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Ayn al Asad Air Base in western Iraq after an Iranian missile attack on Jan. 8. The number of service members experiencing symptoms associated with brain injuries has since topped 100. Photo Credit…Sergey Ponomarev for The New York Times

 

Brain Injuries Are Common in Battle.
The Military Has No Reliable Test for Them.

Traumatic brain injury is a signature wound of the wars in Iraq and Afghanistan. But the military still has no objective way of diagnosing it in the field.

By Dave Philipps and Thomas Gibbons-Neff for nytimes.com, February 15, 2020

 
U.S. troops at Ayn al Asad Air Base in western Iraq hunkered down in concrete bunkers last month as Iranian missile strikes rocked the runway, destroying guard towers, hangars and buildings used to fly drones.
When the dust settled, President Trump and military officials declared that no one had been killed or wounded during the attack. That would soon change.

A week after the blast, Defense Department officials acknowledged that 11 service members had tested positive for traumatic brain injury, or TBI, and had been evacuated to Kuwait and Germany for more screening. Two weeks after the blast, the Pentagon announced that 34 service members were experiencing symptoms associated with brain injuries, and that an additional seven had been evacuated. By the end of January the number of potential brain injuries had climbed to 50. This week it grew to 109.

The Defense Department says the numbers are driven by an abundance of caution. It noted that 70 percent of those who tested positive for a TBI had since returned to duty. But experts in the brain injury field said the delayed response and confusion were primarily caused by a problem both the military and civilian world have struggled with for more than a decade: There is no reliable way to determine who has a brain injury and who does not.

Top military leaders have for years called traumatic brain injury one of the signature wounds of the wars in Iraq and Afghanistan; at the height of the Iraq war in 2008, they started pouring hundreds of millions of dollars into research on detection and treatment. But the military still has no objective tool for diagnosing brain injury in the field. Instead, medical personnel continue to use a paper questionnaire that relies on answers from patients — patients who may have reasons to hide or exaggerate symptoms, or who may be too shaken to answer questions accurately.

The military has long struggled with how to address so-called invisible war wounds, including traumatic brain injury and post-traumatic stress disorder. Despite big investments in research that have yielded advances in the laboratory, troops on the ground are still being assessed with the same blunt tools that have been in use for generations.

The problem is not unique to the military. Civilian doctors struggle to accurately assess brain injuries, and still rely on a process that grades the severity of a head injury in part by asking patients a series of questions: Did they black out? Do they have memory problems or dizziness? Are they experiencing irritability or difficulty concentrating?

“It’s bad, bad, bad. You would never diagnose a heart attack or even a broken bone that way,” said Dr. Jeff Bazarian a professor of emergency medicine at the University of Rochester Medical Center. “And yet we are doing it for an injury to the most complex organ in the body. Here’s how crazy it gets: You are relying on people to report what happened. But the part of the brain most often affected by a traumatic brain injury is memory. We get a lot of false positives and false negatives.”

Without a good diagnosis, he said, doctors often don’t know whether a patient has a minor concussion that might require a day’s rest, or a life-threatening brain bleed, let alone potential long-term effects like depression and personality disorder.

At Ayn al Asad, personnel used the same paper questionnaires that field medics used in remote infantry platoons in 2010. Aaron Hepps, who was a Navy corpsman in a Marines infantry company in Afghanistan at that time, said it did not work well then for lesser cases, and the injuries of many Marines may have been missed. During and after his deployment, he counted brain injuries in roughly 350 Marines — about a third of the battalion.

After the January missile attack, Maj. Robert Hales, one of the top medical providers at the air base, said that the initial tests were “a good start,” but that it took numerous screenings and awareness among the troops to realize that repeated exposure to blast waves during the hourlong missile strikes had affected dozens.

Traumatic brain injuries are among the most common injuries of the wars in Iraq and Afghanistan, in part because armor to protect from bullet and shrapnel wounds has gotten better, but they offer little protection from the shock waves of explosions. More than 350,000 brain injuries have been reported in the military since 2001.

The concrete bunkers scattered around bases like Ain al Assad protect from flying shrapnel and debris, but the small quarters can amplify shock waves and lead to head trauma.

The blasts on Jan. 8, one military official said, were hundreds of times more powerful than the rocket and mortar attacks regularly aimed at U.S. bases, causing at least one concrete wall to collapse atop a bunker with people inside.

Capt. Geoff Hansen was in a Humvee at Ayn al Asad when the first missile hit, blowing open a door. Then a second missile hit.

“That kind of blew me back in,” he said. “Blew debris in my face so I went and sat back down a little confused.”

A tangle of factors make diagnosing head injuries in the military particularly tricky, experts say. Some troops try to hide symptoms so they can stay on duty, or avoid being perceived as weak. Others may play up or even invent symptoms that can make them eligible for the Purple Heart medal or valuable veteran’s education and medical benefits.

And sometimes commanders suspect troops with legitimate injuries of malingering and force them to return to duty. Pentagon officials said privately this week that some of the injuries from the Jan. 8 incident had probably been exaggerated. Mr. Trump seemed to dismiss the injuries at a news conference in Davos, Switzerland, last month. “I heard they had headaches,” he said. “I don’t consider them very serious injuries relative to other injuries I have seen.”

