Critical review of the foundational studies on chronic traumatic encephalopathy in American football players.

Background: Chronic traumatic encephalopathy (CTE) was first reported in American football players twenty years ago and has generated ongoing discussion in the medical/scientific community. Objective: The purposes of this paper are twofold: (1) to critically analyze the methodology and evidence presented in the foundational articles on CTE, and (2) to trace the evolution of ideas about modern CTE in the seminal articles. Methods: This narrative review critically analyzed the foundational, seminal studies on modern CTE. We selected 17 articles from the two main publishing groups to review, based upon our contemporaneous professional in depth familiarity with the subject matter and the high frequency with which the articles have been cited in the medical/scientific literature after publication. Each article was critically analyzed to determine whether the methodology and results supported the conclusions. Results: The definition of, and diagnostic criteria for, modern CTE (twenty-first century, mostly American football players) have changed between 2005 and the present. Proposed etiologies have expanded beyond head trauma to include genetic and environmental factors. The clinical features associated with CTE neuropathology have narrowed. Modern CTE can now only be diagnosed by postmortem brain neuropathology. Aspects of the methodologies employed by researchers, such as the reliance on posthumously obtained clinical information from family members of the deceased, limit the reliability of some data. The evidence reported often does not support the assertions made by authors. Conclusions: The foundational studies do not provide conclusive evidence for the acceptance of modern CTE by the medical community.