Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease found in people who have had multiple head injuries. It is most commonly found in those who have participated in contact sports on a regular basis. Its presence in domestic violence is also being investigated. It can affect high school athletes after only a few years of participation. It is a form of tauopathy.
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Symptoms
Symptoms of CTE, which occur in four stages, generally appear 8 to 10 years after an athlete experiences repetitive mild traumatic brain injury.
First-stage symptoms include attention deficit hyperactivity disorder as well as confusion, disorientation, dizziness, and headaches. Second-stage symptoms include memory loss, social instability, impulsive behavior, and poor judgment. Third and fourth stages include progressive dementia, movement disorders, hypomimia, speech impediments, sensory processing disorder, tremors, vertigo, deafness, depression and suicidality.
Additional symptoms include dysarthria, dysphagia, cognitive disorder such as amnesia, and ocular abnormalities, such as ptosis.
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Pathology
The neuropathological appearance of CTE is distinguished from other tauopathies, such as Alzheimer's disease. The four clinical stages of observable CTE disability have been correlated with tau pathology in brain tissue, ranging in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.
The primary physical manifestations of CTE include a reduction in brain weight, associated with atrophy of the frontal and temporal cortices and medial temporal lobe. The lateral ventricles and the third ventricle are often enlarged, with rare instances of dilation of the fourth ventricle. Other physical manifestations of CTE include anterior cavum septi pellucidi and posterior fenestrations, pallor of the substantia nigra and locus ceruleus, and atrophy of the olfactory bulbs, thalamus, mammillary bodies, brainstem and cerebellum. As CTE progresses, there may be marked atrophy of the hippocampus, entorhinal cortex, and amygdala.
On a microscopic scale, the pathology includes neuronal loss, tau deposition, TAR DNA-binding Protein 43 (TDP 43) beta-amyloid deposition, white matter changes, and other abnormalities. The tau deposition occurs as dense neurofibrillary tangles (NFT), neurites, and glial tangles, which are made up of astrocytes and other glial cells Beta-amyloid deposition is a relatively uncommon feature of CTE.
A small group of individuals with CTE have chronic traumatic encephalomyopathy (CTEM), which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis (ALS). Progressive muscle weakness and balance and gait problems (problems with walking) seem to be early signs of CTEM.
Exosome vesicles created by the brain are potential biomarkers of TBI, including CTE.
A subtype of CTE is dementia pugilistica (DP), also called "punch-drunk syndrome", as it was initially found in those with a history of boxing.
Diagnosis
Currently, CTE can only be definitively diagnosed by direct tissue examination after death, including full autopsies and immunohistochemical brain analyses.
The lack of in vivo techniques to show distinct biomarkers for CTE is the reason CTE cannot currently be diagnosed while a person is alive. The only known diagnosis for CTE occurs by studying the brain tissue after death. Concussions are non-structural injuries and do not result in brain bleeding, which is why most concussions cannot be seen on routine neuroimaging tests such as CT or MRI. Acute concussion symptoms (those that occur shortly after an injury) should not be confused with CTE. Differentiating between prolonged post-concussion syndrome (PCS, where symptoms begin shortly after a concussion and last for weeks, months, and sometimes even years) and CTE symptoms can be difficult. Research studies are currently examining whether neuroimaging can detect subtle changes in axonal integrity and structural lesions that can occur in CTE. Recently, more progress in in-vivo diagnostic techniques for CTE has been made, using DTI, fMRI, MRI, and MRS imaging; however, more research needs to be done before any such techniques can be validated.
PET tracers that bind specifically to tau protein are desired to aid diagnosis of CTE in living individuals. One candidate is the tracer [18F]FDDNP, which is retained in the brain in individuals with a number of dementing disorders such as Alzheimer's disease, Down syndrome, progressive supranuclear palsy, familial frontotemporal dementia, and Creutzfeldt-Jakob disease. In a small study of 5 retired NFL players with cognitive and mood symptoms, the PET scans revealed accumulation of the tracer in their brains. However, [18F]FDDNP binds to beta-amyloid and other proteins as well. Moreover, the sites in the brain where the tracer was retained were not consistent with the known neuropathology of CTE. A more promising candidate is the tracer [18F]-T807, which binds only to tau. It is being tested in several clinical trials.
