Editor(s): Niranjan A. (Pittsburgh, Pa.) 
Lunsford L.D. (Pittsburgh, Pa.) 
Table of Contents
Vol. 28, 2014
Section title:  
Niranjan A, Lunsford LD (eds): Concussion. Prog Neurol Surg. Basel, Karger, 2014, vol 28, pp 38-49

Chronic Traumatic Encephalopathy

Omalu B.
University of California, Davis, Medical Center, Sacramento, Calif., and San Joaquin General Hospital and San Joaquin County Coroner's Division, French Camp, Calif., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative syndrome, which is caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. CTE presents clinically as a composite syndrome of mood disorders and behavioral and cognitive impairment, with or without sensorimotor impairment. Symptoms of CTE may begin with persistent symptoms of acute traumatic brain injury (TBI) following a documented episode of brain trauma or after a latent period that may range from days to weeks to months and years, up to 40 years following a documented episode of brain trauma or cessation of repetitive TBI. Posttraumatic encephalopathy is distinct from CTE, can be comorbid with CTE, and is a clinicopathologic syndrome induced by focal and/or diffuse, gross and/or microscopic destruction of brain tissue following brain trauma. The brain of a CTE sufferer may appear grossly unremarkable, but shows microscopic evidence of primary and secondary proteinopathies. The primary proteinopathy of CTE is tauopathy, while secondary proteinopathies may include, but are not limited to, amyloidopathy and TDP proteinopathy. Reported prevalence rates of CTE in cohorts exposed to TBI ranges from 3 to 80% across age groups. © 2014 S. Karger AG, Basel

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Omalu B, Bailes J, Hamilton RL, Kamboh MI, Hammers J, Case J, Fitzsimmons R: Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 2011;69:173-183, discussion 183.
  2. Small GW, Kepe V, Siddarth P, Ercoli LM, Merrill DA, Donoghue N, Bookheimer SY, Martinez J, Omalu B, Bailes J, Barrio JR: PET scanning of brain tau in retired National Football League players: preliminary findings. Am J Geriatr Psychiatry 2013;21:138-144.
  3. Chen-Plotkin AS, Lee VM, Trojanowski JQ: TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol 2010;6:211-220.
  4. Geddes JF, Vowles GH, Nicoll JA, Revesz T: Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol 1999;98:171-178.
  5. Geddes JF, Vowles GH, Robinson SF, Sutcliffe JC: Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol Appl Neurobiol 1996;22:12-16.
  6. McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET, Price B, Sullivan C, Morin P, Lee HS, Kubilus CA, Daneshvar DH, Wulff M, Budson AE: TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol 2010;69:918-929.
  7. Hazrati LN, Tartaglia MC, Diamandis P, Davis KD, Green RE, Wennberg R, Wong JC, Ezerins L, Tator CH: Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology. Front Hum Neurosci 2013;7:222.
  8. McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC: The spectrum of disease in chronic traumatic encephalopathy. Brain 2013;136:43-64.
  9. Omalu B, Hammers JL, Bailes J, Hamilton RL, Kamboh MI, Webster G, Fitzsimmons RP: Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurg Focus 2011;31:E3.
  10. Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ: National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement 2012;8:1-13.
  11. Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Trojanowski JQ, Vinters HV, Hyman BT; National Institute on Aging; Alzheimer's Association: National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 2012;123:1-11.
  12. Randolph C, Karantzoulis S, Guskiewicz K: Prevalence and characterization of mild cognitive impairment in retired national football league players. J Int Neuropsychol Soc 2013;19:873-880.
  13. McCrory P, Meeuwisse WH, Kutcher JS, Jordan BD, Gardner A: What is the evidence for chronic concussion-related changes in retired athletes: behavioural, pathological and clinical outcomes? Br J Sports Med 2013;47:327-330.
  14. Kaplan HA, Browder J: Observations on the clinical and brain wave patterns of professional boxers. J Am Med Assoc 1954;156:1138-1144.
  15. McCown IA: Protecting the boxer. J Am Med Assoc 1959;169:1409-1413.
  16. McCown IA: Boxing injuries. Am J Surg 1959;98:509-516.

    External Resources

  17. Casson IR, Pellman EJ, Viano DC: Chronic traumatic encephalopathy in a National Football League player. Neurosurgery 2006;59:E1152.
  18. Casson IR, Pellman EJ, Viano DC: Chronic traumatic encephalopathy in a National Football League player. Neurosurgery 2006;58:E1003, author reply E1003, discussion E1003.
  19. Handbook of Neurological Sports Medicine. Champaign, Human Kinetic Publishing, 2014 (in press).
  20. Jordan BD: The clinical spectrum of sport-related traumatic brain injury. Nat Rev Neurol 2013;9:222-230.
  21. Cervos-Navarro J, Lafuente JV: Traumatic brain injuries: structural changes. J Neurol Sci 1991;103(Suppl):S3-S14.
  22. Adams JH, Graham DI, Jennett B: The structural basis of moderate disability after traumatic brain damage. J Neurol Neurosurg Psychiatry 2001;71:521-524.
  23. Proceedings of the Congress of Neurological Surgeons in 1964, Report of the Ad Hoc Committee to Study Head Injury Nomenclature. Clin Neurosurg 1966;12:386-394.
  24. Bailes JE, Petraglia AL, Omalu BI, Nauman E, Talavage T: Role of subconcussion in repetitive mild traumatic brain injury. J Neurosurg 2013;119:1235-1245.
  25. Talavage TM, Nauman EA, Breedlove EL, Yoruk U, Dye AE, Morigaki KE, Feuer H, Leverenz LJ: Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion. J Neurotrauma 2014;31:327-338.
  26. Bigler ED: Neuropathology of acquired cerebral trauma. J Learn Disabil 1987;20:458-473.
  27. Valsamis MP: Pathology of trauma. Neurosurg Clin N Am 1994;5:175-183.

