Chronic traumatic brain injury (Chronic traumatic encephalopathy)

Chronic traumatic brain injury (encephalopathy) is a neurodegenerative disease associated with exposure to repetitive head impacts, such as those incurred in contact or collision sports.

A disorder with specific neuropathological characteristics seen in autopsied brains of decedents with history of repetitive  traumatic brain injury, particularly impact traumatic brain injury caused by the head striking a physical object often in from blunt force.

Most cases have been reported after  participation in contact sports, including football, boxing, wrestling, rugby, hockey, soccer, and even baseball.

CTE has also been noted in repetitive impact traumatic brain injury including domestic abuse, epileptic seizures, and  headbanging behavior.

CTE related lesions have also been reported in association with a single, moderate to severe TBI event.

Military personnel exposed to combat,  and specifically those with blast exposure have clinical presentations that overlap with CTE, including cognitive dysfunction, behavioral changes, mood disorders and disturbances, substance abuse, and suicidality: however pathological studies of the brains infrequently showed findings with CTE and reflected minimal neuropathic changes.

Rates of disease have been found to be about 30% among those with a history of multiple head injuries.

Experiencing concussions and sub-concussive blows is regarded as the most important risk factor.

Concussions are non-structural injuries.

Concussions do not result in brain bleeding, so they cannot be visualized by  routine neuroimaging tests such as CT or MRI.

Differentiating between prolonged post-concussion syndrome (PCS, where symptoms begin shortly after a concussion and last for weeks, months, and sometimes even years and CTE can be difficult. 

The encephalopathy can manifest as behavioral problems, mood problems, and problems with thinking.

The process often gets worse over time and can result in dementia.

Neuropathologically the disease is noted to have deposition of paired helical filament tau aggregates in neurons, astrocytes, and cell processes in an irregular pattern around small blood vessels at the depths of cortical sulci.

The presence of neuronal phosphorylated tau protein deposition in characteristic locations and patterns is pathognomonic for CTE.

With chronic traumatic encephalopathy tau aggregates are observed in the frontal, temporal, and parietal courtiers.

In the later stages of chronic traumatic encephalopathy these tau aggregates are found throughout the cerebral cortex, medial temporal lobe, diencephalon, and brainstem.

It is suspected that the head trauma initiates events leading to inflammation of proteins or misfolding, aggregation of tau proteins that leads to the degeneration of neurons and supporting elements, and the emergence of behavioral and cognitive disturbances years after exposure.

The distribution of the tau aggregates distinguishes chronic traumatic brain injury from other neurodegenerative diseases with tau infiltrates such as Alzheimer’s disease.

Neuropathological histological appearance of CTE is distinguished from other tauopathies.

Pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes.

These findings are at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma, and not restricted to the subpial and superficial region of the sulcus.

The pathognomonic lesions must include p-tau in neurons to distinguish CTE from age related tau astrogliopathy.

Additional findings of CTE are: 

superficial neurofibrillary tangles (NFTs); p–tau in the hippocampus; 

mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus

 p-tau thorn-shaped astrocytes in the subpial region and p-tau dot-like neurites.

Some patients with CTE have chronic traumatic encephalomyopathy (CTEM), which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis (ALS).

Exosome vesicles created by the brain are potential biomarkers of CTE.

Diagnosis of CTE cannot be made in living individuals.

No definitive test proves its existence in a living person. 

Signs are also very similar to that of other neurodegenerative conditions such as Alzheimer’s.

Neurofibrillary tangles have been found in the brains of dementia CTE patients, but not in the same distribution as is usually found in people with Alzheimer’s.

Loss of neurons, scarring of brain tissue, collection of proteinaceous senile plaques, hydrocephalus, attenuation of the corpus callosum, diffuse axonal injury, neurofibrillary tangles, and damage to the cerebellum are also present in the syndrome. 

Aging-related tau astrogliopathy (ARTAG) does not meet the criteria for CTE.

