Iverson, G L
Suicide and Chronic Traumatic Encephalopathy Journal Article
In: Journal of Neuropsychiatry & Clinical Neurosciences, vol. 28, no. 1, pp. 9–16, 2016.
Abstract | BibTeX | Tags: *Brain Injury, *Football/in [Injuries], *Suicide/px [Psychology], Athletic Injuries/di [Diagnosis], Athletic Injuries/ep [Epidemiology], Athletic Injuries/px [Psychology], Brain Injury, Chronic/di [Diagnosis], Chronic/ep [Epidemiology], Chronic/px [Psychology], Football/px [Psychology], Humans, Male, Risk Factors, Suicide/td [Trends]
@article{Iverson2016a,
title = {Suicide and Chronic Traumatic Encephalopathy},
author = {Iverson, G L},
year = {2016},
date = {2016-01-01},
journal = {Journal of Neuropsychiatry \& Clinical Neurosciences},
volume = {28},
number = {1},
pages = {9--16},
abstract = {For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships.},
keywords = {*Brain Injury, *Football/in [Injuries], *Suicide/px [Psychology], Athletic Injuries/di [Diagnosis], Athletic Injuries/ep [Epidemiology], Athletic Injuries/px [Psychology], Brain Injury, Chronic/di [Diagnosis], Chronic/ep [Epidemiology], Chronic/px [Psychology], Football/px [Psychology], Humans, Male, Risk Factors, Suicide/td [Trends]},
pubstate = {published},
tppubtype = {article}
}
Stewart, W; McNamara, P H; Lawlor, B; Hutchinson, S; Farrell, M
Chronic traumatic encephalopathy: a potential late and under recognized consequence of rugby union? Journal Article
In: Qjm, vol. 109, no. 1, pp. 11–15, 2016.
Abstract | BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Brain/pp [Physiopathology], *Football/in [Injuries], *Neurodegenerative Diseases/pp [Physiopathology], Chronic/pa [Pathology], Humans, Magnetic Resonance Imaging, Male, middle aged, neurologic examination
@article{Stewart2016,
title = {Chronic traumatic encephalopathy: a potential late and under recognized consequence of rugby union?},
author = {Stewart, W and McNamara, P H and Lawlor, B and Hutchinson, S and Farrell, M},
year = {2016},
date = {2016-01-01},
journal = {Qjm},
volume = {109},
number = {1},
pages = {11--15},
abstract = {The association between exposure to head injury and increased risk of neurodegenerative disease, specifically chronic traumatic encephalopathy (CTE), is widely recognized. Historically, this was largely considered a phenomenon restricted to boxers, with more recent case series identifying further 'high risk' individuals, such as former American footballers, or military personnel. However, in all cases thus far reported, it is clear that it is the exposure to head injury which is associated with increased dementia risk, and not the circumstances or environment of exposure. As such, there is considerable potential for under-recognition of CTE in patients presenting with neurodegenerative disease, particularly where head injury exposure might have been historical and through sport. This article reviews current understanding of CTE and, via an illustrative case in rugby union, highlights the value of a detailed history on head injury and also draws attention to imaging studies in assessing patients with neurodegenerative disease. Copyright © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},
keywords = {*Brain Concussion/co [Complications], *Brain Injury, *Brain/pp [Physiopathology], *Football/in [Injuries], *Neurodegenerative Diseases/pp [Physiopathology], Chronic/pa [Pathology], Humans, Magnetic Resonance Imaging, Male, middle aged, neurologic examination},
pubstate = {published},
tppubtype = {article}
}
Puvenna, V; Engeler, M; Banjara, M; Brennan, C; Schreiber, P; Dadas, A; Bahrami, A; Solanki, J; Bandyopadhyay, A; Morris, J K; Bernick, C; Ghosh, C; Rapp, E; Bazarian, J J; Janigro, D
Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy Journal Article
In: Brain Research, vol. 1630, pp. 225–240, 2016.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/me [Metabolism], *Epilepsy/me [Metabolism], *tau Proteins/me [Metabolism], 0 (MAPT protein, 0 (tau Proteins), 80 and over, Adolescent, adult, aged, Brain Injury, Brain/pa [Pathology], Brain/su [Surgery], Child, Chronic/me [Metabolism], Chronic/pa [Pathology], ENZYME-linked immunosorbent assay, Epilepsy/pa [Pathology], Epilepsy/su [Surgery], Female, human), Humans, immunohistochemistry, Infant, Male, middle aged, Phosphorylation, Preschool, Young Adult
@article{Puvenna2016,
title = {Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy},
author = {Puvenna, V and Engeler, M and Banjara, M and Brennan, C and Schreiber, P and Dadas, A and Bahrami, A and Solanki, J and Bandyopadhyay, A and Morris, J K and Bernick, C and Ghosh, C and Rapp, E and Bazarian, J J and Janigro, D},
year = {2016},
date = {2016-01-01},
journal = {Brain Research},
volume = {1630},
pages = {225--240},
abstract = {Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P\<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights reserved.},
keywords = {*Brain Injury, *Brain/me [Metabolism], *Epilepsy/me [Metabolism], *tau Proteins/me [Metabolism], 0 (MAPT protein, 0 (tau Proteins), 80 and over, Adolescent, adult, aged, Brain Injury, Brain/pa [Pathology], Brain/su [Surgery], Child, Chronic/me [Metabolism], Chronic/pa [Pathology], ENZYME-linked immunosorbent assay, Epilepsy/pa [Pathology], Epilepsy/su [Surgery], Female, human), Humans, immunohistochemistry, Infant, Male, middle aged, Phosphorylation, Preschool, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Lucke-Wold, B P; Turner, R C; Logsdon, A F; Nguyen, L; Bailes, J E; Lee, J M; Robson, M J; Omalu, B I; Huber, J D; Rosen, C L
Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy Journal Article
In: Journal of Neurosurgery, vol. 124, no. 3, pp. 687–702, 2016.
Abstract | BibTeX | Tags: *Blast Injuries/px [Psychology], *Brain Injury, *Endoplasmic Reticulum Stress/ph [Physiology], *Football/in [Injuries], *Wrestling/in [Injuries], adult, animal, Animals, Blast Injuries/et [Etiology], Blast Injuries/pa [Pathology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Disease Models, Humans, Male, Rats, Sprague-Dawley
@article{Lucke-Wold2016,
title = {Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy},
author = {Lucke-Wold, B P and Turner, R C and Logsdon, A F and Nguyen, L and Bailes, J E and Lee, J M and Robson, M J and Omalu, B I and Huber, J D and Rosen, C L},
year = {2016},
date = {2016-01-01},
journal = {Journal of Neurosurgery},
volume = {124},
number = {3},
pages = {687--702},
abstract = {OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p \< 0.05), improved cognition (t = 6.532, p \< 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p \< 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.},
keywords = {*Blast Injuries/px [Psychology], *Brain Injury, *Endoplasmic Reticulum Stress/ph [Physiology], *Football/in [Injuries], *Wrestling/in [Injuries], adult, animal, Animals, Blast Injuries/et [Etiology], Blast Injuries/pa [Pathology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Disease Models, Humans, Male, Rats, Sprague-Dawley},
pubstate = {published},
tppubtype = {article}
}
Underwood, E
NEUROSCIENCE. Can brain scans reveal concussion-linked disease? Journal Article
In: Science, vol. 352, no. 6288, pp. 881, 2016.
BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Neuroimaging/mt [Methods], *Positron-Emission Tomography/mt [Methods], *tau Proteins/an [Analysis], 0 (7-(6-fluoropyridin-3-yl)-5H-pyrido(4, 0 (Carbolines), 0 (tau Proteins), 3-b)indole, adult, Carbolines/pk [Pharmacokinetics], Chronic/di [Diagnosis], Chronic/et [Etiology], Humans
@article{Underwood2016,
title = {NEUROSCIENCE. Can brain scans reveal concussion-linked disease?},
author = {Underwood, E},
year = {2016},
date = {2016-01-01},
journal = {Science},
volume = {352},
number = {6288},
pages = {881},
keywords = {*Brain Concussion/co [Complications], *Brain Injury, *Neuroimaging/mt [Methods], *Positron-Emission Tomography/mt [Methods], *tau Proteins/an [Analysis], 0 (7-(6-fluoropyridin-3-yl)-5H-pyrido(4, 0 (Carbolines), 0 (tau Proteins), 3-b)indole, adult, Carbolines/pk [Pharmacokinetics], Chronic/di [Diagnosis], Chronic/et [Etiology], Humans},
pubstate = {published},
tppubtype = {article}
}
Noble, J M
The Long Drive Ahead to Better Understanding Chronic Traumatic Encephalopathy: First (Case) and 10 (Years Later) Journal Article
In: JAMA Neurology, vol. 73, no. 3, pp. 263–265, 2016.
