Chronic Traumatic Encephalopathy and Neuropathological Comorbidities

2020 ◽  
Vol 40 (04) ◽  
pp. 384-393
Author(s):  
Thor D. Stein ◽  
John F. Crary
Keyword(s):  
Traumatic Brain Injury ◽  
Chronic Traumatic Encephalopathy ◽  
Lewy Body Disease ◽  
Single Individual ◽  
Contact Sports ◽  
Head Impacts ◽  
Repetitive Head Impacts ◽  
Age Related ◽  
The Relationship ◽  
Lateral Sclerosis

AbstractWith age, the presence of multiple neuropathologies in a single individual becomes increasingly common. Given that traumatic brain injury and the repetitive head impacts (RHIs) that occur in contact sports have been associated with the development of many neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), Alzheimer's disease, Lewy body disease, and amyotrophic lateral sclerosis, it is becoming critical to understand the relationship and interactions between these pathologies. In fact, comorbid pathology is common in CTE and likely influenced by both age and the severity and type of exposure to RHI as well as underlying genetic predisposition. Here, we review the major comorbid pathologies seen with CTE and in former contact sports athletes and discuss what is known about the associations between RHI, age, and the development of neuropathologies. In addition, we examine the distinction between CTE and age-related pathology including primary age-related tauopathy and age-related tau astrogliopathy.

scholarly journals Improving the translational potential of rodent models to study the behavioral and pathophysiological effects of repetitive mild traumatic brain injury

2018 ◽  
Vol 120 (1) ◽  
pp. 1-3
Author(s):  
Megan E. Huibregtse
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Outcome Measures ◽  
Mild Traumatic Brain Injury ◽  
Chronic Traumatic Encephalopathy ◽  
Rodent Models ◽  
Head Impacts ◽  
Repetitive Head Impacts ◽  
The Impact

Chronic traumatic encephalopathy (CTE) is thought to be caused by repetitive head impacts. Consequently, there is a need to develop rodent models to better understand the behavioral and pathophysiological changes of repetitive mild traumatic brain injury (rmTBI) and to determine the link between rmTBI and CTE. This Neuro Forum article reviews recent rodent rmTBI models, comparing the impact methods and outcome measures in terms of translational potential.

scholarly journals COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI)

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Douglas H. Smith ◽  
Jean-Pierre Dollé ◽  
Kamar E. Ameen-Ali ◽  
Abigail Bretzin ◽  
Etty Cortes ◽  
...  
Keyword(s):  
Chronic Traumatic Encephalopathy ◽  
Clinical Information ◽  
Illustrative Case ◽  
Contact Sports ◽  
Head Impacts ◽  
Repetitive Head Impacts ◽  
Dementia Risk ◽  
Stroke Center ◽  
Tissue Specimens ◽  
Multiple Experts

AbstractEfforts to characterize the late effects of traumatic brain injury (TBI) have been in progress for some time. In recent years much of this activity has been directed towards reporting of chronic traumatic encephalopathy (CTE) in former contact sports athletes and others exposed to repetitive head impacts. However, the association between TBI and dementia risk has long been acknowledged outside of contact sports. Further, growing experience suggests a complex of neurodegenerative pathologies in those surviving TBI, which extends beyond CTE. Nevertheless, despite extensive research, we have scant knowledge of the mechanisms underlying TBI-related neurodegeneration (TReND) and its link to dementia. In part, this is due to the limited number of human brain samples linked to robust demographic and clinical information available for research. Here we detail a National Institutes for Neurological Disease and Stroke Center Without Walls project, the COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI), designed to address current limitations in tissue and research access and to advance understanding of the neuropathologies of TReND. As an international, multidisciplinary collaboration CONNECT-TBI brings together multiple experts across 13 institutions. In so doing, CONNECT-TBI unites the existing, comprehensive clinical and neuropathological datasets of multiple established research brain archives in TBI, with survivals ranging minutes to many decades and spanning diverse injury exposures. These existing tissue specimens will be supplemented by prospective brain banking and contribute to a centralized route of access to human tissue for research for investigators. Importantly, each new case will be subject to consensus neuropathology review by the CONNECT-TBI Expert Pathology Group. Herein we set out the CONNECT-TBI program structure and aims and, by way of an illustrative case, the approach to consensus evaluation of new case donations.