    External Resources

  28. Patt S, Brodhun M: Neuropathological sequelae of traumatic injury in the brain. An overview. Exp Toxicol Pathol 1999;51:119-123.
  29. Prince DA, Parada I, Scalise K, Graber K, Jin X, Shen F: Epilepsy following cortical injury: cellular and molecular mechanisms as targets for potential prophylaxis. Epilepsia 2009;50(Suppl 2):30-40.
  30. Diaz-Arrastia R, Agostini MA, Madden CJ, Van Ness PC: Posttraumatic epilepsy: the endophenotypes of a human model of epileptogenesis. Epilepsia 2009;50(Suppl 2):14-20.
  31. Dichter MA: Posttraumatic epilepsy: the challenge of translating discoveries in the laboratory to pathways to a cure. Epilepsia 2009;50(Suppl 2):41-45.
  32. Pitkanen A, Immonen RJ, Grohn OH, Kharatishvili I: From traumatic brain injury to posttraumatic epilepsy: what animal models tell us about the process and treatment options. Epilepsia 2009;50(Suppl 2):21-29.
  33. Hunt RF, Scheff SW, Smith BN: Posttraumatic epilepsy after controlled cortical impact injury in mice. Exp Neurol 2009;215:243-252.
  34. Swartz BE, Houser CR, Tomiyasu U, Walsh GO, DeSalles A, Rich JR, Delgado-Escueta A: Hippocampal cell loss in posttraumatic human epilepsy. Epilepsia 2006;47:1373-1382.
  35. Statler KD: Pediatric posttraumatic seizures: epidemiology, putative mechanisms of epileptogenesis and promising investigational progress. Dev Neurosci 2006;28:354-363.
  36. Povlishock JT, Katz DI: Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil 2005;20:76-94.
  37. Graham DI, Adams JH, Nicoll JA, Maxwell WL, Gennarelli TA: The nature, distribution and causes of traumatic brain injury. Brain Pathol 1995;5:397-406.
  38. Omalu BI, DeKosky ST, Hamilton RL, Minster RL, Kamboh MI, Shakir AM, Wecht CH: Chronic traumatic encephalopathy in a National Football League player: part II. Neurosurgery 2006;59:1086-1092, discussion 1092-1093.
  39. Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH: Chronic traumatic encephalopathy in a National Football League player. Neurosurgery 2005;57:128-134; discussion 128-134.
  40. McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA: Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 2009;68:709-735.
  41. Thom M, Liu JY, Thompson P, Phadke R, Narkiewicz M, Martinian L, Marsdon D, Koepp M, Caboclo L, Catarino CB, Sisodiya SM: Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study. Brain 2011;134:2969-2981.
  42. Critchley M: Punch drunk syndromes: the chronic traumatic encephalopathy of boxers; in: Hommage à Clovis Vincent. Paris, Maloine, 1949, p 131.
  43. Critchley M: Medical aspects of boxing, particularly from a neurological standpoint. Br Med J 1957;1:357-362.
  44. Royal College of Physicians of London. Committee on Boxing. Report on the Medical Aspects of Boxing. London, Royal College of Physicians of London, 1969, p 11.
  45. Roberts AH: Brain Damage in Boxers. A Study of the Prevalence of Traumatic Encephalopathy among Ex-Professional Boxers. London, Pitman Medical and Scientific Publishing Co., 1969.
  46. Orrison WW, Hanson EH, Alamo T, Watson D, Sharma M, Perkins TG, Tandy RD: Traumatic brain injury: a review and high-field MRI findings in 100 unarmed combatants using a literature-based checklist approach. J Neurotrauma 2009;26:689-701.
  47. Stern RA, Daneshvar DH, Baugh CM, Seichepine DR, Montenigro PH, Riley DO, Fritts NG, Stamm JM, Robbins CA, McHale L, Simkin I, Stein TD, Alvarez VE, Goldstein LE, Budson AE, Kowall NW, Nowinski CJ, Cantu RC, McKee AC: Clinical presentation of chronic traumatic encephalopathy. Neurology 2013;81:1122-1129.
  48. Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, Mann DM: Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 2009;117:15-18.
  49. Blennow K, Hardy J, Zetterberg H: The neuropathology and neurobiology of traumatic brain injury. Neuron 2012;76:886-899.
  50. Blaylock RL, Maroon J: Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy - a unifying hypothesis. Surg Neurol Int 2011;2:107.
  51. Walker KR, Tesco G: Molecular mechanisms of cognitive dysfunction following traumatic brain injury. Front Aging Neurosci 2013;5:29.
  52. Le MN, Kim W, Lee S, McKee AC, Hall GF: Multiple mechanisms of extracellular tau spreading in a non-transgenic tauopathy model. Am J Neurodegener Dis 2012;1:316-333.

    External Resources

  53. Jucker M, Walker GF: Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 2013;501:45-51.
  54. Clavaguera F, Lavenir I, Falcon B, Frank S, Goedert M, Tolnay M: ‘Prion-like' templated misfolding in tauopathies. Brain Pathol 2013;23:342-349.

Pay-per-View Options
Direct payment This item at the regular price: USD 33.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 23.00