, Volume 22, Issue 3, pp 270–282 | Cite as

Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae

  • Dragan Pavlovic
  • Sandra Pekic
  • Marko Stojanovic
  • Vera PopovicEmail author


Traumatic brain injury (TBI) causes substantial neurological disabilities and mental distress. Annual TBI incidence is in magnitude of millions, making it a global health challenge. Categorization of TBI into severe, moderate and mild by scores on the Glasgow coma scale (GCS) is based on clinical grounds and standard brain imaging (CT). Recent research focused on repeated mild TBI (sport and non-sport concussions) suggests that a considerable number of patients have long-term disabling neurocognitive and neurobehavioral sequelae. These relate to subtle neuronal injury (diffuse axonal injury) visible only by using advanced neuroimaging distinguishing microstructural tissue damage. With advanced MRI protocols better characterization of TBI is achievable. Diffusion tensor imaging (DTI) visualizes white matter pathology, susceptibility weight imaging (SWI) detects microscopic bleeding while functional magnetic resonance imaging (fMRI) provides closer understanding of cognitive disorders etc. However, advanced imaging is still not integrated in the clinical care of patients with TBI. Patients with chronic TBI may experience many somatic disorders, cognitive disturbances and mental complaints. The underlying pathophysiological mechanisms occurring in TBI are complex, brain injuries are highly heterogeneous and include neuroendocrine dysfunctions. Post-traumatic neuroendocrine dysfunctions received attention since the year 2000. Occurrence of TBI-related hypopituitarism does not correlate to severity of the GCS scores. Complete or partial hypopituitarism (isolated growth hormone (GH) deficiency as most frequent) may occur after mild TBI equally as after moderate-to-severe TBI. Many symptoms of hypopituitarism overlap with symptoms occurring in patients with chronic TBI, i.e. they have lower scores on neuropsychological examinations (cognitive disability) and have more symptoms of mental distress (depression and fatigue). The great challenges for the endocrinologist are: (1) detection of hypopituitarism in patients with TBI prospectively (in the acute phase and months to years after TBI), (2) assessment of the extent of cognitive impairment at baseline, and (3) monitoring of treatment effects (alteration of cognitive functioning and mental distress with hormone replacement therapy). Only few studies recently suggest that with growth hormone (rhGH) replacement in patients with chronic TBI and with abnormal GH secretion, cognitive performance may not change while symptoms related to depression and fatigue improve. Stagnation in post-TBI rehabilitation progress is recommended as a signal for clinical suspicion of neuroendocrine dysfunction. This remains a challenging area for more research.


Traumatic brain injury Mild TBI Neuropathology Cognitive deficits Behavioral dysfunction 


Author contributions

DP, SP, MS and VP reviewed the literature and wrote the manuscript.


This study was supported by a grant from the Ministry of Science of Republic of Serbia (Project 175033).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.


  1. 1.
    Menon DK, Schwab K, Wright DW, Maas AI, on behalf of The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health (2010) Position statement: definition of traumatic brain injury. Arch Phys Med Rehabil 91:1637–1640CrossRefGoogle Scholar
  2. 2.
    Peeters W, van den Brande R, Polinder S, Brazinova A, Steyerberg EW, Lingsma HF, Maas AI (2015) Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien) 157(10):1683–1696CrossRefGoogle Scholar
  3. 3.
    Eme R (2017) Neurobehavioral outcomes of mild traumatic brain injury: a mini review. Brain Sci May 7(5):46CrossRefGoogle Scholar
  4. 4.
    National Center for Injury Prevention and Control (2003) Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. Centers for Disease Control and Prevention: AtlantaGoogle Scholar
  5. 5.
    Mild Traumatic Brain Injury Committee (1993) Head injury interdisciplinary special interest group of the american congress of rehabilitation medicine: definition of mild traumatic brain injury. J Head Trauma Rehabil 8(3):86–87CrossRefGoogle Scholar
  6. 6.
    Carroll LJ, Cassidy JD, Holm L, Kraus J, Coronado VG, WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury (2004) Methodological issues and research recommendations for mild traumatic brain injury: the WHO collaborating centre task force on mild traumatic brain injury. J Rehabil Med 43:113–125CrossRefGoogle Scholar
  7. 7.
