This histopathologic study by scientists from the United States was conducted to examine brain pathology and clinical findings in young, deceased, symptomatic athletes who played contact sports and were younger than 30 years of age at the time of death. 41% of 152 brain donors who were exposed to repeated head impacts and who donated their brain to the UNITE Brain Bank, had chronic traumatic encephalopathy (CTE).

Repeated head impacts can lead to symptomatic concussions and the more common, nonconcussive asymptomatic brain injuries. Long-term exposure to repeated head impacts can result in persistent cognitive and neuropsychiatric symptoms, as well as a progressive, neurodegenerative disease, CTE. Young athletes who play contact sports are also at risk of developing chronic brain disorders, including CTE.

A definitive diagnosis of CTE requires pathological evidence of perivascular hyperphosphorylated tau (p-tau) aggregates in neurons, either with or without astrocytes, typically located at the depths of the sulci in the cerebral cortex. Traumatic encephalopathy syndrome (TES) is the clinical syndrome that is associated with CTE. The diagnostic criteria for TES includes cognitive impairment, particularly episodic memory and executive dysfunction, as well as neurobehavioral and emotional dysregulation.

About the study

This case series analyzes findings from 152 brain donors younger than 30 years of age identified through the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank, who donated their brains from 2008 to 2022. The restriction on brain donors younger than 30 years of age was chosen in order to minimize any contribution from age-related conditions. Most of these young athletes played contact sports only at the amateur level, as members of teams affiliated with educational institutions. 

Online surveys and/or structured and semistructured postmortem telephone interviews were used to perform retrospective clinical evaluations for 143 brain donors. The scales were modified for retrospective use, and they were given to informants of brain donors to assess cognitive, mood and neurobehavioral disorders. The researchers used the following instruments: the BRIEF–A Metacognition Index, Cognitive Difficulties Scale, the Functional Activities Questionnaire, the BRIEF–A Behavioral Regulation Index and Barratt Impulsiveness Scale. Online questionnaires with informants were conducted in a blinded manner.

The histopathologic diagnoses were made based on the NINDS National Institute of Biomedical Imaging and Bioengineering criteria for CTE and established criteria for other neurodegenerative diseases. The brain tissue was also examined for the presence of vascular pathological findings, white matter rarefaction and the presence of perivascular pigment–laden macrophages within the deep cerebral white matter. The four neuropathologists reviewed histopathologic diagnoses.

Results

Among the 152 brain donors, the age at death ranged from 13 to 29 years (the mean age was 22.97 years). There were eleven female (7.2%) and 141 (92.8%) male brain donors. A histopathologic diagnosis of chronic traumatic encephalopathy (CTE) was made in 63 brain donors (41.4%), one of whom was a woman (1.6%). Brain donors with CTE had a higher level of education, such as a college degree or higher. The most prevalent cause of death was suicide, followed by accidental overdose. There were no differences in the cause of death based on CTE status.

Nearly all (95.2%) of the 63 young brain donors with CTE were diagnosed with mild CTE, including 62% with stage I and 33% with stage II. Three cases (4.8%) were diagnosed with stage III. There were no brain donors diagnosed with stage IV of CTE.

Of the 63 athletes with CTE, 71% were men who played amateur sports, and played only at the high school or college level. The group of young athletes with histopathologically confirmed CTE (n = 63) included American football players, ice hockey players, soccer and rugby players, amateur wrestlers, military veterans, and professional wrestlers. The brain donors with CTE were more likely to be older, play American football, and play for a longer time. In football, those with CTE had a longer playing career than those without CTE (mean difference, 2.81 years). These findings show that the development of CTE is influenced by age and duration of exposure to repeated head impacts, even in younger individuals.

The histopathologic diagnosis of CTE was evident as neuronal p-tau aggregates, comprising pathognomonic lesions of p-tau immunoreactive neurofibrillary tangles (NFTs) and dotlike neurites, oriented around a small vessels in the superior frontal, dorsolateral frontal, and superior temporal cortices. In all brain regions, except the mammillary bodies and calcarine cortex, significantly more p-tau NFTs were found in brain donors with CTE compared with those without CTE. In the parenchyma or subpial region, no p-tau astrocytes were found. The absence of p-tau astrocytes was unexpected, as subpial p-tau thorn-shaped astrocytes are a common finding in older individuals with CTE. The absence of p-tau astrocytes indicates that they are not an early or essential feature of CTE.

CTE was frequently accompanied by other pathological abnormalities in the group of young athletes with confirmed CTE. Cavum septum pellucidum, frequently associated with degeneration and thinning of the fornices, was more often found in donors with CTE. Furthermore, there was an enlargement of the frontal horns of the lateral ventricles and notching of the medial thalamus. The number of perivascular pigment–laden macrophages in the frontal subcortical white matter was significantly greater in CTE and was associated with the duration of exposure to repeated head impacts. This suggests that disruption of the blood-brain barrier is increased after repeated head impacts, and it is possible that it plays a critical role in the pathogenesis of CTE.

There were no statistically significant differences between donors with and without CTE diagnosis for any clinical symptom.

Researchers concluded that these findings show that CTE and other brain pathologies can be found in young, symptomatic athletes who play contact sports. They suggested that better clinical characterization of living athletes exposed to repeated head impacts is needed through prospective objective assessment.

This article was published in JAMA Neurology.

Journal Reference

McKee A. C et al. Neuropathologic and Clinical Findings in Young Contact Sport Athletes Exposed to repeated Head Impacts. JAMA Neurol. Published online August 28, 2023.  https://jamanetwork.com/journals/jamaneurology/fullarticle/2808952