A putative biomarker for CTE is the presence in serum of autoantibodies against the brain. The autoantibodies were detected in football players who experienced a large number of head hits but no concussions, suggesting that even sub-concussive episodes may be damaging to the brain. The autoantibodies may enter the brain by means of a disrupted blood-brain barrier, and attack neuronal cells which are normally protected from an immune onslaught. Given the large numbers of neurons present in the brain (86 billion), and considering the poor penetration of antibodies across a normal blood-brain barrier, there is an extended period of time between the initial events (head hits) and the development of any signs or symptoms. Nevertheless, autoimmune changes in blood of players may consist the earliest measurable event predicting CTE.
Robert A. Stern, one of the scientists at the Boston University CTE Center, said in 2015 that "he expected a test to be developed within a decade that will be able to diagnose C.T.E. in living people".
Prevention
Investigators have demonstrated that immobilizing the head during a blast exposure prevented the learning and memory deficits associated with CTE that occurred when the head was not immobilized. This research represents the first case series of postmortem brains from U.S. military personnel who were exposed to a blast and/or a concussive injury.
Epidemiology
Professional level athletes are the largest demographic with CTE, due to frequent concussions from play in contact sport. These contact-sports include American football, ice hockey, rugby, boxing, soccer (by "heading" especially), and wrestling. Other individuals that have been diagnosed with CTE were involved in military service, had a previous history of chronic seizures, victims of domestic abuse, and or were involved in activities resulting in repetitive head collisions.
History
CTE was originally studied in boxers in the 1920s as dementia pugilistica. The seminal work on the disease came from British neurologist Macdonald Critchley, who in 1949 wrote a paper titled "Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers." CTE was first recognized as affecting individuals who took considerable blows to the head, but was believed to be confined to boxers and not other athletes. As evidence pertaining to the clinical and neuropathological consequences of repeated mild head trauma grew, it became clear that this pattern of neurodegeneration was not restricted to boxers, and the term chronic traumatic encephalopathy became most widely used. In the early 2000s, Nigerian neuropathologist Dr. Bennet Omalu worked on the case of American football player Mike Webster, who died following unusual and unexplained behavior. In 2005 Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published his findings in the journal Neurosurgery in a paper which he titled "Chronic Traumatic Encephalopathy in a National Football League Player." This was followed by a paper on a second case in 2006 describing similar pathology.
In 2008, the Sports Legacy Institute joined with the Boston University School of Medicine (BUSM) to form the Center for the Study of Traumatic Encephalopathy (CSTE). Brain Injury Research Institute (BIRI) also studies the impact of concussions.
American football
Beginning in 2005, Dr. Bennet Omalu, a forensic pathologist and neuropathologist in Pittsburgh, Pennsylvania, found CTE in the brains of Mike Webster, Terry Long, Andre Waters, Justin Strzelczyk, and Tom McHale. Omalu, initially a medical examiner, then associate adjunct professor in California, was a co-founder of the Brain Injury Research Institute and reportedly in 2012 participated in the autopsy of Junior Seau. Omalu's participation was halted during the autopsy after Junior Seau's son revoked previously provided oral permission after he received telephone calls from NFL management denouncing Omalu's professional ethics, qualifications, and motivation.
Between 2008 and 2010, the bodies of twelve former professional American football players were diagnosed with CTE postmortem by Dr. Ann McKee.
On December 1, 2012, Kansas City Chiefs linebacker Jovan Belcher killed his girlfriend and drove to Arrowhead Stadium and killed himself in front of then GM Scott Pioli and then head coach Romeo Crennel. A year later, on behalf of Belcher's minor daughter, a family lawyer filed a wrongful-death lawsuit, against the Chiefs, alleging that the team deliberately ignored warning signs of CTE, possibly leading to Belcher's suicide. The lawyer also hired a medical examiner to examine Belcher's brain for signs of CTE. On September 29, 2014, it was confirmed that he had CTE.