BibTeX | Tags: *Brain Injuries, *Brain Injury, Chronic, football, Humans
@article{Noble2016,
title = {The Long Drive Ahead to Better Understanding Chronic Traumatic Encephalopathy: First (Case) and 10 (Years Later)},
author = {Noble, J M},
year = {2016},
date = {2016-01-01},
journal = {JAMA Neurology},
volume = {73},
number = {3},
pages = {263--265},
keywords = {*Brain Injuries, *Brain Injury, Chronic, football, Humans},
pubstate = {published},
tppubtype = {article}
}
Mez, J; Solomon, T M; Daneshvar, D H; Stein, T D; McKee, A C
Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player Journal Article
In: JAMA Neurology, vol. 73, no. 3, pp. 353–355, 2016.
BibTeX | Tags: *Athletic Injuries/co [Complications], *Brain Injury, *Football, adult, Bacterial, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Endocarditis, Fatal Outcome, Heart Arrest, Humans, Male, Staphylococcal Infections
@article{Mez2016,
title = {Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player},
author = {Mez, J and Solomon, T M and Daneshvar, D H and Stein, T D and McKee, A C},
year = {2016},
date = {2016-01-01},
journal = {JAMA Neurology},
volume = {73},
number = {3},
pages = {353--355},
keywords = {*Athletic Injuries/co [Complications], *Brain Injury, *Football, adult, Bacterial, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Endocarditis, Fatal Outcome, Heart Arrest, Humans, Male, Staphylococcal Infections},
pubstate = {published},
tppubtype = {article}
}
O'Kane, J W
Is Heading in Youth Soccer Dangerous Play? Journal Article
In: Physician & Sportsmedicine, vol. 44, no. 2, pp. 190–194, 2016.
Abstract | BibTeX | Tags: *Brain Injuries/et [Etiology], *Brain Injury, *Soccer/in [Injuries], Adolescent, Brain Concussion/et [Etiology], Brain Concussion/pc [Prevention & Control], Brain Injuries/pc [Prevention & Control], Brain Injury, Child, Chronic/et [Etiology], Chronic/pc [Prevention & Control], Humans, Risk Factors, UNITED States
@article{OKane2016,
title = {Is Heading in Youth Soccer Dangerous Play?},
author = {O'Kane, J W},
year = {2016},
date = {2016-01-01},
journal = {Physician \& Sportsmedicine},
volume = {44},
number = {2},
pages = {190--194},
abstract = {BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence.},
keywords = {*Brain Injuries/et [Etiology], *Brain Injury, *Soccer/in [Injuries], Adolescent, Brain Concussion/et [Etiology], Brain Concussion/pc [Prevention \& Control], Brain Injuries/pc [Prevention \& Control], Brain Injury, Child, Chronic/et [Etiology], Chronic/pc [Prevention \& Control], Humans, Risk Factors, UNITED States},
pubstate = {published},
tppubtype = {article}
}
McCarthy, M
Chronic traumatic encephalopathy is reported in 25 year old former American football player Journal Article
In: BMJ, vol. 352, pp. h7027, 2016.
BibTeX | Tags: *Brain Injury, *Football, Chronic, Humans, Play and Playthings
@article{McCarthy2016,
title = {Chronic traumatic encephalopathy is reported in 25 year old former American football player},
author = {McCarthy, M},
year = {2016},
date = {2016-01-01},
journal = {BMJ},
volume = {352},
pages = {h7027},
keywords = {*Brain Injury, *Football, Chronic, Humans, Play and Playthings},
pubstate = {published},
tppubtype = {article}
}
Steiger, B
Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion Journal Article
In: Physician Leadership Journal, vol. 3, no. 2, pp. 8–10, 2016.
Abstract | BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Football, Athletic Injuries/co [Complications], Brain Injury, Chronic, Chronic/et [Etiology], Humans, Motion Pictures as Topic
@article{Steiger2016,
title = {Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion},
author = {Steiger, B},
year = {2016},
date = {2016-01-01},
journal = {Physician Leadership Journal},
volume = {3},
number = {2},
pages = {8--10},
abstract = {The pathologist who discovered chronic traumatic encephalopathy in professional football players didn't set out to attack America's favorite sport. He didn't even know much about the game.},
keywords = {*Brain Concussion/co [Complications], *Brain Injury, *Football, Athletic Injuries/co [Complications], Brain Injury, Chronic, Chronic/et [Etiology], Humans, Motion Pictures as Topic},
pubstate = {published},
tppubtype = {article}
}
Barrio, J R; Small, G W; Wong, K P; Huang, S C; Liu, J; Merrill, D A; Giza, C C; Fitzsimmons, R P; Omalu, B; Bailes, J; Kepe, V
In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344] Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 16, pp. E2039–47, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged
@article{Barrio2015,
title = {In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344]},
author = {Barrio, J R and Small, G W and Wong, K P and Huang, S C and Liu, J and Merrill, D A and Giza, C C and Fitzsimmons, R P and Omalu, B and Bailes, J and Kepe, V},
year = {2015},
date = {2015-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {112},
number = {16},
pages = {E2039--47},
abstract = {Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged},
pubstate = {published},
tppubtype = {article}
}
Svaldi, D O; Joshi, C; Robinson, M E; Shenk, T E; Abbas, K; Nauman, E A; Leverenz, L J; Talavage, T M
Cerebrovascular reactivity alterations in asymptomatic high school football players Journal Article
In: Developmental Neuropsychology, vol. 40, no. 2, pp. 80–84, 2015.
Abstract | BibTeX | Tags: *Athletes, *Brain Concussion/pp [Physiopathology], *Brain Injury, *Cerebrovascular Disorders/pp [Physiopathology], *Football/in [Injuries], Adolescent, Chronic/pp [Physiopathology], Humans, RISK assessment, Schools
@article{Svaldi2015,
title = {Cerebrovascular reactivity alterations in asymptomatic high school football players},
author = {Svaldi, D O and Joshi, C and Robinson, M E and Shenk, T E and Abbas, K and Nauman, E A and Leverenz, L J and Talavage, T M},
year = {2015},
date = {2015-01-01},
journal = {Developmental Neuropsychology},
volume = {40},
number = {2},
pages = {80--84},
abstract = {Cerebrovascular reactivity (CVR) is impaired following brain injury, increasing susceptibility to subsequent injury. CVR was tracked in football and non-collision athletes throughout one season. CVR transiently decreased in football athletes during the first half of the season. Results indicate the brain adapts slowly to increases in loading, increasing risk for injury.},
keywords = {*Athletes, *Brain Concussion/pp [Physiopathology], *Brain Injury, *Cerebrovascular Disorders/pp [Physiopathology], *Football/in [Injuries], Adolescent, Chronic/pp [Physiopathology], Humans, RISK assessment, Schools},
pubstate = {published},
tppubtype = {article}
}
Bieniek, K F; Ross, O A; Cormier, K A; Walton, R L; Soto-Ortolaza, A; Johnston, A E; DeSaro, P; Boylan, K B; Graff-Radford, N R; Wszolek, Z K; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W
Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article
In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks
@article{Bieniek2015,
title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},
author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {6},
pages = {877--889},
abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks},
pubstate = {published},
tppubtype = {article}
}
Faden, A I; Loane, D J
Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Journal Article
In: Neurotherapeutics, vol. 12, no. 1, pp. 143–150, 2015.
Abstract | BibTeX | Tags: *Alzheimer Disease/et [Etiology], *Brain Injuries/co [Complications], *Brain Injury, *Encephalitis/et [Etiology], *Nerve Degeneration/et [Etiology], Alzheimer Disease/pa [Pathology], Animals, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Encephalitis/pa [Pathology], Humans, Nerve Degeneration/pa [Pathology]
@article{Faden2015,
title = {Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?},
author = {Faden, A I and Loane, D J},
year = {2015},
date = {2015-01-01},
journal = {Neurotherapeutics},
volume = {12},
number = {1},
pages = {143--150},
abstract = {It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).},
keywords = {*Alzheimer Disease/et [Etiology], *Brain Injuries/co [Complications], *Brain Injury, *Encephalitis/et [Etiology], *Nerve Degeneration/et [Etiology], Alzheimer Disease/pa [Pathology], Animals, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Encephalitis/pa [Pathology], Humans, Nerve Degeneration/pa [Pathology]},
pubstate = {published},
tppubtype = {article}
}
Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A
Chronic traumatic encephalopathy and athletes Journal Article
In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.