Traumatic brain injury: a risk factor for neurodegenerative diseases

2016 ◽  
Vol 27 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Rajaneesh Gupta ◽  
Nilkantha Sen
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Chronic Traumatic Encephalopathy ◽  
Disease Process ◽  
Acute Effects ◽  
Secondary Progressive ◽  
Lateral Sclerosis

AbstractTraumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.

scholarly journals Detecting a History of Repetitive Head Impacts from a Short Voice Recording

2021 ◽  
Author(s):  
Michael G. Tauro ◽  
Mirco Ravanelli ◽  
Cristian A. Droppelmann
Keyword(s):  
Chronic Traumatic Encephalopathy ◽  
Control Group ◽  
Head Impacts ◽  
Repetitive Head Impacts ◽  
Potential Biomarker ◽  
Increased Risk ◽  
Clinical Diagnoses ◽  
History Of ◽  
Brain Changes ◽  
Fine Tune

Repetitive head impacts (RHI) are associated with an increased risk of developing various neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), and most notably, chronic traumatic encephalopathy (CTE). While the clinical presentation of AD and PD is well established, CTE can only be diagnosed post-mortem. Therefore, a distinction can be made between the pathologically defined CTE and RHI-related functional or structural brain changes (RHI-BC) which may result in CTE. Unfortunately, there are currently no accepted biomarkers of CTE nor RHI-BC, a major hurdle to achieving clinical diagnoses. Interestingly, speech has shown promise as a potential biomarker of both AD and PD, being used to accurately classify individuals with AD and PD from those without. Given the overlapping symptoms between CTE, RHI-BC, PD and AD, we aimed to determine if speech could be used to identify individuals with a history of RHI from those without. We therefore created the Verus dataset, consisting of 13 second voice recordings from 605 professional fighters (RHI group) and 605 professional athletes in non-contact sports (control group) for a total of 1210 recordings. Using a deep learning approach, we achieved 85% accuracy in detecting individuals with a history of RHI from those without. We then used our model trained on the Verus dataset to fine-tune on publicly available AD and PD speech datasets and achieved new state-of-the-art accuracies of 84.99% on the AD dataset and 89% on the PD dataset. Finding a biomarker of CTE and RHI-BC that presents early in disease progression is critical to improve risk management and patient outcome. Our study is the first we are aware of to investigate speech as such a candidate biomarker of RHI-BC.

scholarly journals Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort

2018 ◽  
Vol 77 (12) ◽  
pp. 1091-1100 ◽  
Author(s):  
Gabriel S Walt ◽  
Hannah M Burris ◽  
Christopher B Brady ◽  
Keith R Spencer ◽  
Victor E Alvarez ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Military Service ◽  
Neurodegenerative Disorder ◽  
Chronic Traumatic Encephalopathy ◽  
Neuromuscular Disorder ◽  
Clinical Genetic ◽  
Head Impacts ◽  
Brain Bank ◽  
History Of ◽  
Lateral Sclerosis

Abstract Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive head impacts and has been associated with amyotrophic lateral sclerosis (ALS), a fatal, degenerative neuromuscular disorder. The Department of Veterans Affairs Biorepository Brain Bank (VABBB) is a tissue repository that collects antemortem disease progression data and postmortem central nervous system tissue from veterans with ALS. We set out to determine the frequency of co-morbid ALS and CTE in the VABBB cohort and to characterize the clinical, genetic, and pathological distinctions between participants with ALS only and those with both ALS and CTE (ALS+CTE). Of 155 participants, 9 (5.8%) had neuropathologically confirmed ALS+CTE. Participants with ALS+CTE were more likely to have a history of traumatic brain injury (p < 0.001), served during the first Persian Gulf War (p < 0.05), and to have more severe tau pathology within the frontal cortex and spinal cord (p < 0.05). The most common exposures to head impacts included contact sports (n = 5) and military service (n = 2). Clinically, participants with ALS+CTE were more likely to have bulbar onset ALS (p = 0.006), behavioral changes (p = 0.002), and/or mood changes (p < 0.001). Overall, compared with ALS in isolation, comorbid ALS+CTE is associated with a history of TBI and has a distinct clinical and pathological presentation.

scholarly journals Microglial Turnover in Ageing-Related Neurodegeneration: Therapeutic Avenue to Intervene in Disease Progression

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 150
Author(s):  
Shofiul Azam ◽  
Md. Ezazul Haque ◽  
In-Su Kim ◽  
Dong-Kug Choi
Keyword(s):  
Neurodegenerative Diseases ◽  
Proinflammatory Cytokines ◽  
Chronic Traumatic Encephalopathy ◽  
Prion Diseases ◽  
Well Being ◽  
Age Related ◽  
The Central Nervous System ◽  
Potential Mode ◽  
Therapeutic Avenue ◽  
Lateral Sclerosis

Microglia are brain-dwelling macrophages and major parts of the neuroimmune system that broadly contribute to brain development, homeostasis, ageing and injury repair in the central nervous system (CNS). Apart from other brain macrophages, they have the ability to constantly sense changes in the brain’s microenvironment, functioning as housekeepers for neuronal well-being and providing neuroprotection in normal physiology. Microglia use a set of genes for these functions that involve proinflammatory cytokines. In response to specific stimuli, they release these proinflammatory cytokines, which can damage and kill neurons via neuroinflammation. However, alterations in microglial functioning are a common pathophysiology in age-related neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and prion diseases, as well as amyotrophic lateral sclerosis, frontotemporal dementia and chronic traumatic encephalopathy. When their sentinel or housekeeping functions are severely disrupted, they aggravate neuropathological conditions by overstimulating their defensive function and through neuroinflammation. Several pathways are involved in microglial functioning, including the Trem2, Cx3cr1 and progranulin pathways, which keep the microglial inflammatory response under control and promote clearance of injurious stimuli. Over time, an imbalance in this system leads to protective microglia becoming detrimental, initiating or exacerbating neurodegeneration. Correcting such imbalances might be a potential mode of therapeutic intervention in neurodegenerative diseases.

