Office of Research & Development
Office of Research & Development
VA Research Currents archive
May 7, 2015
Running back Ladainian Tomlinson is tackled during the 2006 Pro Bowl, and U.S. Army soldiers see action in Samarra, Iraq, in 2004. Research on chronic traumatic encephalopathy has involved autopsies on the donated brains of former athletes and combat Veterans. (Photos by Cpl. Michelle M. Dickson/USMC; and Sgt. 1st Class Johancharles Van Boers, USA)
A new review article by a group of VA brain-injury experts strikes a cautionary tone—but also a note of optimism—regarding a long-term brain condition known as chronic traumatic encephalopathy, or CTE.
The authors say scientific questions still abound as to what exactly CTE is—and whether it is in fact a "neuropsychiatric entity" in its own right. They suggest public anxiety over the condition has run ahead of the science, which they say is still in its infancy. And perhaps most important for Veterans and others who have incurred traumatic brain injuries, especially "single, uncomplicated, mild" ones, they emphasize that the short- and long-term outlook for most people with TBIs is brighter than what some have come to believe.
Their review appeared online April 14, 2015, in the journal Current Physical Medicine and Rehabilitation Reports.
Chronic traumatic encephalopathy. Those 11 daunting syllables may be hard to remember, spell, or pronounce for most lay people. Nonetheless, the term has made its way from the medical literature and seeped into the public consciousness, via thousands of news articles and broadcasts over the past decade or so.
"Encephalopathy" refers simply to any disease of the brain that alters function. The first two words mean the condition is ongoing, and that it stems from traumas, or injuries, to the brain.
The trend toward heavy media coverage of what would otherwise be an obscure medical topic is fueled by America's passion for sports. Much of the research on the topic has taken place at Boston University's CTE Center, whose brain bank is at the Bedford (Mass.) VA Medical Center, and has focused on ex-athletes who sustained repeated blows to the head throughout their careers. The research has expanded to include service members and Veterans whose brains were jarred in blasts, but it's still not clear how those injuries resemble or differ from sports concussions.
The media's attention has focused mainly on the sports link. Pathology findings from brain autopsies of retired football players have jumped from the pages of highly technical medical journals into the headlines. This PBS Frontline headline from September 2014 was typical: "76 of 79 Deceased NFL Players Found to Have Brain Disease."
The CTE Center's Dr. Ann McKee, with VA and Boston University, has led most of the athlete brain autopsies and is often quoted in the media. Her group defines CTE as a "progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury." The symptoms begin "insidiously" and slowly develop over decades, they believe, encompassing a wide range of symptoms, from mood changes and memory lapses to suicidal behavior and full-blown dementia. Accompanying the clinical symptoms, they say, are unique patterns of biological damage within the brain. Some of these patterns resemble—but are subtly distinct from—those seen in Alzheimer's, Parkinson's, and other progressive brain diseases.
But whether CTE is in fact a "progressive neurodegenerative disease" in its own right is the topic of debate. Not everyone agrees with McKee and other CTE proponents.
For example, a 2014 review article by Loyola University neuropsychologist Dr. Christopher Randolph challenged the lay press' treatment of CTE as an "established disease." Randolph wrote, "Until further controlled studies are completed, it appears to be premature to consider CTE a verifiable disease." Rather, he suggests, it could be a manifestation of other, known conditions.
The VA authors of the new review think this may be a reasonable theory. Like Randolph, they take issue with some of the scientific methodology and interpretations driving the CTE discussion.
But the debate isn't only about whether CTE is its own disease. The most vexing questions—the ones that have patients and their families worried—center more broadly on the long-range effects of brain injuries. How many TBIs does a soldier have to sustain to be at risk for CTE, or some other degenerative disease? Can long-term brain damage happen even after only one blast exposure? In the civilian sector, how many years of football or wrestling or boxing is too much? Do too many jarring head blows in one's teens, 20s, and 30s inevitably set the course for the slow, agonizing descent into dementia later in life? Should certain contact sports—or "collision" sports, as one football player put it—undergo dramatic rule or equipment changes to make them safer?
The questions are anything but academic.
"It's a conversation topic," says psychiatrist Dr. Hal Wortzel, senior author on the new VA review study. "I have a TBI clinic at the Denver VA. We get people coming with questions about it. 'Do I need to be worried about CTE?' It's not from the medical journals—it's from TV and all the other mass media reports."
Lead author Dr. Robert Shura, a neuropsychologist with VA's Mid-Atlantic Mental Illness Research, Education and Clinical Center, which focuses on post-deployment mental health, offers a similar observation: "We have Veterans who come in and say, 'I'm having memory problems. Do I have that football player thing?'"
Awareness is a good thing, but it can have a downside. The review authors say it's unfortunate that many patients may be pessimistic about their own prognosis, well beyond what the science has firmly established.
