Chronic Traumatic Encephalopathy

Abstract

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease in individuals with a history of multiple concussions or other forms of repetitive brain injury. A definite diagnosis can only be made post‐mortem and it is unclear why some individuals appear more susceptible to progressive neurological symptoms following repetitive brain injury than others. CTE has become a major concern in individuals exposed to increased risk of concussion, for example, sports athletes and some military personnel, but its prevalence in such risk groups is unknown. The condition shares some molecular pathologies with other neurodegenerative disorders and it appears that repetitive concussion can initiate a degenerative process involving protein misfolding that may propagate over the brain many years after the trauma. Clinical manifestations of CTE include a wide range of neurological and psychiatric symptoms. These should be treated but presently there is no disease‐modifying therapy against CTE. In contrast to most other neurodegenerative diseases, the condition is preventable.

Key Concepts

  • Chronic traumatic encephalopathy (CTE) may develop secondary to repetitive mild traumatic brain injuries.
  • A definite diagnosis of CTE can only be made post‐mortem.
  • CTE can be prevented but not cured – prevention and symptomatic treatment are important.
  • Brain changes in CTE should be possible to detect and monitor using biomarkers.
  • It is important to study risk factors for CTE – why do some individuals appear to be more susceptible to chronic and sometimes progressive symptoms following traumatic brain injury than others?

Keywords: chronic traumatic encephalopathy; traumatic brain injury; diffuse axonal injury; concussion; biomarkers; neuropathology; tau; amyloid; contact sports

Figure 1. Schematic representation of the neuropathological events involved in concussion and chronic traumatic encephalopathy (CTE). The most important pathogenic event in concussion is diffuse axonal injury secondary to rapid rotational forces on the brain tissue. Repeated concussions result in new neuropathological cascades that eventually may initiate self‐propagating tau pathology and full‐blown CTE.
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References

Atha J , Yeadon MR , Sandover J and Parsons KC (1985) The damaging punch. British Medical Journal (Clinical Research Ed.) 291: 1756–1757.

Barkhoudarian G , Hovda DA and Giza CC (2011) The molecular pathophysiology of concussive brain injury. Clinics in Sports Medicine 30: 33–48, vii–iii.

Baugh CM , Stamm JM , Riley DO , et al. (2012) Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging and Behavior 6: 244–254.

Beekes M , Thomzig A , Schulz‐Schaeffer WJ and Burger R (2014) Is there a risk of prion‐like disease transmission by Alzheimer‐ or Parkinson‐associated protein particles? Acta Neuropathol 128 (4): 463–476.

Blennow K , Hardy J and Zetterberg H (2012) The neuropathology and neurobiology of traumatic brain injury. Neuron 76: 886–899.

Brooks WM , Stidley CA , Petropoulos H , et al. (2000) Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study. Journal of Neurotrauma 17: 629–640.

Cantu RC (1998) Return to play guidelines after a head injury. Clinics in Sports Medicine 17: 45–60.

Chen XH , Siman R , Iwata A , et al. (2004) Long‐term accumulation of amyloid‐beta, beta‐secretase, presenilin‐1, and caspase‐3 in damaged axons following brain trauma. American Journal of Pathology 165: 357–371.

Constantinidis J and Tissot R (1967) Generalized Alzheimer's neurofibrillary lesions without senile plaques. (Presentation of one anatomo‐clinical case). Schweizer Archiv für Neurologie Neurochirurgie und Psychiatrie 100: 117–130.

Corsellis JA (1989) Boxing and the brain. BMJ 298: 105–109.

Corsellis JA , Bruton CJ and Freeman‐Browne D (1973) The aftermath of boxing. Psychological Medicine 3: 270–303.

DeKosky ST , Blennow K , Ikonomovic MD and Gandy S (2013) Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nature Reviews Neurology 9: 192–200.

Giza CC and Hovda DA (2001) The neurometabolic cascade of concussion. Journal of Athletic Training 36: 228–235.

Glenner GG and Wong CW (1984) Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochemical and Biophysical Research Communications 122: 1131–1135.

Ikonomovic MD , Uryu K , Abrahamson EE , et al. (2004) Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Experimental Neurology 190: 192–203.

Iverson GL , Gaetz M , Lovell MR and Collins MW (2004) Cumulative effects of concussion in amateur athletes. Brain Injury 18: 433–443.

Johnson VE , Stewart W and Smith DH (2010) Traumatic brain injury and amyloid‐beta pathology: a link to Alzheimer's disease? Nature Reviews Neuroscience 11: 361–370.

Johnson VE , Stewart W and Smith DH (2012) Axonal pathology in traumatic brain injury. Experimental Neurology, Vol. 246. 35–45.

Kawai N , Kawanishi M , Kudomi N , et al. (2013) Detection of brain amyloid beta deposition in patients with neuropsychological impairment after traumatic brain injury: PET evaluation using Pittsburgh Compound‐B. Brain Injury 27: 1026–1031.

