Chronic traumatic encephalopathy (CTE)

GENERAL ASPECTS

What is chronic traumatic encephalopathy (CTE)?

It is a neurodegenerative disease that can appear as a consequence of traumatic brain injury (TBI). There are still many unknown aspects regarding its symptoms, mechanism of onset, risk factors and temporal relationship with trauma.

How long has this disease been known?

The association between traumatic brain injury and the development of neurodegenerative disease has been known for almost a century.

In the 1920s this observation began to be described in boxers (“punch-drunk syndrome” or “dementia pugilistica”): in some of them, slowness, tremor, mental confusion and emotional changes began to be observed at the end of their careers. By 1970, specific changes were identified in the brains of boxers with these symptoms (tau protein deposition).

In 2005, these brain changes were observed for the first time in a professional soccer player with similar symptoms. This fact attracted the attention of the media and even Hollywood, where a movie was even produced on the subject (“Concussion” or “La verdad duele”, in Spanish).

What kind of head injuries can cause it?

The frequency, severity and total trauma exposure that can cause this disease is not precisely known. It has been described mostly in association with low-intensity repetitive head injuries, but it is believed that it can also occur after a single more severe head injury that results in loss of consciousness.

What factors determine its appearance?

The factors that determine its appearance are not known with certainty. It is possible that there is a higher risk with a greater number of traumatisms, as well as a genetic and lifestyle influence. The professional practice of contact sports (boxing, American soccer, rugby, field hockey…) is probably a risk factor, so studies are being carried out in these groups.

How long does it take to appear?

In general, it is considered that several years must elapse between exposure to trauma and the development of neurodegenerative disease, although the exact temporal relationship between head injuries and the onset of neurodegenerative disease is a matter of debate.

What are the symptoms it produces?

Cognitive, mood, behavioral and motor ability changes have been described; however, many of these symptoms may be caused by the coexistence of other neurodegenerative diseases and, therefore, are not specific to chronic traumatic encephalopathy. The most widely accepted symptoms are memory impairment, confusion, speech disturbances, irritability, depression, episodes of aggression and violence, and gait disturbances, of progressive course, which may lead to the development of dementia.

DIAGNOSIS

How is chronic traumatic encephalopathy diagnosed?

Currently, the diagnosis of this disease can only be made post-mortem, demonstrating typical features (patchy p-tau deposition) at brain autopsy. In life a diagnosis of suspicion can be made, but it can be complicated by overlapping symptoms and deposition of other proteins common to other neurodegenerative diseases.

Are there any complementary tests that can help in the diagnosis?

Usually an attempt is made to rule out other pathologies that may present with similar symptoms, such as Alzheimer’s disease, frontotemporal dementia or Parkinson’s disease. Therefore, on many occasions the same tests are requested as in these pathologies and, in this way, an attempt is made to rule them out. However, biomarkers are currently being investigated in plasma, cerebrospinal fluid and neuroimaging tests whose alteration can help in the diagnosis.

What do we find in the brains of CTE patients?

There is an abnormal accumulation of phosphorylated tau protein (p-tau) in neurons and other brain cells (astrocytes). These accumulations appear mainly around blood vessels and in the depth of the cerebral sulci, distributed in a patchy manner throughout the brain. This type of deposits and their distribution allow differentiation from other neurodegenerative diseases. However, it is very common to also find the deposition of other proteins, such as TDP-43 or beta-amyloid.

Is there a risk of other neurodegenerative diseases after traumatic brain injury?

Probably yes. As mentioned above, the brain of these patients often shows pathological deposition of several proteins, some of which are those that define other diseases such as Alzheimer’s disease or frontotemporal dementia. Traditionally, a single major trauma with loss of consciousness has been associated with an increased risk of future development of Alzheimer’s disease, but as noted above this also confers a risk of chronic traumatic encephalopathy.

TREATMENT

Is there any treatment available?

There is no approved medication for its treatment. Drugs similar to those used in Alzheimer’s disease (acetylcholinesterase inhibitors or memantine) may be considered, but their benefit is not clearly established. Antidepressants can be used for the treatment of neuropsychiatric symptoms (depression, anxiety…), and occasionally neuroleptics (if there is irritability or aggressiveness). Non-pharmacological measures (caregiver education, home care, dependency aids, etc.) are essential.