Chronic Traumatic Encephalopathy

Chronic Traumatic Encephalopathy
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A comparison of a healthy brain to that of a brain diagnosed with CTE. [27]

Chronic Traumatic Encephalopathy(CTE) is a neurodegenerative disease that is believed to be caused from repeated blows to the head[1]. CTE has recently gained prominence due to big name athletes such as Junior Seau dying as a result of it and the media attention it has received recently [2]. The disease has been found to affect numerous areas of the brain including: frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and the brainstem [3]. The symptoms of CTE include memory loss, impaired cognition, unstable emotional state, and depression and typically start to appear many years after the athlete has retired [4]. Many modern sports feature varying degrees of head contact during action. The most notable being: football, boxing, and hockey. However even sports such as soccer and skiing have been found to result in concussions and can run the risk of developing CTE down the road [3]. CTE is an important illness to study as many athletes and even non-athletes can succumb to head injuries and as a result can possibly develop the illness. Recently, it’s been shown that CTE can be identified in living human brain tissue whereas before this was not possible[5]. However as of yet, there are no cures for CTE so it is important to investigate the onset of this disease on a molecular level and potentially look for ways to hinder the progression of the symptoms.

CTE Background


The first recorded diagnosis of CTE occurred in 1928 when boxers suffering from the illness were deemed to be "punch drunk" and later became known as dementia pugilistica which translates to dementia of a fighter. With the development of more contact sports, athletes from these sports started to show the symptoms of dementia pugilistica resulting in the illness obtaining its current name, Chronic Traumatic Encephalopathy [6]. In 1973 the first neuropathological symptoms of CTE were described from a study of former boxers[7] and in 2005, the histopathological aspects were documented for the first time[8]. CTE really first started receiving significant attention in 2005 when Bennet Omalu presented his findings of two football players who passed away due to the disease. These findings drew the interest of current lead researcher, Ann McKee and resulted in the creation of the world's inaugural centre devoted to the study of CTE, located at the Boston University Medical School[9].Over the past decade CTE has received more media attention sparking a rise in public awareness with regards to the illness and has started to become a hot topic in the sports medicine circles[8].

Clinical Aspects of CTE


CTE is believed to manifest as a result of repeated head blows. Concussions are believed to play a role in triggering and maintaining the worsening of symptoms[10]. It is possible that traumatic brain injury without a symptomatic concussion can also lead to CTE[11]. All though the exact incidence of CTE following repetitive head trauma is not yet known, it is hypothesized that is much more likely to occur. In regards to the severity or how many times head trauma must occur for the onset of CTE to occur, little is known[3][11]. Recently, it was found that one concussion resulted in noticeable atrophy of white matter in the anterior cingulate area and cingulate gyrus. This area of the brain is known to be responsible for functions that are known to be hindered in CTE thus suggesting one concussion may suffice in order for CTE to manifest.[12]


The symptoms of CTE are believed to progressively worsen over time and can vary from patient to patient. The most common symptoms of CTE include dizziness, headache, an unsteady gait (also known as pattern of movements such as walking), fatigue, and dysarthria. Over time, these symptoms can decay further to produce cognitive impairments as well as detrimental social behavior such as memory loss, lack of focus, judgment incapability, emotional instability, and difficulty maintaining a job [10]. The symptoms of CTE were described to occur in three separate phases. During the first phase, psychotic symptoms and affective disturbances are observed. In the second phase, social instability, memory loss, erratic behavior, and initial symptoms of Parkinson's disease begin to appear. Lastly, in the third phase, the illness comprises of general cognitive dysfunction with progression to dementia and it is common to see the full development of Parkinson's disease in addition to the presence of speech and gait abnormalities. It should be noted that the mechanism of progression for these symptoms is not yet fully understood however it is believed the symptoms show up years and possibly decades after the last traumatic brain injury around midlife. Interestingly, there have been cases of early CTE symptoms in teenagers as well as young adults. [3][10][11].


