”
The scientists searched for amyloid precursor protein, which is transmitted between neurons along a fiber known as an axon. TBIs cause those axons to break, and the protein coalesces at those breaks, causing swelling. In car accidents, those swellings are large and bulbous, but in the veterans’ brains they were smaller and formed a honeycomb pattern near blood vessels.
The researchers also noticed that these unusual swellings were particularly evident in the frontal lobes, the seat of executive functions.
Once World War I ended, blast injuries were not the leading cause of combat injury until the American-led invasion of Iraq in 2003. The Vietnam War, however, did produce the first diagnosed cases of post-traumatic stress disorder, which Koliatsos believes has helped to stigmatize IED survivors who return home but have enormous difficulties adjusting.
“We thought it was hysteria in World War I and then came PTSD in Vietnam,” he said, so we continued to think of these [hidden] injuries only as psychological.”
So did the poet Wilfred Owen, one of Great Britain’s most famous shell-shock victims, who spent a year in a psychiatric hospital before returning to the front, where he was killed in action a week before the armistice of 1918.
Of himself and his fellow shell-shock patients, Owen wrote: “These are men whose minds the Dead have ravished.”