Abstract | BibTeX | Tags: *Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]
@article{Meehan3rd2015a,
title = {Chronic traumatic encephalopathy and athletes},
author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},
year = {2015},
date = {2015-01-01},
journal = {Neurology},
volume = {85},
number = {17},
pages = {1504--1511},
abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},
keywords = {*Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]},
pubstate = {published},
tppubtype = {article}
}
Stein, T D; Montenigro, P H; Alvarez, V E; Xia, W; Crary, J F; Tripodis, Y; Daneshvar, D H; Mez, J; Solomon, T; Meng, G; Kubilus, C A; Cormier, K A; Meng, S; Babcock, K; Kiernan, P; Murphy, L; Nowinski, C J; Martin, B; Dixon, D; Stern, R A; Cantu, R C; Kowall, N W; McKee, A C
Beta-amyloid deposition in chronic traumatic encephalopathy Journal Article
In: Acta Neuropathologica, vol. 130, no. 1, pp. 21–34, 2015.
Abstract | BibTeX | Tags: *Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]
@article{Stein2015b,
title = {Beta-amyloid deposition in chronic traumatic encephalopathy},
author = {Stein, T D and Montenigro, P H and Alvarez, V E and Xia, W and Crary, J F and Tripodis, Y and Daneshvar, D H and Mez, J and Solomon, T and Meng, G and Kubilus, C A and Cormier, K A and Meng, S and Babcock, K and Kiernan, P and Murphy, L and Nowinski, C J and Martin, B and Dixon, D and Stern, R A and Cantu, R C and Kowall, N W and McKee, A C},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {1},
pages = {21--34},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid beta peptide (Abeta) levels, the extent of Abeta deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Abeta deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Abeta deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Abeta deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p \< 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Abeta plaques and those without. Abeta deposition was significantly associated with the presence of the APOE epsilon4 allele (p = 0.035), older age at symptom onset (p \< 0.001), and older age at death (p \< 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (beta = 2.43},
keywords = {*Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]},
pubstate = {published},
tppubtype = {article}
}
McKee, A C; Stein, T D; Kiernan, P T; Alvarez, V E
The neuropathology of chronic traumatic encephalopathy Journal Article
In: Brain Pathology, vol. 25, no. 3, pp. 350–364, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]
@article{McKee2015a,
title = {The neuropathology of chronic traumatic encephalopathy},
author = {McKee, A C and Stein, T D and Kiernan, P T and Alvarez, V E},
year = {2015},
date = {2015-01-01},
journal = {Brain Pathology},
volume = {25},
number = {3},
pages = {350--364},
abstract = {Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. Copyright © 2015 International Society of Neuropathology.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]},
pubstate = {published},
tppubtype = {article}
}
Smith, A M; Stuart, M J; Dodick, D W; Roberts, W O; Alford, P W; Ashare, A B; Aubrey, M; Benson, B W; Burke, C J; Dick, R; Eickhoff, C; Emery, C A; Flashman, L A; Gaz, D; Giza, C C; Greenwald, R M; Herring, S; Hoshizaki, T B; Hudziak, J J; Huston 3rd, J; Krause, D; LaVoi, N; Leaf, M; Leddy, J J; MacPherson, A; McKee, A C; Mihalik, J P; Moessner, A M; Montelpare, W J; Putukian, M; Schneider, K J; Szalkowski, R; Tabrum, M; Whitehead, J; Wiese-Bjornstal, D M
Ice Hockey Summit II: zero tolerance for head hits and fighting.[Erratum appears in Clin J Sport Med. 2015 Jul;25(4):379] Journal Article
In: Clinical Journal of Sport Medicine, vol. 25, no. 2, pp. 78–87, 2015.
Abstract | BibTeX | Tags: *Brain Concussion/pc [Prevention & Control], *Brain Injury, *Hockey/in [Injuries], *Violence/pc [Prevention & Control], Adolescent, adult, Brain Concussion/th [Therapy], Brain Injury, Child, Chronic/pc [Prevention & Control], Chronic/th [Therapy], Congresses as Topic, Evidence-Based Medicine, Head Protective Devices/st [Standards], Hockey/st [Standards], Humans, policy, Young Adult
@article{Smith2015a,
title = {Ice Hockey Summit II: zero tolerance for head hits and fighting.[Erratum appears in Clin J Sport Med. 2015 Jul;25(4):379]},
author = {Smith, A M and Stuart, M J and Dodick, D W and Roberts, W O and Alford, P W and Ashare, A B and Aubrey, M and Benson, B W and Burke, C J and Dick, R and Eickhoff, C and Emery, C A and Flashman, L A and Gaz, D and Giza, C C and Greenwald, R M and Herring, S and Hoshizaki, T B and Hudziak, J J and {Huston 3rd}, J and Krause, D and LaVoi, N and Leaf, M and Leddy, J J and MacPherson, A and McKee, A C and Mihalik, J P and Moessner, A M and Montelpare, W J and Putukian, M and Schneider, K J and Szalkowski, R and Tabrum, M and Whitehead, J and Wiese-Bjornstal, D M},
year = {2015},
date = {2015-01-01},
journal = {Clinical Journal of Sport Medicine},
volume = {25},
number = {2},
pages = {78--87},
abstract = {OBJECTIVE: To present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building on the Ice Hockey Summit I action plan (2011) to reduce SRC. METHODS: The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure, for the science and discussion held during Summit II (Mayo Clinic, Rochester MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment: their Relationship to Industry Standards; and (5) Policies and Plans at State, National and Federal Levels to reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were subsequently voted on for purposes of prioritization. The following proceedings include knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. RESULTS: The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. CONCLUSIONS: The highest priority action items identified from the Summit includes the following: (1) eliminate head hits from all levels of ice hockey, (2) change body-checking policies, and (3) eliminate fighting in all amateur and professional hockey.},
keywords = {*Brain Concussion/pc [Prevention \& Control], *Brain Injury, *Hockey/in [Injuries], *Violence/pc [Prevention \& Control], Adolescent, adult, Brain Concussion/th [Therapy], Brain Injury, Child, Chronic/pc [Prevention \& Control], Chronic/th [Therapy], Congresses as Topic, Evidence-Based Medicine, Head Protective Devices/st [Standards], Hockey/st [Standards], Humans, policy, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Omalu, B
Chronic traumatic encephalopathy Journal Article
In: Progress in Neurological Surgery, vol. 28, pp. 38–49, 2014.
Abstract | Links | BibTeX | Tags: *Brain Injuries/pa [Pathology], *Brain Injury, Brain Concussion/pa [Pathology], Chronic Traumatic Encephalopathy Animals, Chronic/pa [Pathology], Humans, Tauopathies
@article{Omalu2014,
title = {Chronic traumatic encephalopathy},
author = {Omalu, B},
url = {http://ovidsp.ovid.com/ovidweb.cgi?T=JS\&CSC=Y\&NEWS=N\&PAGE=fulltext\&D=medl\&AN=24923391},
year = {2014},
date = {2014-01-01},
journal = {Progress in Neurological Surgery},
volume = {28},
pages = {38--49},
abstract = {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.Copyright © 2014 S. Karger AG, Basel.},
keywords = {*Brain Injuries/pa [Pathology], *Brain Injury, Brain Concussion/pa [Pathology], Chronic Traumatic Encephalopathy Animals, Chronic/pa [Pathology], Humans, Tauopathies},
pubstate = {published},
tppubtype = {article}
}
Omalu, B; Hammers, J L; Bailes, J; Hamilton, R L; Kamboh, M I; Webster, G; Fitzsimmons, R P
Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide Journal Article
In: Neurosurgical Focus, vol. 31, no. 5, pp. E3, 2011.
Abstract | BibTeX | Tags: *Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention & Control]
@article{Omalu2011,
title = {Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide},
author = {Omalu, B and Hammers, J L and Bailes, J and Hamilton, R L and Kamboh, M I and Webster, G and Fitzsimmons, R P},
year = {2011},
date = {2011-01-01},
journal = {Neurosurgical Focus},
volume = {31},
number = {5},
pages = {E3},
abstract = {Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.},
keywords = {*Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention \& Control]},
pubstate = {published},
tppubtype = {article}
}
Heilbronner, Robert L; Bush, Shane S; Ravdin, Lisa D; Barth, Jeffrey T; Iverson, Grant L; Ruff, Ronald M; Lovell, Mark R; Barr, William B; Echemendia, Ruben J; Broshek, Donna K
Neuropsychological consequences of boxing and recommendations to improve safety: a National Academy of Neuropsychology education paper Journal Article
In: Archives of Clinical Neuropsychology, vol. 24, pp. 11–19, 2009.
