Chronic Traumatic Encephalopathy: Update on Current Clinical Diagnosis and Management

Abstract

Chronic traumatic encephalopathy is a disease afflicting individuals exposed to repetitive neurotrauma. Unfortunately, diagnosis is made by postmortem pathologic analysis, and treatment options are primarily symptomatic. In this clinical update, we review clinical and pathologic diagnostic criteria and recommended symptomatic treatments. We also review animal models and recent discoveries from pre-clinical studies. Furthermore, we highlight the recent advances in diagnosis using diffusor tensor imaging, functional magnetic resonance imaging, positron emission tomography, and the fluid biomarkers t-tau, sTREM2, CCL11, NFL, and GFAP. We also provide an update on emerging pharmaceutical treatments, including immunotherapies and those that target tau acetylation, tau phosphorylation, and inflammation. Lastly, we highlight the current literature gaps and guide future directions to further improve clinical diagnosis and management of patients suffering from this condition.

MicroRNA Alterations in Chronic Traumatic Encephalopathy and Amyotrophic Lateral Sclerosis

“…MiR-146a-5p and miR-107 along with miR-9-5p, miR-181c-5p and miR-125b-5p are involved in the NF-κB pathway. The NF-κB has been previously implicated in ALS ( Parisi et al, 2016 ; Tahamtan et al, 2018 ; Slota and Booth, 2019 ; Källstig et al, 2021 ) and TBI ( Jassam et al, 2017 ; Pierre et al, 2021 ). Outside of the NF-κB pathway, miR-125b-5p has been directly implicated in hyperphosphorylation of tau ( Banzhaf-Strathmann et al, 2014 ) and might contribute to CTE pathogenesis.…”

Advances Research in Traumatic Encephalopathy

“…The first of these articles provides a review of the latest clinical, imaging, and biomarker tools available for antemortem CTE classification [ 2 ]. This work details the diverse clinical presentations of CTE, ranging from behavioral aggression or impulsivity to cognitive memory, attention, or language decline to mood disorders of depression, mania, or anxiety [ 2 , 3 , 4 ]. Nevertheless, a purely clinical diagnostic criterion of CTE remains a controversial and unlikely prospect.…”

“…Notably, both DTI and FDDNP-PET imaging have also been used to analyze white matter disruption in other neurodegenerative disorders such as Alzheimer’s disease (AD) [ 6 , 8 ]. The biomarkers t-tau, TREM2 (an inflammatory marker), and CCL11 (an eosinophil-attracting chemokine [ 9 ]) were also highlighted as potential markers for CTE in this review [ 2 ]. However, a diagnosis via biomarker remains controversial due to the poorly understood relationship between post-concussive syndrome (PCS), CTE, and AD [ 10 ].…”

Tackling Neuroinflammation After Traumatic Brain Injury: Complement Inhibition as a Therapy for Secondary Injury

“…After the (sub)acute phase of injury, a prolonged state of chronic inflammation may linger for years after TBI and predispose patients to develop other neurodegenerative disorders, such as dementia [8,9]. Probably chronic traumatic encephalopathy is caused by a similar pathophysiology which has been shown to occur after recurrent mild trauma, like sport-related injuries [10].…”