Traumatic Encephalopathy Syndrome in the Late Effects of Traumatic Brain Injury (LETBI) study cohort

Importance:Traumatic encephalopathy syndrome (TES),the suggested clinical manifestation of chronic traumatic encephalopathy(CTE),is believed to result from repetitive head impacts (RHI) and the prevalence of TES and its component symptoms have not been thoroughly investigated in individuals with single TBI.Objective:To use prospectively collected data to operationalize TES per consensus research diagnostic criteria and examine the rates of TES in a sample of individuals with isolated TBI, a subset of whom also had RHI exposure, and to determine whether any demographic or injury factors predicted likelihood of meeting TES diagnostic criteria.Design:295 participants from the Late Effects of TBI (LETBI) study had complete data for all key variables. The sample was categorized by TBI severity and presence of RHI history leading to 6 groups (those with isolated mild, moderate, and severe TBI, with and without RHI). Chi-squared tests were used to compare the proportion of each group that met each of the core clinical criteria overall TES diagnosis. Binary logistic regression models were used to examine the associations of demographic and injury characteristics on TES diagnosis. Levels of functional dependence and levels of certainty for CTE neuropathology in the sample were characterized and applied with the core clinical features to explore consensus-based provisional levels of certainty of CTE pathology across study groups.Results: In addition to history of TBI, 141 (47.7%) participants had RHI exposure meeting the TES criteria exposure threshold. In the full sample, 56.9%, 33.2% and 45.7% of participants met TES core criterion of cognitive impairment, neurobehavioral dysregulation, and progressive course of clinical features, respectively. Overall, 15.2% of this LETBI sample had substantial RHI exposure and met all 3 clinical features, meeting consensus-based TES criteria. When RHI exposure criterion was lifted, 33.5% of the LETBI sample with isolated TBI met all core clinical criteria. No significant differences were found in clinical diagnostic criteria between individuals with and without RHI exposure. When exploring consensus-based Levels of Diagnostic Certainty, rates of suggestive, possible, and probable CTE were found to be 2.7%, 6.8%, and 5.8%, respectively. No injury or demographic variables significantly predicted the likelihood of meeting all 3 Core Clinical Criteria for TES.Conclusion:In this community based TBI sample, we found high rates of TES clinical features among those with and without RHI, across TBI across injury severity groups. Presence of TES core clinical features was greatest among those with isolated TBI, suggesting that chronic and sometimes progressive sequelae of TBI are similar to those described in TES, but may reflect a distinct pathobiological process from CTE neuropathologic change which is very rarely seen in isolated TBI. Findings emphasize the centrality of RHI exposure to the TES diagnostic criteria. Lifetime exposure to TBI and RHI should be well characterized in studies of TES and post-TBI neuropathologies to advance understanding of the underlying biology of progressive clinical symptoms. This work supports further refinement of TES diagnostic criteria, which will require defining RHI exposure thresholds associated with CTE neuropathologic change.