Abstract | BibTeX | Tags: *Brain Injury, Chronic/di [Diagnosis] Neuropsychol
@article{Heilbronner2009,
title = {Neuropsychological consequences of boxing and recommendations to improve safety: a National Academy of Neuropsychology education paper},
author = {Heilbronner, Robert L and Bush, Shane S and Ravdin, Lisa D and Barth, Jeffrey T and Iverson, Grant L and Ruff, Ronald M and Lovell, Mark R and Barr, William B and Echemendia, Ruben J and Broshek, Donna K},
year = {2009},
date = {2009-01-01},
journal = {Archives of Clinical Neuropsychology},
volume = {24},
pages = {11--19},
address = {Chicago Neuropsychology Group and Northwestern University Feinberg School of Medicine, Chicago, IL 60601, USA. r-heilbronner@northwestern.edu},
abstract = {Boxing has held appeal for many athletes and audiences for centuries, and injuries have been part of boxing since its inception. Although permanent and irreversible neurologic dysfunction does not occur in the majority of participants, an association has been reported between the number of bouts fought and the development of neurologic, psychiatric, or histopathological signs and symptoms of encephalopathy in boxers. The purpose of this paper is to (i) provide clinical neuropsychologists, other health-care professionals, and the general public with information about the potential neuropsychological consequences of boxing, and (ii) provide recommendations to improve safety standards for those who participate in the sport.},
keywords = {*Brain Injury, Chronic/di [Diagnosis] Neuropsychol},
pubstate = {published},
tppubtype = {article}
}
Iverson, G L
Suicide and Chronic Traumatic Encephalopathy Journal Article
In: Journal of Neuropsychiatry & Clinical Neurosciences, vol. 28, no. 1, pp. 9–16, 2016.
@article{Iverson2016a,
title = {Suicide and Chronic Traumatic Encephalopathy},
author = {Iverson, G L},
year = {2016},
date = {2016-01-01},
journal = {Journal of Neuropsychiatry \& Clinical Neurosciences},
volume = {28},
number = {1},
pages = {9--16},
abstract = {For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Stewart, W; McNamara, P H; Lawlor, B; Hutchinson, S; Farrell, M
Chronic traumatic encephalopathy: a potential late and under recognized consequence of rugby union? Journal Article
In: Qjm, vol. 109, no. 1, pp. 11–15, 2016.
@article{Stewart2016,
title = {Chronic traumatic encephalopathy: a potential late and under recognized consequence of rugby union?},
author = {Stewart, W and McNamara, P H and Lawlor, B and Hutchinson, S and Farrell, M},
year = {2016},
date = {2016-01-01},
journal = {Qjm},
volume = {109},
number = {1},
pages = {11--15},
abstract = {The association between exposure to head injury and increased risk of neurodegenerative disease, specifically chronic traumatic encephalopathy (CTE), is widely recognized. Historically, this was largely considered a phenomenon restricted to boxers, with more recent case series identifying further 'high risk' individuals, such as former American footballers, or military personnel. However, in all cases thus far reported, it is clear that it is the exposure to head injury which is associated with increased dementia risk, and not the circumstances or environment of exposure. As such, there is considerable potential for under-recognition of CTE in patients presenting with neurodegenerative disease, particularly where head injury exposure might have been historical and through sport. This article reviews current understanding of CTE and, via an illustrative case in rugby union, highlights the value of a detailed history on head injury and also draws attention to imaging studies in assessing patients with neurodegenerative disease. Copyright © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Puvenna, V; Engeler, M; Banjara, M; Brennan, C; Schreiber, P; Dadas, A; Bahrami, A; Solanki, J; Bandyopadhyay, A; Morris, J K; Bernick, C; Ghosh, C; Rapp, E; Bazarian, J J; Janigro, D
Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy Journal Article
In: Brain Research, vol. 1630, pp. 225–240, 2016.
@article{Puvenna2016,
title = {Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy},
author = {Puvenna, V and Engeler, M and Banjara, M and Brennan, C and Schreiber, P and Dadas, A and Bahrami, A and Solanki, J and Bandyopadhyay, A and Morris, J K and Bernick, C and Ghosh, C and Rapp, E and Bazarian, J J and Janigro, D},
year = {2016},
date = {2016-01-01},
journal = {Brain Research},
volume = {1630},
pages = {225--240},
abstract = {Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P\<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lucke-Wold, B P; Turner, R C; Logsdon, A F; Nguyen, L; Bailes, J E; Lee, J M; Robson, M J; Omalu, B I; Huber, J D; Rosen, C L
Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy Journal Article
In: Journal of Neurosurgery, vol. 124, no. 3, pp. 687–702, 2016.
@article{Lucke-Wold2016,
title = {Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy},
author = {Lucke-Wold, B P and Turner, R C and Logsdon, A F and Nguyen, L and Bailes, J E and Lee, J M and Robson, M J and Omalu, B I and Huber, J D and Rosen, C L},
year = {2016},
date = {2016-01-01},
journal = {Journal of Neurosurgery},
volume = {124},
number = {3},
pages = {687--702},
abstract = {OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p \< 0.05), improved cognition (t = 6.532, p \< 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p \< 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Underwood, E
NEUROSCIENCE. Can brain scans reveal concussion-linked disease? Journal Article
In: Science, vol. 352, no. 6288, pp. 881, 2016.
@article{Underwood2016,
title = {NEUROSCIENCE. Can brain scans reveal concussion-linked disease?},
author = {Underwood, E},
year = {2016},
date = {2016-01-01},
journal = {Science},
volume = {352},
number = {6288},
pages = {881},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Noble, J M
The Long Drive Ahead to Better Understanding Chronic Traumatic Encephalopathy: First (Case) and 10 (Years Later) Journal Article
In: JAMA Neurology, vol. 73, no. 3, pp. 263–265, 2016.
@article{Noble2016,
title = {The Long Drive Ahead to Better Understanding Chronic Traumatic Encephalopathy: First (Case) and 10 (Years Later)},
author = {Noble, J M},
year = {2016},
date = {2016-01-01},
journal = {JAMA Neurology},
volume = {73},
number = {3},
pages = {263--265},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mez, J; Solomon, T M; Daneshvar, D H; Stein, T D; McKee, A C
Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player Journal Article
In: JAMA Neurology, vol. 73, no. 3, pp. 353–355, 2016.
@article{Mez2016,
title = {Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player},
author = {Mez, J and Solomon, T M and Daneshvar, D H and Stein, T D and McKee, A C},
year = {2016},
date = {2016-01-01},
journal = {JAMA Neurology},
volume = {73},
number = {3},
pages = {353--355},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
O'Kane, J W
Is Heading in Youth Soccer Dangerous Play? Journal Article
In: Physician & Sportsmedicine, vol. 44, no. 2, pp. 190–194, 2016.
@article{OKane2016,
title = {Is Heading in Youth Soccer Dangerous Play?},
author = {O'Kane, J W},
year = {2016},
date = {2016-01-01},
journal = {Physician \& Sportsmedicine},
volume = {44},
number = {2},
pages = {190--194},
abstract = {BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
McCarthy, M
Chronic traumatic encephalopathy is reported in 25 year old former American football player Journal Article
In: BMJ, vol. 352, pp. h7027, 2016.
@article{McCarthy2016,
title = {Chronic traumatic encephalopathy is reported in 25 year old former American football player},
author = {McCarthy, M},
year = {2016},
date = {2016-01-01},
journal = {BMJ},
volume = {352},
pages = {h7027},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Steiger, B
Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion Journal Article
In: Physician Leadership Journal, vol. 3, no. 2, pp. 8–10, 2016.
@article{Steiger2016,
title = {Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion},
author = {Steiger, B},
year = {2016},
date = {2016-01-01},
journal = {Physician Leadership Journal},
volume = {3},
number = {2},
pages = {8--10},
abstract = {The pathologist who discovered chronic traumatic encephalopathy in professional football players didn't set out to attack America's favorite sport. He didn't even know much about the game.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Barrio, J R; Small, G W; Wong, K P; Huang, S C; Liu, J; Merrill, D A; Giza, C C; Fitzsimmons, R P; Omalu, B; Bailes, J; Kepe, V
In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344] Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 16, pp. E2039–47, 2015.
@article{Barrio2015,
title = {In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344]},
author = {Barrio, J R and Small, G W and Wong, K P and Huang, S C and Liu, J and Merrill, D A and Giza, C C and Fitzsimmons, R P and Omalu, B and Bailes, J and Kepe, V},
year = {2015},
date = {2015-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {112},
number = {16},
pages = {E2039--47},
abstract = {Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Svaldi, D O; Joshi, C; Robinson, M E; Shenk, T E; Abbas, K; Nauman, E A; Leverenz, L J; Talavage, T M
Cerebrovascular reactivity alterations in asymptomatic high school football players Journal Article
In: Developmental Neuropsychology, vol. 40, no. 2, pp. 80–84, 2015.
