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      Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology

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          Abstract

          Background: Chronic traumatic encephalopathy (CTE) is the term coined for the neurodegenerative disease often suspected in athletes with histories of repeated concussion and progressive dementia. Histologically, CTE is defined as a tauopathy with a distribution of tau-positive neurofibrillary tangles (NFTs) that is distinct from other tauopathies, and usually shows an absence of beta-amyloid deposits, in contrast to Alzheimer's disease (AD). Although the connection between repeated concussions and CTE-type neurodegeneration has been recently proposed, this causal relationship has not yet been firmly established. Also, the prevalence of CTE among athletes with multiple concussions is unknown.

          Methods: We performed a consecutive case series brain autopsy study on six retired professional football players from the Canadian Football League (CFL) with histories of multiple concussions and significant neurological decline.

          Results: All participants had progressive neurocognitive decline prior to death; however, only 3 cases had post-mortem neuropathological findings consistent with CTE. The other 3 participants had pathological diagnoses of AD, amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Moreover, the CTE cases showed co-morbid pathology of cancer, vascular disease, and AD.

          Discussion: Our case studies highlight that not all athletes with history of repeated concussions and neurological symptomology present neuropathological changes of CTE. These preliminary findings support the need for further research into the link between concussion and CTE as well as the need to expand the research to other possible causes of taupathy in athletes. They point to a critical need for prospective studies with good sampling methods to allow us to understand the relationship between multiple concussions and the development of CTE.

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          Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury.

          Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.
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            Chronic traumatic encephalopathy in a National Football League player.

            We present the results of the autopsy of a retired professional football player that revealed neuropathological changes consistent with long-term repetitive concussive brain injury. This case draws attention to the need for further studies in the cohort of retired National Football League players to elucidate the neuropathological sequelae of repeated mild traumatic brain injury in professional football. The patient's premortem medical history included symptoms of cognitive impairment, a mood disorder, and parkinsonian symptoms. There was no family history of Alzheimer's disease or any other head trauma outside football. A complete autopsy with a comprehensive neuropathological examination was performed on the retired National Football League player approximately 12 years after retirement. He died suddenly as a result of coronary atherosclerotic disease. Studies included determination of apolipoprotein E genotype. Autopsy confirmed the presence of coronary atherosclerotic disease with dilated cardiomyopathy. The brain demonstrated no cortical atrophy, cortical contusion, hemorrhage, or infarcts. The substantia nigra revealed mild pallor with mild dropout of pigmented neurons. There was mild neuronal dropout in the frontal, parietal, and temporal neocortex. Chronic traumatic encephalopathy was evident with many diffuse amyloid plaques as well as sparse neurofibrillary tangles and tau-positive neuritic threads in neocortical areas. There were no neurofibrillary tangles or neuropil threads in the hippocampus or entorhinal cortex. Lewy bodies were absent. The apolipoprotein E genotype was E3/E3. This case highlights potential long-term neurodegenerative outcomes in retired professional National Football League players subjected to repeated mild traumatic brain injury. The prevalence and pathoetiological mechanisms of these possible adverse long-term outcomes and their relation to duration of years of playing football have not been sufficiently studied. We recommend comprehensive clinical and forensic approaches to understand and further elucidate this emergent professional sport hazard.
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              Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy.

              Chronic traumatic encephalopathy (CTE) has been linked to participation in contact sports such as boxing and American football. CTE results in a progressive decline of memory and cognition, as well as depression, suicidal behavior, poor impulse control, aggressiveness, parkinsonism, and, eventually, dementia. In some individuals, it is associated with motor neuron disease, referred to as chronic traumatic encephalomyelopathy, which appears clinically similar to amyotrophic lateral sclerosis. Results of neuropathologic research has shown that CTE may be more common in former contact sports athletes than previously believed. It is believed that repetitive brain trauma, with or possibly without symptomatic concussion, is responsible for neurodegenerative changes highlighted by accumulations of hyperphosphorylated tau and TDP-43 proteins. Given the millions of youth, high school, collegiate, and professional athletes participating in contact sports that involve repetitive brain trauma, as well as military personnel exposed to repeated brain trauma from blast and other injuries in the military, CTE represents an important public health issue. Focused and intensive study of the risk factors and in vivo diagnosis of CTE will potentially allow for methods to prevent and treat these diseases. Research also will provide policy makers with the scientific knowledge to make appropriate guidelines regarding the prevention and treatment of brain trauma in all levels of athletic involvement as well as the military theater. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                1662-5161
                24 May 2013
                2013
                : 7
                : 222
                Affiliations
                [1] 1Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada
                [2] 2Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto Toronto, ON, Canada
                [3] 3Division of Neurology, Krembil Neuroscience Centre, University Health Network, University of Toronto Toronto, ON, Canada
                [4] 4Division of Neurosurgery, Krembil Neuroscience Centre, University Health Network, University of Toronto Toronto, ON, Canada
                [5] 5Division of Brain, Imaging, and Behaviour – Systems Neuroscience, Toronto Western Research Institute, University Health Network Toronto, ON, Canada
                [6] 6Department of Surgery, University of Toronto Toronto, ON, Canada
                [7] 7Institute of Medical Science, University of Toronto Toronto, ON, Canada
                [8] 8Research, Cognitive Neurorehabilitation Sciences Lab, Toronto Rehabilitation Institute, University of Toronto Toronto, ON, Canada
                [9] 9Executive Director, Canadian Football League Alumni Association, Members of the Canadian Sports Concussion Project at the Krembil Neuroscience Centre, Toronto Western Hospital and University of Toronto Toronto, ON, Canada
                Author notes

                Edited by: Alvaro Pascual-Leone, Beth Israel Deaconess Medical Center, USA

                Reviewed by: Donna R. Roberts, Medical University of South Carolina, USA; Giuliana Lucci, IRCCS Santa Lucia of Rome, Italy

                *Correspondence: Lili-Naz Hazrati, Tanz Center for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, University of Toronto, 6 Queen's Park Crescent West, Toronto, ON M5S 3H2, Canada. e-mail: lilinaz.hazrati@ 123456utoronto.ca
                Article
                10.3389/fnhum.2013.00222
                3662898
                23745112
                9bac3df5-4fb3-459c-9e03-83a72889bbf8
                Copyright © 2013 Hazrati, Tartaglia, Diamandis, Davis, Green, Wennberg, Wong, Ezerins and Tator.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 21 December 2012
                : 08 May 2013
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 22, Pages: 9, Words: 6096
                Categories
                Neuroscience
                Original Research Article

                Neurosciences
                chronic traumatic encephalopathy,repetitive brain injury,professional athletes,dementia,neurodegenerative disease

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