Doctors study link between combat and brain disease

Dr. Jo Manette Nousak examines McGuire during a hearing exam at Landstuhl Regional Medical Center last month. McGuire was in a roadside bomb blast during a convoy last June while deployed to Iraq. Some service members who sustain mild traumatic brain injury due to a blast or other head-impact injury report experiencing hearing loss which must be evaluated by an audiologist. A leading researcher in brain injuries is studying whether troops who suffer mild TBI will develop degenerative brain disease later in life.


By SETH ROBBINS | STARS AND STRIPES Published: January 23, 2010

The California neuropathologist who discovered damage in the brains of former professional football players has found similar damage in the brain of a deceased Vietnam veteran — a potentially groundbreaking finding that suggests combat troops who suffer head trauma might be susceptible to a degenerative brain disease.

Dr. Bennet Omalu, an expert in forensic neuropathology and the chief medical examiner of San Joaquin County, Calif., said the 61-year-old Army veteran had a history of drug and alcohol abuse, as well as psychotic behavior, much of which had been attributed to a diagnosis of post-traumatic stress disorder.

But the autopsy showed something else: an abnormal buildup of harmful proteins in the vet’s brain, the same proteins linked to repetitive concussions in boxers, and now football players.

“This is a sentinel case,” Omalu said. “The brain findings in this deceased Army veteran are similar to the brain findings in the retired contact-sport athletes. Now, we need to look at more brains.”

The case suggests that some veterans diagnosed with post-traumatic stress disorder, a psychological disorder, may actually have brain disease caused by concussions, he said.

Links between concussions, brain function and PTSD are being widely and carefully explored by military researchers such as Dr. James Kelly, a leading concussion expert who is overseeing long-term studies on troops.

Not all researchers agree that concussion-related brain disease is a main or important culprit. But all say that more brains and more time are needed to crack open the mystery of how a head injury can affect a combat veteran’s mind.

Doctors hope such findings will lead to earlier diagnoses of problems inside the brain, and eventually to the development of drugs that can slow the deterioration process.

The tau factor

Omalu autopsied the veteran soldier, whose name cannot be released due to patient privacy laws, after he died suddenly of a heart attack at his home in 2007.

It was a routine examination, but Omalu became suspicious after the medical history revealed a litany of psychological disorders, such as PTSD and manic depression. Many of the former football players Omalu autopsied had similar histories, so he kept the veteran’s brain for further testing.

Shavings of the brain were bathed in chemicals that react to abnormal proteins, marking them as brown and red splotches. Omalu recognized what he saw. “I saw tau,” he said, “the same protein I saw in the contact-sport athletes.”

Though he cannot prove the veteran suffered head trauma from blasts in combat, Omalu said it’s possible, because the former soldier had never shown any signs of psychotic behavior or drug use prior to going to Vietnam, according to family members and medical records.

It has long been known that boxers who suffer too many blows to the head can suffer long-term brain damage — a condition dubbed dementia pugilistica. Now, there is growing scientific evidence that persistent head trauma, like repeated concussions in football, can contribute to the build up of tau.

Tau “impairs normal functioning and eventually kills the brain cells,” Omalu said. It causes a degenerative neurological condition known as chronic traumatic encephalopathy, or CTE. The condition can mimic Alzheimer’s disease: its symptoms include dementia, memory loss and depression. But the condition differs from Alzheimer’s in that only tau is detected in the brain cells, rather than in combination with beta-amyloids, other proteins thought to play a part in Alzheimer’s.

Also with CTE, tau is only found in certain regions of the brain rather than spread throughout it, as in Alzheimer’s. Tau cannot be detected by MRIs or CT scans, and as of now can only be tested for during an autopsy.

In 2002, Omalu diagnosed the first known case of CTE in a former professional football player after studying the brain of former Pittsburgh Steelers center Mike Webster. Omalu, then a medical examiner in Pittsburgh, published his findings in the medical journal Neurosurgery.

Doctors employed by the NFL challenged his work, but family members of former football players asked Omalu to test for CTE, and he diagnosed several more cases in deceased players, including two more Steelers, guard Terry Long and offensive lineman Justin Strzelczyk, and Philadelphia Eagles safety Andre Waters.

Now, excessive tau has been found in the brains of 11 deceased NFL players, two professional wrestlers and a hockey player.

“Every time your brain receives a jolt that would move it back and forth at a high rate of speed in your head, irreversible brain damage may occur,” Omalu said.

The brain does not simply heal itself, Omalu explained, and even concussions in which a person does not lose consciousness or recovers quickly may result in brain damage later. Whether head trauma is solely responsible for triggering the buildup of harmful proteins within the brain cells is not known, and doctors are researching if steroid and drug use or genetics augment the development of CTE.

“There is no exclusive cause,” Omalu said, “But (head) trauma is a significant contributing factor.”

New research front

Since 2000, about 160,000 servicemembers have been diagnosed with mild traumatic brain injuries, or concussions, caused by powerful explosions.

