Chronic traumatic encephalopathy ( CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, , and problems with thinking.
Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, mixed martial arts, and contact sports such as rugby union, rugby league, American football, Australian rules football, professional wrestling, and ice hockey. It is also an issue in association football, but largely as a result of heading the ball rather than player contact.[ The exact amount of trauma required for the condition to occur is unknown, and as of 2025 definitive diagnosis can only occur at autopsy.][ The disease is classified as a tauopathy.][
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There is no specific treatment for the disease.[ however, population rates are unclear.][ Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as dementia pugilistica or "boxer's dementia", "boxer's madness", or "punch drunk syndrome".][
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Signs and symptoms
Symptoms of CTE, which occur in four stages, generally appear eight to ten years after an individual experiences repetitive mild traumatic brain injuries.
First-stage symptoms are confusion, disorientation, dizziness, and headache. 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, , vertigo, deafness, depression and suicidality.
Additional symptoms include dysarthria, dysphagia, cognitive disorders such as amnesia, and ocular abnormalities, such as ptosis.
Cause
Most documented cases have occurred in athletes with mild repetitive head impacts (RHI) over an extended period. Evidence indicates that repetitive concussive and subconcussive blows to the head cause CTE.[
] In particular, it is associated with contact sports such as boxing, American football, Australian rules football, wrestling, mixed martial arts, ice hockey, Rugby football, and association football.[ In association football, whether this is just associated with prolific headers or other injuries is unclear as of 2017.][ Although many military personnel are around blasts and explosions very often, it is very rare for these personnel to be diagnosed with CTE. Studies have shown that only 4.4% of deceased military veterans have been diagnosed with CTE.][
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Pathology
The Neuropathology 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.
On a microscopic scale, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped , at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma, and not restricted to the subpial and superficial region of the sulcus; the pathognomonic lesion must include p-tau in neurons to distinguish CTE from aging-related tau astrogliopathy (ARTAG).
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.
Loss of , scarring of brain tissue, collection of senile plaques, hydrocephalus, attenuation of the corpus callosum, diffuse axonal injury, neurofibrillary tangles, and damage to the cerebellum are implicated in the syndrome. Neurofibrillary tangles have been found in the brains of dementia pugilistica patients, but not in the same distribution as is usually found in people with Alzheimer's.
Increased exposure to concussions and subconcussive blows is regarded as the most important risk factor. In boxing, this exposure can depend on the total number of fights, number of knockout losses, duration of career, fight frequency, age of retirement, and boxing style.[Jordan, B. D. (2009). "Brain injury in boxing". Clinics in Sports Medicine, 28(4), 561–78, vi.]
Diagnosis
Diagnosis of CTE cannot be made in living individuals; a clear diagnosis is only possible during an autopsy.[Turner, Ryan C., et al. "Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities", Brain Injury, 11 August 2016. Accessed 28 December 2021. "Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE) have long been recognized as sharing some similar neuropathological features, mainly the presence of neurofibrillary tangles and hyperphosphorylated tau, but have generally been described as distinct entities. Evidence indicates that neurotrauma increases the risk of developing dementia and accelerates the progression of disease. Findings are emerging that CTE and AD may be present in the same patients."]
The lack of distinct is the reason CTE cannot typically be diagnosed while a person is alive. 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.
PET tracers that bind specifically to tau protein are desired to aid the diagnosis of CTE in living individuals. One candidate is the tracer , which is retained in the brain in individuals with several dementing disorders such as Alzheimer's disease, Down syndrome, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia, and Creutzfeldt–Jakob disease.[
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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 using a disrupted blood-brain barrier, and attack neuronal cells which are normally protected from an immune onslaught.[John Mangels, Cleveland Plain Dealer, 2013/03.] 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 between the initial events (head hits) and the development of any signs or symptoms. Nevertheless, autoimmune changes in blood of players may constitute the earliest measurable event predicting CTE.
