(1) Background: Chronic traumatic encephalopathy (CTE) is a complex pathological condition characterized by neurodegeneration, as a result of repeated head traumas. Currently, the diagnosis of CTE can only be assumed postmortem. Thus, the clinical manifestations associated with CTE are referred to as traumatic encephalopathy syndrome (TES), for which diagnostic multiple sets of criteria can be used. (2) Objectives: In this study, we aimed to present and discuss the limitations of the clinical and neuropathological diagnostic criteria for TES/CTE and to suggest a diagnostic algorithm enabling a more accurate diagnostic procedure. (3) Results: The most common diagnostic criteria for TES/CTE discriminate between possible, probable, and improbable. However, several key variations between the available diagnostic criteria suggest that the diagnosis of CTE can still only be given with postmortem neurophysiological examination. Thus, a TES/CTE diagnosis during life imposes a different level of certainty. Here, we are proposing a comprehensive algorithm of diagnosis criteria for TES/CTE based on the similarities and differences between the previous criteria. (4) Conclusions: The diagnosis of TES/CTE requires a multidisciplinary approach; thorough investigation for other neurodegenerative disorders, systemic illnesses, and/or psychiatric conditions that can account for the symptoms; and also complex investigations of patient history, psychiatric assessment, and blood and cerebrospinal fluid biomarker evaluation.
Keywords: brain imaging; chronic traumatic encephalopathy; diagnosis algorithm; neuropathological features; traumatic brain injury; traumatic encephalopathy syndrome.