As of November 2016, 90 of 94 former National Football League (NFL) players were diagnosed post-mortem with CTE by Dr. McKee. Former Detroit Lions lineman and eight-time Pro Bowler Lou Creekmur, former Houston Oilers and Miami Dolphins linebacker John Grimsley, former Tampa Bay Buccaneers guard Tom McHale, former Cincinnati Bengals wide receiver Chris Henry, former Chicago Bears safety Dave Duerson, and former New England Patriots and Philadelphia Eagles running back Kevin Turner have all been diagnosed post-mortem with CTE. Other football players diagnosed with CTE include former Buffalo Bills star running back Cookie Gilchrist and Wally Hilgenberg.
An autopsy conducted by Dr. McKee in 2010 on the brain of Owen Thomas, a 21-year-old junior lineman at the University of Pennsylvania who died of suicide, showed early stages of CTE, making him the second youngest person to be diagnosed with the condition. Thomas was the second amateur football player diagnosed with CTE; Mike Borich, who died at 42, was also diagnosed by Dr. McKee. The doctors who performed the autopsy indicated that they found no causal connection between the nascent CTE and Thomas's suicide. There was no indication that Thomas missed playing time due to concussions; however, as a player who played hard and "loved to hit people", Thomas may have played through concussions and received thousands of subconcussive impacts on the brain.
In October 2010, 17-year-old Nathan Stiles died hours after his high-school homecoming football game, where he took a hit that would be the final straw in a series of subconcussive and concussive blows to the head for the highschooler. The CSTE diagnosed him with CTE, making him the youngest reported CTE case to date.
In July, 2011, Colt tight-end John Mackey died after several years of deepening symptoms of frontotemporal dementia. BUSM was reported to be planning to examine his brain for signs of CTE. The CSTE found CTE in his brain post-mortem.
In 2012, retired NFL player Junior Seau died of suicide with a gunshot wound to the chest. There was speculation that he had brain damage due to CTE. Seau's family donated his brain tissue to the National Institute of Neurological Disorders and Stroke. On January 10, 2013, the brain pathology report was revealed and Seau did have evidence of CTE.
On July 27, 2012, an autopsy report concluded that the former Atlanta Falcons safety Ray Easterling, who died from suicide in April 2012, had CTE.
The NFL has taken measures to help prevent CTE. As of July 2011, the NFL has changed its return-to-play rules. The number of contact practices has been reduced, based on the recent collective bargaining agreement.
In 2012, some four thousand former NFL players "joined civil lawsuits against the League, seeking damages over the League's failure to protect players from concussions, according to Judy Battista of the [New York] Times".
On August 30, 2013, the NFL reached a $765 million settlement with the former NFL players over the head injuries. The settlement created a $675 million compensation fund from which former NFL players can collect depending on the extent of their conditions. Severe conditions such as Lou Gehrig's disease and postmortem diagnosed chronic traumatic encephalopathy would be entitled to payouts as high as $5 million. From the remainder of the settlement, $75 million will be used for medical exams, and $10 million will be used for research and education. However, in January, 2014, U.S. District Judge Anita B. Brody refused to accept the agreed settlement because "the money wouldn't adequately compensate the nearly 20,000 men not named in the suit". In the settlement Brody did accept, she argued that people "cannot be compensated for C.T.E. in life because no diagnostic or clinical profile of C.T.E. exists, and the symptoms of the disease, if any, are unknown".
On September 17, 2014, Patrick Risha died from suicide at the age of 32. He played football as a running back for Deerfield Academy in Massachusetts and Dartmouth University in New Hampshire. After graduation from college he moved to Pittsburgh and started experiencing CTE symptoms. His family started the Patrick Risha CTE Awareness Foundation, StopCTE.org to spread awareness of the disease.
On April 22, 2015, a final settlement was reached between players and the NFL in the case adjudicated by Judge Brody. Terms include payments to be made by the NFL for $75 million for "baseline medical exams" for retired players, $10 million for research and education, as well an uncapped amount for retirees "who can demonstrate that they suffer from one of several brain conditions covered by the agreement", with total payments expected to exceed $1 billion over 65 years.
