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Emerging Histomorphologic Phenotypes of Chronic Traumatic Encephalopathy in American Athletes

Omalu, Bennet MD, MBA, MPH*‡; Bailes, Julian MD‡§; Hamilton, Ronald L MD‡¶; Kamboh, M Ilyas PhD‡¶; Hammers, Jennifer DO‡‖; Case, Mary MD‡#; Fitzsimmons, Robert JD‡**

doi: 10.1227/NEU.0b013e318212bc7b
Concepts, Innovations, and Techniques
Press Release

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.

*University of California, Davis, California; ‡Brain Injury Research Institute, West Virginia University, Morgantown, West Virginia; §West Virginia University, Morgantown, West Virginia; ¶University of Pittsburgh, Pittsburgh, Pennsylvania; ‖New York University, New York, New York; #St. Louis University, St. Louis, Missouri; **Fitzsimmons Law Offices, Wheeling, West Virginia

Received, October 17, 2009.

Accepted, December 16, 2010.

Published Online, February 24, 2011.

Correspondence: Bennet Omalu, MD, MBA, MPH, 1132 Junewood Court, Lodi, CA 95242. E-mail:

Copyright © by the Congress of Neurological Surgeons