@article{Svaldi2015,
title = {Cerebrovascular reactivity alterations in asymptomatic high school football players},
author = {Svaldi, D O and Joshi, C and Robinson, M E and Shenk, T E and Abbas, K and Nauman, E A and Leverenz, L J and Talavage, T M},
year = {2015},
date = {2015-01-01},
journal = {Developmental Neuropsychology},
volume = {40},
number = {2},
pages = {80--84},
abstract = {Cerebrovascular reactivity (CVR) is impaired following brain injury, increasing susceptibility to subsequent injury. CVR was tracked in football and non-collision athletes throughout one season. CVR transiently decreased in football athletes during the first half of the season. Results indicate the brain adapts slowly to increases in loading, increasing risk for injury.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bieniek, K F; Ross, O A; Cormier, K A; Walton, R L; Soto-Ortolaza, A; Johnston, A E; DeSaro, P; Boylan, K B; Graff-Radford, N R; Wszolek, Z K; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W
Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article
In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.
@article{Bieniek2015,
title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},
author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {6},
pages = {877--889},
abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Faden, A I; Loane, D J
Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Journal Article
In: Neurotherapeutics, vol. 12, no. 1, pp. 143–150, 2015.
@article{Faden2015,
title = {Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?},
author = {Faden, A I and Loane, D J},
year = {2015},
date = {2015-01-01},
journal = {Neurotherapeutics},
volume = {12},
number = {1},
pages = {143--150},
abstract = {It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A
Chronic traumatic encephalopathy and athletes Journal Article
In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.
@article{Meehan3rd2015a,
title = {Chronic traumatic encephalopathy and athletes},
author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},
year = {2015},
date = {2015-01-01},
journal = {Neurology},
volume = {85},
number = {17},
pages = {1504--1511},
abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Stein, T D; Montenigro, P H; Alvarez, V E; Xia, W; Crary, J F; Tripodis, Y; Daneshvar, D H; Mez, J; Solomon, T; Meng, G; Kubilus, C A; Cormier, K A; Meng, S; Babcock, K; Kiernan, P; Murphy, L; Nowinski, C J; Martin, B; Dixon, D; Stern, R A; Cantu, R C; Kowall, N W; McKee, A C
Beta-amyloid deposition in chronic traumatic encephalopathy Journal Article
In: Acta Neuropathologica, vol. 130, no. 1, pp. 21–34, 2015.
@article{Stein2015b,
title = {Beta-amyloid deposition in chronic traumatic encephalopathy},
author = {Stein, T D and Montenigro, P H and Alvarez, V E and Xia, W and Crary, J F and Tripodis, Y and Daneshvar, D H and Mez, J and Solomon, T and Meng, G and Kubilus, C A and Cormier, K A and Meng, S and Babcock, K and Kiernan, P and Murphy, L and Nowinski, C J and Martin, B and Dixon, D and Stern, R A and Cantu, R C and Kowall, N W and McKee, A C},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {1},
pages = {21--34},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid beta peptide (Abeta) levels, the extent of Abeta deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Abeta deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Abeta deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Abeta deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p \< 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Abeta plaques and those without. Abeta deposition was significantly associated with the presence of the APOE epsilon4 allele (p = 0.035), older age at symptom onset (p \< 0.001), and older age at death (p \< 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (beta = 2.43},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
McKee, A C; Stein, T D; Kiernan, P T; Alvarez, V E
The neuropathology of chronic traumatic encephalopathy Journal Article
In: Brain Pathology, vol. 25, no. 3, pp. 350–364, 2015.
@article{McKee2015a,
title = {The neuropathology of chronic traumatic encephalopathy},
author = {McKee, A C and Stein, T D and Kiernan, P T and Alvarez, V E},
year = {2015},
date = {2015-01-01},
journal = {Brain Pathology},
volume = {25},
number = {3},
pages = {350--364},
abstract = {Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. Copyright © 2015 International Society of Neuropathology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Smith, A M; Stuart, M J; Dodick, D W; Roberts, W O; Alford, P W; Ashare, A B; Aubrey, M; Benson, B W; Burke, C J; Dick, R; Eickhoff, C; Emery, C A; Flashman, L A; Gaz, D; Giza, C C; Greenwald, R M; Herring, S; Hoshizaki, T B; Hudziak, J J; Huston 3rd, J; Krause, D; LaVoi, N; Leaf, M; Leddy, J J; MacPherson, A; McKee, A C; Mihalik, J P; Moessner, A M; Montelpare, W J; Putukian, M; Schneider, K J; Szalkowski, R; Tabrum, M; Whitehead, J; Wiese-Bjornstal, D M
Ice Hockey Summit II: zero tolerance for head hits and fighting.[Erratum appears in Clin J Sport Med. 2015 Jul;25(4):379] Journal Article
In: Clinical Journal of Sport Medicine, vol. 25, no. 2, pp. 78–87, 2015.
@article{Smith2015a,
title = {Ice Hockey Summit II: zero tolerance for head hits and fighting.[Erratum appears in Clin J Sport Med. 2015 Jul;25(4):379]},
author = {Smith, A M and Stuart, M J and Dodick, D W and Roberts, W O and Alford, P W and Ashare, A B and Aubrey, M and Benson, B W and Burke, C J and Dick, R and Eickhoff, C and Emery, C A and Flashman, L A and Gaz, D and Giza, C C and Greenwald, R M and Herring, S and Hoshizaki, T B and Hudziak, J J and {Huston 3rd}, J and Krause, D and LaVoi, N and Leaf, M and Leddy, J J and MacPherson, A and McKee, A C and Mihalik, J P and Moessner, A M and Montelpare, W J and Putukian, M and Schneider, K J and Szalkowski, R and Tabrum, M and Whitehead, J and Wiese-Bjornstal, D M},
year = {2015},
date = {2015-01-01},
journal = {Clinical Journal of Sport Medicine},
volume = {25},
number = {2},
pages = {78--87},
abstract = {OBJECTIVE: To present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building on the Ice Hockey Summit I action plan (2011) to reduce SRC. METHODS: The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure, for the science and discussion held during Summit II (Mayo Clinic, Rochester MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment: their Relationship to Industry Standards; and (5) Policies and Plans at State, National and Federal Levels to reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were subsequently voted on for purposes of prioritization. The following proceedings include knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. RESULTS: The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. CONCLUSIONS: The highest priority action items identified from the Summit includes the following: (1) eliminate head hits from all levels of ice hockey, (2) change body-checking policies, and (3) eliminate fighting in all amateur and professional hockey.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Omalu, B
Chronic traumatic encephalopathy Journal Article
In: Progress in Neurological Surgery, vol. 28, pp. 38–49, 2014.
@article{Omalu2014,
title = {Chronic traumatic encephalopathy},
author = {Omalu, B},
url = {http://ovidsp.ovid.com/ovidweb.cgi?T=JS\&CSC=Y\&NEWS=N\&PAGE=fulltext\&D=medl\&AN=24923391},
year = {2014},
date = {2014-01-01},
journal = {Progress in Neurological Surgery},
volume = {28},
pages = {38--49},
abstract = {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.Copyright © 2014 S. Karger AG, Basel.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Omalu, B; Hammers, J L; Bailes, J; Hamilton, R L; Kamboh, M I; Webster, G; Fitzsimmons, R P
Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide Journal Article
In: Neurosurgical Focus, vol. 31, no. 5, pp. E3, 2011.
@article{Omalu2011,
title = {Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide},
author = {Omalu, B and Hammers, J L and Bailes, J and Hamilton, R L and Kamboh, M I and Webster, G and Fitzsimmons, R P},
year = {2011},
date = {2011-01-01},
journal = {Neurosurgical Focus},
volume = {31},
number = {5},
pages = {E3},
abstract = {Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Iverson, G L
Suicide and Chronic Traumatic Encephalopathy Journal Article
In: Journal of Neuropsychiatry & Clinical Neurosciences, vol. 28, no. 1, pp. 9–16, 2016.
Abstract | BibTeX | Tags: *Brain Injury, *Football/in [Injuries], *Suicide/px [Psychology], Athletic Injuries/di [Diagnosis], Athletic Injuries/ep [Epidemiology], Athletic Injuries/px [Psychology], Brain Injury, Chronic/di [Diagnosis], Chronic/ep [Epidemiology], Chronic/px [Psychology], Football/px [Psychology], Humans, Male, Risk Factors, Suicide/td [Trends]
@article{Iverson2016a,
title = {Suicide and Chronic Traumatic Encephalopathy},
author = {Iverson, G L},
year = {2016},
date = {2016-01-01},
journal = {Journal of Neuropsychiatry \& Clinical Neurosciences},
volume = {28},
number = {1},
pages = {9--16},
abstract = {For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships.},
keywords = {*Brain Injury, *Football/in [Injuries], *Suicide/px [Psychology], Athletic Injuries/di [Diagnosis], Athletic Injuries/ep [Epidemiology], Athletic Injuries/px [Psychology], Brain Injury, Chronic/di [Diagnosis], Chronic/ep [Epidemiology], Chronic/px [Psychology], Football/px [Psychology], Humans, Male, Risk Factors, Suicide/td [Trends]},
pubstate = {published},
tppubtype = {article}
}
Stewart, W; McNamara, P H; Lawlor, B; Hutchinson, S; Farrell, M
Chronic traumatic encephalopathy: a potential late and under recognized consequence of rugby union? Journal Article
In: Qjm, vol. 109, no. 1, pp. 11–15, 2016.