In September 2015, researchers with the Department of Veterans Affairs and Boston University announced that they had identified CTE in 96 percent of NFL players that they had examined and in 79 percent of all football players.
On January 26, 2016, an autopsy report released by the family of former New York Giants safety Tyler Sash confirmed he had CTE at the time of his death at age 27 in September 2015.
On February 4, 2016, an autopsy report from Massachusetts confirmed discovered high Stage 3 chronic traumatic encephalopathy (CTE) in Ken Stabler's brain after his death.
On March 14, 2016, the top NFL official, Jeff Miller, publicly admitted that there is a link between football and CTE at the roundtable discussion on concussions.
Heisman Trophy winner and former NFL All-Pro Bo Jackson said in a 2017 interview with USA Today that if he knew about the risks associated with CTE's, he would never have played football and discourages his children from doing so.
On July 25, 2017, the Journal of the American Medical Association released an updated study reporting that out of 111 brains of deceased former NFL players studied, 110 (99%) had CTE. This also led to players retiring very early in their career.
On September 21, 2017, an autopsy report from Boston University announced that former New England Patriot tight end Aaron Hernandez was found to have had Stage 3 CTE at the time of his death at age 27 in April of 2017.
Early retirements
In the 2015 off-season, a number of NFL players retired early with concussion- and other health-risk as expressed or possible motive. The youngest, in March, Chris Borland, 24, would have been entering his second year in the league after a third-round draft out of University of Wisconsin and a "stellar" rookie season with the San Francisco 49ers. Explaining his decision to ESPN, Borland said "I just honestly want to do what's best for my health. ... From what I've researched and what I've experienced, I don't think it's worth the risk."
Patrick Willis, a seven-time All-Pro linebacker also with the 49ers, [had previously] announced that he was retiring rather than risk further injury. However Willis' decision to retire has nothing to do with CTE, but rather as he explained: "You've seen me break my hand on Sunday, have surgery on Monday and play on Thursday with a cast on," Willis said. "But there's something about these feet. And those are what made me who I am. They had you all saying, 'Wow, where'd he come from?' "I know I no longer have it in these feet to go out there and give you guys that kind of 'Wow.'" Cornerback Cortland Finnegan of the St. Louis Rams, quarterback Jake Locker of the Tennessee Titans and linebacker Jason Worilds of the Pittsburgh Steelers have all retired this off-season as well. Worilds, who was paid $9.75 million by the Steelers in 2014, was expected to sign a big contract with another team as a free agent. [Borland] won Rookie of the Week honors twice and was Defensive Rookie of the Month in November [in 2014]. He earned the league-minimum $420,000 and a bonus of $154,000, according to Overthecap.com.
ESPN noted that four of the retirees--Borland, Willis, Locker and Worilds--were under 30 years of age and that Borland had replaced Willis during the season due to a Willis toe injury and had been expected to replace him in the coming year. It also recounted Borland's course of decision from a possible concussion he "played through" in training camp as he was trying to make the team to the post-season decision. He said in making his decision he'd "read about Mike Webster and Dave Duerson and Ray Easterling"--two of them suicides, all, per ESPN, "diagnosed with the devastating brain disease Chronic traumatic encephalopathy, or CTE, after their deaths"--and he had talked to "prominent concussion researchers and former players" after the season.
In the 2016 off-season, A.J. Tarpley, Husain Abdullah, and Eugene Monroe all announced early retirements from the NFL, each citing concern over sustaining further head trauma as the main factor in their decision.
In the 2017 off-season, John Urschel also announced early retirement from the NFL, two days after the study from AMA.
Ice hockey
Athletes from other sports have also been identified as having CTE, such as hockey player Bob Probert. Neuropathologists at Boston University diagnosed Reg Fleming as the first hockey player known to have the disease. This discovery was announced in December 2009, six months after Fleming's death.
Rick Martin, best known for being part of the Buffalo Sabres' French Connection, was diagnosed with CTE after his brain was posthumously analyzed. Martin was the first documented case of an ice hockey player not known as an enforcer to have developed CTE; Martin was believed to have developed the disease primarily as a result of a severe concussion he received in 1977 while not wearing a helmet. The disease was low-grade and asymptomatic in his case, not affecting his cognitive functions. He died of a heart attack in March 2011 at the age of 59.
