Misplaced Pages

Chronic traumatic encephalopathy

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
(Redirected from Punchdrunk) Neurodegenerative disease caused by head injury "Punch drunk" redirects here. For other uses, see Punch drunk (disambiguation).

Medical condition
Chronic traumatic encephalopathy
Other namesTraumatic encephalopathy syndrome, dementia pugilistica, punch drunk syndrome
A normal brain (left) and one with advanced CTE (right)
SpecialtyNeurology, psychiatry, sports medicine
SymptomsBehavioral problems, mood problems, problems with thinking
ComplicationsBrain damage, dementia, aggression, depression, suicide
Usual onsetYears after initial injuries
CausesRepeated head injuries
Risk factorsContact sports, military service, repeated banging of the head
Diagnostic methodAutopsy
Differential diagnosisAlzheimer's disease, Parkinson's disease
TreatmentSupportive care
PrognosisWorsens over time
FrequencyUncertain

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse over time and can result in dementia.

Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, mixed martial arts, and Muay Thai 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 (soccer), but largely as a result of heading the ball rather than player contact. Other risk factors include being in the military (combat arms), prior domestic violence, and repeated banging of the head. The exact amount of trauma required for the condition to occur is unknown, and as of 2022 definitive diagnosis can only occur at autopsy. The disease is classified as a tauopathy.

There is no specific treatment for the disease. Rates of CTE have been found to be about 30% among those with a history of multiple head injuries; 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". It has been proposed that the rules of some sports be changed as a means of prevention.

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 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 disorders such as amnesia, and ocular abnormalities, such as ptosis. The condition manifests as dementia, or declining mental ability, problems with memory, dizzy spells or lack of balance to the point of not being able to walk under one's own power for a short time and/or Parkinsonism, or tremors and lack of coordination. It can also cause speech problems and an unsteady gait. Patients with CTE may be prone to inappropriate or explosive behavior and may display pathological jealousy or paranoia.

Cause

See also: Chronic traumatic encephalopathy in sports

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, and association football. In association football (soccer), whether this is just associated with prolific headers or other injuries is unclear as of 2017. Other potential risk factors include military personnel (repeated exposure to explosive charges or large caliber ordnance), domestic violence, and repeated impact to the head. 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. An improvised explosive device is a homemade explosive that is commonly used in war. The blast from one IED can produce many symptoms of CTE. Another cause of CTE is an excessive buildup of misfolded Tau proteins, which is where the protein misfolds, setting off a reaction that slowly kills the brain cells. The exact amount of trauma required for the condition to occur is unknown, although it is believed that it may take years to develop.

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, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes, 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). Supporting features of CTE are: superficial neurofibrillary tangles (NFTs); p–tau in CA2 and CA4 hippocampus; p-tau in: mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus; p-tau thorn-shaped astrocytes (TSA) in the subpial region; p-tau dot-like neurites. Purely astrocytic perivascular p-tau pathology represents ARTAG and does not meet the criteria for 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.

Loss of neurons, scarring of brain tissue, collection of proteinaceous 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. One group examined slices of brain from patients having had multiple mild traumatic brain injuries and found changes in the cells' cytoskeletons, which they suggested might be due to damage to cerebral blood vessels.

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.

Diagnosis

Diagnosis of CTE cannot be made in living individuals; a clear diagnosis is only possible during an autopsy. Though there are signs and symptoms some researchers associate with CTE, there is no definitive test to prove the existence in a living person. Signs are also very similar to those of other neurological conditions, such as Alzheimer's.

The lack of distinct biomarkers 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. 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 examining whether neuroimaging can detect subtle changes in axonal integrity and structural lesions that can occur in CTE. By the early 2010s, more progress in in-vivo diagnostic techniques for CTE had 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 the diagnosis of CTE in living individuals. One candidate is the tracer FDDNP, 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. 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, 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 -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 using 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 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. Imaging techniques include the use of magnetic resonance imaging, nuclear magnetic resonance spectroscopy, CT scan, single-photon emission computed tomography, Diffusion MRI, and Positron emission tomography (PET). One specific use of imaging is the use of a PET scan is to evaluate for tau deposition, which has been conducted on retired NFL players.