    Pavlović D (1999) Behavioral neurology of brain trauma. Belgrade, Serbia (in Serbian)Google Scholar
  8. 8.
    Blennow K, Brody D, Kochanek P, Levin H, McKee A, Ribbers G, Yaffe K, Zettergerg H (2016) Traumatic brain injury. Nat Rev Dis Primer 17:1–20Google Scholar
  9. 9.
    Fehily B, Fitzgerald M (2017) Repeated mild traumatic brain injury: potential mechanisms of damage. Cell Transplant 26(7):1131–1155CrossRefGoogle Scholar
  10. 10.
    Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, Büki A, Chesnut RM, Citerio G, Coburn M, Cooper DJ, Crowder AT, Czeiter E, Czosnyka M, Diaz-Arrastia R, Dreier JP, Duhaime AC, Ercole A, van Essen TA, Feigin VL, Gao G, Giacino J, Gonzalez-Lara LE, Gruen RL, Gupta D, Hartings JA, Hill S, Jiang JY, Ketharanathan N, Kompanje EJO, Lanyon L, Laureys S, Lecky F, Levin H, Lingsma HF, Maegele M, Majdan M, Manley G, Marsteller J, Mascia L, McFadyen C, Mondello S, Newcombe V, Palotie A, Parizel PM, Peul W, Piercy J, Polinder S, Puybasset L, Rasmussen TE, Rossaint R, Smielewski P, Söderberg J, Stanworth SJ, Stein MB, von Steinbüchel N, Stewart W, Steyerberg EW, Stocchetti N, Synnot A, Te Ao B, Tenovuo O, Theadom A, Tibboel D, Videtta W, Wang KKW, Williams WH, Wilson L, Yaffe K (2017) InTBIR participants and investigators: traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol 16(12):987–1048CrossRefGoogle Scholar
  11. 11.
    Gold EM, Vasilevko V, Hasselmann J, Tiefenthaler C, Hoa D, Ranawaka K, Cribbs DH, Cummings BJ (2018) Repeated mild closed head injuries induce long-term white matter pathology and neuronal loss that are correlated with behavioral deficits. ASN Neuro. Google Scholar
  12. 12.
    Manley G, Gardner AJ, Schneider KJ, Guskiewicz KM, Bailes J, Cantu RC, Castellani RJ, Turner M, Jordan BD, Randolph C, Dvořák J, Hayden KA, Tator CH, McCrory P (2017) Iverson GL A systematic review of potential long-term effects of sport-related concussion. Br J Sports Med 51(12):969–977CrossRefGoogle Scholar
  13. 13.
    McCrory P, Feddermann-Demont N, Dvořák J, Cassidy JD, McIntosh A, Vos PE, Echemendia RJ, Meeuwisse W, Tarnutzer AA (2017) What is the definition of sports-related concussion: a systematic review. Br J Sports Med 51(11):877–887CrossRefGoogle Scholar
  14. 14.
    Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J (2006) A systematic review of brain injury epidemiology in Europe. Acta Neurochirugica 148:255–268CrossRefGoogle Scholar
  15. 15.
    Prince C, Bruhns ME (2017) Evaluation and treatment of mild traumatic brain injury: the role of neuropsychology. Brain Sci 7(8):pii: E105CrossRefGoogle Scholar
  16. 16.
    Feigin VLV, Theadom A, Barker-Collo S, Starkey NJ, McPherson K, Kahan M, Dowell A, Brown P, Parag V, Kydd R, Jones K, Jones A, Ameratunga S, BIONIC Study Group (2013) Incidence of traumatic brain injury in New Zealand: a population-based study. Lancet Neurol 12:53–64CrossRefGoogle Scholar
  17. 17.
    Centers for Disease Control and Prevention (2015) Report to Congress on traumatic brain injury in the United States: epidemiology and rehabilitation. Accessed 1 Dec 2018
  18. 18.
    Fu TS, Jing R, Fu WW, Cusimano MD (2016) Epidemiological trends of traumatic brain injury identified in the emergency department in a publicly-insured population, 2002–2010. PLoS ONE 11:e0145469CrossRefGoogle Scholar
  19. 19.
