T

he 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.

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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.

Concussions, or even more mild, repetitive head trauma, may lead to a degenerative brain disorder called chronic traumatic encephalopathy. Alex Hogan, Hyacinth Empinado/STAT

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.”

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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. 

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  • I played linebacker/running back for years in middle, high school, and AFL, CTE awareness is very important I have rage moments all the time sparked by nothing, depression at times and have contemplated my purpose here at times. I’ve ruined relationships, gotten into trouble with the law due to anger, and scare people at my presence at times because of past incidents. I have had many concussions a few sever and in one year as many as 5 small ones. I take anxiety/depression medication to help isolate it some but doesn’t really work all the time. If there is help out there or advice I’m open to listen for it. I believe I may patient to this, though can’t be proven! Thank you and good luck and god rest to whoever is out there going threw this, trust me you aren’t alone.

  • I have CTE from severe head trauma; auto accident head on into cement bridge embucment at age 20, 1990. I spent 5.5 weeks in a coma Glasgow score of 3. I went to college for rehabilitation but now am beginning to suffer dire symptoms within my brain. There is also a large Smokey foggy white area at the back of my head, in which my Piedmont Neuro states he does not know what this is.

  • what can be done now. I need someone to help my daughter before I lose her. She had a accident and hit her head at 13. She had problems after that but nothing like after she turned 18. seizures, anger, out of control in 2007 she had another brain injury and had to learn how to do everything again. She still had problems pretty bad. she stabbed herself in the stomach. It has been a very hard life for her. when she needs help police treat her like a criminal and family wants nothing to do with her. the court appointed me guardian in 2007, If she needed help I could call the police and they would mental health warrant her. They will no longer do that. she started using drugs (meth) because it made her not feel the hurt and pain. she becomes very aggressive and violent and has put her hands on me. after getting a chemical(clr) from her she begin to bang her head over and over on the wall. she finally asked me to call 911 because she cant handle life any more. She is now in psychiatric to keep her safe, she will be released in 2 days and it will start all over. I don’t want to lose her. she needs to see the right doctor to help her and get in a study she has pseudo seizures, a lot of banging her head. she has had more hits and bangs to her head I would say over hundreds of times over the years, I chose to take care of her and I prayed for a reason she was this way and then I saw the movie concussion, I finally got an answer but now what do I do. Please help! I cant stand to see her suffer any more
    thank you
    sandra peloquin 281-888-1966 call any time or email me gailpeloquin54@hotmail.com

  • i had a dirt bike accident with no helmet in 2008 serve concussion. two years ago i started forgetting things and was fired from my job I’m 56 now and two years ago i was able to run half marathons and now i can barely walk and my gait looks like I’m walking drunk. I’ve been seeing neurologist for over a year with no success. Is there any chance that i can get that CTE scan.

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