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, both have been shown to reduce direct head trauma. Although there is no significant research to support the use of helmets to reduce the risk of concussions, there is evidence to support that helmet use reduces impact forces. The sports in which a helmet was effective in preventing TBI and concussions were skiing and snowboarding. Mouth guards have been shown to decrease dental injuries, but again have not shown significant evidence to reduce concussions. Because repeated impacts are thought to increase the likelihood of CTE development, a growing area of practice is improved recognition and treatment for concussions and other head trauma; removal from sport participation during recovery from these traumatic injuries is essential. Proper return-to-play protocol after possible brain injuries is also important in decreasing the significance of future impacts.

Efforts are being made to change the rules of contact sports to reduce the frequency and severity of blows to the head. Examples of these rule changes are the evolution of tackling technique rules in American football, such as the banning of helmet-first tackles, and the addition of rules to protect defenseless players. Likewise, another growing area of debate is better implementation of rules already in place to protect athletes.

Because of the concern that boxing may cause CTE, there is a movement among medical professionals to ban the sport. Medical professionals have called for such a ban as early as the 1950s.

Management

No cure exists for CTE, and it cannot be diagnosed until a post-mortem autopsy is performed. Treatment is supportive as with other forms of dementia. Those with CTE-related symptoms may receive medication and non-medication-related treatments. Currently, there is no way to stop or slow the development of chronic traumatic encephalopathy (CTE). However, medications like Aricept (donepezil) and Namenda (memantine) can mitigate memory loss and confusion, and Aricept can improve memory, motivation, and attention by increasing acetylcholine levels in the brain. Memantine is a cognitive enhancer that can help with memory loss and confusion. These medications are also treatments for Alzheimer's disease and dementia. There are also antidepressants like selective serotonin reuptake inhibitors (SSRIs), which can potentially help manage some of the behavioral and emotional symptoms associated with chronic traumatic encephalopathy (CTE) and may have a small improvement in memory function, mood, and alertness. SSRIs are often the first choice of treatment for CTE due to their effectiveness.

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. These contact-sports include American football, Australian rules football, ice hockey, Rugby football (Rugby union and Rugby league), boxing, kickboxing, mixed martial arts, association football, and wrestling. In association football, only prolific headers are known to have developed CTE.

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 seizures, 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. The term "punch-drunk" was replaced with "dementia pugilistica" in 1937 by J.A. Millsbaugh, as he felt the term was condescending to former boxers. The initial diagnosis of dementia pugilistica was derived from the Latin word for boxer, pugil (akin to pugnus 'fist', pugnāre 'to fight').

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.

British neurologist, Macdonald Critchley, wrote a 1949 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 2005, Dr. Bennet Omalu performed an autopsy on American football player Mike Webster, and he concluded that he was the first person to be officially diagnosed with chronic traumatic encephalopathy. He originally looked over the brain, expecting to see a brain affected by Alzheimer's. After an external examination of the brain, Dr. Omalu saw nothing out of the ordinary. However, after fixing and dissecting the brain, he observed abnormal proteins clump tangles that were distinct from those observed in Alzheimer’s disease.

The most famous case of CTE is that of former NFL player Aaron Hernandez. In 2012, he was accused of shooting and killing Daniel de Abreu and Safrio Furtado. He was convicted of killing Odin Lloyd, and all evidence pointed towards him. Two years into his jail sentence, he was found hanging in his cell. His brain was donated for science, where it was determined he had the worst case of CTE ever seen for his age. He had CTE stage 3, second in severity only to stage 4. His brain has been stated to be the most significant donation ever received.

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. To date, the VA-BU-CLF Brain Bank is the largest CTE tissue repository in the world, with over 1000 brain donors.

On December 21, 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. Additionally, in 2010 the National Football League gave the BU CTE Center 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 VA-BU-CLF Brain Bank after their deaths. In 2009, NFL Pro Bowlers Matt Birk, Lofa Tatupu, and Sean Morey pledged to donate their brains to the VA-BU-CLF Brain Bank.

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.

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.

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. Duerson left 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 gift was the first time of which he was aware that such a request had been made by someone who had committed suicide that was 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 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.

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 (SMs) 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 to study brain injuries in military veterans. 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.

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. A post-mortem examination revealed that Green was suffering from one of the most "severe forms" of CTE. Professor Michael Buckland said Green had "an organic brain disease which robbed him of his decision-making and impulse control." He added Green would likely have been "symptomatic for some time."