According to a 2017 study on the brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE. Players still alive are not able to be tested.
Imaging
Although the diagnosis of CTE cannot be determined by imaging, the effects of head trauma may be seen with the use of structural imaging.
Prevention
The use of helmets and mouth guards has been put forward as a possible preventative measure; though neither has significant research to support its use,
Efforts are being made to change the rules of contact sports to reduce the frequency and severity of blows to the head.
Because of the concern that boxing may cause CTE, there is a movement among medical professionals to ban the sport.
Management
No cure exists for CTE, and it cannot be diagnosed until a post-mortem autopsy is performed.
Epidemiology
Rates of disease are about 30% among those with a history of multiple head injuries.[ Population rates, however, are unclear.][ Tracking the epidemiology of CTE is difficult due to the inability to diagnose this syndrome during life.]
Professional level athletes are the largest group with CTE, due to frequent concussions and sub-concussive impacts from play in contact sport.
Cases of CTE were also recorded in baseball.
According to a 2017 study on brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE.
As reported in a study published by Roberts, about 11% of the retired boxers he examined had a mild case of CTE, and about 6% of the boxers had major neurological problems. Through these clinical examinations, Roberts was able to establish associations between exposure to violence and the effects of CTE. He stated that among the boxers who are over the age of 50 and fought in over 150 fights, about 50% of them had CTE. This number was compared to the 7% of the boxers who had CTE and had less than 50 fights.
Other individuals diagnosed with CTE were those involved in military service, had a previous history of chronic , were domestically abused, or were involved in activities resulting in repetitive head collisions.
History
CTE was originally studied in boxers in the 1920s as "punch-drunk syndrome." The punch-drunk syndrome was first described in 1928 by a forensic pathologist, Harrison Stanford Martland, who was the chief medical examiner of Essex County in Newark, New Jersey, in a Journal of the American Medical Association article, in which he noted the tremors, slowed movement, confusion and speech problems typical of the condition.[ Pugilism (origin), retrieved on 2 February 2013.][NCERx. 2005. Brain Trauma, Subdural Hematoma and Dementia Pugilistica . About – dementia.com. Retrieved on 19 December 2007.]
Other terms for the condition have included chronic boxer's encephalopathy, traumatic boxer's encephalopathy, boxer's dementia, pugilistic dementia, chronic traumatic brain injury associated with boxing (CTBI-B), and punch-drunk syndrome.
Neurologist Macdonald Critchley wrote a 1949 paper titled "Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers".[ "'Concussion' Subject Bennet Omalu Exaggerated His Role, Researchers Say". CBS New York. 17 December 2015.] 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 2005, Bennet Omalu
A famous case of CTE is that of former NFL player Aaron Hernandez.
In October 2022, the United States National Institutes of Health formally acknowledged there was a causal link between repeated blows to the head and 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 Center for the Study of Traumatic Encephalopathy at the BU School of Medicine (now the BU CTE Center) started the VA-BU-CLF Brain Bank at the Bedford Veterans Administration Hospital to analyze the effects of CTE and other neurodegenerative diseases on the brain and spinal cord of athletes, military veterans, and civilians.
On 21 December 2009, the National Football League Players Association announced that it would collaborate with the BU CTE Center to support the center's study of repetitive brain trauma in athletes.[Staff. "NFL Players Association to Support Brain Trauma Research at Boston University", Center for the Study of Traumatic Encephalopathy press release dated 21 December 2009. Accessed 17 August 2010.] Additionally, in 2010 the National Football League gave the BU CTE Center a $1 million gift with no strings attached.[ Support and Funding , Center for the Study of Traumatic Encephalopathy. Accessed 17 August 2010.][Alan Schwarz. "N.F.L. Donates $1 Million for Brain Studies", The New York Times, 20 April 2010. Accessed 17 August 2010.] 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 VA-BU-CLF Brain Bank after their deaths.[Staff. "Three active NFL Pro Bowl players to donate brains to research", Center for the Study of Traumatic Encephalopathy press release dated 14 September 2009. Accessed 17 August 2010.]