Abstract | BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Brain/pp [Physiopathology], *Football/in [Injuries], *Neurodegenerative Diseases/pp [Physiopathology], Chronic/pa [Pathology], Humans, Magnetic Resonance Imaging, Male, middle aged, neurologic examination
@article{Stewart2016,
title = {Chronic traumatic encephalopathy: a potential late and under recognized consequence of rugby union?},
author = {Stewart, W and McNamara, P H and Lawlor, B and Hutchinson, S and Farrell, M},
year = {2016},
date = {2016-01-01},
journal = {Qjm},
volume = {109},
number = {1},
pages = {11--15},
abstract = {The association between exposure to head injury and increased risk of neurodegenerative disease, specifically chronic traumatic encephalopathy (CTE), is widely recognized. Historically, this was largely considered a phenomenon restricted to boxers, with more recent case series identifying further 'high risk' individuals, such as former American footballers, or military personnel. However, in all cases thus far reported, it is clear that it is the exposure to head injury which is associated with increased dementia risk, and not the circumstances or environment of exposure. As such, there is considerable potential for under-recognition of CTE in patients presenting with neurodegenerative disease, particularly where head injury exposure might have been historical and through sport. This article reviews current understanding of CTE and, via an illustrative case in rugby union, highlights the value of a detailed history on head injury and also draws attention to imaging studies in assessing patients with neurodegenerative disease. Copyright © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},
keywords = {*Brain Concussion/co [Complications], *Brain Injury, *Brain/pp [Physiopathology], *Football/in [Injuries], *Neurodegenerative Diseases/pp [Physiopathology], Chronic/pa [Pathology], Humans, Magnetic Resonance Imaging, Male, middle aged, neurologic examination},
pubstate = {published},
tppubtype = {article}
}
Puvenna, V; Engeler, M; Banjara, M; Brennan, C; Schreiber, P; Dadas, A; Bahrami, A; Solanki, J; Bandyopadhyay, A; Morris, J K; Bernick, C; Ghosh, C; Rapp, E; Bazarian, J J; Janigro, D
Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy Journal Article
In: Brain Research, vol. 1630, pp. 225–240, 2016.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/me [Metabolism], *Epilepsy/me [Metabolism], *tau Proteins/me [Metabolism], 0 (MAPT protein, 0 (tau Proteins), 80 and over, Adolescent, adult, aged, Brain Injury, Brain/pa [Pathology], Brain/su [Surgery], Child, Chronic/me [Metabolism], Chronic/pa [Pathology], ENZYME-linked immunosorbent assay, Epilepsy/pa [Pathology], Epilepsy/su [Surgery], Female, human), Humans, immunohistochemistry, Infant, Male, middle aged, Phosphorylation, Preschool, Young Adult
@article{Puvenna2016,
title = {Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy},
author = {Puvenna, V and Engeler, M and Banjara, M and Brennan, C and Schreiber, P and Dadas, A and Bahrami, A and Solanki, J and Bandyopadhyay, A and Morris, J K and Bernick, C and Ghosh, C and Rapp, E and Bazarian, J J and Janigro, D},
year = {2016},
date = {2016-01-01},
journal = {Brain Research},
volume = {1630},
pages = {225--240},
abstract = {Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P\<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights reserved.},
keywords = {*Brain Injury, *Brain/me [Metabolism], *Epilepsy/me [Metabolism], *tau Proteins/me [Metabolism], 0 (MAPT protein, 0 (tau Proteins), 80 and over, Adolescent, adult, aged, Brain Injury, Brain/pa [Pathology], Brain/su [Surgery], Child, Chronic/me [Metabolism], Chronic/pa [Pathology], ENZYME-linked immunosorbent assay, Epilepsy/pa [Pathology], Epilepsy/su [Surgery], Female, human), Humans, immunohistochemistry, Infant, Male, middle aged, Phosphorylation, Preschool, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Lucke-Wold, B P; Turner, R C; Logsdon, A F; Nguyen, L; Bailes, J E; Lee, J M; Robson, M J; Omalu, B I; Huber, J D; Rosen, C L
Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy Journal Article
In: Journal of Neurosurgery, vol. 124, no. 3, pp. 687–702, 2016.
Abstract | BibTeX | Tags: *Blast Injuries/px [Psychology], *Brain Injury, *Endoplasmic Reticulum Stress/ph [Physiology], *Football/in [Injuries], *Wrestling/in [Injuries], adult, animal, Animals, Blast Injuries/et [Etiology], Blast Injuries/pa [Pathology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Disease Models, Humans, Male, Rats, Sprague-Dawley
@article{Lucke-Wold2016,
title = {Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy},
author = {Lucke-Wold, B P and Turner, R C and Logsdon, A F and Nguyen, L and Bailes, J E and Lee, J M and Robson, M J and Omalu, B I and Huber, J D and Rosen, C L},
year = {2016},
date = {2016-01-01},
journal = {Journal of Neurosurgery},
volume = {124},
number = {3},
pages = {687--702},
abstract = {OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p \< 0.05), improved cognition (t = 6.532, p \< 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p \< 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.},
keywords = {*Blast Injuries/px [Psychology], *Brain Injury, *Endoplasmic Reticulum Stress/ph [Physiology], *Football/in [Injuries], *Wrestling/in [Injuries], adult, animal, Animals, Blast Injuries/et [Etiology], Blast Injuries/pa [Pathology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Disease Models, Humans, Male, Rats, Sprague-Dawley},
pubstate = {published},
tppubtype = {article}
}
Underwood, E
NEUROSCIENCE. Can brain scans reveal concussion-linked disease? Journal Article
In: Science, vol. 352, no. 6288, pp. 881, 2016.
BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Neuroimaging/mt [Methods], *Positron-Emission Tomography/mt [Methods], *tau Proteins/an [Analysis], 0 (7-(6-fluoropyridin-3-yl)-5H-pyrido(4, 0 (Carbolines), 0 (tau Proteins), 3-b)indole, adult, Carbolines/pk [Pharmacokinetics], Chronic/di [Diagnosis], Chronic/et [Etiology], Humans
@article{Underwood2016,
title = {NEUROSCIENCE. Can brain scans reveal concussion-linked disease?},
author = {Underwood, E},
year = {2016},
date = {2016-01-01},
journal = {Science},
volume = {352},
number = {6288},
pages = {881},
keywords = {*Brain Concussion/co [Complications], *Brain Injury, *Neuroimaging/mt [Methods], *Positron-Emission Tomography/mt [Methods], *tau Proteins/an [Analysis], 0 (7-(6-fluoropyridin-3-yl)-5H-pyrido(4, 0 (Carbolines), 0 (tau Proteins), 3-b)indole, adult, Carbolines/pk [Pharmacokinetics], Chronic/di [Diagnosis], Chronic/et [Etiology], Humans},
pubstate = {published},
tppubtype = {article}
}
Noble, J M
The Long Drive Ahead to Better Understanding Chronic Traumatic Encephalopathy: First (Case) and 10 (Years Later) Journal Article
In: JAMA Neurology, vol. 73, no. 3, pp. 263–265, 2016.
BibTeX | Tags: *Brain Injuries, *Brain Injury, Chronic, football, Humans
@article{Noble2016,
title = {The Long Drive Ahead to Better Understanding Chronic Traumatic Encephalopathy: First (Case) and 10 (Years Later)},
author = {Noble, J M},
year = {2016},
date = {2016-01-01},
journal = {JAMA Neurology},
volume = {73},
number = {3},
pages = {263--265},
keywords = {*Brain Injuries, *Brain Injury, Chronic, football, Humans},
pubstate = {published},
tppubtype = {article}
}
Mez, J; Solomon, T M; Daneshvar, D H; Stein, T D; McKee, A C
Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player Journal Article
In: JAMA Neurology, vol. 73, no. 3, pp. 353–355, 2016.
