New clinical and neuropathological diagnostic criteria for chronic traumatic encephalopathy: a narrative review

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease resulting from the accumulation of numerous head injuries, for which there is no definitive lifetime diagnosis or specific treatment. Associated risk factors include exposure to contact sports that predispose to repeated clinical and subclinical head injuries, the presence of apolipoprotein E4, and age. On a microscopic scale, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes, at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma in an irregular pattern, which may sometimes be accompanied by other abnormal protein deposits and prevalent in other entities such as beta-amyloid plaques, TDP-43 and/or alpha-synuclein. Clinically, it is characterized by a slow and insidious course that begins with mild cognitive symptoms, behavioral disturbances, and emotional dysregulation and progresses to the onset of Parkinsonian-like motor symptoms and dementia. The only way to definitively diagnose CTE is after death during an autopsy of the brain. Although promising diagnostic criteria have been proposed, they are not currently validated. Biomarkers are being developed to determine the pathophysiological changes of the entity in life without the need for biopsy.