Research into the genetic component of CTE is evolving and well summarized in a recent review. The minor allele of TMEM106B is associated with a protective phenotype.

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. Also in 2023, a study was published on August 28 in JAMA Neurology regarding brain autopsies of athletes, one of whom was the first American female athlete diagnosed with CTE; her name is unknown, but she died at age 28 and was a collegiate soccer player.

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. His brain had been donated by his family to the Neurological Foundation Human Brain Bank at the University of Auckland, with post-mortem analyses conducted in New Zealand and Australia eventually finding "background changes consistent with global hypoxic ischaemic encephalopathy", as well as trauma-induced cavum septum pellucidum and age-related tau deposits.

See also

References

  1. ^ Asken BM, Sullan MJ, DeKosky ST, et al. (1 October 2017). "Research Gaps and Controversies in Chronic Traumatic Encephalopathy: A Review". JAMA Neurology. 74 (10): 1255–62. doi:10.1001/jamaneurol.2017.2396. PMID 28975240. S2CID 24317634.
  2. ^ Stein TD, Alvarez VE, McKee AC (2014). "Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel". Alzheimer's Research & Therapy. 6 (1): 4. doi:10.1186/alzrt234. PMC 3979082. PMID 24423082.
  3. ^ "Alzheimer's & Dementia". Alzheimer's Association. Retrieved 21 September 2017.
  4. McKee AC, Stein TD, Huber BR, et al. (April 2023). "Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts". Acta Neuropathologica. 145 (4): 371–394. doi:10.1007/s00401-023-02540-w. PMC 10020327. PMID 36759368.
  5. ^ Maroon JC, Winkelman R, Bost J, et al. (2015). "Chronic Traumatic Encephalopathy in Contact Sports: A Systematic Review of All Reported Pathological Cases". PLOS One. 10 (2): e0117338. Bibcode:2015PLoSO..1017338M. doi:10.1371/journal.pone.0117338. PMC 4324991. PMID 25671598. (Erratum: doi:10.1371/journal.pone.0130507, PMID 26039052,  Retraction Watch. If the erratum has been checked and does not affect the cited material, please replace {{erratum|...}} with {{erratum|...|checked=yes}}.)
  6. ^ McKee AC, Cantu RC, Nowinski CJ, et al. (2009). "Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury". J Neuropathol Exp Neurol. 68 (7): 709–35. doi:10.1097/NEN.0b013e3181a9d503. PMC 2945234. PMID 19535999.
  7. Fesharaki-Zadeh A (2019). "Chronic Traumatic Encephalopathy: A Brief Overview". Frontiers in Neurology. 10: 713. doi:10.3389/fneur.2019.00713. PMC 6616127. PMID 31333567.
  8. ^ Corsellis, et al. (1973). "The Aftermath of Boxing". Psychological Medicine. 3 (3): 270–303. doi:10.1017/S0033291700049588. PMID 4729191. S2CID 41879040.
  9. ^ Mendez MF (1995). "The neuropsychiatric aspects of boxing". International Journal of Psychiatry in Medicine. 25 (3): 249–62. doi:10.2190/CUMK-THT1-X98M-WB4C. PMID 8567192. S2CID 20238578.
  11. Nitrini R (2017). "Soccer (Football Association) and chronic traumatic encephalopathy: A short review and recommendation". Dementia & Neuropsychologia. 11 (3): 218–20. doi:10.1590/1980-57642016dn11-030002. PMC 5674664. PMID 29213517.
  12. Ruprecht M (8 June 2022). "Evidence of CTE Rare in Military Personnel". MedPage Today. Retrieved 15 December 2024.
  13. "Study Shows First Case Series of Chronic Traumatic Encephalopathy in Blast-Exposed Military Service Personnel and Mechanism of Injury in Blast Neurotrauma | Chobanian & Avedisian School of Medicine". www.bumc.bu.edu. Retrieved 19 November 2024.
  14. "What is CTE?". Concussion Legacy Foundation. Retrieved 19 November 2024.
  15. ^ McKee AC, Stern RA, Nowinski CJ, et al. (2013). "The spectrum of disease in chronic traumatic encephalopathy". Brain. 136 (Pt 1): 43–64. doi:10.1093/brain/aws307. PMC 3624697. PMID 23208308.