When brains with CTE are examined, the majority show very similar pathology. Reduction in brain weight, enlargement of the third and lateral ventricles are characteristic of the disease. In addition the thinning of the corpus callosum. atrophy of temporal, frontal, parietal and occipital(rarely) lobes occurs. The atrophy of the thalamus, mammillary bodies, olfactory bulbs and brainstem is also observed on top of lack of dark substance in the substantia nigra and locus coeruleus . Finally a cavum septum pellucidum has been shown to occur in CTE patients.[3][10][11]. When the disease is very severe, atrophy of the hippocampus, entorhinal cortex and amygdala can be observed [3] At the molecular level, CTE can be considered a taupathy, indicating the presence of neurofibrillary tangles. An abundance of TAR DNA binding protein (TDP-43) are also present. [10][11]. The presence of TDP-43 provides an interesting aspect to CTE as this is a characteristic of amyotrophic lateral sclerosis (ALS) which is a disease involving the degeneration of motor neurons. This could provide insight as to why some patients with CTE have shown to have motor neuron degeneration,[13]. CTE also shares a common pathology with Alzheimer's Disease (AD) however the deposition of beta-amyloid is not persistently found in CTE. Another variance CTE and AD share is the location of tau deposition in CTE which tends to favor the neocortical layers II and III. It has also been noted that the tau deposition is denser in CTE compared to AD. [10]. CTE has been found to have a quicker onset of symptoms than that of sporadic AD or Fronto-Temporal Dementia however the memory loss associated with CTE has been found to not be as severe as that in AD[11].

Sports with known cases of CTE


Boxing is the sport that is most commonly linked to CTE. Professional boxers were the first athletes to be diagnosed with the disease and as such have been extensively studied the subject of many studies[3][14]. Due to lack of head protective gear, boxing experiences relatively high rates of CTE among its retired players. A study done nearly 50 years ago estimates the occurrence of the disease to be at approximately 17%. To date, this is considered to be the best estimate available for the rate of CTE among the sport[15]. Among potential risk factors, ApoE e4 genotype, Caucasian race, poor performances and slugging type fighters rank among the most frequently cited factors however repetitive head blows remains the most common risk factor[15]. To this day, chronic traumatic brain injury remains the most significant health concern in the sport[14].

A quick summary of CTE including the prevalence of the disease among Boxing and MMA [28]


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Junior Seau played in the NFL for 20 seasons [29]

In 1994, the committee for Mild Traumatic Brain Injury formed in the NFL in order to study the early retirement of various players due to post-concussion syndrome. One year later, the committee proposed to the NFL to fund independent scientists and the study of traumatic brain injury. Since then, the field on traumatic brain injury has not progressed far[16].In 2002, the first brain tissue of CTE from a deceased ex-NFL payer were published [17]. Numerous ex-players have committed suicide including former greats Junior Seau[18] and Andre Waters [19] both who were known for heavy hitting. As expected these players were found to have CTE. In addition it was shown in a study that retired NFL players who sustained three or more concussions were three times more likely to suffer from memory impairment and up to five times more likely to develop early onset of AD and/or clinical depression [19]. Approximately 1.9% of Retired NFL players aged from 30 to 49 were reported to have some form of memory problem, dementia, depression, and/or cognitive impairment. This rate is found to be twenty times greater than the rate in general population of the same age category[8]. CTE has been found in football players as young as 17 and 18 as well suggesting that the disease can begin to develop early on in life too[18]. Recently it was estimated that football players at certain positions(lineman) may endure up to 1400 sub-concussive impacts and high school players may endure up to 2000 due to playing on both defense and offense which may further increase the risk of traumatic brain injury and the development of CTE [11][18].


Over the past few decades, the association of CTE with contact sports aside from boxing and football has grown. Rugby, hockey, soccer, and wrestling have all been linked to at least one case of CTE. Other contact sports that are believed to be at risk for developing CTE include basketball, field hockey, volleyball, and lacrosse [8]. Two notable cases of CTE occurred when Chris Benoit, a former WWE wrestler who committed suicide after taking the life of his son and wife and was later found to have been suffering from CTE[20]. Derek Boogaard, a former NHL enforcer was found dead in his hotel room after overdosing on pain killers and alcohol during recover from concussion. Further tests showed he had CTE[21]

Where does CTE Currently stand?

Current Research

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A comparison of Tau levels using FDDNP in ex-NFL players and control patient [30]

Currently, the centre for the study of traumatic encephalopathy in Boston University led by Ann McKee has the largest repository for brains diagnosed with CTE and continue to lead the way in studying the neurodegenerative disease[18]. A study, published at UCLA showed that using FDDNP, a marker for tau protein that various areas of the brain showed elevated levels of tau in athletes believed to have CTE. The regions included the amygdala as well as subcortical regions. This is believed to be the first findings that document a diagnosis of CTE in a living patient. The only downside to the results is the low number of patients so it will be critical for another study like this to be performed but with a larger amount of patients[5]. Furthermore, it is currently hypothesized that the APOE gene may play a role in increased risk for developing CTE. Albeit low numbers, studies have shown a prevalence of CTE as well as other neurodegenerative diseases to occur to carriers of the APOE e4 gene variant [3][11]. As of right now, no effective prevention measures are in place for CTE other than attempting to prevent traumatic brain injury through better equipment or taking out contact all together. [8]. Monitoring players after receiving a concussive and even a sub-concussive blow is also a prevention measure in place that is currently receiving attention and further being developed to lower the risks of traumatic brain injury[22].