    Majdan M, Plancikova D, Brazinova A, Rusnak M, Nieboer D, Feigin V, Maas A (2016) Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis based on hospital discharge statistics and death certificates in 2012. Lancet Public Health 1:e76–e83CrossRefGoogle Scholar
  20. 20.
    Bakhos LL, Lockhart GR, Myers R, Linakis JG (2010) Emergency department visits for concussion in young child athletes. Pediatrics 126(3):e550–e556CrossRefGoogle Scholar
  21. 21.
    Bazarian JJ, McClung J, Shah MN, Cheng YT, Flesher W, Kraus J (2005) Mild traumatic brain injury in the United States, 1998–2000. Brain Inj 19(2):85–91CrossRefGoogle Scholar
  22. 22.
    Grady MF (2010) Concussion in the adolescent athlete. Curr Probl Pediatr Adolesc Health Care. 40(7):154–169CrossRefGoogle Scholar
  23. 23.
    Wilk JE, Thomas JL, McGurk DM, Riviere LA, Castro CA, Hoge CW (2010) Mild traumatic brain injury (concussion) during combat: lack of association of blast mechanism with persistent postconcussive symptoms. J Head Trauma Rehabil 25(1):9–14CrossRefGoogle Scholar
  24. 24.
    Lasry O, Liu EY, Powell GA, Ruel-Laliberté J, Marcoux J, Buckeridge DL (2017) Epidemiology of recurrent traumatic brain injury in the general population: a systematic review. Neurology 89(21):2198–2209CrossRefGoogle Scholar
  25. 25.
    Masel BE, DeWitt DS (2010) Traumatic brain injury: a disease process, not an event. J Neurotrauma 27(8):1529–1540CrossRefGoogle Scholar
  26. 26.
    Gaetz M (2004) The neurophysiology of brain injury. Clin Neurophysiol 115(1):4–18CrossRefGoogle Scholar
  27. 27.
    Cernak I (2005) Animal models of head trauma. NeuroRx 2(3):410–422CrossRefGoogle Scholar
  28. 28.
    Bramlett HM, Dietrich WD (2015) Long-term consequences of traumatic brain injury: current status of potential mechanisms of injury and neurological outcomes. J Neurotrauma 32(23):1834–1848CrossRefGoogle Scholar
  29. 29.
    Karton C, Blaine Hoshizaki T (2018) Concussive and subconcussive brain trauma: the complexity of impact biomechanics and injury risk in contact sport. Handb Clin Neurol 158:39–49CrossRefGoogle Scholar
  30. 30.
    Orrison WW, Gentry LR, Stimac GK, Tarrel RM, Espinosa MC, Cobb LC (1994) Blinded comparison of cranial CT and MR in closed head injury evaluation. AJNR Am J Neuroradiol 15:351–356Google Scholar
  31. 31.
    Toth A (2015) Magnetic resonance imaging application in the area of mild and acute traumatic brain injury: implications for diagnostic markers? In: Kobeissy FH (ed) Brain neurotrauma: molecular, neuropsychological, and rehabilitation aspects (Chap. 24). CRC Press/Taylor & Francis, Boca RatonGoogle Scholar
  32. 32.
    Paterakis K, Karantanas AH, Komnos A, Volikas Z (2000) Outcome of patients with diffuse axonal injury: the significance and prognostic value of MRI in the acute phase. J Trauma 49:1071–1075CrossRefGoogle Scholar
  33. 33.
    Haghbayan H, Boutin A, Laflamme M, Lauzier F, Shemilt M, Moore L, Zarychanski R, Douville V, Fergusson D, Turgeon AF (2017) The prognostic value of MRI in moderate and severe traumatic brain injury: a systematic review and meta-analysis. Crit Care Med 45:e1280–1288CrossRefGoogle Scholar
  34. 34.
    Studerus-Germann AM, Gautschi OP, Bontempi P, Thiran JP, Daducci A, Romascano D, von Ow D, Hildebrandt G, von Hessling A, Engel DC (2018) Central nervous system microbleeds in the acute phase are associated with structural integrity by DTI one year after mild traumatic brain injury: a longitudinal study. Neurol Neurochir Pol 52(6):710–719CrossRefGoogle Scholar
  35. 35.
    Singla A, Leinweber B, Monteith S, Oskouian RJ, Tubbs RS (2018) The anatomy of concussion and chronic traumatic encephalopathy. A comprehensive review. Clin Anat Nov. Google Scholar
  36. 36.