In the early years of the war in Iraq, troops with concussions were often given little medical treatment and were not eligible for the Purple Heart. It was only after clearly wounded troops began complaining of poor treatment that Congress got involved and military leaders began pressing for better diagnostic technology.

Damir Janigro, who directed cerebrovascular research at the Cleveland Clinic for more than a decade, said relying on the questionnaire makes accurate diagnosing extremely difficult.

“You have the problem of the cheaters, and the problem of the ones who don’t want to be counted,” he said. “But you have a third problem, which is that even if people are being completely honest, you still don’t know who is really injured.”

In civilian emergency rooms, the uncertainty leads doctors to approve unnecessary CT scans, which can detect bleeding and other damage to the brain, but are expensive and expose patients to radiation. At the same time doctors miss other patients who may need care. In a war zone, bad calls can endanger lives, as troops are either needlessly airlifted or kept in the field when they cannot think straight.

Mr. Janigro is at work on a possible solution. He and his team have developed a test that uses proteins found in a patient’s saliva to diagnose brain injuries. Other groups are developing a blood test.

Both tests work on a similar principle. When the brain is hit by a blast wave or a blow to the head, brain cells are stretched and damaged. Those cells then dispose of the damaged parts, which are composed of distinctive proteins. Abnormal levels of those proteins are dumped into the bloodstream, where for several hours they can be detected in both the blood and saliva. Both tests, and another test being developed that measures electrical activity in the brain, were funded in part by federal grants, and have shown strong results in clinical trials. Researchers say they could be approved for use by the F.D.A. in the next few years.

The saliva test being developed by Mr. Janigro will look a bit like an over-the-counter pregnancy test. Patients with suspected brain injuries would put sensors in their mouths, and within minutes get a message that says that their brain protein levels are normal, or that they should see a doctor.

But the new generation of testing tools may fall short, said Dr. Gerald Grant, a professor of neurosurgery at Stanford University and a former Air Force lieutenant colonel who frequently treated head injuries while deployed to Iraq in 2005.

Even sophisticated devices had trouble picking up injuries from roadside bombs, he said.

“You’d get kids coming in with blast injuries,” he said, “and they clearly had symptoms, but the CT scans would be negative.”

He was part of an earlier effort to find a definitive blood test, which he said in an interview was “the holy grail.” But progress was slow. The grail was never found, he said, and the tests currently being developed are helpful for triaging cases, but too vague to be revolutionary.

“Battlefield injuries are complex,” he said. “We still haven’t found the magic biomarker.”

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What’s the difference between all the different head scans (X-Ray, CT, MRI, MRA, PET scan)? And what do they show in the head?

Michael S. Tehrani, M.D.Follow Founder & CEO at MedWell Medical

 
Ever wonder what’s the difference between all the different head scans (xray, CT, MRI, MRA, PET scan) and what they show in the head. Well wonder no more. The Dr. T easy to understand version…

X-Ray: shows bone/skull only. Does not show the brain. Best used to detect if there are bone fractures.

CT: a quick test. Shows brain but detail not great. Shows if any larger bleed, stroke, lesions, or masses.

MRI: a long test. Shows brain and detail is great. Shows smaller bleeds, stroke, lesions, or masses.

MRA:
shows the flow of blood in the vasculature system of the brain. If there is vessel narrowing or blockage this test would show it.

PET scan: shows how active different parts of the brain is. An active brain uses sugar as energy and pet scan detects how much sugar is being used by lighting up and turning different colors. The more sugar being used the more that area will light up and be different in colors. Cancer cells use the most sugar so cancer cells light up the most. PET scan is used to see if there are cancer cells. (Cancer cells replicate at a very fast and uncontrolled rate hence use a lot of sugar to allow that replication hence why they light up so much).

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High school injury reports analyzed by InvestigateWest and Pamplin Media show that girls are twice as likely to get concussions as boys in Oregon. Girls in the 13U age group, pictured above, are the youngest allowed to use headers.
 

The Concussion Gap: Head injuries in girls soccer are an ‘Unpublicized Epidemic’

Lee van der Voo, InvestigateWest, photos by David Ball / Pamplin Media Group

 
When it comes to concussion in sports, all eyes are on football, or so it seems. But it’s not just football that causes a high number of head injuries among young athletes.

Another culprit? Girls soccer.

National research has found girls are more likely to suffer a concussion than boys in any sport. In 2017, researchers at Northwestern University generated national headlines when they found concussion rates among young female soccer players were nearly as high as concussion rates for boys playing football — and roughly triple the rate of concussions in boys soccer.

In Oregon, injury reports from public high schools analyzed by InvestigateWest and Pamplin Media Group mirrored that trend, showing soccer concussions were second to those from football between 2015 and 2017. What’s more, at the schools that included the gender of injured athletes, there were nearly twice as many reports of possible concussions for girls playing soccer than boys in the sport.

The rate of concussions in girls soccer worries local experts like Jim Chesnutt, a doctor in sports medicine at Oregon Health & Science University, who says those injuries are not widely recognized, even as concussion rates rise for girls playing soccer.