  16. ^ Baugh CM, Stamm JM, Riley DO, et al. (2012). "Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma". Brain Imaging Behavior. 6 (2): 244–54. doi:10.1007/s11682-012-9164-5. PMID 22552850. S2CID 15955018.
  17. Jancin B (1 June 2011). "Chronic traumatic encephalopathy test sought". Internal Medicine News. Retrieved 15 December 2013.
  18. ^ Bienek KF, al e (21 February 2021). "The Second NINDS/NIBIB Consensus Meeting to Define Neuropathological Criteria for the Diagnosis of Chronic Traumatic Encephalopathy". Neuropathology and Experimental Neurology. 80 (3): 210–219. doi:10.1093/jnen/nlab001. PMC 7899277. PMID 33611507.
  19. McKee AC, al e (January 2016). "The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy". Acta Neuropathologica. 131 (1): 75–86. doi:10.1007/s00401-015-1515-z. PMC 4698281. PMID 26667418.
  20. Taylor DD, Gercel-Taylor C (2014). "Exosome platform for diagnosis and monitoring of traumatic brain injury". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 369 (1652): 20130503. doi:10.1098/rstb.2013.0503. PMC 4142024. PMID 25135964.
  21. Hof PR, Bouras C, Buée L, et al. (1992). "Differential Distribution of Neurofibrillary Tangles in the Cerebral Cortex of Dementia Pugilistica and Alzheimer's Disease Cases". Acta Neuropathologica. 85 (1): 23–30. doi:10.1007/BF00304630. PMID 1285493. S2CID 11624928.
  22. Geddes JF, Vowles GH, Nicoll JA, et al. (1999). "Neuronal Cytoskeletal Changes are an Early Consequence of Repetitive Head Injury". Acta Neuropathologica. 98 (2): 171–78. doi:10.1007/s004010051066. PMID 10442557. S2CID 24694052.
  23. Jordan, B. D. (2009). "Brain injury in boxing". Clinics in Sports Medicine, 28(4), 561–78, vi.
  24. Concannon L (2014). "Counseling Athletes on the Risk on Chronic Traumatic Encephalopathy". Sports Health. 6 (5): 396–401. doi:10.1177/1941738114530958. PMC 4137675. PMID 25177414.
  25. Turner, Ryan C., et al. "Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities", Brain Injury, August 11, 2016. Accessed December 28, 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."
  26. Poirier MP (2003). "Concussions: Assessment, management, and recommendations for return to activity". Clinical Pediatric Emergency Medicine. 4 (3): 179–85. doi:10.1016/S1522-8401(03)00061-2.
  27. Villemagne VL, Fodero-Tavoletti MT, Masters CL, et al. (2015). "Tau imaging: early progress and future directions". The Lancet. Neurology. 14 (1): 114–24. doi:10.1016/S1474-4422(14)70252-2. PMID 25496902. S2CID 10502833.
  28. Small GW, Kepe V, Siddarth P, et al. (2013). "PET scanning of brain tau in retired national football league players: preliminary findings". Am J Geriatr Psychiatry. 21 (2): 138–44. CiteSeerX 10.1.1.372.2960. doi:10.1016/j.jagp.2012.11.019. PMID 23343487.
  29. ^ Montenigro PH, Corp DT, Stein TD, et al. (2015). "Chronic traumatic encephalopathy: historical origins and current perspective". Annual Review of Clinical Psychology. 11: 309–30. doi:10.1146/annurev-clinpsy-032814-112814. PMID 25581233.
  30. John Mangels, Cleveland Plain Dealer, 2013/03.
  31. Marchi N, Bazarian JJ, Puvenna V, et al. (2013). "Consequences of repeated blood-brain barrier disruption in football players". PLOS ONE. 8 (3): e56805. Bibcode:2013PLoSO...856805M. doi:10.1371/journal.pone.0056805. PMC 3590196. PMID 23483891.
  32. ^ "BU Researchers Find CTE in 99% of Former NFL Players Studied". Boston University. 26 July 2017.
  33. ^ Concannon L (October 2014). "Counseling Athletes on the Risk of Chronic Traumatic Encephalopathy". Sports Health. 6 (5): 396–401. doi:10.1177/1941738114530958. PMC 4137675. PMID 25177414.