Kokjohn TA , Maarouf CL , Daugs ID , et al. (2013) Neurochemical profile of dementia pugilistica. Journal of Neurotrauma 30: 981–997.

Lee RR and Huang M (2014) Magnetoencephalography in the diagnosis of concussion. Progress in Neurological Surgery 28: 94–111.

Martland H (1928) Punch drunk. JAMA 91: 1103–1107.

Masters CL , Simms G , Weinman NA , et al. (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proceedings of the National Academy of Sciences of the United States of America 82: 4245–4249.

McCrory P , Meeuwisse W , Johnston K , et al. (2009) Consensus statement on concussion in sport – the Third International Conference on Concussion in Sport held in Zurich, November 2008. The Physician and Sportsmedicine 37: 141–159.

McKee AC , Cantu RC , Nowinski CJ , et al. (2009) Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. Journal of Neuropathology and Experimental Neurology 68: 709–735.

McKee AC , Gavett BE , Stern RA , et al. (2010) TDP‐43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. Journal of Neuropathology and Experimental Neurology 69: 918–929.

McKee AC , Stern RA , Nowinski CJ , et al. (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136: 43–64.

Miele VJ and Bailes JE (2007) Objectifying when to halt a boxing match: a video analysis of fatalities. Neurosurgery 60: 307–315; discussion 315–306.

Millspaugh J (1937) Dementia pugilistica. United States Naval Bulletin 35: 297–302.

Neselius S , Brisby H , Granholm F , Zetterberg H and Blennow K (2014) Monitoring concussion in a knocked‐out boxer by CSF biomarker analysis. Knee Surgery, Sports Traumatology, Arthroscopy.

Neselius S , Brisby H , Theodorsson A , et al. (2012) CSF‐biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma. PLoS One 7: e33606.

Neselius S , Zetterberg H , Blennow K , et al. (2013) Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma. Brain Injury 27: 425–433.

New Zealand Guidelines Group (2006) Traumatic brain injury: diagnosis, acute management and rehabilitation. New Zealand Guidelines Group: Wellington, NZ.

Omalu BI , DeKosky ST , Hamilton RL , et al. (2006) Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery 59: 1086–1092; discussion 1092–1083.

Omalu BI , DeKosky ST , Minster RL , et al. (2005) Chronic traumatic encephalopathy in a National Football League player. Neurosurgery 57: 128–134; discussion 128–134.

Roberts GW , Allsop D and Bruton C (1990) The occult aftermath of boxing. Journal of Neurology, Neurosurgery and Psychiatry 53: 373–378.

Roberts GW , Gentleman SM , Lynch A , et al. (1994) Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease. Journal of Neurology, Neurosurgery and Psychiatry 57: 419–425.

Roe C , Sveen U , Alvsaker K and Bautz‐Holter E (2009) Post‐concussion symptoms after mild traumatic brain injury: influence of demographic factors and injury severity in a 1‐year cohort study. Disability and Rehabilitation 31: 1235–1243.

Saatman KE , Creed J and Raghupathi R (2010) Calpain as a therapeutic target in traumatic brain injury. Neurotherapeutics 7: 31–42.

Shahim P , Tegner Y , Wilson DH , et al. (2014) Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA Neurology 71: 684–692.

Small GW , Kepe V , Siddarth P , et al. (2013) PET scanning of brain tau in retired national football league players: preliminary findings. The American Journal of Geriatric Psychiatry 21: 138–144.

Smith DH and Meaney DF (2000) Axonal damage in traumatic brain injury. The Neuroscientist 6: 483–495.

Stern RA , Daneshvar DH , Baugh CM , et al. (2013) Clinical presentation of chronic traumatic encephalopathy. Neurology 81: 1122–1129.

Weiner MW , Friedl KE , Pacifico A , et al. (2013) Military risk factors for Alzheimer's disease. Alzheimers Dement 9: 445–451.

Williams WH , Potter S and Ryland H (2010) Mild traumatic brain injury and Postconcussion Syndrome: a neuropsychological perspective. Journal of Neurology, Neurosurgery and Psychiatry 81: 1116–1122.

Zetterberg H , Hietala MA , Jonsson M , et al. (2006) Neurochemical aftermath of amateur boxing. Archives of Neurology 63: 1277–1280.

Zetterberg H , Smith DH and Blennow K (2013) Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nature Reviews Neurology 9: 201–210.

Zhu DC , Covassin T , Nogle S , et al. (2014) A Potential Biomarker in Sports‐Related Concussion: Brain Functional Connectivity Alteration of the Default‐Mode Network Measured with Longitudinal Resting‐State fMRI over 30 Days. J Neurotrauma.

Further Reading

Lancet Editorial (2013) Concussion in sport: fair play for young people. Lancet 382: 1536.

Omalu B (2014) Chronic traumatic encephalopathy. Progress in Neurological Surgery 28: 38–49.

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How to Cite close
Zetterberg, Henrik(Jan 2015) Chronic Traumatic Encephalopathy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025819]