    Kasturi BS, Stein DG (2009) Traumatic brain injury causes long-term reduction in serum growth hormone and persistent astrocytosis in the cortico-hypothalamo-pituitary axis of adult male rats. J Neurotrauma 26:1315–1324CrossRefGoogle Scholar
  37. 37.
    Osterstock G, El Yandouzi T, Romanò N, Carmignac D, Langlet F, Coutry N, Guillou A, Schaeffer M, Chauvet N, Vanacker C, Galibert E, Dehouck B, Robinson IC, Prévot V, Mollard P, Plesnila N, Méry PF (2014) Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice. Endocrinology 155:1887–1898CrossRefGoogle Scholar
  38. 38.
    Allouchery G, Moustafa F, Roubin J, Pereira B, Schmidt J, Raconnat J, Pic D, Sapin V, Bouvier D (2018) Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients. Clin Chem Lab Med 56(11):1897–1904CrossRefGoogle Scholar
  39. 39.
    Oris C, Pereira B, Durif J, Simon-Pimmel J, Castellani C, Manzano S, Sapin V, Bouvier D (2018) The biomarker S100B and mild traumatic brain injury: a meta-analysis. Pediatrics. 141(6):pii: e20180037CrossRefGoogle Scholar
  40. 40.
    Mercier E, Boutin A, Lauzier F, Fergusson DA, Simard JF, Zarychanski R, Moore L, McIntyre LA, Archambault P, Lamontagne F, Légaré F, Randell E, Nadeau L, Rousseau F, Turgeon AF (2013) Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. Br Med Journal 346:f1757CrossRefGoogle Scholar
  41. 41.
    Mercier E, Tardif PA, Cameron PA, Batomen Kuimi BL, Émond M, Moore L, Mitra B, Frenette J, De Guise E, Ouellet MC, Bordeleau M, Le Sage N (2018) Prognostic value of S-100β protein for prediction of post-concussion symptoms after a mild traumatic brain injury: systematic review and meta-analysis. J Neurotrauma 35(4):609–622CrossRefGoogle Scholar
  42. 42.
    Kornguth S, Rutledge N (2018) Integration of biomarkers into a signature profile of persistent traumatic brain injury involving autoimmune processes following water hammer injury from repetitive head impacts. Biomark Insights 13:1–8CrossRefGoogle Scholar
  43. 43.
    Bogoslovsky T, Wilson D, Chen Y, Hanlon D, Gill J, Jeromin A, Song L, Moore C, Gong Y, Kenney K, Diaz-Arrastia R (2017) Increases of plasma levels of glial fibrillary acidic protein, tau, and amyloid β up to 90 days after traumatic brain injury. J Neurotrauma 34(1):66–73CrossRefGoogle Scholar
  44. 44.
    Bennett ER, Reuter-Rice K, Laskowitz DT (2016) Genetic influences in traumatic brain injury. In: Laskowitz D, Grant G (eds) Translational research in traumatic brain injury (Chap. 9). CRC Press/Taylor and Francis Group, Boca RatonGoogle Scholar
  45. 45.
    Kurowski BG, Treble-Barna A, Pitzer AJ, Wade SL, Martin LJ, Chima RS, Jegga A (2017) Applying systems biology methodology to identify genetic factors possibly associated with recovery after traumatic brain injury. J Neurotrauma 34:2280–2290CrossRefGoogle Scholar
  46. 46.
    Pan YB, Sun ZL, Feng DF (2017) The role of microRNA in traumatic brain injury. Neuroscience 367:189–199CrossRefGoogle Scholar
  47. 47.
    Adams SM, Conley YP, Wagner AK, Jha RM, Clark RS, Poloyac SM, Kochanek PM, Empey PE (2017) The pharmacogenomics of severe traumatic brain injury. Pharmacogenomics 18:1413–1425CrossRefGoogle Scholar
  48. 48.
    Riggio S, Wong M (2009) Neurobehavioral sequelae of traumatic brain injury. Mt Sinai J Med 76(2):163–172CrossRefGoogle Scholar
  49. 49.
    Murray DA, Meldrum D, Lennon O (2017) Can vestibular rehabilitation exercises help patients with concussion? A systematic review of efficacy, prescription and progression patterns. Br J Sports Med 51(5):442–451CrossRefGoogle Scholar
  50. 50.
