Concussion complexities

Adelaide-based neuroscientist Professor Robert Vink says general practitioners and other health practitioners involved in contact sports must ensure they are informed about the latest research into traumatic brain injury and its links to concussion.

Prof Vink says recent research provides ‘irrefutable evidence’ that there’s a link between repeated concussions and the potential for developing chronic traumatic encephalopathy (CTE),’ Prof Vink says. ‘But there are still questions over how to manage players who demonstrate symptoms and behaviours associated with concussion, and especially those who have been repeatedly concussed.

CTE is a progressive and fatal brain disease associated with the accumulation of a protein known as hyperphosphorylated tau that affects cognition and behaviour.

In February, the Boston University CTE Center announced that it had diagnosed 345 former National Football League (NFL) players with CTE among 376 former players studied.

‘Everyone reacts to concussion differently, and GPs and others must recognise that,’ Prof Vink says. ‘Research has shown that 20 per cent of people don’t recover in 12 days. We know children take longer to recover. Girls take longer to recover.

‘It’s the ones who have persistent symptoms who we think are at risk of developing CTE.’

‘We’re asking GPs and other health professionals to become educated about the symptoms and behaviours that indicate a player has not recovered from the concussion and if there are persisting symptoms, then the player does not return to play until a health professional has provided the OK.

Professor Vink is a University of South Australia neuroscientist whose interest in sport-related concussion came through his background in traumatic brain injury (TBI) research and the long-term consequences of TBI. He is the immediate Past President of the International Neurotrauma Society and the current Chair of the Board of Connectivity: Traumatic Brain Injury Australia.

‘I have always been puzzled as to why players with an injured knee will not return to the field for two or three weeks – or whatever the accepted medical recommendation is for that injury – but when a player injures their brain, there’s a rush to get them back on the field,’ Prof Vink says.

‘Fortunately, that’s changed. But we are still in need of strict rules and guidelines that prevent a player returning to the field after a concussion, and especially repeated concussions.

‘We need guidelines that recognise that each person must be managed individually, according to their symptoms and behaviours.

‘Players’ long-term health must trump any short-term desire for on-field success.’

As recently as 2019 professional sport was reluctant to accept that CTE was linked to TBI incurred during sports contests. The Australian Sports Commission’s 2019 Concussion Position Statement noted that ‘there is currently no reliable evidence clearly linking sport-related concussion with (CTE)’ and suggested that studies ‘have not adequately controlled for the potential contribution of confounding variables such as alcohol abuse, drug abuse, genetic disposition and psychiatric illness’.

But four years later, Prof Vink says, there is no doubt. Even the Australian Government is convinced: the Senate Community Affairs References Committee is due to report in June 2023 on what it learned from witnesses and submissions to its inquiry into sportsrelated concussion.

‘Concussion in sport is not a new phenomenon and despite occurring over decades and being very poorly managed relative to modern standards, we do not see an epidemic of CTE in the community, either in Australia, the US or anywhere else in the world,’ he says.

There is mounting evidence. Prof Vink says post-mortem studies have shown that donated brains from US professional football (NFL) players have a CTE incidence of 99%. This falls markedly to about 8% when brains are randomly selected and all US football exposure is included (amateur youth, high school, college and professional NFL), suggesting that professional NFL football is a major contributor to the high incidence of CTE in US football.

US research has also shown an incidence in all athletes of less than 5% while the general, non-athletic population had a CTE incidence of approximately 1%.

‘Presumably, the general population sample included cases of domestic violence, assault, exposure to explosive devices and epilepsy, all of which can also result in CTE,’ he says.

‘A much smaller Australian study reported an incidence of 57% in donated brains of professional athletes who played in sports with risks of repetitive head injury, and markedly lower incidence of CTE in the general population.

‘In summary,’ he wrote in his submission to the Senate inquiry, it seems clear that repetitive head injury in professional football athletes is a major risk factor for CTE development.’

Prof Vink’s research, published in Scientific Reports in 2021, found that a single concussive episode does not activate the biochemical pathways that have been linked to development of CTE. At least three concussive events are required to activate these pathways, and even then, if there is sufficient time for total brain recovery between concussive events, these CTE pathways are not activated.

‘With concussion, we saw recovery quite quickly. But with repeated concussion, there was not such quick recovery.

Biochemical things were happening in the brain. These things, as it turns out, are associated with CTE,’ he says.

‘It is allowing time for total recovery from concussion that is the critical factor in reducing the likelihood of CTE.’

In the Scientific Reports paper, Prof Vink and his colleagues show how repeated concussions can cause CTE and a way to block it with a specially developed drug.

‘Tau protein tangles are a feature of CTE, which reportedly leads to memory problems, confusion, personality changes, aggression, depression and suicidal thinking,’ Prof Vink says.

‘Our research shows that by blocking substance P with a specific drug, we can prevent the tau protein tangles from developing in the brain and causing neurological problems.’

The treatment was successfully tested in animal models, giving hope that CTE can be prevented in humans.

He says the treatment has been proven safe in phase 1 trials and is ‘ready to go’. However, trials cannot proceed until a biomarker is found that will enable its efficacy to be tested on living people suspected of having CTE.

‘We’re just waiting for the development of a surrogate marker for CTE a living person. Once you have that, you can look at the effects of the drug on the marker.

‘But there’s a lot of research, especially in the US, looking for that blood biomarker.’

For now, Prof Vink says, concussion must be managed using best-practice guidelines customised to the individual and their symptoms. He says everyone involved in sport – players, coaches, teachers, managers and health practitioners – should be educated to identify and manage the symptoms of concussion, and to understand the risks if it is not managed correctly.

He also advises that players be required to complete a course to ensure they understand the risks and are less likely to insist on competing too soon after a concussion, and agrees that a ‘national concussion registry’ be established to record incidents and their management and to track brain health over time.

He says Connectivity offers courses to educate people about CTE and the risks posed by repeated concussions.

‘I don’t believe any sports administrator wants to see a player injured or at greater risk of brain damage in later life, Prof Vink says. ‘I think they just need more education.

‘With GPs and health practitioners providing informed guidance, and acceptance of the very real danger of repeated concussions, you can reduce the incidence of CTE.’

Information about Connectivity Traumatic Brain Injury Australia courses and other education and research programs is available on its website

Red area shows where the brain is inflamed, which has been shown to occur after concussion