• Grant L Iverson, Andrew J Gardner, Sandy R Shultz, Gary S Solomon, Paul McCrory, Ross Zafonte, George Perry, Lili-Naz Hazrati, C Dirk Keene, and Rudolph J Castellani.
• Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA.
• Brain. 2019 Dec 1; 142 (12): 3672-3693.

AbstractIn the 20th century, chronic traumatic encephalopathy (CTE) was conceptualized as a neurological disorder affecting some active and retired boxers who had tremendous exposure to neurotrauma. In recent years, the two research groups in the USA who have led the field have asserted definitively that CTE is a delayed-onset and progressive neurodegenerative disease, with symptoms appearing in midlife or decades after exposure. Between 2005 and 2012 autopsy cases of former boxers and American football players described neuropathology attributed to CTE that was broad and diverse. This pathology, resulting from multiple causes, was aggregated and referred to, in toto, as the pathology 'characteristic' of CTE. Preliminary consensus criteria for defining the neuropathology of CTE were forged in 2015 and published in 2016. Most of the macroscopic and microscopic neuropathological findings described as characteristic of CTE, in studies published before 2016, were not included in the new criteria for defining the pathology. In the past few years, there has been steadily emerging evidence that the neuropathology described as unique to CTE may not be unique. CTE pathology has been described in individuals with no known participation in collision or contact sports and no known exposure to repetitive neurotrauma. This pathology has been reported in individuals with substance abuse, temporal lobe epilepsy, amyotrophic lateral sclerosis, multiple system atrophy, and other neurodegenerative diseases. Moreover, throughout history, some clinical cases have been described as not being progressive, and there is now evidence that CTE neuropathology might not be progressive in some individuals. Considering the current state of knowledge, including the absence of a series of validated sensitive and specific biomarkers, CTE pathology might not be inexorably progressive or specific to those who have experienced repetitive neurotrauma.© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.

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