Chronic Traumatic Encephalopathy (CTE)
Prof Lindy Fitzgerald:
CTE stands for 'chronic traumatic encephalopathy' and it is a condition that is characterised
by particular deposits of protein in the brain and it is a form of neurodegeneration.
Dr Jenna Ziebell:
Is there a difference between chronic traumatic encephalopathy and dementia pugilistica?
Prof Lindy Fitzgerald:
Dementia pugilistica is the initial condition that was described 100 years ago, referred to as
being "punch drunk," where people who had been engaged in martial arts or boxing were
staggering around after their injuries and had that continued, and it was known to be a form
of neurodegeneration. It was described as CTE once we actually got to the stage where the
brains could be analysed and the pathology identified. So CTE is likely to be the same as
dementia pugilistica and they both describe the same condition.
Dr Jenna Ziebell:
What are the specific symptoms of CTE?
Prof Lindy Fitzgerald:
CTE, like all neurodegenerative conditions, leads to a loss of the ability to think, an altered
cognitive state, reduced ability to make good decisions and process information. In addition
to that, CTE is thought to be characterised by particularly altered emotional control, that
can lead to suicide and risk-taking behaviour and also has been linked to increase of
irritability, aggression and personality changes.
Now it's important to bear in mind that CTE can only be diagnosed after someone has died.
We need to look at the brain in order to make an accurate diagnosis of CTE. So it's therefore
a little bit difficult to clearly link specific symptoms to CTE, because the person cannot be
diagnosed while they're still living.
Dr Jenna Ziebell:
Is there specific pathology that is directly linked to a diagnosis of chronic traumatic
encephalopathy?
Prof Lindy Fitzgerald:
There is a specific pathology that is observed in the brains of people who are diagnosed with
CTE. There is a particular protein called 'tau' and that protein tau can be
hyperphosphorylated, which means it's got extra phosphorus atoms on it, basically, and
those tau proteins can become aggregated and can be observed under the microscope,
when you look at sections of the brain. And in particular with CTE, you see these depositions
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of hyperphosphorylated tau in the folds of the brain, in a particular brain region. Folds occur
in the cortex and at the base of the cortex when you see this hyperphosphorylated tau
deposited, that is where we define that the person has experienced CTE. The
hyperphosphorylated tau is also found in Alzheimer's disease, but it's the nature of the
deposition, that pattern of deposition, that's different in CTE, that allows pathologists to
distinguish whether the person actually had CTE or some other form of neurodegenerative
disease or dementia.
Dr Jenna Ziebell:
Are there any genetic links to chronic traumatic encephalopathy?
Prof Lindy Fitzgerald:
Quite recently there's been some developments where a particular gene has been linked to
enhanced susceptibility to CTE. There is a particular transmembrane protein called
TMEM106B and a different allele of that, or a slightly modified version of that gene, is linked
to reduced susceptibility to CTE.
Dr Jenna Ziebell:
Can you only get CTE after brain injury?
Prof Lindy Fitzgerald:
It is possible for people to not have had a history of concussion or traumatic brain injury and
still be diagnosed with CTE following their death; however these people generally have had
some kind of exposure to sub-concussive injuries. So these are injuries which may be not
severe enough to be classified as a concussion but still leading to some kind of force upon
the brain. So we're talking about repeated very mild hits in the sporting context or repeated
exposure, for example, to blasts in the military context. So they might not have been severe
enough to be classified as a concussion, but it is these injuries, it's increasingly becoming
understood, may also be a factor in the development of CTE. But in general terms, people
with CTE have always been exposed to some kind of insult to the brain.
Dr Jenna Ziebell:
Are you at risk of developing CTE from a moderate to severe traumatic brain injury?
Prof Lindy Fitzgerald:
Following a moderate to severe traumatic brain injury, there is a risk of developing CTE. The
single one of these more severe injuries can lead to CTE, whereas with the concussions it's
much more common in people who have experienced repeated injuries. So there does seem
to be a bit of a relationship between the severity of the injury and the likelihood of CTE
developing, although this is a difficult thing to study.
Dr Jenna Ziebell:
What is the risk or chance of developing CTE after a traumatic brain injury?
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Prof Lindy Fitzgerald:
It's very difficult to determine the risk of CTE following traumatic brain injury. These studies
need to be longitudinal, so they need to occur over time. Particularly given the fact that we
can't diagnose CTE until after someone has died, it's quite difficult to conduct a study that is
well controlled.
So a number of studies have been conducted of footballers, and so forth, who have donated
their brains, and then the relationship between the number of their injuries and the
development of CTE has been reported. However, it's important to recognise that these
studies may be prone to bias, because the people that might donate their brains for such a
study may perhaps have been a bit worried about it and might have been perhaps at greater
likelihood of having CTE. So they may have decided to donate their brains, or their families
might have decided to do that, which might lead to a bias, because there's not enough
control samples in the group, where people who are not concerned or people who have not
experienced any CTE-like symptoms have decided to donate their brain. So we find
ourselves relying on studies that aren't particularly well controlled, or perhaps single case
studies where people are reported of having CTE symptoms, and yes they have developed
CTE and that's found in their brains after they've died, but these studies really lack those
controls to enable us to answer the question of exactly what are the risk factors, and how
many injuries must one have experienced in order to have a certain percentage chance of
developing CTE.
It's important not to overemphasise the problem of CTE due to the lack of controlled
studies. There is not yet enough evidence to say that just because someone has experienced
repeated concussion that one will go on to develop CTE. In fact, there are lots of people who
have experienced repeated concussion and have had no symptoms of CTE. So we need to
not overpathologise and over dwell upon the possibilities of CTE following repeated
concussion, as there really is not enough evidence yet to be able to make the definitive
cause and effect relationship.
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