  34. Stern RA, Adler CH, Chen K, et al. (2019). "Tau Positron-Emission Tomography in Former National Football League Players". New England Journal of Medicine. 380 (18): 1716–25. doi:10.1056/NEJMoa1900757. ISSN 0028-4793. PMC 6636818. PMID 30969506.
  35. Sone JY, Kondziolka D, Huang JH, et al. (1 March 2017). "Helmet efficacy against concussion and traumatic brain injury: a review". Journal of Neurosurgery. 126 (3): 768–81. doi:10.3171/2016.2.JNS151972. ISSN 1933-0693. PMID 27231972.
  36. Saffary R (2012). "From Concussion to Chronic Traumatic Encephalopathy: A Review". Journal of Clinical Sport Psychology: 315–62.
  37. Emery CA, Black AM, Kolstad A, et al. (1 June 2017). "What strategies can be used to effectively reduce the risk of concussion in sport? A systematic review". British Journal of Sports Medicine. 51 (12): 978–984. doi:10.1136/bjsports-2016-097452. ISSN 0306-3674. PMID 28254746. S2CID 36589540.
  38. "Alzheimer's & Dementia". Alzheimer's Association. alz.org. Retrieved 21 September 2017.
  39. "Treating CTE". NHS Choices. GOV.UK. 1 October 2017. Retrieved 14 February 2018.
  40. Cantu R, Budson A (October 2019). "Management of chronic traumatic encephalopathy". Expert Review of Neurotherapeutics. 19 (10): 1015–23. doi:10.1080/14737175.2019.1633916. PMID 31215252. S2CID 195064872.
  41. "CTE Treatments". Concussion Legacy Foundation. Retrieved 19 November 2024.
  42. Memory and aging center WI. "A Healthcare Provider's Guide To Chronic Traumatic Encephalopathy (CTE):" (PDF).
  43. Stein T (16 October 2024). "Concussion in Chronic Traumatic Encephalopathy". SpringerNature Link.
  44. Saulle M, Greenwald BD (2012). "Chronic traumatic encephalopathy: a review" (PDF). Rehabil Res Pract. 2012: 1–9. doi:10.1155/2012/816069. PMC 3337491. PMID 22567320.
  45. "CTE discovered in Polly Farmer's brain in AFL-first". 26 February 2020.
  46. ^ Stone, Paul (18 March 2014). "First Soccer and Rugby Players Diagnosed With CTE". Neurologic Rehabilitation Institute at Brookhaven Hospital. Retrieved 21 March 2016.
  47. ^ Ling H, Morris HR, Neal JW, et al. (March 2017). "Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players". Acta Neuropathologica. 133 (3): 337–52. doi:10.1007/s00401-017-1680-3. PMC 5325836. PMID 28205009.
  48. Daneshvar DH, Nowinski CJ, McKee AC, et al. (2011). "The epidemiology of sport-related concussion". Clin Sports Med. 30 (1): 1–17, vii. doi:10.1016/j.csm.2010.08.006. PMC 2987636. PMID 21074078.
  49. Cohen N (2 November 2018). "Baseball's New Three-Letter Word: CTE". The Good Men Project.
  50. Iverson G (19 October 2024). "Suicide and Chronic Traumatic Encephalopathy". Neuropsychiatry. 28: 9–16.
  51. Daneshvar DH, Riley DO, Nowinski CJ, et al. (2011). "Long-term consequences: effects on normal development profile after concussion". Phys Med Rehabil Clin N Am. 22 (4): 683–700, ix. doi:10.1016/j.pmr.2011.08.009. PMC 3208826. PMID 22050943.
  52. Shetty T (2016). "Imaging in Chronic Traumatic Encephalopathy and Traumatic Brain Injury". Sports Health. 8 (1): 26–36. doi:10.1177/1941738115588745. PMC 4702153. PMID 26733590.
  53. Martland HS (1928). "Punch Drunk". Journal of the American Medical Association. 91 (15): 1103–07. doi:10.1001/jama.1928.02700150029009.
  54. Castellani RJ, Perry G (7 November 2017). "Dementia Pugilistica Revisited". Journal of Alzheimer's Disease. 60 (4): 1209–21. doi:10.3233/JAD-170669. PMC 5676846. PMID 29036831.
  55. Pugilism (origin), retrieved on 2 February 2013.
  56. NCERx. 2005. Brain Trauma, Subdural Hematoma and Dementia Pugilistica Archived 27 May 2007 at the Wayback Machine. About – dementia.com. Retrieved on 19 December 2007.
  57. "'Concussion' Subject Bennet Omalu Exaggerated His Role, Researchers Say". CBS New York. 17 December 2015.
