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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}
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}
}