Chronic traumatic encephalopathy - confusion and controversies

Abstract

The term chronic traumatic encephalopathy (CTE) has recently entered public consciousness via media reports and even a Hollywood movie. However, in contrast to general impressions, the incidence of CTE is unknown, the clinical diagnostic criteria have not been agreed upon and the current neuropathological characterization of CTE is acknowledged as preliminary. Additionally, few studies have compared the pathologies of CTE with those of other neurodegenerative disorders or of age-matched controls. Consequently, disagreement continues about the neuropathological aspects that make CTE unique. Furthermore, CTE is widely considered to be a consequence of exposure to repeated head blows, but evidence suggests that a single moderate or severe traumatic brain injury can also induce progressive neuropathological changes. These unresolved aspects of CTE underlie disparate claims about its clinical and pathological features, leading to confusion among the public and health-care professionals alike.

Fig. 1|. Historical timeline of developments and the cumulative number of published cases of dementia pugilistica and CTE.

The association between exposure to brain injury in boxing and the risk of neurodegenerative disease was first reported in 1928. Since the first description of the pathology in a former American National Football League player in 2005, a marked increase in case identification and reporting has been seen. Nevertheless, the cumulative number of unique chronic traumatic encephalopathy (CTE) cases reported is currently just over 300.

Fig. 2|. Neuropathologies identified as being associated with neurodegeneration after TBI.

For both repetitive mild traumatic brain injury (TBI) and single moderate or severe TBI, post-mortem neuropathology studies have identified tau and amyloid-β (Aβ) pathologies, brain atrophy, axonal degeneration and persistent neuroinflammation. However, thus far, 43 kDa transactive response (TAR) DNA-binding protein (TDP43) pathology has only been identified after repetitive mild TBI.