Also within a few months in 2011, the deaths of three hockey "enforcers"--Derek Boogaard from a combination of too many painkillers and alcohol, Rick Rypien, an apparent suicide, and Wade Belak, who, like Rypien, was reportedly depressed; and all with a record of fighting, blows to the head and concussions--led to more concerns about CTE. Boogaard's brain was examined by BUSM, which in October 2011 determined the presence of CTE. One National Hockey League player known in part for leading "the thump parade", former Boston Bruin and current Florida Panthers right winger Shawn Thornton mulled over the "tragic coincidence" of the three recent league deaths and agreed that their deaths were due to the same cause, yet still defended the role of fighting on the rink.
In 2016, Stephen Peat, then 36 years old and formerly an enforcer for the Washington Capitals during his professional career, was reported to be suffering severe symptoms of CTE. His father Walter was reported to worry that his son would join the "dead before turning 50 ... since 2010" list of enforcers including Boogaard, Rypien, Belak, Steve Montador and Todd Ewen.
Professional wrestling
In 2000, Bret Hart was forced to retire due to post-concussion problems after fellow wrestler Goldberg kicked Hart in the head, giving him a severe concussion. Despite the concussion, Hart recovered consciousness and was able to finish the match.
In 2007, neuropathologists from the Sports Legacy Institute (an organization co-founded by Christopher Nowinski, himself a former professional wrestler) examined the brain of Chris Benoit, a professional wrestler with the WWE, who had apparently killed his wife and son before committing suicide. The suicide and double murder were originally attributed to anabolic steroid abuse, but a brain biopsy confirmed pathognomonic CTE tissue changes: large aggregations of tau protein as manifested by neurofibrillary tangles and neuropil threads, which cause neurodegeneration.
In 2009, Bennet Omalu discovered CTE in recently retired wrestler Andrew "Test" Martin, who died at age 33 from an accidental medicine overdose.
On February 9, 2016, Daniel Bryan was forced to retire early due to signs of CTE and post-concussion seizures.
After their deaths in February and April 2016 respectively, former ECW wrestlers Axl Rotten and Balls Mahoney were found to have had CTE.
In July 2016, 53 professional wrestlers filed a lawsuit against WWE, looking to hold the organization accountable for their "long-term neurological injuries" due to multiple concussions and CTE.
Mixed martial arts
It is believed that former mixed martial artists Gary Goodridge and James Leahy have CTE, as a result of repeated head trauma from their fighting careers. Delayed onset is becoming increasingly common as with Leahy, whose symptoms developed many years after any sporting activity.
In October 2016, Dr. Bennet Omalu announced that CTE had been detected in the brain of Jordan Parsons, an MMA fighter who had been killed the previous May by a drunk driver.
Association football (soccer)
In 2012, Patrick Grange, a semi-professional footballer, was diagnosed in an autopsy with Stage 2 CTE with motor neuron disease. "The fact that Patrick Grange was a prolific header is important", Christopher Nowinski, co-founder of the Sports Legacy Institute, said in an e-mail. "We need a larger discussion around at what age we introduce headers, and how we set limits to exposure once it is introduced." Grange played soccer in high school; college at Illinois-Chicago and New Mexico; in the Premier Development League; for Albuquerque Asylum; and for Chicago Fire Premier. He died of ALS at age 29 in 2012 with a posthumous diagnosis of CTE.
In 2014, Brazilian footballer Bellini was posthumously diagnosed with CTE. Bellini, along with Pelé, led Brazil to FIFA World Cup victories in 1958 and 1962.
West Bromwich Albion forward Jeff Astle died in January 2002 following five years of deteriorating mental health. Originally diagnosed as Alzheimer's, Astle's condition was later rediagnosed as CTE. In 2014 following 12 years of campaigning from his family and fans at his former club West Bromwich Albion, Jeff Astle officially became the first British footballer listed to have died as a result of heading a football. The campaign was known as the "Justice for Jeff" campaign, its awareness raised by West Bromwich Albion supporters minutes of applause on the 9th minute of every match (his squad number). Astle was particularly noted for his powerful heading of the ball; it is believed that this, combined with the weight of the old fashioned leather soccer balls, contributed to his CTE.
