Neuropathologic and Clinical Findings in Young Contact Sport Athletes Exposed to Repetitive Head Impacts

Abstract

ImportanceYoung contact sport athletes may be at risk for long-term neuropathologic disorders, including chronic traumatic encephalopathy (CTE).ObjectiveTo characterize the neuropathologic and clinical symptoms of young brain donors who were contact sport athletes.Design, Setting, and ParticipantsThis case series analyzes findings from 152 of 156 brain donors younger than 30 years identified through the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank who donated their brains from February 1, 2008, to September 31, 2022. Neuropathologic evaluations, retrospective telephone clinical assessments, and online questionnaires with informants were performed blinded. Data analysis was conducted between August 2021 and June 2023.ExposuresRepetitive head impacts from contact sports.Main Outcomes and MeasuresGross and microscopic neuropathologic assessment, including diagnosis of CTE, based on defined diagnostic criteria; and informant-reported athletic history and informant-completed scales that assess cognitive symptoms, mood disturbances, and neurobehavioral dysregulation.ResultsAmong the 152 deceased contact sports participants (mean [SD] age, 22.97 [4.31] years; 141 [92.8%] male) included in the study, CTE was diagnosed in 63 (41.4%; median [IQR] age, 26 [24-27] years). Of the 63 brain donors diagnosed with CTE, 60 (95.2%) were diagnosed with mild CTE (stages I or II). Brain donors who had CTE were more likely to be older (mean difference, 3.92 years; 95% CI, 2.74-5.10 years) Of the 63 athletes with CTE, 45 (71.4%) were men who played amateur sports, including American football, ice hockey, soccer, rugby, and wrestling; 1 woman with CTE played collegiate soccer. For those who played football, duration of playing career was significantly longer in those with vs without CTE (mean difference, 2.81 years; 95% CI, 1.15-4.48 years). Athletes with CTE had more ventricular dilatation, cavum septum pellucidum, thalamic notching, and perivascular pigment-laden macrophages in the frontal white matter than those without CTE. Cognitive and neurobehavioral symptoms were frequent among all brain donors. Suicide was the most common cause of death, followed by unintentional overdose; there were no differences in cause of death or clinical symptoms based on CTE status.Conclusions and RelevanceThis case series found that young brain donors exposed to repetitive head impacts were highly symptomatic regardless of CTE status, and the causes of symptoms in this sample are likely multifactorial. Future studies that include young brain donors unexposed to repetitive head impacts are needed to clarify the association among exposure, white matter and microvascular pathologic findings, CTE, and clinical symptoms.

Unusual combinations of neurodegenerative pathologies with chronic traumatic encephalopathy (CTE) complicates clinical prediction of CTE

“…Except for one individual who showed solely focal CTE lesions, all of the cases showed a wide range of pathologies. Interestingly, only the youngest participant had evidence of a single pathology of CTE‐NC, which is consistent with previous pathological reports of individuals with repetitive concussions [38–41] as well as in neurodegenerative diseases in general [42]. Numerous studies have now reported that copathologies are prevalent in CTE, especially in older age [17, 22, 38, 40].…”

“…CTE-NC as a sole pathology has been seen in younger patients [40,41], and may facilitate the accumulation of other proteinopathies as the person ages. The phenotype of CTE-NC warrants further study, and biomarkers for its detection are in dire need.…”

Chronic traumatic encephalopathy neuropathologic change in former Australian rugby players

“…The TES criteria acknowledge that neurobehavioural dysregulation alone limits the diagnostic certainty of CTE-NC to 'suggestive of CTE' [22]. However, a recent study of 152 young contact and collision sport athletes under 30 years of age also did not find an association between clinical symptoms, including neurobehavioral dysregulation, and CTE-NC status (41.4% had CTE-NC), despite a high frequency of cognitive and neurobehavioural symptoms in this convenience sample [49]. Similarly, psychiatric features are also used to draw inferences relating to provisional levels of certainty that a research subject might harbour CTE-NC.…”

“…CTE-NC and ARTAG have been shown to share molecular and histopathological features, indicating a potential common aetiology [47]. However, it has been suggested that astrocyte pathology is more common in more advanced stages of CTE-NC [48] and is less common in younger individuals with CTE-NC [49]. Of the two cases that did not meet the criteria for CTE-NC, both had significant ARTAG in the form of granular fuzzy astrocytes in the cortex (Case 4) and thorny astrocytes in the subpial, subependymal, perivascular (Case 4) and white matter (Cases 4 and 5) [32].…”

JAMA Neurology—The Year in Review, 2023

“…The journal receives a high number of quality submissions (Table) with an acceptance rate of 9% overall and 6% for research articles, and we continue to emphasize service to authors in the hopes of making the process more efficient and useful. We focus tremendously on rapid turnaround for submitted manuscripts, and in 2023, the median time from receipt to first decision was 5 days without peer review and just more than a month with peer review.…”