Whether troops will suffer the same long-term damage as head-crunching football players or punch-drunk boxers is of paramount importance to the military, whose researchers in recent years have also wondered about links between concussions on the battlefield and PTSD. The military is currently funding some 50 studies looking into TBI, PTSD and other brain disorders.

Military researchers are developing databases and studies that will follow troops with mild traumatic brain injuries to see if they exhibit neurological problems as they age, said Kelly, the neurologist, who is working with the military as part of the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injuries.

“It’s a complex picture,” Kelly said. “We don’t have a handle on the long-term effects of what happens to these people.”

Kelly said he had never heard of CTE being diagnosed in a combat veteran, and would not comment on Omalu’s findings because Omalu had not yet published them.

Kelly, who is directing a research group and clinic dedicated to the study of mild traumatic brain injuries in troops, said his team would be in an ideal position to examine combat vets for CTE because they will be able to match extensive clinical records with autopsy findings.

“We are concerned that CTE is a condition that we need to watch for,” he said, “We will be looking into these possibilities with diligence. That is what the center is intended to do.”

Kelly said doctors are already looking at the neuropathology behind PTSD, citing a recent study that shows hyperactivity in some regions of the brain.

There was also a study, which Kelly worked on, showing that troops with PTSD who have never had concussions can show the same cognitive and emotional problems as those with mild traumatic brain injuries.

“Our job is to look at the problems that they have now and help them,” Kelly said of combat veterans with mild traumatic brain injuries. “And we don’t want to guess at what is going to happen to them down the road.”

Blasts near the brain

When a bomb explodes, violent waves of air called overpressures can rupture hollow organs, such as the intestines and lungs, and bruise solid organs. The force also affects the brain’s structure and functioning, said Dr. Shawna Scully, an Army major and chief of neurology at Landstuhl Regional Medical Center in Germany.

“There is going to be a question now,” Scully said. “Are there links between repeated exposure to concussion in the combat environment that could be culminating in a risk to our servicemembers in the future?”

Omalu said combat veterans who suffer head trauma from their proximity to blasts will likely receive the same type of jolts — quick acceleration and deceleration forces of the brain slamming into the skull — as football players or boxers do. Neurologist Dr. Ann McKee, who has examined the brains of several former athletes as the director of neuropathology services for the New England Veterans Administration, thought likewise.

“Some of the injury is probably quite similar,” she said, “but I would have to examine individuals who have had blast injuries.”

All the doctors interviewed agreed that there is scant information about how blasts affect the brain, since it’s only recently that combat vets have been able to survive such blasts in large numbers, thanks to improvements in body armor and better first aid on the battlefield.

Also, blasts damage many parts of the body, and troops injured in them often arrive at hospitals with gashes from shrapnel, profuse blood loss, severed limbs, damaged lungs, burns and often more than one of the above. All these injuries can alter the brain’s ability to function, Scully said.

Scully, however, was cautious about linking harmful proteins in the brain to PTSD and possible long-term brain damage in servicemembers with mild traumatic brain injuries.

“When you are talking about chronic neurodegenerative disorders, you are going to see accumulations like this,” she said of the buildup of tau proteins, “and you are going to see other concerns as well.”

Treatment hopes

McKee, who is also the director of Boston University’s brain bank and co-director of an institute dedicated to the study of CTE, said she has suspicions of a link between concussions and PTSD.

“In my personal opinion,” she said, “there may be a significant subset of patients with PTSD that actually have brain disease.”

A person’s mood, Omalu explained, is maintained by a delicate balance of neurotransmitters, such as serotonin and dopamine.

“Tau kills the brain cells that synthesize these neurotransmitters and you lose your ability to maintain your mood,” he said. “No matter how much Prozac you give them, you are not going to stop that destruction.”

When the athletes diagnosed with CTE reached their 40s, some even earlier, they began to suffer depression, memory loss, severe mood swings and dementia. The football players were also prone to suicide. Long drank anti-freeze, Waters shot himself in his home, and Strzelczyk slammed his car into an oncoming tractor-trailer.

Omalu and his colleague — neurosurgeon Dr. Julian Bailes — are trying to find ways to test for tau in a living person by tapping the spinal fluid or examining the blood. They are also working with pharmaceutical companies to possibly develop drugs that would prevent the buildup of these harmful proteins after head trauma.

“I think we can develop some sort of intervention treatment that will mitigate the advancement of traumatic brain injuries,” Omalu said.

He also hopes servicemembers, especially those who have been diagnosed with PTSD or who have suffered concussions on the battlefield, will agree to let their brains be studied after their deaths.

“I’ve met military personnel diagnosed with schizophrenia who before they went into the Army to serve were fine,” Omalu said. “We’re talking about drug treatment to prevent these diseases. We’re just beginning to understand the science of brain trauma, and we can only get better at it.”

Army Sgt. 1st Class David McGuire waits for the hearing-test portion of his exam to begin at Landstuhl Regional Medical Center in Germany last month. McGuire is from Headquarters and Headquarters Company, 170th Infantry Brigade Combat Team (Heavy) at Baumholder, Germany.