CTE can begin soon after head injury, even in teens, BU study finds

The degenerative brain disease known as CTE starts faster and earlier than previously recognized, as jolts to the head trigger abnormalities even in teenagers, according to new research led by Boston University.

The scientists examined the brains of four deceased teenage athletes, and found surprising signs that CTE — chronic traumatic encephalopathy, a disabling condition blamed on blows to the head — had been set in motion as early as one day after a head injury.

They also describe experiments in mice subjected to impacts similar to what athletes and soldiers experience, which showed that CTE starts to form right away, and after even one hit.

“We see it early, we see it persist, and we see it progress. It’s very alarming,’’ said Dr. Lee E. Goldstein, the study’s lead author. “Once you get this thing started, you don’t have to have additional injuries to keep it going.’’

The report, published Thursday in the journal Brain, also provides what Goldstein called “the best evidence to date’’ supporting the theory that CTE is caused not just by concussions, but rather by any blow to the head, including mild impacts. Instead of diagnosing and responding to concussions, he said, coaches would do better to protect children from all hits to the head.

CTE causes difficulty thinking and planning, impulsive behavior, memory loss, and emotional instability.

The 37-page paper — unusual for combining research in both humans and animals — is the latest effort to understand a condition that has bedeviled the National Football League and worried parents of young athletes.

The sprawling investigation involved 46 researchers from 11 institutions in addition to BU, including the Lawrence Livermore National Laboratory in California and universities in Israel, Canada, and the United Kingdom.

Steven E. Kornguth, research professor in neurology at the Dell Medical School, University of Texas at Austin — who was not involved with BU project — called the paper “profound, a major contribution to the field’’ because it showed microscopic precursors of CTE in very young people.

The BU researchers, with their unique brain bank, have diagnosed CTE in hundreds of deceased football players, including Aaron Hernandez, the former New England Patriots tight end who killed himself last year at age 27. Hernandez had the most severe CTE case ever seen in a person younger than 30.

The teenagers in Thursday’s study were nowhere near as severely affected as Hernandez, said Goldstein, a psychiatrist and associate professor BU’s School of Medicine and College of Engineering.

But they were a decade younger when they died, and Goldstein said he was surprised to find any damage at all in these otherwise healthy young people.

“What we saw is pretty much all the fingerprints that we see in later-stage CTE — only in these cases it’s very early in the course,’’ he said.

Because CTE can be diagnosed only after death, scientists have been unable to observe its progress within the brain. But with the donation of the teenagers’ brains, the researchers were able to study what happens soon after the injury, rather than years or decades later. The teenagers were injured playing sportsone day to four months before death.

The teenagers, two 17-year-olds and two 18-year-olds, were all male athletes who suffered concussions playing a variety of sports, including snowboarding, rugby, and football. Two died of suicide and two died of rare complications from mild sports-related head injuries.

The four brains showed the blood-vessel damage and inflammation associated with CTE. Two of them also bore the hallmark of CTE — the clumps of malformed proteins know as tau. And one of those two was diagnosed with full-blown CTE. “That’s staggering,’’ Goldstein said.

The BU group had previously diagnosed CTE in two other teenaged brains. But the four brains in Thursday’s study were significant because the injuries were recent, and because researchers also had a control group. For comparison, they examined the brains of four people of the same age who did not have a recent head injury, and found no signs of CTE.

In the mouse experiments, Goldstein and colleagues engineered devices that subject rodents to head motions like those that occur in two different circumstances: sports-related impacts and wartime explosions.

These experiments enabled researchers to glimpse what happens immediately after a hit. They found that direct impacts and blasts both had the same effect in the brain. And they delineated the physiological mechanisms that lead to CTE. In particular, they saw the toxic tau proteins cluster around leaky blood vessels, showing that vascular damage plays a major role in triggering CTE.

To duplicate the effects of a blast, they sent compressed gases through a 27-foot stainless steel tube to create a shock wave equivalent to those produced by the improvised explosive devices that soldiers encountered on the roads of Iraq and Afghanistan. The blast caused a sudden head motion.

None of the mice subjected to blasts suffered concussions. They emerged from the tube looking as if nothing had happened to them, Goldstein said. But when their brains were examined, all had CTE.

Among the mice that received direct impacts, some did suffer concussions, but the severity of the concussion was unrelated to the severity of the CTE diagnosed in their brains.

These experiments, Goldstein said, “show that the concussion is not the causal determinant of CTE. It’s the hit — the rapid head motion from the hit. By focusing on the concussion we’re missing people that are hit and hurt and not getting helped.’’

Dr. Sam Gandy, professor of neurology and psychiatry at the Icahn School of Medicine at Mount Sinai in New York, said the BU report “provides important advances in our attempts to understand precisely which pathological features of brain trauma are most likely to be responsible for clinical features.’’ The study, he said in an e-mail, will guide other researchers seeking to do head-injury research on animals.

Kornguth, the University of Texas researcher, who hasstudied brain injury in soccer players, said such mouse experiments are critical to understanding how CTE develops over time, a multifaceted process that remains invisible in humans.

And he notes that, as scary as CTE may be, not everyone who suffers head trauma develops the disease.

As research continues to pinpoint the mechanisms that drive CTE, Kornguth said, researchers will be better able to determine why some people who get hit develop a horrible brain disease, and others walk away unscathed.