    Vallat-Azouvi C, Paillat C, Bercovici S, Morin B, Paquereau J, Charanton J, Ghout I, Azouvi P (2018) Subjective complaints after acquired brain injury: presentation of the brain injury complaint questionnaire (BICoQ). J Neurosci Res 96:601–611CrossRefGoogle Scholar
  51. 51.
    Rabinowitz AR, Li X, Levin HS (2014) Sport and nonsport etiologies of mild traumatic brain injury: similarities and differences. Annu Rev Psychol 65:301–331CrossRefGoogle Scholar
  52. 52.
    Wang ML, Li WB (2016) Cognitive impairment after traumatic brain injury: the role of MRI and possible pathological basis. J Neurol Sci 370:244–250CrossRefGoogle Scholar
  53. 53.
    Levin HS, Mattis S, Ruff RM, Eisenberg HM, Marshall LF, Tabaddor K, High WM Jr, Frankowski RF (1987) Neurobehavioral outcome following minor head injury: a three-center study. J Neurosurg 66:234–243CrossRefGoogle Scholar
  54. 54.
    Pavlovic D, Pekic S, Stojanovic M, Zivkovic V, Djurovic B, Jovanovic V, Miljic N, Medic-Stojanoska M, Doknic M, Miljic D, Djurovic M, Casanueva F, Popovic V (2010) Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults. Eur J Neurol 17:696–702CrossRefGoogle Scholar
  55. 55.
    Deijen JB, de Boer H, Blok GJ, van der Veen EA (1996) Cognitive impairments and mood disturbances in growth hormone deficient men. Psychoneuroendocrinology 21:313–322CrossRefGoogle Scholar
  56. 56.
    Bülow B, Hagmar L, Ørbaek P, Osterberg K, Erfurth EM (2002) High incidence of mental disorders, reduced mental well-being and cognitive function in hypopituitary women with GH deficiency treated for pituitary disease. Clin Endocrinol 56:183–193CrossRefGoogle Scholar
  57. 57.
    Popovic V, Pekic S, Pavlovic D, Maric N, Jasovic-Gasic M, Djurovic B, Medic Stojanoska M, Zivkovic V, Stojanovic M, Doknic M, Milic N, Djurovic M, Dieguez C, Casanueva FF (2004) Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress. J Endocrinol Invest 27:1048–1054CrossRefGoogle Scholar
  58. 58.
    Arwert LI, Veltman DJ, Deijen JB, van Dam PS, Drent ML (2006) Effects of growth hormone substitution therapy on cognitive functioning in growth hormone deficient patients: a functional MRI study. Neuroendocrinology 83:12–19CrossRefGoogle Scholar
  59. 59.
    Falleti MG, Maruff P, Burman P, Harris A (2006) The effects of growth hormone (GH) deficiency and GH replacement on cognitive performance in adults: a meta-analysis of the current literature. Psychoneuroendocrinology 31:681–691CrossRefGoogle Scholar
  60. 60.
    Nyberg F, Hallberg M (2013) Growth hormone and cognitive function. Nat Rev Endocrinol 9:357–365CrossRefGoogle Scholar
  61. 61.
    Nieves-Martinez E, Sonntag WE, Wilson A, Donahue A, Molina DP, Brunso-Bechtold J, Nicolle MM (2010) Early-onset GH deficiency results in spatial memory impairment in mid-life and is prevented by GH supplementation. J Endocrinol 204:31–36CrossRefGoogle Scholar
  62. 62.
    Chaplin JE, Kriström B, Jonsson B, Tuvemo T, Albertsson-Wikland K (2015) Growth hormone treatment improves cognitive function in short children with growth hormone deficiency. Horm Res Paediatr 83:390CrossRefGoogle Scholar
  63. 63.
    Burman P, Broman JE, Hetta J, Wiklund I, Erfurth EM, Hagg E, Karlsson FA (1995) Quality of life in adults with growth hormone (GH) deficiency: response to treatment with recombinant human GH in a placebo-controlled 21-month trial. J Clin Endocrinol Metab 80:3585–3590CrossRefGoogle Scholar
  64. 64.