“In a lot of ways, it’s a growing epidemic for young girls that I think has gone unpublicized,” said Chesnutt, co-director of the Oregon Concussion Awareness and Management Program and a member of the Governor’s Task Force on Traumatic Brain Injury.

More exposure, more injury

It’s understandable that much of the youth concussion conversation centers on football, given the physical contact that is visibly — and audibly — evident on every play, as well as the large rosters and the lengthy lists of players who are injured.

But if you compare girls soccer with football, and only look at the high school participation and injury data, “you’re missing a gigantic part of the picture,” according to Michael Koester, a doctor of sports medicine at the Slocum Center in Eugene. He directs its sports concussion program and serves as the chair of the Sports Medicine Advisory Committee for the National Federation of State High School Associations.

Koester notes that high school boys play eight to 10 football games per season, and typically play other sports in the off-season.

Girls, however, play 15 to 20 soccer games in a high school season, but when that season ends, they may play another 80-plus games throughout the winter, spring and summer with club teams, said Koester, who, like Chesnutt, is a medical adviser to the Oregon Schools Activities Association.

“If we’re looking at injury risk by athletic exposure,” which is one practice or game, a standard in evaluating risk, Koester said, female soccer players probably are playing five if not 10 times more practices and games than football players.

And Koester doesn’t see the trend ending.

“The thought used to be that this was all revolving around, ‘Wow! They want to get their kid a scholarship,’ ” he said. “Now it’s kind of gotten to the point where there’s so much single-sport participation that we see kids that are specializing in sport early, just so they’ll be able to make their high school team.”

Single-sport athletes are more prone to injury in any sport. According to a study by scientists at the University of Wisconsin, high school athletes who specialized in just one sport at an early age were twice as likely to suffer injuries to their lower extremities.

“We see a lot of overuse injury among girls playing soccer,” Koester said. “We see a lot of ACL injury among girls playing soccer. It’s a well-known problem.”

Aggressive play

Another factor is the evolution of sports.

Angella Bond is an athletic trainer for Tuality Sports Medicine and works on the sidelines with athletes at Hillsboro schools. Anecdotally, she said, all athletes push to be bigger, faster and stronger. Soccer is no exception, nor are girls.

As athletes develop, they take bigger hits at higher speeds, and competitive games build on their momentum. As competition grows in girls soccer, the sport is trending to be more aggressive, she said.

“Unfortunately, I think that happens with girls sports,” she said. “Arms fly a little bit more.”

Chesnutt agreed. “I think over the years, soccer has become more physical,” he said. “And I think the physical contact and the aggressive nature of that physical contact is more associated with concussions.”

According to the American Academy of Pediatrics, soccer — unlike football, ice hockey and lacrosse — is not a “collision sport.” But it is a “contact sport” because athletes “routinely make contact with each other or inanimate objects.”

Header balls, though often singled out as a source of concussions, are not necessarily to blame.

The force created when a soccer ball meets a head can rattle a brain, but data increasingly points to other factors when competitors vie for a ball in the air.

According to a study by The Research Institute at Nationwide Children’s Hospital, while headers accounted for 27 percent of concussions, it was knocks with other players on aerial play — including head-to-head contact and arms and elbows to the head — and contact with the ground that accounted for 70 percent of those concussions in girls soccer, suggesting aggressive play is a factor in most concussions involving headers.

Why girls?

But why are girls more prone to concussions than boys while playing soccer? The prevailing theories focus on their weaker neck-muscle development, weaker body strength (needed to stabilize the neck and head during aerial play), and more frequent contact with the ground. A year ago, a study in the Journal of the American Osteopathic Association found that female high school soccer players took twice as long as male players to recover.

It’s also possible that girls don’t benefit as much from early treatment. A recent study published by the American Academy of Pediatrics found that girls are five times more likely than boys to stay on the pitch and play through a head injury.

And the soccer community has been slow to recognize the hard hits its girls are taking. Instead, soccer is at the forefront of the cultural empowerment of girls.

Local experts concerned about concussion risk note that sports, including girls soccer, have plenty of benefits. Just being physically active is good for kids, and sports like soccer help establish lifelong fitness habits, teach team-building skills, and promote character development and assertiveness.

“The worry is that the take-home message is that (girls soccer) is healthy and fantastic and nothing can be bad about it,” said Koester, who says an opposite negative message, equally extreme, is more often associated with boys playing football.

Greater awareness needed

Concussion education and awareness in girls soccer is paramount, according to local experts such as Chesnutt.

“I think the way to decrease it is to really analyze how we can modify the amount of body contact that goes on in soccer to limit the dangerous aggressive behavior that is associated with concussion,” he said.

Unlike youth football, a sport that’s adjusting to new information about concussions all the time, soccer has largely failed to address new information about concussions, Chesnutt said.

Football, for example, has reduced head-to-head helmet play, limited full-contact practices and games, and zeroed in on the specialty teams with the highest concussion rates.