  58. Martland H (1928). "Punch Drunk". The Journal of the American Medical Association. 91 (15): 1103–07. doi:10.1001/jama.1928.02700150029009.
  59. Gavett BE, Stern RA, McKee AC (2011). "Chronic traumatic encephalopathy: a potential late effect of sport-related concussive and subconcussive head trauma". Clin Sports Med. 30 (1): 179–88, xi. doi:10.1016/j.csm.2010.09.007. PMC 2995699. PMID 21074091.
  60. "Physician who discovered CTE in NFL players gets AMA's highest honor". American Medical Association. 12 November 2016. Retrieved 19 November 2024.
  61. "tag page". FRONTLINE. Retrieved 19 November 2024.
  62. Levenson E (21 October 2024). "A timeline of Aaron Hernandez's football career, criminal cases and death". CNN. Retrieved 19 November 2024.
  63. Bracken T (20 January 2020). "Aaron Hernandez's CTE Worst Seen in a Young Person". Boston University. Retrieved 19 November 2024.
  64. "US health body rules collision sports cause CTE in landmark change". The Guardian. 24 October 2022. Retrieved 25 October 2022.
  65. Omalu BI, DeKosky ST, Hamilton RL, et al. (1 November 2006). "Chronic traumatic encephalopathy in a national football league player: part II". Neurosurgery. 59 (5): 1086–1092, discussion 1092–1093. doi:10.1227/01.NEU.0000245601.69451.27. ISSN 1524-4040. PMID 17143242. S2CID 7460284.
  66. "VA-BU-CLF Brain Bank | CTE Center". www.bu.edu. Retrieved 12 August 2021.
  67. "1000 Reasons | Concussion Legacy Foundation". concussionfoundation.org. Retrieved 12 August 2021.
  68. 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.
  69. Support and Funding Archived 15 July 2010 at the Wayback Machine, Center for the Study of Traumatic Encephalopathy. Accessed 17 August 2010.
  70. Schwarz, Alan. "N.F.L. Donates $1 Million for Brain Studies", The New York Times, 20 April 2010. Accessed 17 August 2010.
  71. "Welch to donate brain for concussion study". Edmonton Journal. Archived from the original on 6 October 2010. Retrieved 18 December 2008.
  72. 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.
  73. 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.
  74. Boren, Cindy. "Dale Earnhardt Jr. plans to donate his brain for concussion research", The Washington Post, March 28, 2016. Accessed December 28, 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."
  75. "A Study on the Association Between Football Exposure and Dementia in Retired Football Players". UNC College of Arts and Sciences. Archived from the original on 11 August 2012. Retrieved 1 August 2012.
  76. Smith, Michael David, "Boston researchers request Junior Seau's brain". NBC Sports Pro Football Talk, 3 May 2012. Retrieved 3 May 2012.
  77. Kusinski P (1 February 2011). "Dave Duerson Committed Suicide: Medical Examiner". NBC Chicago. Retrieved 20 February 2011.
  78. Schwarz A (20 February 2011). "Before Suicide, Duerson Asked for Brain Study". The New York Times.
  79. Deardorff, Julie (2 May 2011). "Study: Duerson had brain damage at time of suicide". Los Angeles Times. Retrieved 2 May 2011.
  80. Schwarz, Alan (2 March 2011). "Hockey Brawler Paid Price, With Brain Trauma". The New York Times. Retrieved 14 March 2011.
  81. "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.
  82. Jordan B (12 August 2013). "Obama Introduces New PTSD and Education Programs". military.com. Retrieved 2 May 2014.
  83. "Obama administration to research TBI, PTSD in new efforts Read more: Chronic Effects of Neurotrauma Consortium". fiercegovernment.com. Archived from the original on 2 May 2014. Retrieved 2 May 2014.
  84. "DoD, VA Establish Two Multi-Institutional Consortia to Research PTSD and TBI". va.gov. Retrieved 2 May 2014.