BibTeX | Tags: *Athletic Injuries/co [Complications], *Brain Injury, *Football, adult, Bacterial, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Endocarditis, Fatal Outcome, Heart Arrest, Humans, Male, Staphylococcal Infections
@article{Mez2016,
title = {Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player},
author = {Mez, J and Solomon, T M and Daneshvar, D H and Stein, T D and McKee, A C},
year = {2016},
date = {2016-01-01},
journal = {JAMA Neurology},
volume = {73},
number = {3},
pages = {353--355},
keywords = {*Athletic Injuries/co [Complications], *Brain Injury, *Football, adult, Bacterial, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Endocarditis, Fatal Outcome, Heart Arrest, Humans, Male, Staphylococcal Infections},
pubstate = {published},
tppubtype = {article}
}
O'Kane, J W
Is Heading in Youth Soccer Dangerous Play? Journal Article
In: Physician & Sportsmedicine, vol. 44, no. 2, pp. 190–194, 2016.
Abstract | BibTeX | Tags: *Brain Injuries/et [Etiology], *Brain Injury, *Soccer/in [Injuries], Adolescent, Brain Concussion/et [Etiology], Brain Concussion/pc [Prevention & Control], Brain Injuries/pc [Prevention & Control], Brain Injury, Child, Chronic/et [Etiology], Chronic/pc [Prevention & Control], Humans, Risk Factors, UNITED States
@article{OKane2016,
title = {Is Heading in Youth Soccer Dangerous Play?},
author = {O'Kane, J W},
year = {2016},
date = {2016-01-01},
journal = {Physician \& Sportsmedicine},
volume = {44},
number = {2},
pages = {190--194},
abstract = {BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence.},
keywords = {*Brain Injuries/et [Etiology], *Brain Injury, *Soccer/in [Injuries], Adolescent, Brain Concussion/et [Etiology], Brain Concussion/pc [Prevention \& Control], Brain Injuries/pc [Prevention \& Control], Brain Injury, Child, Chronic/et [Etiology], Chronic/pc [Prevention \& Control], Humans, Risk Factors, UNITED States},
pubstate = {published},
tppubtype = {article}
}
McCarthy, M
Chronic traumatic encephalopathy is reported in 25 year old former American football player Journal Article
In: BMJ, vol. 352, pp. h7027, 2016.
BibTeX | Tags: *Brain Injury, *Football, Chronic, Humans, Play and Playthings
@article{McCarthy2016,
title = {Chronic traumatic encephalopathy is reported in 25 year old former American football player},
author = {McCarthy, M},
year = {2016},
date = {2016-01-01},
journal = {BMJ},
volume = {352},
pages = {h7027},
keywords = {*Brain Injury, *Football, Chronic, Humans, Play and Playthings},
pubstate = {published},
tppubtype = {article}
}
Steiger, B
Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion Journal Article
In: Physician Leadership Journal, vol. 3, no. 2, pp. 8–10, 2016.
Abstract | BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Football, Athletic Injuries/co [Complications], Brain Injury, Chronic, Chronic/et [Etiology], Humans, Motion Pictures as Topic
@article{Steiger2016,
title = {Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion},
author = {Steiger, B},
year = {2016},
date = {2016-01-01},
journal = {Physician Leadership Journal},
volume = {3},
number = {2},
pages = {8--10},
abstract = {The pathologist who discovered chronic traumatic encephalopathy in professional football players didn't set out to attack America's favorite sport. He didn't even know much about the game.},
keywords = {*Brain Concussion/co [Complications], *Brain Injury, *Football, Athletic Injuries/co [Complications], Brain Injury, Chronic, Chronic/et [Etiology], Humans, Motion Pictures as Topic},
pubstate = {published},
tppubtype = {article}
}
Barrio, J R; Small, G W; Wong, K P; Huang, S C; Liu, J; Merrill, D A; Giza, C C; Fitzsimmons, R P; Omalu, B; Bailes, J; Kepe, V
In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344] Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 16, pp. E2039–47, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged
@article{Barrio2015,
title = {In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344]},
author = {Barrio, J R and Small, G W and Wong, K P and Huang, S C and Liu, J and Merrill, D A and Giza, C C and Fitzsimmons, R P and Omalu, B and Bailes, J and Kepe, V},
year = {2015},
date = {2015-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {112},
number = {16},
pages = {E2039--47},
abstract = {Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged},
pubstate = {published},
tppubtype = {article}
}
Svaldi, D O; Joshi, C; Robinson, M E; Shenk, T E; Abbas, K; Nauman, E A; Leverenz, L J; Talavage, T M
Cerebrovascular reactivity alterations in asymptomatic high school football players Journal Article
In: Developmental Neuropsychology, vol. 40, no. 2, pp. 80–84, 2015.
Abstract | BibTeX | Tags: *Athletes, *Brain Concussion/pp [Physiopathology], *Brain Injury, *Cerebrovascular Disorders/pp [Physiopathology], *Football/in [Injuries], Adolescent, Chronic/pp [Physiopathology], Humans, RISK assessment, Schools
@article{Svaldi2015,
title = {Cerebrovascular reactivity alterations in asymptomatic high school football players},
author = {Svaldi, D O and Joshi, C and Robinson, M E and Shenk, T E and Abbas, K and Nauman, E A and Leverenz, L J and Talavage, T M},
year = {2015},
date = {2015-01-01},
journal = {Developmental Neuropsychology},
volume = {40},
number = {2},
pages = {80--84},
abstract = {Cerebrovascular reactivity (CVR) is impaired following brain injury, increasing susceptibility to subsequent injury. CVR was tracked in football and non-collision athletes throughout one season. CVR transiently decreased in football athletes during the first half of the season. Results indicate the brain adapts slowly to increases in loading, increasing risk for injury.},
keywords = {*Athletes, *Brain Concussion/pp [Physiopathology], *Brain Injury, *Cerebrovascular Disorders/pp [Physiopathology], *Football/in [Injuries], Adolescent, Chronic/pp [Physiopathology], Humans, RISK assessment, Schools},
pubstate = {published},
tppubtype = {article}
}
Bieniek, K F; Ross, O A; Cormier, K A; Walton, R L; Soto-Ortolaza, A; Johnston, A E; DeSaro, P; Boylan, K B; Graff-Radford, N R; Wszolek, Z K; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W
Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article
In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks
@article{Bieniek2015,
title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},
author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {6},
pages = {877--889},
abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks},
pubstate = {published},
tppubtype = {article}
}
Faden, A I; Loane, D J
Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Journal Article
In: Neurotherapeutics, vol. 12, no. 1, pp. 143–150, 2015.
Abstract | BibTeX | Tags: *Alzheimer Disease/et [Etiology], *Brain Injuries/co [Complications], *Brain Injury, *Encephalitis/et [Etiology], *Nerve Degeneration/et [Etiology], Alzheimer Disease/pa [Pathology], Animals, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Encephalitis/pa [Pathology], Humans, Nerve Degeneration/pa [Pathology]
@article{Faden2015,
title = {Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?},
author = {Faden, A I and Loane, D J},
year = {2015},
date = {2015-01-01},
journal = {Neurotherapeutics},
volume = {12},
number = {1},
pages = {143--150},
abstract = {It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).},
keywords = {*Alzheimer Disease/et [Etiology], *Brain Injuries/co [Complications], *Brain Injury, *Encephalitis/et [Etiology], *Nerve Degeneration/et [Etiology], Alzheimer Disease/pa [Pathology], Animals, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Encephalitis/pa [Pathology], Humans, Nerve Degeneration/pa [Pathology]},
pubstate = {published},
tppubtype = {article}
}
Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A
Chronic traumatic encephalopathy and athletes Journal Article
In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.
Abstract | BibTeX | Tags: *Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]
@article{Meehan3rd2015a,
title = {Chronic traumatic encephalopathy and athletes},
author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},
year = {2015},
date = {2015-01-01},
journal = {Neurology},
volume = {85},
number = {17},
pages = {1504--1511},
abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},
keywords = {*Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]},
pubstate = {published},
tppubtype = {article}
}
Stein, T D; Montenigro, P H; Alvarez, V E; Xia, W; Crary, J F; Tripodis, Y; Daneshvar, D H; Mez, J; Solomon, T; Meng, G; Kubilus, C A; Cormier, K A; Meng, S; Babcock, K; Kiernan, P; Murphy, L; Nowinski, C J; Martin, B; Dixon, D; Stern, R A; Cantu, R C; Kowall, N W; McKee, A C
Beta-amyloid deposition in chronic traumatic encephalopathy Journal Article
In: Acta Neuropathologica, vol. 130, no. 1, pp. 21–34, 2015.