    Burman P, Hetta J, Wide L, Månsson JE, Ekman R, Karlsson FA (1996) Growth hormone treatment affects brain neurotransmitters and thyroxine. Clin Endocrinol 44:319–324CrossRefGoogle Scholar
  65. 65.
    Deijen JB, de Boer H, van der Veen EA (1998) Cognitive changes during growth hormone replacement in adult men. Psychoneuroendocrinology 23:45–55CrossRefGoogle Scholar
  66. 66.
    High WM Jr, Briones-Galang M, Clark JA, Gilkison C, Mossberg KA, Zgaljardic DJ, Masel BE, Urban RJ (2010) Effect of growth hormone replacement therapy on cognition after traumatic brain injury. J Neurotrauma 27:1565–1575CrossRefGoogle Scholar
  67. 67.
    Devesa J, Reimunde P, Devesa P, Barberá M, Arce V (2013) Growth hormone (GH) and brain trauma. Horm Behav 63:331–344CrossRefGoogle Scholar
  68. 68.
    Devesa J, Díaz-Getino G, Rey P, García-Cancela J, Loures I, Nogueiras S, Hurtado de Mendoza A, Salgado L, González M, Pablos T, Devesa P (2015) Brain recovery after a plane crash: treatment with growth hormone (GH) and neurorehabilitation: a case report. Int J Mol Sci 16:30470–30482CrossRefGoogle Scholar
  69. 69.
    Moreau OK, Cortet-Rudelli C, Yollin E, Merlen E, Daveluy W, Rousseaux M (2013) Growth hormone replacement therapy in patients with traumatic brain injury. J Neurotrauma 30:998–1006CrossRefGoogle Scholar
  70. 70.
    Mossberg KA, Durham WJ, Zgaljardic DJ, Gilkison CR, Danesi CP, Sheffield-Moore M, Masel BE, Urban RJ (2017) Functional changes after recombinant human growth hormone replacement in patients with chronic traumatic brain injury and abnormal growth hormone secretion. J Neurotrauma 34:845–852CrossRefGoogle Scholar
  71. 71.
    Maric NP, Doknic M, Pavlovic D, Pekic S, Stojanovic M, Jasovic-Gasic M, Popovic V (2010) Psychiatric and neuropsychological changes in growth hormone-deficient patients after traumatic brain injury in response to growth hormone therapy. J Endocrinol Invest 33:770–775CrossRefGoogle Scholar
  72. 72.
    Gardner CJ, Mattsson AF, Daousi C, Korbonits M, Koltowska-Haggstrom M, Cuthbertson DJ (2015) GH deficiency after traumatic brain injury: improvement in quality of life with GH therapy: analysis of the KIMS database. Eur J Endocrinol 172:371–381CrossRefGoogle Scholar
  73. 73.
    Knight B (1996) Forensic pathology. Arnold, LondonGoogle Scholar
  74. 74.
    McKee AC, Abdolmohammadi B, Stein TD (2018) The neuropathology of chronic traumatic encephalopathy. Handb Clin Neurol 158:297–307CrossRefGoogle Scholar
  75. 75.
    Tharmaratnam T, Iskandar MA, Tabobondung TC, Tobbia I, Gopee-Ramanan P, Tabobondung TA (2018) Chronic traumatic encephalopathy in professional american football players: where are we now? Front Neurol 9:445CrossRefGoogle Scholar
  76. 76.
    Kenney K, Iacono D, Edlow BL, Katz DI, Diaz-Arrastia R, Dams-O’Connor K, Daneshvar DH, Stevens A, Moreau AL, Tirrell LS, Varjabedian A, Yendiki A, van der Kouwe A, Mareyam A, McNab JA, Gordon WA, Fischl B, McKee AC, Perl DP (2018) Dementia after moderate-severe traumatic brain injury: coexistence of multiple proteinopathies. J Neuropathol Exp Neurol 77(1):50–63CrossRefGoogle Scholar
  77. 77.
    Ling H, Neal JW, Revesz T (2017) Evolving concepts of chronic traumatic encephalopathy as a neuropathological entity. Neuropathol Appl Neurobiol 43(6):467–476CrossRefGoogle Scholar
  78. 78.
    Vile AR, Atkinson L (2017) Chronic traumatic encephalopathy: the cellular sequela to repetitive brain injury. J Clin Neurosci 41:24–29CrossRefGoogle Scholar
  79. 79.