“Football has really done, I think, an exceptional job of identifying some areas where there have been some definite higher incidents and some problems,” said Chesnutt, who lectures nationally about youth concussions. “As a group of coaches, leagues, parents and referees, they’ve all looked at it and come up with some solutions that have decreased concussion rates. And I think it’s time for soccer to do the same thing.”

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New Rules to Protect Your Kid’s Noggin

May 25, 2019, Parents Magazine

 
Children bonk their head all the time when they’re wrestling with siblings, playing soccer, and just being clumsy-and it’s easy to worry that a bump could turn into something bigger. After all, more than 800,000 kids in the U.S. get a concussion every year. For the first time, the Centers for Disease Control and Prevention has released specific “return to learn” and “return to play” guidelines for head injuries, based on 25 years of research. One doctor shares the big takeaways.

ALWAYS take any injury beyond a light head bump seiously. A concussion occurs when a bump, blow, or jolt to the head or a hit to the body makes the brain bounce or twist in the skull. This creates chemical changes and can sometimes damage brain cells. “If your child complains of a headache or dizziness, is nauseous or vomiting, appears dazed, or sleeps more or less than usual, it’s time to get a doctor’s evaluation,” says Dennis Cardone, D.O., associate professor of orthopedic surgery and pediatrics and co-director of the NYU Langone Concussion Center. Even toddlers can get a concussion from a tumble, so look for changes in their behavior such as not wanting to nurse or eat or losing interest in toys.

If diagnosed with a concussion, your child will need menlal rest, says Dr. Cardone. That means taking a break from all activities for two to three days, and after that, starting with light aerobic activity. He may need to attend school for only half the day or do little to no homework (he won’t mind this rule!). However, he shouldn’t return to any sports or strenuous activities that have a high risk of falling or contact (think: field hockey, gymnastics, climbing a tree) until he’s been cleared by his doctor, which should be within a few weeks.

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Junior Seau, shown at his beloved Pacific Ocean in the ESPN Films “30 for 30” documentary “Seau,” which premieres Thursday. (ESPN Films)

ESPN hits the mark with documentary ‘Seau’

By Tom Krasovic, September 20, 2018, San Diego Union Tribune

An aerial view of the Oceanside coast, in full sparkle and splendor below, grandly eases viewers into “Seau,” an ESPN Films documentary in the “30 for 30” series that debuts Thursday on the streaming service ESPN+.

It’s a sunny scene, the Pacific Ocean’s turquoise waves illuminated as they roll toward the white beach. The late Junior Seau told friends he found peace paddling on these waters, deep into his life alongside the town where he’d grown up.

Up at dawn with a yellow long-board and oar in hand, Seau had only a short walk from his beachfront home to the water.

Yet the former Chargers linebacker, role model and local philanthropist was then also writing in a journal of bouts with depression, memory loss and perceived guilt. There were headaches, too, and nights plagued by insomnia. “Buddy,” he’d told a friend and professional soccer player who’d suffered a brain injury from heading a ball, “I’ve had a concussion since I was 15.”

Diary entries also revealed feelings of humiliation and embarrassment over not living up to expectations of others and himself, and of feeling used by others.

“The world has nothing for me,” Seau pens in one entry, the cursive words all too legible.

One of Seau’s surviving adult children, after reading the grim line aloud, wonders why his father didn’t regard his family as something in this apparent world of nothing.

Why couldn’t they have been a lifeline for him to reach out and grasp?

“Seau,” produced and directed by Kirby Bradley, lets viewers draw their own conclusions about a complicated life that ended one May morning six years ago, at age 43, with a self-inflicted gunshot wound to the chest, but not before we hear from an array of family members, friends and experts in football and brain science.

At the end of the 90-minute film, themes of redemption and hope are raised.

“Let’s all walk from here being better for having known Junior Seau and the impact he had on our lives,” NFL quarterback Drew Brees, a former Chargers teammate of the Hall of Fame linebacker, concludes near the film’s end.

Former Chargers lineman Aaron Taylor notes that in death, Seau drew extraordinary attention to the link between head trauma and a degenerative brain disease, CTE, revealed in a tissue sample sent to a brain scientists at the family’s request.

Exciting beginnings and success are a thread to the film, followed often by bitter detours or hurtful endings.

Seau took to sports at Oceanside High with a passion that rivaled his stunning blend of size, speed and agility. If he was slamming into football ball-carriers or catching passes, scoring baskets or throwing the discus and shot, he was a “force of nature” for the green-and-white-clad Pirates, observers said.

A flood of football scholarship offers came to the small home where Seau and his brothers slept in a tiny garage.

Jubilation ensued when Seau chose USC, keeping him close to his parents and siblings and the tight-knit Samoan-American community in Oceanside. A similar celebration arose in 1990 when the Chargers drafted him fifth overall. “I’m a real momma’s boy,” Seau said, pulling on a blue team cap.

Playing for his beloved “Diego,” he led the long-struggling Chargers to the playoffs in just his third season, and their first Super Bowl two years later. “Now the world is gonna know the San Diego Chargers,” he told some 70,000 celebrants in Mission Valley after the team returned from claiming the 1994 AFC title in Pittsburgh.

The flip side?

If Oceanside lost a game in which he played, Junior lost his lunch money. It was the price his father exacted.

The thrill of signing with USC gave way to humiliation when a failed admittance test made him ineligible as a freshman. His father refused to talk to him in response, deeming the failure an embarrassment to the family. After a dominant junior year with USC, there would be no senior year. Making money was the next step, in no small part because he wanted to support his parents and other family members.

The Chargers couldn’t build upon their Super Bowl season, and the team’s constant losing wore on Seau.

When the Chargers traded him in the spring of 2003, after 13 seasons with the club, Seau was hurt that the team — Stay Unclassy, San Diego? — called not him but his agent to tell him the news. “I know that was hard on him,” said the agent, Steve Feldman.

Gina Seau was working for the Chargers in marketing when she first met Seau early in his NFL career.

She recalled “very kind eyes” and a “very soft voice” that almost “didn’t match the size and stature.”

The two would marry, but erratic behavior that Gina Seau linked to numerous football-related head injuries — “My head is on fire,” he told her — led to a divorce in 2002. The two remained friends. Believing that driving off a steep coastal cliff in October 2010 wasn’t an accident, Gina pleaded with her former husband to get help.

Here’s hoping that if there’s a “Seau II,” events yet to transpire bring more developments of redemption. Say, a cure for CTE.

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Ann C. McKee, chief of neuropathology at the VA Boston Healthcare System, which houses the world’s largest brain bank devoted to CTE research, examines a brain earlier this month.(Photo: Robert Deutsch, USA TODAY)

Researchers close in on CTE diagnosis in living, one brain at a time

By Nancy Armour, August 24, 2018, USA TODAY

BOSTON – Submerged in chemicals in the stainless-steel bowl is the key to life and, researchers hope, death.

It’s a human brain. That of a man who played college football in the 1950s, to be exact. His family donated his brain to get answers for themselves, but what’s found could lead to more answers about chronic traumatic encephalopathy, the devastating neurodegenerative disease linked to concussions and repetitive head trauma from football and other contact sports.

“Our main objective, our overarching goal, is to help the people who are living. To be able to diagnose this disease during life,” says Ann McKee, chief of neuropathology at the VA Boston Healthcare System, which houses the world’s largest brain bank devoted to CTE research.

“If we can diagnose it, we can monitor it and test therapies to see if they’re effective in treating this disease,” says McKee, director of the CTE Center at Boston University’s School of Medicine. “It would really dramatically increase our ability to point out genetic susceptibilities for this. We’d be able to look at how much is too much in certain individuals or certain positions in certain sports.”

As another football season begins, it inevitably leads to questions and fears about head trauma and its long-term damage. How many hits are too many? What can parents do to protect their children or players do to protect themselves? Are athletes in certain sports more susceptible?

Most important, which athletes will develop CTE – or Parkinson’s or ALS (amyotrophic lateral sclerosis) – and why?

The answers will come from brains such as the one McKee dissected this month, when USA TODAY Sports toured the brain bank.

The brain bank has more than 500 brains, most of them donated by former athletes or their families who suspected CTE because of mood swings, behavioral changes, depression or dementia. Of those brains, more than 360 had CTE, McKee says.

SEARCHING FOR CLUES

The arrival of a brain sets two teams in motion. One set of clinicians talks to the family to find out more about the donors. Did they play any sports? If so, what and for how long? When did they start? Did they experience any other kind of head trauma, say from an automobile accident, domestic violence or military service? Did they have drug or alcohol problems? How did their mental health change, and when did that occur?

Separately, and usually without any information about the person whose brain it was, McKee and her researchers study the brain. It is cut in half, and one half is stored in a minus-80-degree freezer, so it will be available for molecular, genetic and biochemical studies.

The other half is then photographed and sectioned. After removing the brain stem, McKee uses what looks like a bread knife to cut slices of the brain about a quarter-inch thick.


Ann C. McKee slices the brain into segments about a quarter-inch thick as part of in-depth, time consuming research on the organ. McKee hopes the work will unlock answers to CTE. (Photo: Robert Deutsch, USA TODAY)
 
Simply by looking at the brain, McKee can tell a few things. The brain of this man, who was in his 80s when he died, has shrunk, noticeably smaller than it should be for a man who once played football. The folds of the brain, normally pressed tightly against one another, are loose and have gaps between them, some large enough that the tip of a finger could be inserted.

She points to the ventricles, chambers in the middle of his brain that are filled with fluid during life. They should be small, but these are “just gigantic.”

“As the brain shrinks, they expand. What this indicates is there’s been enormous shrinkage of the brain,” McKee says. “Those are huge.”

The hippocampus, a section in the middle of the brain that controls memory, is small but not abnormally so for a man in his 80s. If it was, that could be an indication of Alzheimer’s. But a membrane that runs from one side of the brain to the other, normally thick like a rubber band, has shrunk. In some spots, it’s almost invisible.

“This is looking more like frontal predominant atrophy, and that could mean CTE because Alzheimer’s almost always affects the hippocampus,” McKee says. “At this point, I always want to know, ‘What is it? Let’s look under the microscope.’ But you have to wait.”

CTE can’t be seen by the naked eye, and it takes at least three weeks to prepare slides of the brain tissue.


 
CTE is caused by tau, a protein in the brain released as a result of head trauma. When tau clumps together, it damages brain cells and can change the brain’s function. Though tau causes Alzheimer’s, McKee says, the tau that causes CTE looks distinctly different.

Under a microscope, it can be seen in telltale brown spots.

“CTE is very focal. In fact, in its early stages, it’s in the crevices. It just piles up. And that’s around blood vessels,” McKee says. “That’s very different. Alzheimer’s never does that.”

As CTE progresses, those clusters or clumps of tau will spread, and the disease will become more severe. That’s why, in the early stages of disease, stages 1 and 2, the symptoms usually relate to behavioral changes or mood swings. In stages 3 and 4, the disease is exhibited in memory loss.

“We think there may be more pathology in the young players than we’re appreciating just with the tau protein,” McKee says. “We think there’s maybe white matter structural changes or maybe inflammatory changes that are responsible for that loss of control, which is so difficult for the individuals.”

‘EVERY CASE IS A MYSTERY’

Once the slides have been examined, the pathologists and clinicians will come together for a conference. At this point, neither knows what the other does. The clinicians detail what they’ve learned about the brain donor’s history and suggest a diagnosis. The pathologists will then say whether the brain tissue confirms it.

“Every case is a mystery,” McKee says. “It’s not the same way you usually solve a mystery. I solve the pathology first, and then you go back and find out (the history). And then you try and put the two together.”

Some former players and their families once were reluctant to donate their brains, but that stigma largely has disappeared. So much so that McKee said brains arrive at the Boston bank almost every day.

Though that lengthens the time it takes to reach a definitive diagnosis, it will shorten the time before a living diagnosis can be found. In addition to the work done in her lab, McKee shares tissue samples with researchers around the world.

“What we want to do is establish the risk, educate people, educate parents, educate players,” McKee says. “So if they’re unwilling to risk that future self, if they’re unwilling to take that risk because it’s too high for them personally, we want to give them enough data so they can make a very sound and wise decision.”

When that day comes, it will change sports forever.

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Traumatic brain injury causes widespread damage to neurons, leading to deficits in learning and memory. Cypin activators restore neuronal survival and function in mice, allowing for normal learning and memory. Credit: Mihir Patel/Rutgers University-New Brunswick

Traumatic brain injury: Discovery of two molecules could lead to new drug treatments

By Todd B. Bates, July 27, 2018, Rutgers University

After 10 years of research, a Rutgers-led team of scientists has identified two molecules that protect nerve cells after a traumatic brain injury and could lead to new drug treatments.

The molecules promote full recovery after traumatic brain injury (TBI) in mice, according to the study published online in Neurobiology of Disease. Traumatic brain injury is the leading cause of death for people under 45 years old in the United States and is associated with disability, early-onset dementia, cognitive disorders, mental illness and epilepsy.

Nearly all approaches for treating TBI focus on trying to prevent neurons, or nerve cells, from degenerating or on attempting to promote their survival, the study notes. TBI typically alters neural circuits within injured brain regions.

“The big issue with treatment after TBI is that there are no drugs that work well on patients to restore memory, and we’re targeting reconnectivity of neural circuitry,” said Bonnie L. Firestein, senior author of the study and a professor in the Department of Cell Biology and Neuroscience at Rutgers University-New Brunswick. “That means we want our neurons to function properly and connect with other neurons. We want to allow people to retain their cognition and ability to remember and learn, so our angle is novel.”

The researchers studied the protein cypin, an enzyme that breaks down guanine, which is an important building block for DNA and RNA in cells. The scientists previously showed that cypin is involved in promoting the proper shape in neurons and “keeping them happy,” Firestein said. This study found that speeding the breakdown of guanine protects neurons from injury and retains brain functioning.

Scientists at Rutgers-New Brunswick, University of Pennsylvania, Fox Chase Chemical Diversity Center Inc. and Columbia University want to develop drugs from the molecules for further studies.

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With better devices, science can get closer to a more complete picture of how neurons interact for cognitive functionality. (Photo/iStock)

Are we getting closer to a complete brain mapping? New devices explore more regions safely

By Breanne Grady, April 13, 2018, viterbischool.usc.edu

Researchers have developed thin, flexible polymer-based materials that record activity in more subregions of the brain with safer, more specific placement.

Science has yet to unravel a complete understanding of the brain and all its intricate workings. It’s not for lack of effort.

Over many decades, multiple research studies have sought to understand the dizzying “talk,” or interconnectivity, between thousands of microscopic entities in the brain, in particular neurons. The goal: to one day arrive at a complete brain “mapping” — a feat that could unlock tremendous therapeutic potential.

Researchers at the USC Viterbi School of Engineering have developed thin, flexible polymer-based materials for use in microelectrode arrays that record activity more deeply in the brain and with more specific placement than ever before. What’s more is that each microelectrode array is made up of eight “tines,” each with eight microelectrodes which can record from a total 64 subregions of the brain at once.