  85. ^ "Fact Sheet: Largest federal grant in VCU's history". spectrum.vcu.edu. Retrieved 2 May 2014.
  86. ^ "VCU to lead major study of concussions". grpva.com. Archived from the original on 3 May 2014. Retrieved 2 May 2014.
  87. ^ "Brain trust – the US consortia tacking military PTSD and brain injury". army-technology.com. 9 March 2014. Retrieved 2 May 2014.
  88. ^ "DOD partners to combat brain injury". army.mil. 19 August 2013. Retrieved 2 May 2014.
  89. "RTI to research mild traumatic brain injury effects in US soldiers". army-technology.com. 2 August 2013. Retrieved 2 May 2014.
  90. Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil. 2006; 21 (5): 398–402.
  91. "DoD Worldwide Numbers for TBI". dvbic.dcoe.mil. Archived from the original on 17 January 2014. Retrieved 4 February 2013.
  92. Scholten JD, Sayer NA, Vanderploeg RD, et al. (2012). "Analysis of US Veterans Health Administration comprehensive evaluations for traumatic brain injury in Operation Enduring Freedom and Operation Iraqi Freedom Veterans". Brain Inj. 26 (10): 1177–84. doi:10.3109/02699052.2012.661914. PMID 22646489. S2CID 37365962.
  93. Taylor BC, Hagel EM, Carlson KF, et al. (2012). "Prevalence and costs of co-occurring traumatic brain injury with and without psychiatric disturbance and pain among Afghanistan and Iraq War Veteran V.A. users". Med Care. 50 (4): 342–46. doi:10.1097/MLR.0b013e318245a558. PMID 22228249. S2CID 29920171.
  94. Weppner J, Linsenmeyer M, Ide W (1 August 2019). "Military Blast-Related Traumatic Brain Injury". Current Physical Medicine and Rehabilitation Reports. 7 (4). Brain Injury Medicine and Rehabilitation: 323–32. doi:10.1007/s40141-019-00241-8. S2CID 199407324. Retrieved 10 May 2020.
  95. "Fact Sheet: The Obama Administration's Work to Honor Our Military Families and Veterans". whitehouse.gov. 1 August 2013. Retrieved 2 May 2014 – via National Archives.
  96. "Fact Sheet: VCU will lead $62 million study of traumatic brain injuries in military personnel". news.vcu.edu. Retrieved 2 May 2014.
  97. About Us Archived 22 December 2015 at the Wayback Machine, Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University. Retrieved 21 December 2015.
  98. Kilgore A (9 November 2017). "Aaron Hernandez suffered from most severe CTE ever found in a person his age". Washington Post. Retrieved 12 July 2020.
  99. Proszenko A. "Paul Green's brain donated to Australian Sports Brain Bank". Brisbane Times. Nine Media. Retrieved 18 August 2022.
  100. Waterworth B (22 October 2022). "'Daddy's brain was sick': Paul Green's wife Amanda reveals truth behind death that rocked NRL". foxsports.com.au. News Corporation Australia. Retrieved 26 October 2022.
  101. ^ Abdolmohammadi B, Dupre A, Evers L, et al. (August 2020). "Genetics of Chronic Traumatic Encephalopathy". Seminars in Neurology. 40 (4): 420–429. doi:10.1055/s-0040-1713631. ISSN 1098-9021. PMID 32712945. S2CID 220798883.
  102. "Heather Anderson diagnosed with CTE in 1st case for female athlete". ESPN. 4 July 2023.
  103. Mozes A (29 August 2023). "Autopsy Study of Athletes Who Died Young Shows Many Had Signs of CTE".
  104. ^ RNZ (14 March 2024). "Brain injury from head knocks discovered in late Blues halfback". The New Zealand Herald. Retrieved 16 March 2024.
  105. ^ Aylwin M (14 March 2024). "First professional rugby union player confirmed to have died with CTE". The Guardian. ISSN 0261-3077. Retrieved 16 March 2024.

External links

ClassificationD
Neurotrauma
Traumatic brain injury
Spinal cord injury
Peripheral nerves
Trauma
Principles
Assessment
Clinical prediction rules
Investigations
Management
Principles
Procedures
Pathophysiology
Injury
Mechanism
Region
Demographic
Complications
Categories: