Chronic traumatic encephalopathy
Chronic traumatic encephalopathy (CTE) is a form of encephalopathy that is a progressive degenerative disease, which can only be definitively diagnosed postmortem in individuals with a history of multiple concussions and other forms of head injury. The disease was previously called dementia pugilistica (DP), as it was initially found in those with a history of boxing. CTE has been most commonly found in professional athletes participating in American football, ice hockey, professional wrestling and other contact sports who have experienced repetitive brain trauma. It has also been found in soldiers exposed to a blast or a concussive injury, in both cases resulting in characteristic degeneration of brain tissue and the accumulation of tau protein. Individuals with CTE may show symptoms of dementia, such as memory loss, aggression, confusion and depression, which generally appear years or many decades after the trauma.
Repeated concussions and injuries less serious than concussions ("sub-concussions") incurred during the play of contact sports over a long period can result in CTE. In the case of blast injury, a single exposure to a blast and the subsequent violent movement of the head in the blast wind can cause the condition.
CTE is a neurological degenerative disease found in individuals who have been subjected to repetitive traumatic brain injuries by way of the acceleration and deceleration of the head on impact and the subsequent damage to axons. While repetitive brain trauma is thought to be necessary to cause CTE, it is not sufficient, meaning that not everyone exposed to repetitive brain trauma will get the disease. Other risk factors are possible but have not yet been reported, due to the donated brains in the brain bank at the Boston University School of Medicine and elsewhere, which consists mostly of the brains of athletes with a history of professional participation in contact sports. Professional level athletes are the largest demographic to suffer from CTE due to frequent concussions from play in contact-sport. These contact-sports include American football, ice hockey, rugby, boxing, 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 head-banging. Reports of CTE have steadily increased in younger athletes, most likely due to increased awareness of the issue and perhaps due in part to athletes becoming bigger and stronger producing greater magnitudes of force in collision.
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 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 relatively uncommon feature of CTE.
A small group of individuals with CTE have chronic traumatic encephalomyopathy (CTEM), characterized by motor neuron disease symptoms and mimics Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s disease. Progressive muscle weakness and balance and gait problems seem to be early signs of CTEM.
Signs and symptoms 
Other than repeated brain trauma, the risk factors for CTE remain unknown. So far, CTE can only be diagnosed posthumously. Research studies are looking into possible genetic, exposure level, and other risk factors.
Researchers who conducted a CTE pilot study at UCLA described the findings as a significant step toward being able to diagnose CTE, in living patients. 
Clinical symptoms of CTE are only beginning to be understood. They are thought to include changes in mood(i.e. depression, suicidality, apathy, anxiety), cognition (i.e. memory loss, executive dysfunction), behavior (short fuse, aggression), and in some cases motor disturbance (i.e. difficulty with balance and gait). While the pathology of CTE has been broken up into stages  the clinical symptoms and clinical progression of CTE are not yet fully understood.
No agreement has been reached about how much or little head trauma is needed for CTE to develop, or the overarching mechanism of injury. Recently, investigators 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. 
The lack of in-vivo techniques to show distinct biomarkers for CTE is the reason for why CTE cannot be diagnosed during lifetime. 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.
CTE was first noticed as a “peculiar condition” casually referred to as a “punch-drunk” syndrome in boxers and prizefighters before the 1930s. It was recognized as affecting individuals who took considerable blows to the head, but was believed to be confined to boxers and not other athletes. 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 
In 2002, 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, in 2012 a medical examiner and associate adjunct professor in California, was a co-founder of BIRI and reportedly in 2012 participated in the autopsy of Junior Seau.
As of December 2012, thirty-three former National Football League (NFL) players have been diagnosed post-mortem with CTE. 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, and former Chicago Bears safety Dave Duerson, 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., among others.
An autopsy conducted in 2010 on the brain of Owen Thomas, a 21-year-old junior lineman at the University of Pennsylvania who committed 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, after Mike Borich, who died at 42. The doctors who performed the autopsy indicated that they found no causal connection between the nascent CTE and Thomas's suicide. There were no records of Thomas missing any playing time due to concussion, but 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 committed suicide with a gunshot wound to the chest. There was speculation that he suffered 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 Junior did have evidence of CTE.
The NFL has taken measures to help prevent CTE. As of July 2011, the NFL has not only changed its return-to-play rules but is also spreading the risk of youth concussions to younger leagues. The number of contact practices has been reduced, based on the recent collective bargaining agreement These changes will likely impact university-level, high school and middle school football as well, but the extent of future sport-wide changes remains elusive.
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".
Bernie Kosar, who sustained several concussions during his twelve-year NFL career and has shown symptoms of CTE, has submitted himself to an experimental treatment program led by Dr. Rick Sponaugle of Florida that has alleviated many of his symptoms. The program, the details of which are proprietary, involves increasing blood flow to damaged portions of the brain. He has spoken out in public about his successes with the treatment in the hopes that others who suffer from the disease can find relief and avoid the fates of Duerson and Seau, both of whom were personal friends of Kosar's. The efficacy of Dr. Sponaugle's treatment has not been validated through any published clinical trials or other validated scientific process, nor has this treatment been supported by any reputable medical group conducting research into CTE.
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 suffered 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, had reportedly suffered from depression; 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", Shawn Thornton of the Boston Bruins, 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 2007, neuropathologists from the Sports Legacy Institute (an organization co-founded by Christopher Nowinski) 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 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 and Matt Morgan also agreed to donate their brains upon their deaths. Also in 2010, MLS soccer 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 Mickey 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 Dr. Robert Stern, a co-director of the research group. Dr. 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.
Other athletes diagnosed with CTE 
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American football 
Canadian football 
Professional wrestling 
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