Interaction of Medical Conditions and Football Exposures Associated with Premortem Chronic Traumatic Encephalopathy Diagnosis in Former Professional American Football Players.

BACKGROUND AND OBJECTIVE: Despite being a postmortem diagnosis, former professional American-style football players report receiving chronic traumatic encephalopathy (CTE) diagnoses from medical care providers. However, many players also report other health conditions that manifest with cognitive and psychological symptoms. The purpose of this study was to identify how medical conditions, psychological disorders, and football exposure combinations are associated with former athletes reporting a premortem CTE diagnosis. METHODS: This study was a cross-sectional cohort survey from 2015 to 2019 of 4033 former professional American-style football players. Demographics (age, race, domestic status, primary care recipient), football-related factors (position, years of professional play, burden of symptoms following head impacts, performance-enhancing drug use), and comorbidities (sleep apnea, psychological disorder status [depression and anxiety; either depression or anxiety; neither depression nor anxiety], diabetes mellitus, attention-deficit/hyperactivity disorder, hypertension, heart conditions, high cholesterol, stroke, cancer, low testosterone, chronic pain, current and maximum body mass index) were recorded. A Chi-square automatic interaction detection (CHAID) decision tree model identified interactive effects between demographics, health conditions, and football exposures on the CTE diagnosis. RESULTS: Depression showed the strongest univariate association with premortem CTE diagnoses (odds ratio [OR] = 9.5, 95% confidence interval [CI] 6.0-15.3). CHAID differentiated participants with premortem CTE diagnoses with 98.2% accuracy and area under the curve = 0.81. Participants reporting both depression and anxiety were more likely to have a CTE diagnosis compared with participants who reported no psychological disorders (OR = 12.2; 95% CI 7.3-21.1) or one psychological disorder (OR = 4.5; 95% CI 1.9-13.0). Sleep apnea was also associated with a CTE diagnosis amongst those with both depression and anxiety (OR = 2.7; 95% CI 1.4-5.2). CONCLUSIONS: Clinical phenotypes including psychological disorders and sleep apnea were strongly associated with an increased likelihood of having received a pre-mortem CTE diagnosis in former professional football players. Depression, anxiety, and sleep apnea produce cognitive symptoms, are treatable conditions, and should be distinguished from neurodegenerative disease.

Encefalopatía traumática crónica, definición, diagnóstico y prevención: revisión de la literatura / Chronic traumatic encephalopathy, definition, diagnosis and prevention: review of literature

La encefalopatía traumática crónica (ETC) es una enfermedad neurodegenerativa que se produce como consecuencia traumatismos cerebrales repetitivos; concusiones, que son un síndrome clínico que se caracteriza por una alteración de la función cerebral. Una concusión, bajo su estricta definición, no debiese causar cambios estructurales en el cerebro por lo que no sería visible a través de imágenes, sí existen cambios a nivel microscópicos, bioquímicos y biomecánicos. La mayoría de los pacientes tienen completa resolución de sus síntomas dentro de 10 días (90 por ciento), pero existe un pequeño porcentaje que persiste con estos, pudiendo presentarse como un síndrome postconcusional, síndrome de segundo impacto o una encefalopatía traumática crónica. La ETC se caracteriza por la acumulación de prot-tau hiperfosforilada en neuronas y astrocitos. Estas se van a presentar en forma de ovillos o hilos neurofibrilares. En etapas iniciales las encontraremos de forma focalizada en la corteza frontal y en las formas más severas su distribución será más generalizada, distribuyéndose en la mayoría de las regiones del cerebro. Su diagnóstico se realiza a través de histopatología, por lo que hasta el momento sólo se ha logrado post-mortem. Se está trabajando en nuevas tecnologías asociadas a biomarcadores y PET para lograr una diagnostico premortem. El mayor énfasis en el manejo de esta taupatía es la prevención y adecuado manejo de las concusiones.

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease which is produced as a consequence of repeated brain trauma: concussions, which are a clinical syndrome characterized by an alteration in brain functions. A concussion, understrict definition, should not cause structural changes to the brain. Therefore, it would not be possible to see through images if there were changes at a microscopic, biochemical level. Most patients see their symptoms completely resolved within 10 days (90 percent), but there is a small percentage which persists, and these might cause a post-concussional syndrome, second impact syndrome of chronic traumatic encephalopathy. CTE is characterized by the accumulation of hyper-phosphorylated Tau protein in neurons and astrocytes. These appear in the form of neurofibrillary tangles. During the initial stages they are focalized in the frontal cortex and, in more severe cases, their distribution is more generalized, spreading through the majority of the regions in the brain. It is diagnosis is done through histopathology. Thus, it has only been possible to do post mortem. New technologies associated with bio-markers and PET are being worked on to achieve a pre-mortem diagnosis. The greatest emphasis in the handling of this tauopathy lies in the prevention and the adequate handling of concussions.

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. METHODS: Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. RESULTS: All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. CONCLUSIONS: Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Post-traumatic amnesia and confusional state: hazards of retrospective assessment.

Retrospective assessment of post-traumatic amnesia (PTA) must take into account factors other than traumatic brain injury (TBI) which may impact on memory both at the time of injury and subsequent to the injury. These include analgesics, anaesthesia required for surgery, and the development of acute or post-traumatic stress disorder. This is relevant in clinical and medicolegal settings. Repeated assessments of the post-injury state, involving tests for continuing amnesia, risk promoting recall of events suggested by the examiner, or generating confabulations. The PTA syndrome affects the categorical autobiographical memory, and is accompanied by confusion as an essential component; this should be suspected from the initial or early Glasgow Coma Scale score (13-14/15) if not directly recorded by clinical staff. PTA by itself is only one of several indices of severity of TBI. The nature of the head injury, including observers' accounts, clinical and neuroimaging data, the possible role of other external injuries, blood loss, acute stress disorder and the potential for hypoxic brain injury, must be taken into account as well as concomitant alcohol or substance abuse, and systemic shock. A plausible mechanism for a TBI must be demonstrable, and other causes of amnesia excluded.