Abstract | BibTeX | Tags: *Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]
@article{Stein2015b,
title = {Beta-amyloid deposition in chronic traumatic encephalopathy},
author = {Stein, T D and Montenigro, P H and Alvarez, V E and Xia, W and Crary, J F and Tripodis, Y and Daneshvar, D H and Mez, J and Solomon, T and Meng, G and Kubilus, C A and Cormier, K A and Meng, S and Babcock, K and Kiernan, P and Murphy, L and Nowinski, C J and Martin, B and Dixon, D and Stern, R A and Cantu, R C and Kowall, N W and McKee, A C},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {1},
pages = {21--34},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid beta peptide (Abeta) levels, the extent of Abeta deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Abeta deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Abeta deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Abeta deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p \< 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Abeta plaques and those without. Abeta deposition was significantly associated with the presence of the APOE epsilon4 allele (p = 0.035), older age at symptom onset (p \< 0.001), and older age at death (p \< 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (beta = 2.43},
keywords = {*Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]},
pubstate = {published},
tppubtype = {article}
}
McKee, A C; Stein, T D; Kiernan, P T; Alvarez, V E
The neuropathology of chronic traumatic encephalopathy Journal Article
In: Brain Pathology, vol. 25, no. 3, pp. 350–364, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]
@article{McKee2015a,
title = {The neuropathology of chronic traumatic encephalopathy},
author = {McKee, A C and Stein, T D and Kiernan, P T and Alvarez, V E},
year = {2015},
date = {2015-01-01},
journal = {Brain Pathology},
volume = {25},
number = {3},
pages = {350--364},
abstract = {Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. Copyright © 2015 International Society of Neuropathology.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]},
pubstate = {published},
tppubtype = {article}
}
Smith, A M; Stuart, M J; Dodick, D W; Roberts, W O; Alford, P W; Ashare, A B; Aubrey, M; Benson, B W; Burke, C J; Dick, R; Eickhoff, C; Emery, C A; Flashman, L A; Gaz, D; Giza, C C; Greenwald, R M; Herring, S; Hoshizaki, T B; Hudziak, J J; Huston 3rd, J; Krause, D; LaVoi, N; Leaf, M; Leddy, J J; MacPherson, A; McKee, A C; Mihalik, J P; Moessner, A M; Montelpare, W J; Putukian, M; Schneider, K J; Szalkowski, R; Tabrum, M; Whitehead, J; Wiese-Bjornstal, D M
Ice Hockey Summit II: zero tolerance for head hits and fighting.[Erratum appears in Clin J Sport Med. 2015 Jul;25(4):379] Journal Article
In: Clinical Journal of Sport Medicine, vol. 25, no. 2, pp. 78–87, 2015.
Abstract | BibTeX | Tags: *Brain Concussion/pc [Prevention & Control], *Brain Injury, *Hockey/in [Injuries], *Violence/pc [Prevention & Control], Adolescent, adult, Brain Concussion/th [Therapy], Brain Injury, Child, Chronic/pc [Prevention & Control], Chronic/th [Therapy], Congresses as Topic, Evidence-Based Medicine, Head Protective Devices/st [Standards], Hockey/st [Standards], Humans, policy, Young Adult
@article{Smith2015a,
title = {Ice Hockey Summit II: zero tolerance for head hits and fighting.[Erratum appears in Clin J Sport Med. 2015 Jul;25(4):379]},
author = {Smith, A M and Stuart, M J and Dodick, D W and Roberts, W O and Alford, P W and Ashare, A B and Aubrey, M and Benson, B W and Burke, C J and Dick, R and Eickhoff, C and Emery, C A and Flashman, L A and Gaz, D and Giza, C C and Greenwald, R M and Herring, S and Hoshizaki, T B and Hudziak, J J and {Huston 3rd}, J and Krause, D and LaVoi, N and Leaf, M and Leddy, J J and MacPherson, A and McKee, A C and Mihalik, J P and Moessner, A M and Montelpare, W J and Putukian, M and Schneider, K J and Szalkowski, R and Tabrum, M and Whitehead, J and Wiese-Bjornstal, D M},
year = {2015},
date = {2015-01-01},
journal = {Clinical Journal of Sport Medicine},
volume = {25},
number = {2},
pages = {78--87},
abstract = {OBJECTIVE: To present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building on the Ice Hockey Summit I action plan (2011) to reduce SRC. METHODS: The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure, for the science and discussion held during Summit II (Mayo Clinic, Rochester MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment: their Relationship to Industry Standards; and (5) Policies and Plans at State, National and Federal Levels to reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were subsequently voted on for purposes of prioritization. The following proceedings include knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. RESULTS: The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. CONCLUSIONS: The highest priority action items identified from the Summit includes the following: (1) eliminate head hits from all levels of ice hockey, (2) change body-checking policies, and (3) eliminate fighting in all amateur and professional hockey.},
keywords = {*Brain Concussion/pc [Prevention \& Control], *Brain Injury, *Hockey/in [Injuries], *Violence/pc [Prevention \& Control], Adolescent, adult, Brain Concussion/th [Therapy], Brain Injury, Child, Chronic/pc [Prevention \& Control], Chronic/th [Therapy], Congresses as Topic, Evidence-Based Medicine, Head Protective Devices/st [Standards], Hockey/st [Standards], Humans, policy, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Omalu, B
Chronic traumatic encephalopathy Journal Article
In: Progress in Neurological Surgery, vol. 28, pp. 38–49, 2014.
Abstract | Links | BibTeX | Tags: *Brain Injuries/pa [Pathology], *Brain Injury, Brain Concussion/pa [Pathology], Chronic Traumatic Encephalopathy Animals, Chronic/pa [Pathology], Humans, Tauopathies
@article{Omalu2014,
title = {Chronic traumatic encephalopathy},
author = {Omalu, B},
url = {http://ovidsp.ovid.com/ovidweb.cgi?T=JS\&CSC=Y\&NEWS=N\&PAGE=fulltext\&D=medl\&AN=24923391},
year = {2014},
date = {2014-01-01},
journal = {Progress in Neurological Surgery},
volume = {28},
pages = {38--49},
abstract = {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.Copyright © 2014 S. Karger AG, Basel.},
keywords = {*Brain Injuries/pa [Pathology], *Brain Injury, Brain Concussion/pa [Pathology], Chronic Traumatic Encephalopathy Animals, Chronic/pa [Pathology], Humans, Tauopathies},
pubstate = {published},
tppubtype = {article}
}
Omalu, B; Hammers, J L; Bailes, J; Hamilton, R L; Kamboh, M I; Webster, G; Fitzsimmons, R P
Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide Journal Article
In: Neurosurgical Focus, vol. 31, no. 5, pp. E3, 2011.
Abstract | BibTeX | Tags: *Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention & Control]
@article{Omalu2011,
title = {Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide},
author = {Omalu, B and Hammers, J L and Bailes, J and Hamilton, R L and Kamboh, M I and Webster, G and Fitzsimmons, R P},
year = {2011},
date = {2011-01-01},
journal = {Neurosurgical Focus},
volume = {31},
number = {5},
pages = {E3},
abstract = {Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.},
keywords = {*Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention \& Control]},
pubstate = {published},
tppubtype = {article}
}
Heilbronner, Robert L; Bush, Shane S; Ravdin, Lisa D; Barth, Jeffrey T; Iverson, Grant L; Ruff, Ronald M; Lovell, Mark R; Barr, William B; Echemendia, Ruben J; Broshek, Donna K
Neuropsychological consequences of boxing and recommendations to improve safety: a National Academy of Neuropsychology education paper Journal Article
In: Archives of Clinical Neuropsychology, vol. 24, pp. 11–19, 2009.
Abstract | BibTeX | Tags: *Brain Injury, Chronic/di [Diagnosis] Neuropsychol
@article{Heilbronner2009,
title = {Neuropsychological consequences of boxing and recommendations to improve safety: a National Academy of Neuropsychology education paper},
author = {Heilbronner, Robert L and Bush, Shane S and Ravdin, Lisa D and Barth, Jeffrey T and Iverson, Grant L and Ruff, Ronald M and Lovell, Mark R and Barr, William B and Echemendia, Ruben J and Broshek, Donna K},
year = {2009},
date = {2009-01-01},
journal = {Archives of Clinical Neuropsychology},
volume = {24},
pages = {11--19},
address = {Chicago Neuropsychology Group and Northwestern University Feinberg School of Medicine, Chicago, IL 60601, USA. r-heilbronner@northwestern.edu},
abstract = {Boxing has held appeal for many athletes and audiences for centuries, and injuries have been part of boxing since its inception. Although permanent and irreversible neurologic dysfunction does not occur in the majority of participants, an association has been reported between the number of bouts fought and the development of neurologic, psychiatric, or histopathological signs and symptoms of encephalopathy in boxers. The purpose of this paper is to (i) provide clinical neuropsychologists, other health-care professionals, and the general public with information about the potential neuropsychological consequences of boxing, and (ii) provide recommendations to improve safety standards for those who participate in the sport.},
keywords = {*Brain Injury, Chronic/di [Diagnosis] Neuropsychol},
pubstate = {published},
tppubtype = {article}
}