An Autopsy Proven Child Onset Chronic Traumatic Encephalopathy

Lee, Kyuho; Kim, Seong Ik; Lee, Yujin; Won, Jae Kyung; Park, Shin Young

doi:10.5607/en.2017.26.3.172

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…CTE was neuropathologically diagnosed in 177 athletes [87%, median age at death, 67 years (IQR 52, 77); mean years of football participation, 15.1 years (5.2 SD)], including 0 of 2 pre-high school (0%), 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semi-professional (64%), 7 of 8 Canadian Football League (88%) and 110 of 111 NFL players (99%). The median age at death for American football players with mild CTE pathology (stages I and II) was 44 years (IQR 29, 64), and for participants with severe CTE pathology (stages III and IV) 71 years (IQR 64,79). In all 177 cases, pathognomonic lesions of CTE were found in the cortex.…”

Section: American Footballmentioning

confidence: 98%

Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts

et al. 2023

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Over the last 17 years, there has been a remarkable increase in scientific research concerning chronic traumatic encephalopathy (CTE). Since the publication of NINDS–NIBIB criteria for the neuropathological diagnosis of CTE in 2016, and diagnostic refinements in 2021, hundreds of contact sport athletes and others have been diagnosed at postmortem examination with CTE. CTE has been reported in amateur and professional athletes, including a bull rider, boxers, wrestlers, and American, Canadian, and Australian rules football, rugby union, rugby league, soccer, and ice hockey players. The pathology of CTE is unique, characterized by a pathognomonic lesion consisting of a perivascular accumulation of neuronal phosphorylated tau (p-tau) variably alongside astrocytic aggregates at the depths of the cortical sulci, and a distinctive molecular structural configuration of p-tau fibrils that is unlike the changes observed with aging, Alzheimer’s disease, or any other tauopathy. Computational 3-D and finite element models predict the perivascular and sulcal location of p-tau pathology as these brain regions undergo the greatest mechanical deformation during head impact injury. Presently, CTE can be definitively diagnosed only by postmortem neuropathological examination; the corresponding clinical condition is known as traumatic encephalopathy syndrome (TES). Over 97% of CTE cases published have been reported in individuals with known exposure to repetitive head impacts (RHI), including concussions and nonconcussive impacts, most often experienced through participation in contact sports. While some suggest there is uncertainty whether a causal relationship exists between RHI and CTE, the preponderance of the evidence suggests a high likelihood of a causal relationship, a conclusion that is strengthened by the absence of any evidence for plausible alternative hypotheses. There is a robust dose–response relationship between CTE and years of American football play, a relationship that remains consistent even when rigorously accounting for selection bias. Furthermore, a recent study suggests that selection bias underestimates the observed risk. Here, we present the advances in the neuropathological diagnosis of CTE culminating with the development of the NINDS–NIBIB criteria, the multiple international studies that have used these criteria to report CTE in hundreds of contact sports players and others, and the evidence for a robust dose–response relationship between RHI and CTE.

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Section: American Footballmentioning

confidence: 98%

Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts

et al. 2023

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“…Similarly, investigators at other North American institutions have published studies that describe the presence of CTE pathology in military veterans (60) and former athletes in American football (10,23,24,(61)(62)(63)(64), amateur and professional wrestling (23,65), and ice hockey (24). Investigators have also reported CTE pathology in Scotland (Glasgow TBI Brain Bank) (28,48,66), England (Queen Square Brain Bank for Neurological Disorders, University College London) (29,67,68), Ireland (Dublin Brain Bank) (27,69), France (GIE Neuro-CEB Brain Bank) (30), Australia (Australian Sports Brain Bank) (25,70,71), Brazil (Biobank for Aging Studies at the University of São Paulo) (26), and South Korea (72). In these reports, CTE pathology was described in the brains of former soccer, rugby, Australian rules football, and boxing athletes as well as a young individual who exhibited head-banging behavior (72).…”

