Post-Concussion Syndrome and Chronic Traumatic Encephalopathy: Narrative Review on the Neuropathology, Neuroimaging and Fluid Biomarkers

Traumatic brain injury is a significant public health issue and represents the main contributor to death and disability globally among all trauma-related injuries. Martial arts practitioners, military veterans, athletes, victims of physical abuse, and epileptic patients could be affected by the consequences of repetitive mild head injuries (RMHI) that do not resume only to short-termed traumatic brain injuries (TBI) effects but also to more complex and time-extended outcomes, such as post-concussive syndrome (PCS) and chronic traumatic encephalopathy (CTE). These effects in later life are not yet well understood; however, recent studies suggested that even mild head injuries can lead to an elevated risk of later-life cognitive impairment and neurodegenerative disease. While most of the PCS hallmarks consist in immediate consequences and only in some conditions in long-termed processes undergoing neurodegeneration and impaired brain functions, the neuropathological hallmark of CTE is the deposition of p-tau immunoreactive pre-tangles and thread-like neurites at the depths of cerebral sulci and neurofibrillary tangles in the superficial layers I and II which are also one of the main hallmarks of neurodegeneration. Despite different CTE diagnostic criteria in clinical and research approaches, their specificity and sensitivity remain unclear and CTE could only be diagnosed post-mortem. In CTE, case risk factors include RMHI exposure due to profession (athletes, military personnel), history of trauma (abuse), or pathologies (epilepsy). Numerous studies aimed to identify imaging and fluid biomarkers that could assist diagnosis and probably lead to early intervention, despite their heterogeneous outcomes. Still, the true challenge remains the prediction of neurodegeneration risk following TBI, thus in PCS and CTE. Further studies in high-risk populations are required to establish specific, preferably non-invasive diagnostic biomarkers for CTE, considering the aim of preventive medicine.