Current lead researcher, Ann McKee briefly talks about the current stance on CTE [31]

Future Considerations

CTE has been shown to be found in military veterans resulting from exposure to blasts in the field of combat[4][23]. This suggests the potential of CTE developing in non-athletes and presents this field with a new facet of patients with this illness. This could also provide a new alleyway for discovering a novel mechanism of action for this disease since memory and learning impairment due to blast exposure in mice was found to be reduced when the head was immobilized [23]. The development of the FDDNP marker as well as other bio markers for cell injury provide a basis for identifying Traumatic brain injury and possibly CTE. The potential for new markers for the neuropathological signs of CTE and hypothesized role of the APOE gene provide future optimism for potentially identifying those at risk for developing the illness [3][5][11][25]. ALS, and Alzheimer's disease have been shown to have similarity with CTE. As such, it is possible to look ahead at developing treatments for CTE that can also be applied to AD or ALS or vice-versa with treatments for ALS and AD being applied to CTE patients [11][13]. Recently, there has been opposition on the current stance that repetitive head trauma and concussions can lead to CTE suggesting that the link between concussions and developing CTE is not very significant[25] therefore perhaps there is a different mechanism of development of CTE and this is a definite possibility due to the novelty of the field. A study was performed on those suffering from dementia and no previous history of TBI and comparing the clinical profile of those suffering from dementia who had suffered from TBI previously. The results revealed that those who had a history of TBI performed better on the fluency and verbal memory tests in addition to a later onset of decline. However, these patients were observed to have poorer health than the patients who had not suffered from TBI. They were found to suffer from motor deficiencies and had a higher prevalence of seeking medical attention for depression. These findings suggest that the onset of CTE and CTE-like symptoms may be mediated through a different pathway than the dementia symptoms observed in the general public [26]