Same Quality, More Safety

In addition, the polymer-based material, called Parylene C, is less invasive and damaging to surrounding cells and tissue than previous devices comprised of silicon or microwires. However, the long and thin probes can easily buckle upon insertion, making it necessary to add a dissolvable brace made up of polyethylene glycol (PEG) that prevents it from bending.

Professor Ellis Meng of the USC Viterbi Department of Biomedical Engineering said that the performance of the new polymer-based material is on par with microwires in terms of recording fidelity and sensitivity. “The information that we can get out is equivalent, but the damage is much less,” Meng said. “Polymers are gentler on the brain, and because of that, these devices get recordings of neuronal communication over long periods of time.”

As with any prosthetic implant, caution must be exercised in terms of the body’s natural immune response to a foreign element. In addition to inflammation, previous microelectrode brain implants made of silicon or microwires have caused neuronal death and glial scarring, which is damage to connective tissue in the nervous system. However, Parylene C is biocompatible and can be microfabricated in extremely thin form to mold well to specific subregions of the brain, allowing for exploration with minimal damage.

Listening In

So far, these arrays have been used to record synaptic responses of individual neurons within the hippocampus, a part of the brain responsible for memory formation. If injured, the hippocampus may be compromised, resulting in a patient’s inability to form new memories. Meng, a faculty member of the Michelson Center for Convergent Bioscience, said that the polymer-based material can conform to a specific location in the hippocampus and “listen in on a conversation” between neurons. Because there are many such “eavesdroppers” (the microelectrodes), much more information about their interconnectivity can be gleaned.

“I can pick where I want my electrodes to be, so I can match up to the anatomy of the brain,” Meng, the Dwight C. and Hildagarde E. Baum Chair, said. “Along the length of a tine, I can put a group of electrodes here and a group of electrodes there, so if we plant to a certain depth, it’s going to be near the neurons I want to record from.”

Up Next

Future research will determine the recording lifetime of polymer-based arrays and their long-term “signal-to-noise” (SNR) stability. Also, the team plans to create devices with even higher density, including a double-sided microelectrode array with 64 electrodes per tine instead of eight — making for a total of around 4,000 electrodes placed in the brain at once.

In addition to Meng, Professor Ted Berger, the David Packard Chair in Engineering, and Research Professor Dong Song (both of the USC Viterbi School of Engineering) were co-authors along with Ph.D. students Huijing Xu and Ahuva Weltman Hirschberg and post-doctoral scholar Kee Scholten. Funding was provided be the National Science Foundation (NSF) and the National Institutes of Health (NIH). The study titled “Acute in vivo testing of a conformal polymer microelectrode array for multi-region hippocampal recordings” now published in the Journal of Neural Engineering.

About the Michelson Center

The USC Michelson Center for Convergent Bioscience brings together a diverse network of premier scientists and engineers under one roof, thanks to a generous $50 million gift from orthopedic spinal surgeon, inventor and philanthropist Gary K. Michelson, and his wife, Alya Michelson. At the Michelson Center, scientists and engineers from the USC Dornsife College of Letters, Arts and Sciences, USC Viterbi School of Engineering and Keck School of Medicine of USC are working to solve some of the greatest intractable problems of the 21st century in biomedical science, including a fundamentally new understanding of the cell and new approaches for cancer, neurological and cardiovascular disease.

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The radial-arm water maze is a common test to assess working memory in rodents.

Memory-enhancing drug reverses effects of traumatic brain injury in mice

By Ryan Cross, Jul. 10, 2017, sciencemag.org

Whether caused by a car accident that slams your head into the dashboard or repeated blows to your cranium from high-contact sports, traumatic brain injury can be permanent. There are no drugs to reverse the cognitive decline and memory loss, and any surgical interventions must be carried out within hours to be effective, according to the current medical wisdom. But a compound previously used to enhance memory in mice may offer hope: Rodents who took it up to a month after a concussion had memory capabilities similar to those that had never been injured.

The study “offers a glimmer of hope for our traumatic brain injury patients,” says Cesario Borlongan, a neuroscientist who studies brain aging and repair at the University of South Florida in Tampa. Borlongan, who reviewed the new paper, notes that its findings are especially important in the clinic, where most rehabilitation focuses on improving motor—not cognitive—function.

Traumatic brain injuries, which cause cell death and inflammation in the brain, affect 2 million Americans each year. But the condition is difficult to study, in part because every fall, concussion, or blow to the head is different. Some result in bleeding and swelling, which must be treated immediately by drilling into the skull to relieve pressure. But under the microscope, even less severe cases appear to trigger an “integrated stress response,” which throws protein synthesis in neurons out of whack and may make long-term memory formation difficult.

In 2013, the lab of Peter Walter, a biochemist at the University of California, San Francisco (UCSF), discovered a compound—called ISRIB—that blocked the stress response in human cells in a dish. Surprisingly, when tested in healthy mice, ISRIB boosted their memory. Wondering whether the drug could also reverse memory impairment, Walter teamed up with UCSF neuroscientist Susanna Rosi to study mouse models of traumatic brain injury. First, they showed that the stress response remains active in the hippocampus, a brain region important for learning and memory, for at least 28 days in injured mice. And they wondered whether administering ISRIB would help.