In 2010, 20 more NFL players and former players pledged to join the VA-BU-CLF 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 VA-BU-CLF Brain Donation Registry consists of over 250 current and former athletes.[Staff. "20 more NFL stars to donate brains to research", Center for the Study of Traumatic Encephalopathy press release dated 1 February 2010. Accessed 17 August 2010.]
In 2011, former North Queensland Cowboys player Shaun Valentine became the first Australian National Rugby League 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 2018, NASCAR driver Dale Earnhardt Jr., who retired in 2017 citing multiple concussions, became the first auto racing competitor to agree to donate his brain upon his death.[Boren, Cindy. "Dale Earnhardt Jr. plans to donate his brain for concussion research", The Washington Post, 28 March 2016. Accessed 28 December 2021. "He announced the most Dale Earnhardt Jr. way possible, with a nonchalant tweet on a Saturday night. That's how NASCAR's most popular driver disclosed that he would donate his brain posthumously to science. His announcement came in response to a Sports Illustrated tweet and responses about three members of the Oakland Raiders decided to donate their brains to the Concussion Legacy Foundation after learning that Hall of Famer Ken Stabler's brain showed evidence of chronic traumatic encephalopathy at autopsy."]
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, former NFL player Dave Duerson committed suicide via a gunshot to his chest, thus leaving his brain intact.[Smith, Michael David, "Boston researchers request Junior Seau's brain". NBC Sports Pro Football Talk, 3 May 2012. Retrieved 3 May 2012.] Duerson left text messages to loved ones asking that his brain be donated to research for 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 was the second NHL player from the program at the BU CTE Center to be diagnosed with CTE postmortem.
The BU CTE Center 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 VA-BU-CLF Brain Bank at the Bedford, Massachusetts VA Medical Center.[ "Researchers Discover Brain Trauma in Sports May Cause a New Disease That Mimics ALS", BUSM press release, 17 August 2010 3:41 pm. Retrieved 11 September 2011.]
In 2013, 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 (SMs) and veterans.
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),[Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil. 2006; 21 (5): 398–402.]
After a competitive application process, a consortium led by Virginia Commonwealth University was awarded funding to study brain injuries in military veterans.[ About Us , Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University. Retrieved 21 December 2015.] 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,
In 2017, Aaron Hernandez, a former professional football player and convicted murderer, committed suicide at the age of 27 while in prison. His family donated his brain to the BU CTE Center. Ann McKee, the head of Center, concluded that "Hernandez had Stage 3 CTE, which researchers had never seen in a brain younger than 46 years old."
In 2022, former NRL player and coach Paul Green died by suicide at the age of 49. Green's brain was donated to the Australian Sports Brain Bank, with his family posting on the website "In memory of our beloved Paul, we ask that you support the pioneering work of the Australian Sports Brain Bank" to raise money for further understanding of CTE.
Research into the genetic component of CTE is evolving and well summarized in a recent review.
In 2023, Australian rules football player Heather Anderson became the first female athlete diagnosed with CTE after her death by suicide on 13 November 2022, at the age of 28. Her brain, which was donated to the Australian Sports Brain Bank, was found to contain multiple CTE lesions, and abnormalities were found "nearly everywhere" in the cortex.
In March 2024, former rugby union player Billy Guyton became the first New Zealand-based athlete diagnosed with CTE following his forced retirement in 2018, due to the complications of multiple concussions, and his death by suspected suicide in 2023.
See also
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Acquired brain injury
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Brain damage
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Chronic traumatic encephalopathy in sports
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Concussions in American football
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Concussions in rugby union
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Health issues in American football
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List of NFL players with chronic traumatic encephalopathy
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Chuck Bednarik
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The Hit (Chuck Bednarik)
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Traumatic brain injury
External links