scholarly journals Neuroimaging in contact sports: Determining brain fitness before and after a bout

2017 ◽  
Vol 29 (1) ◽  
pp. 1-4
Author(s):  
N Sethi
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Chronic Traumatic Encephalopathy ◽  
Personalised Medicine ◽  
The United States ◽  
Medical Community ◽  
Acute Subdural Hematoma ◽  
Individual Risk ◽  
Contact Sports ◽  
Professional Boxing

Background: Professional boxing and mixed martial arts (MMA) are popular contact sports with high risk for both acute and chronic traumatic brain injury (TBI). Although rare, combatants have died in the ring/cage or soon after the completion of the bout. The cause of death in these cases is usually acute subdural hematoma, acute epidural hematoma, subarachnoid haemorrhage, intracranial haemorrhage, or second-impact syndrome (SIS). Neuroimaging or brain imaging is currently included in the process of registering for a license to fight in a combat sport in most states in the United States and around the world. However, the required imaging specifics and frequency vary.Discussion: Neuroimaging serves two distinct roles in the individualised care of a combatant, representing a step towards personalised medicine and individual risk stratification. Neuroimaging prior to licensure helps to identify and/or exclude coincidental or clinically suspected brain lesions which may pose a risk for rupture, bleeding or other catastrophic and important brain injury. Neuroimaging in the immediate aftermath of a bout primarily serves to rule out acute traumatic brain injury. Neuroimaging may also be carried out to assess for evidence of structural brain injury which may make a combatant more likely to express late-life neuropsychiatric sequelae of brain injury, such as chronic traumatic encephalopathy. As such, neuroimaging plays a prognostic role and aids in the determination of whether the combatant should be allowed to continue to participate in future bouts or not.Conclusion: Currently there are no established neuroimaging guidelines for contact sports. Standardising neuroimaging guidelines both for licensure as well as neuroimaging modality, and protocols to assess for both acute and chronic traumatic brain injury. This will assist in protecting the combatant’s health and safety, both in the ring/cage, and after their professional careers have ended. Some suggested guidelines are provided based on currently available medical literature. It is recommended that these guidelines be debated vigorously by the scientific community and that evidence-based guidelines be developed by the medical community in conjunction with professional boxing and MMA governing bodies.

scholarly journals Role of subconcussion in repetitive mild traumatic brain injury

2013 ◽  
Vol 119 (5) ◽  
pp. 1235-1245 ◽  
Author(s):  
Julian E. Bailes ◽  
Anthony L. Petraglia ◽  
Bennet I. Omalu ◽  
Eric Nauman ◽  
Thomas Talavage
Keyword(s):  
Diffusion Tensor ◽  
Chronic Traumatic Encephalopathy ◽  
Neuropsychological Testing ◽  
Axonal Injury ◽  
Laboratory Data ◽  
Neurological Dysfunction ◽  
Neurological Injury ◽  
Cumulative Impact ◽  
Contact Sports ◽  
Head Impacts

Research now suggests that head impacts commonly occur during contact sports in which visible signs or symptoms of neurological dysfunction may not develop despite those impacts having the potential for neurological injury. Recent biophysics studies utilizing helmet accelerometers have indicated that athletes at the collegiate and high school levels sustain a surprisingly high number of head impacts ranging from several hundred to well over 1000 during the course of a season. The associated cumulative impact burdens over the course of a career are equally important. Clinical studies have also identified athletes with no readily observable symptoms but who exhibit functional impairment as measured by neuropsychological testing and functional MRI. Such findings have been corroborated by diffusion tensor imaging studies demonstrating axonal injury in asymptomatic athletes at the end of a season. Recent autopsy data have shown that there are subsets of athletes in contact sports who do not have a history of known or identified concussions but nonetheless have neurodegenerative pathology consistent with chronic traumatic encephalopathy. Finally, emerging laboratory data have demonstrated significant axonal injury, blood-brain barrier permeability, and evidence of neuroinflammation, all in the absence of behavioral changes. Such data suggest that subconcussive level impacts can lead to significant neurological alterations, especially if the blows are repetitive. The authors propose “subconcussion” as a significant emerging concept requiring thorough consideration of the potential role it plays in accruing sufficient anatomical and/or physiological damage in athletes and military personnel, such that the effects of these injuries are clinically expressed either contemporaneously or later in life.

Sign in / Sign up

Export Citation Format

Share Document