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Cited by 146Traumatic Brain Injury ResearchAlzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular Disturbances

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

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Hazrati, Lili-Naz, Tartaglia, Maria C., Diamandis, Phedias, Davis, Karen D., Green, Robin E., Wennberg, Richard, Wong, Janice C., Ezerins, Leo, Tator, Charles H.·2013·Frontiers in Human Neuroscience
DOI 10.3389/fnhum.2013.00222PMC PMC3662898
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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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Crossref · 10.3389/fnhum.2013.00222

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Figure 1 Gross macroscopic findings on neuropathological examination. Selected examples from each case are presented as three vertical panels with lateral views of the unsectioned brain (upper panel), coronal sections through various parts of the cerebrum (middle panel), and axial sections through the brainstem (lower panel). (A) Case 1: There is mild-to-moderate atrophy with ventricular enlargement and cavum septi pellucidi. Thinning of the corpus callosum and mild depigmentation of the substantia nigra is also evident. (B) Case 2: Unsectioned brain, ventricles, and sections of the midbrain and substantia nigra appear within normal limits with no apparent evidence of neurodegeneration. (C) Case 3: Preferential mild-to-moderate atrophy of frontal and temporal lobes with significant enlargement of ventricles seen on coronal sections. A fenestrated septum pellucidum and atrophied amygdala and hippocampus are also seen on this section. The substantia nigra of this patient shows significant loss of pigmentation. (D) Case 4: There is mild frontal and temporal lobe atrophy with enlarged ventricles and cavum septi pellucidi. Axial sections of the brainstem show normal appearing substantia nigra and a metastatic lesion in the pons. (E) Case 5: Atrophic brain is seen with moderately enlarged ventricles and a normally pigmented substantia nigra. (F) Case 6: Minimal atrophy and ventricular enlargement are seen, and there is mild loss in the substantia nigra.
Figure 1 Gross macroscopic findings on neuropathological examination. Selected examples from each case are presented as three vertical panels with lateral views of the unsectioned brain (upper panel), coronal sections through various parts of the cerebrum (middle panel), and axial sections through the brainstem (lower panel). (A) Case 1: There is mild-to-moderate atrophy with ventricular enlargement and cavum septi pellucidi. Thinning of the corpus callosum and mild depigmentation of the substantia nigra is also evident. (B) Case 2: Unsectioned brain, ventricles, and sections of the midbrain and substantia nigra appear within normal limits with no apparent evidence of neurodegeneration. (C) Case 3: Preferential mild-to-moderate atrophy of frontal and temporal lobes with significant enlargement of ventricles seen on coronal sections. A fenestrated septum pellucidum and atrophied amygdala and hippocampus are also seen on this section. The substantia nigra of this patient shows significant loss of pigmentation. (D) Case 4: There is mild frontal and temporal lobe atrophy with enlarged ventricles and cavum septi pellucidi. Axial sections of the brainstem show normal appearing substantia nigra and a metastatic lesion in the pons. (E) Case 5: Atrophic brain is seen with moderately enlarged ventricles and a normally pigmented substantia nigra. (F) Case 6: Minimal atrophy and ventricular enlargement are seen, and there is mild loss in the substantia nigra.CC BY · PubMed Central
Figure 2 Selected microscopic findings on neuropathological examination. (A) Case 1: High power view of sample of cerebral cortex stained for hyperphosphorylated-tau shows concentration of neurofibrillary tangles predominantly in the superficial layers of the gray matter and in the depths of sulci, which is characteristic of CTE. (B) Case 2: Magnified motor neuron in ventral horn of spinal cord shows a representative intracytoplasmic TDP-43 inclusion. Inset shows a hyalin inclusion. (C) Case 3: Alpha-synuclein staining showing Lewy bodies and neurites which are seen throughout the cortex, substantia nigra, and locus ceruleus. This patient also had features of CTE (not shown). Inset shows higher power view of cytoplasmic Lewy body. (D) Case 4: Immunohistochemisty showing widespread reactivity against tau-positive neurofibrillary and astrocytic tangles in multiple layers. (E) Case 5: Bielschowsky silver stain showing numerous neurofibrillary tombstones in the hippocampus. (F) Case 6: HandE/LFB and alpha-synuclein staining of representative cortical section showing diffuse Lewy bodies and Lewy neurites. Inset shows Lewy body.
Figure 2 Selected microscopic findings on neuropathological examination. (A) Case 1: High power view of sample of cerebral cortex stained for hyperphosphorylated-tau shows concentration of neurofibrillary tangles predominantly in the superficial layers of the gray matter and in the depths of sulci, which is characteristic of CTE. (B) Case 2: Magnified motor neuron in ventral horn of spinal cord shows a representative intracytoplasmic TDP-43 inclusion. Inset shows a hyalin inclusion. (C) Case 3: Alpha-synuclein staining showing Lewy bodies and neurites which are seen throughout the cortex, substantia nigra, and locus ceruleus. This patient also had features of CTE (not shown). Inset shows higher power view of cytoplasmic Lewy body. (D) Case 4: Immunohistochemisty showing widespread reactivity against tau-positive neurofibrillary and astrocytic tangles in multiple layers. (E) Case 5: Bielschowsky silver stain showing numerous neurofibrillary tombstones in the hippocampus. (F) Case 6: HandE/LFB and alpha-synuclein staining of representative cortical section showing diffuse Lewy bodies and Lewy neurites. Inset shows Lewy body.CC BY · PubMed Central

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Authors
Hazrati, L.-N., Tartaglia, M. C., Diamandis, P., Davis, K. D., Green, R. E., Wennberg, R., Wong, J. C., Ezerins, L., & Tator, C. H.
Affiliations
  • University of Toronto (CA)
  • University Health Network (CA)
Corresponding author
Hazrati, Lili-Naz
ORCID
Venue
Frontiers in Human Neuroscience
Publisher
Frontiers Media SA
Published
2013
Volume
7
Pages
222-222
ISSN
1662-5161 (ISSN-L)
DOI
10.3389/fnhum.2013.00222
PMC
PMC3662898
OpenAlex
W2127938589
Cited by
146
References
27
Citations by year
2026: 1 · 2025: 2 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 15 · 2017: 16 · 2016: 17 · 2015: 26 · 2014: 13 · 2013: 7
FWCI
15.33
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Human Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship@McGill (McGill) (submittedVersion)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by)
Funders
Physicians' Services Incorporated Foundation
Topics
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
chronic traumatic encephalopathy, repeated concussions, Canadian Football League, tauopathy, neurofibrillary tangles, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, postmortem neuropathology, neurocognitive decline

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