External Links

1. Gavett, B. Stern, R., McKee, A. (2011). Chronic Traumatic Encephalopathy: “A Potential Late Effect of Sport-Related Concussive and Subconcussive Head Trauma”. Clinical Journal of Sports Medicine, 30(1): 179-xi.
2. Samson, K. (2013) “NIH: NFL’s Junior Seau had Chronic Traumatic Encephalopathy”. Neurology Today, 13(4): 12-15
3. McKee, A., Cantu, R., Nowinski, C., Hedley-Whyte, T., Gavett, B., Budson, A., Santini, V., Lee, H., Kubilus, C., Stern, R. (2009).” Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy following Repetitive Head Injury”. Journal of Neuropathology and Experimental Neurology, 68(7): 709–735.
4. Yi, J., Padalino, D., Chin, L., Montenegro, P., Cantu, R. (2013) “Chronic Traumatic Encephalopathy”. Current Sports Medicine Reports, 12(1): 28-32.
5. Small, G. Kepe, V. Siddarth, P. Ercoli, L. Merrill, D. Donoghue, N. Bookheimer, S. Martinez, J. Omalu, B. Bailes, J. Barrio, J. (2013). “PET Scanning of Brain Tau in Retired National Football League Players: Preliminary Findings”. American Journal of Geriatric Psychiatry, 21(2):138-144.
6. Saulle, M. Greenwald, B. (2012). “Chronic Traumatic Encephalopathy: A Review”. Rehabilitation Research and Practice, 2012, 816069. doi:10.1155/2012/816069: 1-9.
7. Gavett, B. Stern, R. McKee, A. (2011). “Chronic Traumatic Encephalopathy: A Potential Late Effect of Sport-Related Concussive and Subconcussive Head Trauma”. Clinics in Sports Medicine, 30(1): 179-188.
8. Yi, J. Padalino, D. Chin, L. Montenegro, P. Cantu, R. (2013). “Chronic Traumatic Encephalopathy”. Current Sports Medicine Reports: Head, Neck and Spine, 12(1): 28-32.
9. Chronic Traumatic Encephalopathy. In Sports Legacy Institute. Retrieved March 30, 2013, from
10. Chin, L. Toshkezi, G. Cantu, R. (2011). “Traumatic Encephalopathy related to Sports Injury”. US Neurology,7(1):33–6.
11. Stern, R. Riley, D. Daneshvar, D. Nowinski, C. Cantu. R. McKee, A. (2011). “Long-term Consequences of Repetitive Brain Trauma: Chronic Traumatic Encephalopathy”. American Academy of Physical Medicine and Rehabilitation, 3(10S2):460-467.
12. Zhou, Y. Kierans, A. Kenul, D. Ge, Y. Rath, J. Reaume, J. Grossman, R. Lui, Y. (2013). “Mild Traumatic Brain Injury: Longitudinal Regional Brain Volume Changes”. Radiology, DOI: 10.1148/radiol.13122542.
13. McKee, A. Gavett, B. Stern, R. Nowinski, C. Cantu, R. Kowall, N. Perl, D. Hedley-Whyte, T. Price, B. Sullivan, C. Morin, P. Lee, H. Kubilus, C. Daneshvar, D. Wulff, M. Budson, A. (2010). “TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy”. Journal of Neuropathology & Experimental Neurology, 69(9): 918-929.
14. Jordan, B. Relkin, N. Ravdin, L. Jacobs, A. Bennett, A. Gandy, S. (1997). “Apolipoprotein E ε4Associated With Chronic Traumatic Brain Injury in Boxing”. The Journal of the American Medical Association, 278(2): 136-140.
15. Costanza, A. Weber, K. Gandy, S. Bouras, C. Hof, P. Giannakopoulos, P. Canuto, A. (2011). “Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates” Neuropathology and Applied Neurobiology 37: 570–584.
16. Omalu, B. DeKosky, S. Minster, R. Kmaboh, I. Hamilton, R. Wecht, C. (2005). “CHRONIC TRAUMATIC ENCEPHALOPATHY IN A NATIONAL FOOTBALL LEAGUE PLAYER”. Congress of Neurological Surgeons, 57(1):128-134.
17. Omalu, B. Bailes, J. Hammers, J. Fitzsimmons, R. (2010). “Chronic Traumatic Encephalopathy, Suicides and Parasuicides in Professional American Athletes:The Role of the Forensic Pathologist”. The American Journal of Forensic Medicine and Pathology, 31(2): 130-132.
18. Samson, K. (2013). “NIH: NFL’S JUNIOR SEAU HAD CHRONIC TRAUMATIC ENCEPHALOPATHY”. Neurology Today, 13(4): 1,12-15.
19. Cantu, R. (2007). “Chronic Traumatic Encephalopathy in National Football League”. Neurosurgery, 61(2): 223-225.
20. Sports Legacy Institute (2007-09-05). "Wrestler Chris Benoit Brain's Forensic Exam Consistent With Numerous Brain Injuries". ScienceDaily. Retrieved 2013-03-31. From
21. John Branch. (December 5, 2011). “Derek Boogaard: A Brain ‘Going Bad’. In The New York Times”. Retrieved March 31, 2013, from
22. Giza, C. Kutcher, J. Ashwal S. Barth, J. Getchius, T. Gioia, G. Gronseth, G. Guskiewicz, K. Mandel, S. Manley, G. McKeag, D. Thurman, D. Zafonte, R. (2013). “Summary of evidence-based guideline update: Evaluation and management of concussion in sports”. Neurology, Doi: 10.1212/WNL.0b013e31828d57dd.
23. Goldstein, L. Fisher, A. Tagge, C. Zhang, X. Velisek, L. Sullivan, J. Upreti, C. Kracht, J. Ericsson, M. Wojnarowicz, M. Goletiani, C. Maglakelidze, G. Casey, N. Moncaster, J. Minaeva, O. Moir, R. Nowinski, C. Stern, R. Cantu, R. Geiling, J. Blusztajn, J. Wolozin, B. Ikzeu, T. Stein, T. Budson, A. Kowall, N. Chargin, D. Sharon, A. Saman, S. Hall, G. Moss, W. Cleveland, R. Tanzi, R. Stanton, P. McKee, A. (2012). “Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model” Science Translational Medicine, 4 (134): 1-16.
24. Zetterberg, H. Smith, D. Blennow, K. (2013). “Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood” Nature Reviews Neurology,doi:10.1038/nrneurol.2013.9:
25. McCrory, P. Meeuwisse, W. Kutcher, J. Jordan, B. Gardner, A. (2013). “What is the evidence for chronic concussion-related changes in retired athletes: behavioural, pathological and clinical outcomes?”. British Journal of Sports Medicine, 47:327-330.
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27. [A comparison of a healthy brain to that of a brain diagnosed with CTE]. Retrieved from,
28. NMANewsDirect. (April 20, 2013). Study examines chronic traumatic encephalopathy threshold on boxers, MMA fighters [video file]. Retrieved from,
29. [Junior Seau played in the NFL for 20 seasons]. Retrieved from,
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31. Brainline. (January 6, 2011). Repetitive Brain Injury: What we know now [video file]. Retreived from,

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