Rosi and her team first used mechanical pistons to hit anesthetized mice in precise parts of their surgically exposed brains, resulting in contusive injuries, focused blows that can also result from car accidents or being hit with a heavy object. After 4 weeks of rest, Rosi trained the mice to swim through a water maze, where they used cues to remember the location of a hidden resting platform. Healthy mice got better with practice, but the injured ones didn’t improve. However, when the injured mice were given ISRIB 3 days in a row, they were able to solve the maze just as quickly as healthy mice up to a week later, the researchers report today in the Proceedings of the National Academy of Sciences.

“We kept replicating experiments, thinking maybe something went wrong,” Rosi says. So the team decided to study ISRIB in a second model of traumatic brain injury known as a closed head injury, which resembles a concussion from a fall. They again used a mechanical piston, but this time landed a broad blow to the back of the skull. Two weeks later, the mice were trained on a tougher maze, full of bright lights and loud noise. They had to scurry around a tabletop with 40 holes, looking for the one with an escape hatch. Again, while the uninjured mice improved at the task, the concussed mice never got the hang of it. But after four daily doses of ISRIB, the concussed mice performed as well as their healthy counterparts. “This is the most exciting piece of work I’ve ever done, no doubt,” Rosi says.

“Paradigm shift is not too strong a term to use,” says Ramon Diaz-Arrastia, neurologist and director of clinical traumatic brain injury research at the University of Pennsylvania. “This … shows for the first time that a therapy in the chronic period of traumatic brain injury can have pretty potent effects.” Walter agrees. “Normally you would give up on these mice and say nothing can be done here,” he says. “But ISRIB just magically brings the cognitive ability back.”

Still, Borlongan cautions that studies in animals often don’t pan out when tested in humans. He says that this drug has a leg up, though, because it was tested in two models and also readily crosses the blood-brain barrier, which prevents many drugs that look good on paper from entering the brain and having an effect.

If the therapy translates to humans, it could be a boon for soldiers returning from war, who sometimes wait weeks between leaving the battlefield and arriving home for treatment. Brian Head, a neurobiologist at the VA San Diego Healthcare System in California notes that traumatic brain injury is still hard to diagnose, especially with veterans that show up to the clinic long after the injury. “But right now nothing else is working, and giving a compound [that works] a month later is really impressive.”

In 2015, ISRIB was licensed to the secretive Google spinout company Calico, which studies the biology of aging and life span. Walter says his lab has a research agreement with Calico to pursue “basic mechanistic work” on ISRIB, but that the new study was not funded by Calico. Google declined to comment on the new research.

Although the protein target of ISRIB is known, the exact manner in which the drug restores memory is hazy. The team hypothesizes that ISRIB may work by allowing normal protein synthesis—essential for making new neuronal connections and thus forming new memories—to resume, which would otherwise be blunted by the integrated stress response. “Even if this drug doesn’t materialize, other ways of manipulating the integrated stress response may lead to an effective treatment in the future,” Walter says.

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CARSON, CA – AUGUST 03: Bronze medal winner Dave Mirra speaks in a press conference after the Rally Car race during the summer X Games 14 at Home Depot Center on August 3, 2008 in Carson, California. (Photo by Christian Petersen/Getty Images)

Months after committing suicide, Dave Mirra has become the first action sports athlete to be diagnosed with CTE

by Robert Silverman, vocativ.com (May 24, 2016)
 
After BMX biking legend Dave Mirra committed suicide on February 4 of this year, his wife had his brain tested for chronic traumatic encephalopathy. Sadly, the result came back positive, rife with tau proteins dotting both his temporal and frontal lobes after years of enduring an unknown amount of concussive and sub-concussive trauma. This makes Mirra the first action sports athlete to be diagnosed with CTE.

The neuropathologist went so far as to equate the condition of his brain to that of NFL players and other contact sport athletes that have been posthumously diagnosed with the disease. “I couldn’t tell the difference,” Dr. Lili-Naz Hazrati said.

In an exclusive interview with ESPN: The Magazine, Mirra’s wife Lauren describes the agonizing final weeks of his life, the transformation of his formerly vibrant personality into something different and darker, prone to wild mood swings and unprovoked crying jags or bouts of exhaustion, his mind clouded and wracked with depression.

“I remember seeing him sitting on our bed one day, in the last month of his life,” she said. “I had just gotten out of the shower and saw him hunched over with the blankest lost look. I sat down next to him and held his hand. I said, ‘What is wrong? Are you OK?’ And he just shrugged his shoulders. He couldn’t even speak. He didn’t know. He couldn’t put it into words. He was lost. He was helpless. It was completely different from who he was.”

“He was gone. I could see straight through him,” she continued. “It was the hardest thing to see, looking at someone you love, and you can’t have a conversation with them, and you can see straight through their eyes.”

Lauren Mirra doesn’t know what her exact plans might be for the future, but her overarching hope is that she’ll be able to find a forum in which to speak out, to encourage best practices and prevention measures, without coming across as an ideologue out to ban action sports altogether.

“Through him we have an opportunity to help and change,” she said. “Beauty from ashes. That’s how I will always choose to see it.”

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