Rugby
Researchers found Australian rugby union player Barry "Tizza" Taylor died in 2013 of complications of severe CTE with dementia at age 77. Taylor played for 19 years in amateur and senior leagues before becoming a coach.
In 2013, Dr Willie Stewart, Consultant Neuropathologist at the Institute of Neurological Sciences at the Southern General Hospital in Glasgow, identified CTE in the brain of a former amateur rugby player in his 50s which is believed to be the first confirmed case of early onset dementia caused by CTE in a rugby player.
Australian rules football
Australian rules football player Greg Williams is thought to have CTE as a result of concussions over a 250-game career.
In March 2016 Justin Clarke of the Australian Football League (AFL) team the Brisbane Lions was forced to retire at just 22 years of age due to a serious concussion sustained during off-season training two months earlier. He was the fifth AFL player in the previous ten months to retire with concussion related injuries, with Sam Blease (25 yo, Melbourne and Geelong), Leigh Adams (27 yo, North Melbourne), Matt Maguire (32 yo, Brisbane and St Kilda), and Brent Reilly (32 yo, Adelaide) all having retired since May 2015. All the retirements were linked to a crackdown on head injuries by the AFL and fears of CTE associated with local and international sportspeople, especially American footballers.
Baseball
In 2012, the brain tissue of Ryan Freel was tested after his death. It was found that he had Stage 2 CTE. Freel was the first Major League Baseball player to be diagnosed with chronic traumatic encephalopathy.
Extreme sports
In 2016, BMX biker and extreme sport icon Dave Mirra was diagnosed post-mortem with CTE. He died of suicide by gunshot on February 4, 2016, and his brain was examined by Dr. Lili-Naz Hazrati of the University of Toronto, who confirmed the diagnosis. In 2017, Ty Pozzobon was the first PBR rider diagnosed with the disease
In popular culture
Rocky V, the fifth film in the Rocky series, tells about Rocky suffering from chronic traumatic encephalopathy.
On December 7, 2011, the television show Law & Order: Special Victims Unit aired the episode "Spiraling Down", which featured a character suffering from CTE.
On October 8, 2013, PBS aired an episode of its Frontline documentary television series concerning CTE and the NFL. The episode was re-aired in December 2015 with additional updated information.
Concussion is a 2015 film starring Will Smith dramatizing the efforts of Bennet Omalu's fight against the NFL's efforts to suppress his research on brain damage in professional football players.
House M.D. Season 8 Episode 16 "Gut Check".
A Gifted Man Season 1 Episode 6 "In Case of Memory Loss." A former American football star, now homeless, suffers from CTE.
Research
In 2005 forensic pathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published a paper, "Chronic Traumatic Encephalopathy in a National Football League Player", in the journal Neurosurgery, based on analysis of the brain of deceased former NFL center Mike Webster. This was then followed by a paper on a second case in 2006 describing similar pathology, based on findings in the brain of former NFL player Terry Long.
In 2008, the CSTE at Boston University at the BU School of Medicine started the CSTE brain bank at the Bedford VA Hospital to analyze the effects of CTE and other neurodegenerative diseases on the brain and spinal cord of athletes, military veterans, and civilians To date, the CSTE Brain Bank is the largest CTE tissue repository in the world. On December 21, 2009, the National Football League Players Association announced that it would collaborate with the CSTE at the Boston University School of Medicine to support the Center's study of repetitive brain trauma in athletes. Additionally, in 2010 the National Football League gave the CSTE a $1 million gift with no strings attached. In 2008, twelve living athletes (active and retired), including hockey players Pat LaFontaine and Noah Welch as well as former NFL star Ted Johnson, committed to donate their brains to CSTE after their deaths. In 2009, NFL Pro Bowlers Matt Birk, Lofa Tatupu, and Sean Morey pledged to donate their brains to the CSTE. In 2010, 20 more NFL players and former players pledged to join the CSTE Brain Donation Registry, including Chicago Bears linebacker Hunter Hillenmeyer, Hall of Famer Mike Haynes, Pro Bowlers Zach Thomas, Kyle Turley, and Conrad Dobler, Super Bowl Champion Don Hasselbeck and former pro players Lew Carpenter, and Todd Hendricks. In 2010, Professional Wrestlers Mick Foley, Booker T and Matt Morgan also agreed to donate their brains upon their deaths. Also in 2010, MLS player Taylor Twellman, who had to retire from the New England Revolution because of post-concussion symptoms, agreed to donate his brain upon his death. As of 2010, the CSTE Brain Donation Registry consists of over 250 current and former athletes. In 2011, former North Queensland Cowboys player Shaun Valentine became the first rugby player to agree to donate his brain upon his death, in response to recent concerns about the effects of concussions on Rugby League players, who do not use helmets. Also in 2011, boxer Micky Ward, whose career inspired the film The Fighter, agreed to donate his brain upon his death.
