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Cited by 383Traumatic Brain Injury ResearchAlzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular Disturbances

Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes

Omalu, Bennet, Bailes, Julian, Hamilton, Ronald L, Kamboh, M Ilyas, Hammers, Jennifer, Case, Mary, Fitzsimmons, Robert·2011·Neurosurgery
DOI 10.1227/neu.0b013e318212bc7b
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Abstract

BACKGROUND: We define chronic traumatic encephalopathy (CTE) as a progressive neurodegenerative syndrome caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. OBJECTIVE: We present emerging histomorphologic phenotypes of CTE that we identified in our cohort of CTE cases with apolipoprotein E genotyping and causes and manners of death. METHODS: Autopsy brain tissue of 14 professional athletes and 3 high school football players was examined after unexpected deaths. Histochemical and immunohistochemical tissue staining was performed with apolipoprotein E genotyping. RESULTS: Ten of 14 professional athletes (71%) were positive for CTE: 7 of 8 football players, 2 of 4 wrestlers, and 1 boxer. One of 3 high school players manifested incipient CTE. The age range of those with CTE was 18 to 52 years; they were all male athletes. In all cases of CTE, Alzheimer-type cerebral cortical atrophy was absent; negligible to mild neocortical neuronal dropout was present. The fundamental neuropathologic feature of CTE was the topographic distribution of sparse, moderate, and frequent band-shaped, flame-shaped, small and large globose neurofibrillary tangles and neuritic threads in the cerebral cortex, subcortical nuclei/basal ganglia, hippocampus, and brainstem nuclei. Sparse to frequent diffuse amyloid plaques may accompany tauopathy and was seen in only 2 CTE cases. No α-synucleinopathy was present. All 7 CTE-positive professional athletes with known apolipoprotein E genotypes had at least 1 E3 allele comprising 5 E3/E3 (71%) and 2 E3/E4 (29%). Alcohol- and drug-related deaths, suicides, and accidental deaths were overrepresented in our CTE cohort. CONCLUSION: The emerging histomorphologic features of our CTE cohort may specify histologic criteria for CTE diagnosis, may identify emerging histologic variants of CTE and may facilitate more objective surveillance and accurate identification of sentinel CTE cases.

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  • Prior to 2015, there were no agreed upon neuropathological criteria for CTE, and the criteria put forward by the two research groups in the US differed.

    “Prior to 2015, there were no agreed upon neuropathological criteria for CTE, and the criteria put forward by the two research groups in the US differed [15, 16].”

    From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [15]

  • The consensus panel did not adopt the four neuropathological phenotypes or stages of CTE, and indicated that the preliminary criteria were a first step along the path to standardizing the neuropathology of CTE.

    “The consensus panel did not adopt the four neuropathological phenotypes [15] or stages of CTE [16], and indicated that the preliminary criteria were a “first step along the path to standardizing the neuropathology of CTE” [30].”

    From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [15]

  • Over the past decade, the clinical features attributed to CTE have been expanded greatly and include virtually any mental health or neurological symptom or problem present prior to death.

    “Over the past decade, the clinical features attributed to CTE have been expanded greatly and include virtually any mental health or neurological symptom or problem present prior to death”

    From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [15]

  • Prior to 2016, there were no agreed upon neuropathological criteria for CTE, and the criteria published by the 2 leading research groups in the United States differed substantially.

    “Prior to 2016, there were no agreed upon neuropathological criteria for CTE, and the criteria published by the 2 leading research groups in the United States differed substantially (7,14).”

    From Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma (2019) · cites this paper as [7]

  • In different autopsy series, the percentage of former professional American football players who have died and donated their brains to research varies from 50%, 80%, to 97%.

    “In different autopsy series, the percentage of former professional American football players who have died and donated their brains to research varies from 50 % [88], 80 % [146], to 97 %) [128].”

    From The neuropathology of sport (2014) · cites this paper as [146]

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Authors
Omalu, B., Bailes, J., Hamilton, R. L., Kamboh, M. I., Hammers, J., Case, M., & Fitzsimmons, R.
Affiliations
West Virginia University (US)
Corresponding author
  • Omalu, Bennet
  • Fitzsimmons, Robert
ORCID
Venue
Neurosurgery
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-07
Volume
69
Issue
1
Pages
173-183
ISSN
0148-396X (ISSN-L)
DOI
10.1227/neu.0b013e318212bc7b
OpenAlex
W1985345440
Cited by
381
References
22
Citations by year
2026: 4 · 2025: 10 · 2024: 9 · 2023: 21 · 2022: 17 · 2021: 18 · 2020: 20 · 2019: 31 · 2018: 30 · 2017: 41 · 2016: 39 · 2015: 44 · 2014: 35 · 2013: 36 · 2012: 16
FWCI
22.77
Type
journal article
Language
en
Open access
closed
Locations
  • Neurosurgery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
chronic traumatic encephalopathy, histopathology, neurofibrillary tangles, tauopathy, APOE genotype, professional athletes, football players, boxing, wrestling, causes of death, autopsy brain tissue, neurodegeneration
MeSH terms
Adolescent, Adult, Americas, Athletic Injuries, Autopsy, Brain, Cause of Death, Humans, Male, Middle Aged, Phenotype, Cohort Studies, Cerebral Amyloid Angiopathy, Neurofibrillary Tangles, Brain Injury, Chronic, Young Adult, Plaque, Amyloid

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