Concussion in Chronic Traumatic Encephalopathy

Abstract

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE.

Repeated mild traumatic brain injury causes focal response in lateral septum and hippocampus

“…Our results show the most prominent cellular response is in the lateral septum and hippocampus, directly below the corpus callosum, which is consistent with results from computer generated modeling that predict the highest rate of strain to occur in the corpus callosum [14]. It is important to note that structural damage to the septal region may be linked to fenestrated and/or cavum septum pellucidum, which is a common feature of CTE [4]. A recent MRI study shows the prevalence, grade and length of cavum septum pellucidum are higher in retired American profootball players compared with memory clinic controls [37].…”

Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy

“…We have previously shown in a heterogeneous cohort of deceased contact sport athletes and military personnel that the number of years of exposure to RHI significantly predicts increased CTE stage as defined by the extent of ptau pathology [5, 9]. Furthermore, a cumulative head impact index based on position, level of play, and impact frequencies from helmet accelerometer studies in American football players was associated with later-life cognitive and neurobehavioral impairment [8].…”

“…Furthermore, a cumulative head impact index based on position, level of play, and impact frequencies from helmet accelerometer studies in American football players was associated with later-life cognitive and neurobehavioral impairment [8]. In contrast, the reported number of concussions was not significantly correlated with CTE stage [5, 9] and was less predictive than the cumulative head impact index of cognitive and neurobehavioral impairment [8]. Furthermore, 16 % of individuals diagnosed with CTE had no reported history of concussions suggesting subconcussive hits are sufficient for the development of the disease [10].…”

Does a Unique Neuropsychiatric Profile Currently Exist for Chronic Traumatic Encephalopathy?

“…Several lines of evidence demonstrates that the extent of risk for dementia subsequent to TBI follows a dose-response curve model, with more severe injury and greater numbers of repetitive traumas leading to greater risk (50). The relevance of these risk factors increases if the repetitive head injuries occurred in close temporal proximity, occurred early in life or occurred over an extended period of time (53,55,57). Thus, the populations thought by CTE researchers to be most at risk for CTE are those patients who were previously involved in high impact sports (e.g., boxing, mixed-martial arts, American football, ice hockey, lacrosse) and potentially military personnel.…”