In related research, the Center for the Study of Retired Athletes, which is part of the Department of Exercise and Sport Science at the University of North Carolina at Chapel Hill, is conducting research funded by National Football League Charities to "study former football players, a population with a high prevalence of exposure to prior Mild Traumatic Brain Injury (MTBI) and sub-concussive impacts, in order to investigate the association between increased football exposure and recurrent MTBI and neurodegenerative disorders such as cognitive impairment and Alzheimer's disease (AD)".
In February 2011, Dave Duerson committed suicide, leaving text messages to loved ones asking that his brain be donated to research for CTE. The family got in touch with representatives of the Boston University center studying the condition, said Robert Stern, the co-director of the research group. Stern said Duerson's was the first time he was aware of that such a request had been left by a suicide potentially linked to CTE. Stern and his colleagues found high levels of the protein tau in Duerson's brain. These elevated levels, which were abnormally clumped and pooled along the brain sulci, are indicative of CTE.
In July 2010, NHL enforcer Bob Probert died of heart failure. Before his death, he asked his wife to donate his brain to CTE research because it was noticed that Probert experienced a mental decline in his 40s. In March 2011, researchers at Boston University concluded that Probert had CTE upon analysis of the brain tissue he donated. He is the second NHL player from the program at the Center for the Study of Traumatic Encephalopathy to be diagnosed with CTE postmortem.
BUSM has also found indications of links between Amyotrophic lateral sclerosis (ALS) and CTE in athletes who have participated in contact sports. Tissue for the study was donated by twelve athletes and their families to the CSTE Brain Bank at the Bedford, Massachusetts VA Medical Center.
In 2013, President Barack Obama announced the creation of the Chronic Effects of Neurotrauma Consortium or CENC, a federally funded research project devised to address the long-term effects of mild traumatic brain injury in military service personnel (SM's) and Veterans. The CENC is a multi-center collaboration linking premiere basic science, translational, and clinical neuroscience researchers from the DoD, VA, academic universities, and private research institutes to effectively address the scientific, diagnostic, and therapeutic ramifications of mild TBI and its long-term effects. Nearly 20% of the more than 2.5 million U.S. Service Members (SMs) deployed since 2003 to Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have sustained at least one traumatic brain injury (TBI), predominantly mild TBI (mTBI), and almost 8% of all OEF/OIF Veterans demonstrate persistent post-TBI symptoms more than six months post-injury. Unlike those head injuries incurred in most sporting events, recent military head injuries are most often the result of blast wave exposure. After a competitive application process, a consortium led by Virginia Commonwealth University was awarded funding. The project principal investigator for the CENC is David Cifu, Chairman and Herman J. Flax professor of the Department of Physical Medicine and Rehabilitation (PM&R) at Virginia Commonwealth University (VCU) in Richmond, Virginia, with co-principal investigators Ramon Diaz-Arrastia, Professor of Neurology, Uniformed Services University of the Health Sciences, and Rick L. Williams, statistician at RTI International.
Some researchers have argued that prospective longitudinal studies, following subjects over time, are needed to more completely understand the causes and progression of CTE.
As of September 2015, the CSTE had diagnosed CTE in 96% of NFL players analyzed in postmortem brain studies.
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