    McKee AC, Cairns NJ, Dickson DW, Folkerth RD, Keene CD, Litvan I, Perl DP, Stein TD, Vonsattel JP, Stewart W, Tripodis Y, Crary JF, Bieniek KF, Dams-O’Connor K, Alvarez VE, Gordon WA (2016) TBI/CTE group. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 131(1):75–86CrossRefGoogle Scholar
  80. 80.
    Perry DC, Sturm VE, Peterson MJ, Pieper CF, Bullock T, Boeve BF, Miller BL, Guskiewicz KM, Berger MS, Kramer JH, Welsh-Bohmer KA (2016) Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis. J Neurosurg 124:511–526CrossRefGoogle Scholar
  81. 81.
    Strub RL, Black FW (1989) Neurobehavioral disorders: a clinical approach. F.A. Davis Company, PhiladelphiaGoogle Scholar
  82. 82.
    Gavett BE, Stern RA, McKee AC (2011) Chronic traumatic encephalopathy: a potential late effect of sportrelated concussive and subconcussive head trauma. Clin Sports Med 30:179–188CrossRefGoogle Scholar
  83. 83.
    McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW et al (2010) TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol 69:918–929CrossRefGoogle Scholar
  84. 84.
    Omalu B, Small GW, Bailes J, Ercoli LM, Merrill DA, Wong KP, Huang SC, Satyamurthy N, Hammers JL, Lee J, Fitzsimmons RP, Barrio JR (2018) Postmortem autopsy-confirmation of antemortem [F-18]FDDNP-PET scans in a football player with chronic traumatic encephalopathy. Neurosurgery 82:237–246CrossRefGoogle Scholar
  85. 85.
    Coughlin JM, Wang Y, Minn I, Bienko N, Ambinder EB, Xu X, Peters ME, Dougherty JW, Vranesic M, Koo SM, Ahn HH, Lee M, Cottrell C, Sair HI, Sawa A, Munro CA, Nowinski CJ, Dannals RF, Lyketsos CG, Kassiou M, Smith G, Caffo B, Mori S, Guilarte TR, Pomper MG (2017) Imaging of glial cell activation and white matter integrity in brains of active and recently retired national football league players. JAMA Neurol 74:67–74CrossRefGoogle Scholar
  86. 86.
    Gardner AJ, Iverson GL, Wojtowicz M, Levi CR, Kay-Lambkin F, Schofield PW, Zafonte R, Shultz SR, Lin AP, Stanwell P (2017) MR spectroscopy findings in retired professional rugby league players. Int J Sports Med 38:241–252CrossRefGoogle Scholar
  87. 87.
    Amen DG, Willeumier K, Omalu B, Newberg A, Raghavendra C, Raji CA (2016) Perfusion neuroimaging abnormalities alone distinguish national football league players from a healthy population. J Alzheimers Dis 53:237–241CrossRefGoogle Scholar
  88. 88.
    Randolph C (2018) Chronic traumatic encephalopathy is not a real disease. Arch Clin Neuropsychol 33:644–648CrossRefGoogle Scholar
  89. 89.
    Fleminger S, Oliver DL, Lovestone S, Rabe-Hesketh S, Giora A (2003) Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 74:857–862CrossRefGoogle Scholar
  90. 90.
    LoBue C, Cullum CM, Didehbani N, Yeatman K, Jones B, Kraut MA, Hart J Jr (2018) Neurodegenerative dementias after traumatic brain injury. J Neuropsychiatry Clin Neurosci Winter 30:7–13CrossRefGoogle Scholar
  91. 91.
    Pavlović DM (2008) Dementias—clinical diagnostics, 2nd edn. Kaligraf, Belgrade (in Serbian)Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Dragan Pavlovic
    • 1
  • Sandra Pekic
    • 2
    • 3
  • Marko Stojanovic
    • 2
    • 3
  • Vera Popovic
    • 3
    Email author
  1. 1.Faculty for Special Education and RehabilitationUniversity of BelgradeBelgradeSerbia
  2. 2.Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic DiseasesClinical Centre of SerbiaBelgradeSerbia
  3. 3.Medical FacultyUniversity of BelgradeBelgradeSerbia

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