Beta-amyloid is not a feature of CTE.’

The four clinical stages of observable CTE disability correlate with tau pathology in brain tissue.

Tau involvement ranges in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.

CTE results in a reduction in brain weight, associated with atrophy of the frontal and temporal cortices and medial temporal lobe, lateral ventricle and third ventricle are often enlarged, with rare instances of dilation of the fourth ventricle.

Additional brain changes include anterior cavum septi pellucidi and posterior fenestrations, pallor of the substantia nigra, locus ceruleus, and atrophy of the olfactory bulbs, thalamus, mammillary bodies, brainstem and cerebellum.

There may be marked atrophy of the hippocampus, entorhinal cortex, and amygdala.

Chronic traumatic encephalopathy involves neuritic amyloid-beta plaque deposition only in advanced stages of disease, unlike Alzheimer’s disease.

The number of years of playing tackle football is associated with the severity of tau deposition.

No associations have been demonstrated however with impaired range of neuropsychological test results and the amount of tau deposition ( The number of patients is very small).

Patients with chronic traumatic encephalopathy have been reported to have cognitive impairment, mood disturbance, and behavior changes.

PET scans can measure tau levels in the brain.

PET scans that bind specifically to tau protein can help in the diagnosis.

Autoantibodies have been detected in athletes  who have experienced a large number of head hits but no concussions, suggesting that even sub-concussive episodes may be damaging to the brain. 

It is hypothesized that such antibodies made it into the brain via the blood brain barrier that has been damaged by the trauma, and subsequently they attack neuronal cells.

An extended period of time is required, because of the large number of the brain neurons and the poor penetration of antibodies across a normal blood brain barrier, before the development of any signs or symptoms.

These autoimmune changes may constitute the earliest measurable event predicting the onset of CTE.

Diagnosis can only occur at autopsy.

The disease is classified as a tauopathy.

Rates of CTE have been found to be about 30% among those with a history of multiple head injuries.

Symptoms of CTE, which occur in four stages.

CTE appears eight to ten years after an individual experiences repetitive mild traumatic brain injuries.

Stages of CTE:

First-stage symptoms are confusion, disorientation, dizziness, and headaches. 

Second-stage symptoms include memory loss, social instability, impulsive behavior, and poor judgment. 

Third and fourth stages include progressive dementia, movement disorders, hypomimia, speech impediments, sensory processing disorder, tremors, vertigo, deafness, depression and suicidality, dysarthria, dysphagia, cognitive disorders such as amnesia, and ocular abnormalities, such as ptosis.

Symptoms include: declining mental ability, problems with memory, dizzy spells or lack of balance to the point of not being able to walk under one’s own power for a short time and/or Parkinsonism, or tremors and lack of coordination, proneness to inappropriate or explosive behavior and may display pathological jealousy or paranoia.

Most documented cases of CTE have occurred in athletes with mild repetitive brain trauma over an extended period of time. 

Autopsy studies show the brains of deceased athletes have very high levels of findings of CTE, that correlate with the extent of brain trauma:

deceased football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players.

The diagnosis of CTE cannot be determined by imaging.

Brain imaging techniques include the use of magnetic resonance imaging, nuclear magnetic resonance spectroscopy, CT scan, single-photon emission computed tomography, Diffusion MRI, and Positron emission tomography (PET).


The use of helmets and mouth-guards have been shown to reduce direct head trauma, but  neither has significant research to support its use.

There is no significant research to support the use of helmets to reduce the risk of concussions, but there is evidence to support that helmets  reduce  impact forces.

Mouth guards have been shown to decrease dental injuries, but has not shown significant evidence to reduce concussions.

Removal from games following traumatic incidences is essential.

Return-to-play protocols after possible brain injuries is important to decrease the significance of future impacts.

Changing the rules of contact sports to reduce the frequency and severity of blows to the head: banning of helmet-first tackles, and the addition of rules to protect defenseless players. 


No cure currently exists for CTE.

Treatment is supportive.

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