"There are studies that have shown that expectations can predict outcomes," says Wortzel. "If people are convinced they're going to have a terrible outcome from their single uncomplicated mild TBI, that may actually become a self-fulfilling prophecy to some extent. Negative expectations can contribute to poor outcomes that are otherwise avoidable."
To be fair, the CTE Center experts make clear that they believe the condition arises only after repetitive head traumas—not from a single injury. And they caution that "not everyone with a history of repeated brain trauma develops this disease," and it is likely other factors, such as genetics, play a role.
But Shura and company wonder whether the fine points of that message have gotten lost on much of the public.
Dr. Katherine Taber, a VA neurobiologist and coauthor on the new review, confirms that "the TBI community is very aware of CTE, but not from the scientific publications. It's from the headlines." And those news reports, even when they are factually accurate, may still serve to magnify people's fears.
Shura notes the wide benefits, both in the sports and military worlds, of greater TBI awareness. But he says "these processes of increasing research and public awareness, and improving prevention, have gone on prior to and independent of the CTE surge in the media."
That "surge," he says, has come close to creating a "craze in the populace, where a Veteran comes in who 10 years ago had a concussion, and now he's worried he's going to develop a neurodegenerative disorder and die by suicide."
Wortzel acknowledges there may be a "silver lining" to the heightened media attention on CTE, in that it has raised awareness and probably helped increase research funding. However, he says, "it's also coming with the consequence of some unnecessary poor outcomes for patients, based on the widespread anxiety that has been generated."
Shura and his group say they would like to see more use of gold-standard research techniques in CTE research. In some CTE studies, they say, the autopsied brains belonged to people who may indeed have been hit in the head too many times, but who also had issues such as depression or substance abuse, which could contribute to brain degeneration over time.
By the same token, many of the brains have been donated by families who were worried about some potential brain illness while their loved one was still alive. But this constitutes a "convenience sample" of brains. A random sample, instead, would add rigor to the research.
Shura's group advocates for stronger sampling techniques and "blinded" studies in which the scientist analyzing a brain doesn't know the history of the person who donated it.
They point to the shifting definitions of CTE in recent years, in terms of the precise forms of brain damage observed under the microscope. Some of the findings, they say, could even be typical of normal aging brains, or may not have any clinical relevance. They say reasonable experts could easily disagree on how to interpret some of the findings to date.
"You always have to ask, what's the clinical relevance?" says Shura. "There are lots of people walking around with all sorts of pathologies in the brain, but without any clinical manifestations. It's always important to consider, how are these people functioning despite having this pathology?"
Taber suggests one type of research that is sorely needed is "studies that do the imaging in the brain before that brain is cut for microscopy, so that you can have some basis for correlating what you see under the microscope and what you might see on an image. This is an essential stage before you can hope to interpret what you're seeing in a living human being."
In their review, the team critiques the existing literature on CTE, frames it in light of what is known about TBI, and underscores the need for "larger, prospective and/or longitudinal using improved methodology."
Pending more rigorous and longer-term studies, CTE remains more a "research curiosity" than a clinical reality, says Shura. "We certainly don't have the knowledge to diagnose it clinically," he says.
McKee's group, too, acknowledges that currently, the condition can be diagnosed only after someone has died, through an autopsy, and not through any type of brain scan or lab test. They say they are studying ways to do so while a person is still alive.
Be that as it may, some patients are showing up in Shura's clinic or Wortzel's, or presumably other clinics throughout VA, wanting to know whether they might have CTE—in some cases, with a referral from their doctor. Plain and simple, says Shura, CTE is not yet a diagnosis that should be rendered, at least not until there's "solid research evidence."
Controversies over CTE aside, Shura and company say they want to spread the message that long-term brain degeneration is not typical of most mild TBIs, especially those involving only one blow or blast exposure.
"Most people who have a single uncomplicated mild TBI can expect an excellent prognosis," says Wortzel. "The sky is not falling in the way that some of these media reports have suggested."
Adds Shura: "For the most part, we expect that a single concussion [or mild TBI] is going to have an excellent prognosis, in both the short and long term. Patients are typically back to baseline within days to weeks after the event."
Importantly, he adds that in cases of repeated mild TBI, not uncommon among Iraq and Afghanistan Veterans or contact athletes, "the prognosis is excellent as well, although there's some evidence to suggest that recovery is slowed and more complex."
Is there a certain subset of patients, especially among those with repeated mild TBI, who should be concerned about their long-term outlook? Shura points to a number of factors that clinicians look at:
"When you move from a single TBI to repeated TBIs, things become inherently more complex. You open up questions like, how many TBIs did they sustain? How long was the time of recovery between each one? We're still learning more about these risk factors."
All in all, Shura remains skeptical about the research suggesting a clear link between mild TBIs and CTE, or any form of later-life dementia—"it's tenuous at best," he says. VA and the Department of Defense continue to study that issue, such as in one trial focused on Vietnam Veterans with a history of TBI or PTSD.
Until scientists come up with more answers, says Shura, clinicians would do well to keep the focus on education and prevention, to help patients from injuring their head yet again.