Concussion researchers spark hope with a new tool to diagnose brain damage

The diagnosis begins with the brain being pulled out of the skull.

Then, to determine whether someone had a condition associated with repeated concussions, the pathologist preserves the tissue in formalin, slices it thin enough for light to shine through, washes it with chemicals, and peers at it through a microscope. If some areas remain blotched with reddish brown, then the pathologist can definitively diagnose the person with chronic traumatic encephalopathy, or CTE.

The procedure has helped scientists advance their understanding of the condition but it has done little to help thousands of football players, former service members, and others who have CTE.

On Tuesday, researchers at the Icahn School of Medicine at Mount Sinai in New York reported they had developed a potential method to diagnose CTE while patients are still alive. Instead of taking out the brain to douse it and slice it, doctors inject chemicals that will flow up into the brain, and then send the patient into a brain scanner.

The stakes for this science are high. CTE is an incurable neurodegenerative disease that has been associated with everything from depression, anxiety, and aggression to progressive, Alzheimer’s-like dementia. So a diagnosis is not something to take lightly — and could be disastrous if gotten wrong.

“There are cases out there, unfortunately, of people who were convinced they had CTE and committed suicide, and then were found in autopsy not to have CTE,” said Dr. Christopher Giza, director of the UCLA Steve Tisch BrainSPORT program, who was not involved in the study.

It’s hard to say exactly how good the new diagnostic test might be because this study was conducted on just one retired NFL player, and he is still alive.

“These findings in this patient strongly suggest a diagnosis — they probably have CTE — but we can’t definitely say that without an autopsy,” said Dr. Cyrus Raji, a CTE researcher at the University of California, San Francisco, who was also not involved in the study.

CTE was first described in 1928, when a pathologist coined the term “punch-drunk” to talk about how repeated head-bashings affected boxers. The more official diagnosis of dementia pugilistica — literally, “fighters’ dementia” — was subsequently found in cases of physical abuse, epilepsy, rugby, and even “dwarf-throwing.” But it was only described in football players in 2005.

For years, the National Football League resisted science showing that repeatedly hitting your head may cause lasting brain damage.

Neurologists think that the brain damage associated with CTE is linked to a protein called tau, which is an essential part of normal, healthy neurons. “The structure is maintained by an internal skeleton of the nerve cell, and that skeleton is composed of tau,” explained Dr. Samuel Gandy, the Mount Sinai neurologist who led the new study.

But with each head trauma, scientists think, some neurons release that tau into the rest of the brain, and as it moves around, bits of this protein get tangled and stuck together.

“Once it gets a foothold, then its progression accelerates and even after you stop taking hits, it keeps accumulating and keeps getting worse,” said Eric Nauman, a biomedical engineer at Purdue University, who studies brain trauma.

Those accumulations of tau are what pathologists are looking for during autopsies. And earlier this year, a group of the top brain scientists agreed that what distinguishes CTE from other tau-related disorders like Alzheimer’s is a peculiar pattern of protein buildup deep in the folds of the brain.

Gandy looked for a way to pick up the same pattern while the patient was alive. To do that, he used a molecule — what scientists call a ligand — that is safe to inject but would also stick onto the tangles of tau.

“The shape of the tau in the normal neurons is basically like a piece of spaghetti,” he said. “With the tangles, it’s twisted and kinked, and it’s those kinks where the ligand binds.”

By linking up this molecule to a radioactive atom and then injecting it into the patient, Gandy could use a PET scanner to track its progress through the brain. Wherever these radioactive chains got stuck was a tangle of tau. And in this patient, the tangles of tau were strikingly similar to the pattern seen during autopsies that allows for an official diagnosis.

The patient is a 39-year-old retired NFL player who has complained mostly of poor moods and episodes of rage. “He certainly is not demented. He runs his own business. He’s independent and functional and has a family,” said Gandy.

While the new study may represent a step forward, it will not be accepted as diagnostic tool until a large study is done of both affected and non-affected brains, while the patients are alive and then after death. “On the basis of that test, you’re going to make a pretty important determination: ‘You’re depressed because you need to see a therapist or need medication,’ or ‘You’re depressed because you have an incurable degenerative disease.’ I would want to be very, very convinced before I declare judgment on patients one way or another,” said Giza, of UCLA.

In spite of the uncertainty, Gandy said, 100 service members have already come forward, wanting to be scanned. The first ones will visit his clinic in October.

Correction: A previous version of this article mischaracterized the relationship between CTE and symptoms such as depression, anxiety, aggression, and dementia.