Section: Consistencymentioning

confidence: 99%

“…Investigators have also reported CTE pathology in Scotland (Glasgow TBI Brain Bank) (28,48,66), England (Queen Square Brain Bank for Neurological Disorders, University College London) (29,67,68), Ireland (Dublin Brain Bank) (27,69), France (GIE Neuro-CEB Brain Bank) (30), Australia (Australian Sports Brain Bank) (25,70,71), Brazil (Biobank for Aging Studies at the University of São Paulo) (26), and South Korea (72). In these reports, CTE pathology was described in the brains of former soccer, rugby, Australian rules football, and boxing athletes as well as a young individual who exhibited head-banging behavior (72). This growing congruous evidence from independent investigators profiling individuals with a range of RHI exposure profiles is certainly in agreement with Hill's consistency criterion.…”

Section: Consistencymentioning

confidence: 99%

Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy

Nowinski¹,

Bureau²,

Buckland

et al. 2022

Front. Neurol.

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Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with a history of repetitive head impacts (RHI). CTE was described in boxers as early as the 1920s and by the 1950s it was widely accepted that hits to the head caused some boxers to become “punch drunk.” However, the recent discovery of CTE in American and Australian-rules football, soccer, rugby, ice hockey, and other sports has resulted in renewed debate on whether the relationship between RHI and CTE is causal. Identifying the strength of the evidential relationship between CTE and RHI has implications for public health and medico-legal issues. From a public health perspective, environmentally caused diseases can be mitigated or prevented. Medico-legally, millions of children are exposed to RHI through sports participation; this demographic is too young to legally consent to any potential long-term risks associated with this exposure. To better understand the strength of evidence underlying the possible causal relationship between RHI and CTE, we examined the medical literature through the Bradford Hill criteria for causation. The Bradford Hill criteria, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework to determine if one can justifiably move from an observed association to a verdict of causation. The Bradford Hill criteria include nine viewpoints by which to evaluate human epidemiologic evidence to determine if causation can be deduced: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. We explored the question of causation by evaluating studies on CTE as it relates to RHI exposure. Through this lens, we found convincing evidence of a causal relationship between RHI and CTE, as well as an absence of evidence-based alternative explanations. By organizing the CTE literature through this framework, we hope to advance the global conversation on CTE mitigation efforts.

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“…TBI has been associated with the development of an Alzheimer’s-like pathology known as CTE (McKee et al, 2013). Commonly seen in athletes who participate in physical contact sports, such as hockey and football (Omalu et al, 2005; McKee et al, 2013; Kiernan et al, 2015), CTE has also been reported in military veterans (Goldstein et al, 2012) and patients with self-injurious behaviors such as head-banging (Geddes et al, 1999; Lee et al, 2017a). While there appears to be distinct differences between AD and CTE clinical appearance (McKee et al, 2013), the pathology between the two diseases is quite similar.…”

Section: Traumatic Brain Injury As a Contributing Factor To Alzheimermentioning

confidence: 99%

The Use of Pigs as a Translational Model for Studying Neurodegenerative Diseases

Hoffe

Holahan

2019

Front. Physiol.

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In recent years, the move to study neurodegenerative disease using larger animal models with brains that are more similar to humans has gained interest. While pigs have been used for various biomedical applications and research, it has only been recently that they have been used to study neurodegenerative diseases due to their neuroanatomically similar gyrencephalic brains and similar neurophysiological processes as seen in humans. This review focuses on the use of pigs in the study of Alzheimer’s disease (AD) and traumatic brain injury (TBI). AD is considered the most common neurodegenerative disease in elderly populations. Head impacts from falls are the most common form of injury in the elderly and recent literature has shown an association between repetitive head impacts and the development of AD. This review summarizes research into the pathological mechanisms underlying AD and TBI as well as the advantages and disadvantages of using pigs in the neuroscientific study of these disease processes. With the lack of successful therapeutics for neurodegenerative diseases, and an increasing elderly population, the use of pigs may provide a better translational model for understanding and treating these diseases.

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An Autopsy Proven Child Onset Chronic Traumatic Encephalopathy

Cited by 6 publications

References 16 publications

Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts

Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts

Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy

The Use of Pigs as a Translational Model for Studying Neurodegenerative Diseases

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