Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy (CTE), formerly known as repetitive head injury syndrome, is a progressive neurodegenerative condition commonly observed in individuals involved in contact sports or military service associated with an increased risk of repeated head injuries. This condition is characterized by regional atrophy, ventriculomegaly, and specific brain abnormalities. Historically, CTE has been linked to repeated head trauma, with early descriptions highlighting its association with "punch drunk" syndrome and ''dementia pugilistica" in boxers. The condition has evolved into a significant topic within the sports medicine community, with ongoing investigations into its pathophysiology, diagnostic criteria, and potential therapeutic approaches.

Historical Background

Harrison Martland was the first to mention "perivascular microhemorrhages" that progressively evolved into "replacement gliosis," resulting in punch drunk syndrome. Abram Bowman and Karl Blau then coined the term CTE to better characterize the condition. N. Corsellis subsequently identified neurofibrillary tangles (NFTs), along with ventricular dilatation, cavum septum pellucidum, thinning of the corpus callosum, and cerebellar tonsillar scarring in affected individuals. Additional neuropathological changes in CTE were later documented by Jennian Geddes, who noted perivascular neurofibrillary encasement within cortical sulci, and Bennet Omalu, who described amyloid plaques, tau-positive neurofibrillary tangles, and neuropil threads associated with the condition.

Ann McKee proposed neuropathological diagnostic and grading criteria for CTE, characterized by patchy deposits of phosphorylated tau (p-tau)–positive NFTs and astrocytic tangles located perivascularly within the neocortex, at the depths of cerebral sulci, and in the superficial layers of the cortex, primarily in the temporal lobe. The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have established criteria for diagnosing CTE, focusing on perivascular foci of p-tau NFTs and astrocytic tangles in the cortex, with a preference for their presence at sulcal depths and in the superficial layers of the cerebral cortex.

In 2021, the panel refined the definition of the pathognomonic lesion to emphasize that perivascular p-tau aggregates must involve neurons and extend deeper than the subpial layer. Additionally, the panel introduced the classifications "Low CTE" and "High CTE" to indicate the presence of NFTs in specific brain regions, such as the thalamus, mammillary bodies, hippocampus, amygdala, and entorhinal cortex, to assist neuropathologists in their assessments.

While CTE can only be definitively diagnosed through postmortem examination, recent consensus guidelines have established criteria for identifying its clinical manifestations, referred to as traumatic encephalopathy syndrome (TES). Montenegro et al proposed the clinical diagnostic criteria for CTE comprising cognitive, behavioral, and mood symptomatology as 3 core elements alongside 9 other supportive features, including impulsivity, anxiety, apathy, paranoia, suicidality, headache, motor signs, documented decline, and delayed onset.