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expert reaction to imaging study looking at brains of elite adult rugby players

A study published in Brain Communications looks at white matter abnormalities in active elite adult rugby players.

This Roundup accompanied an SMC Briefing.

 

Dr Virginia Newcombe, Academy of Medical Sciences / Health Foundation Clinician Scientist Fellow, University of Cambridge, said:

Over the past few years there has been a growing concern that contact sports which are prone to repeated blows to the head, like rugby, have the potential to lead to long-term problems. These may range from problems with mood and thinking, including in the most severe cases a type of dementia commonly known as Chronic Traumatic Encephalopathy. So far the diagnosis of CTE has largely been made post-mortem (after death). However, being able to detect injury while a player is still playing is key to be able to offer earlier advice and treatment, manage symptoms appropriately (as misdiagnosis is common) and improve the long-term outcomes of these players. Such knowledge is also crucial to inform ways to ensure that sports can be played safely and minimise any long-term risks while still allowing sport to be enjoyed by all.

“This study is important as it uses advanced magnetic resonance imaging, including diffusion tensor imaging (a technique that allows for assessment of microstructural damage), to assess for injury in current players; and does so at two different points over a period of a year. The results suggest that there are changes in structure. What is less clear is what these changes may mean. As the longitudinal MRI controls were healthy volunteers it can’t be ruled out that some of the temporal changes seen may be secondary to positive effects of sport. However, the increased presence of small microhaemorrhages (bleeds) and the types of structural changes seen on the MRI makes it likely that at least some of the findings may indicate damage, and potentially neurodegeneration. The small participant numbers (particularly at the second timepoint when n = 18) means that these findings are preliminary and more work is needed to confirm this.

“What is now required are studies with much larger numbers and repeated assessment of participants over many years. Relating any imaging changes seen to any problems players experience will be crucial to help understand the implications of these changes, as well as understand the link between head injuries sustained while playing sport and any long-term consequences.“

 

Prof Derek Hill, Professor of Medical Imaging Science, UCL, said:

“This paper applies advanced brain imaging and analysis methods to compare the brains of elite rugby players with controls. The methods used are research tools often used in the study of patients with neurodegenerative diseases like Alzheimer’s.

“The results suggest that there are measurable differences in the rugby player’s brains which might be due to brain injury especially in the brain ‘wiring” (white matter).

“However these results should be considered preliminary for three reasons.

“Firstly, it is a relatively small study and in particular some of the sub groups (like those with acute injury) are very small.  Small studies increase the chance that the results are pure chance.

“Secondly,  the brain differences might not be damage. The MRI methods they use are sensitive to changes, but are not specific to the cause of the change. Brain scans can be changed by factors other than irreversible brain damage. For example dehydration and some medicines can result in change in fluid balance in the brain that can be picked up by advanced MRI.

“Thirdly, if rugby has resulted in brain injury visible in MRI, the long term implications of this damage are not clear. A longer study would be needed to determine of the brain changes lead to harmful long term effects.”

 

Prof Huw Williams, Associate Professor of Clinical Neuropsychology, University of Exeter, said:

Does the press release accurately reflect the science?

“Yes

Is this good quality research?  Are the conclusions backed up by solid data?

“Yes. The authors are to be commended for producing a very well-considered and important study. The authors note a number of limitations. I would say that this is an excellent  preliminary investigation. A key limitation is that the numbers of rugby players and controls is very small. Analyses were taken with great care. But the effects noted may not be robust. It indicates that there could be a general effect of playing a contact (or collision) sport with changes in brain structures – in particular the long connective tissues in brain networks. But when there are a few players contributing to the “effect” – then we don’t know how this would map onto the larger populations who play such sports. Importantly, there did not seem to be a link between history of head injury/ concussion with changes in brain systems. With the suggestion it’s a general effect of cumulative impact of “hits” over time being  a causal mechanism. But this is, as noted, speculation at present. Nor was there a link between brain differences and any issues in cognitive functions (any differences between groups seem to be premorbid). And there were no apparent changes in motor skills – which could have been a harbinger of longer term problems. Importantly, there may have been a pre-adult period of exposure that could have been important to consider. Such as, playing contact sports in teenage years might be linked to brain systems being injured.

How does this work fit with the existing evidence?

“This fits well within what we know so far. There have been large scale meta-analyses of studies of this type showing some indication of brain changes from sports concussion. Although the effects are not necessarily very robust – ie many studies do not find difference while some do. As noted above, there is a concern in the general TBI literature over injury in adolescence being potentially more impactful than in adulthood. This may be because the brain is undergoing rapid changes in development and myelination (white matter tracts being formed and links being made across the brain). It could be that differences found here may be due to such injuries in younger life.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“As noted above, the limitations largely relate to the small sample size, as the effects of one or two individuals having an issue could unduly influence the results for the whole group. But the authors very carefully consider such issues.

What are the implications in the real world?  Is there any overspeculation?  

“The study certainly makes it clear that there is a possible effect on brain systems of participating in “collision” sports. And that this can be linked to increased changes over time in response to greater “dosage” of exposure.

How concerned should we be about these findings? What more research is needed to better understand the potential impact elite rugby has on players?

“This is a very good study, albeit, preliminary. There is a need for much larger studies. There should be longitudinal follow up (over a number of years) of such payers using these techniques and using data from pre-season testing of all players (eg on cognitive measures) etc. and making use of other techniques recently developed to identify concussive blows very early after injury (see work of Tony Belli using RNA to show presence of a concussion).

Can this tell us anything about non-professional collision sports?  

“Concussive blows are more common in amateur and school level rugby. Therefore there is a need to also undertake related research work in these groups. In particular to understand the effects of concussive blows in younger brains and what helps with enhancing recovery. And, of course, whether further changes in the game may be needed to reduce risk. Such as more emphasis on touch rugby at younger ages etc.

“More generally, this work is fundamentally important as Mild TBI is incredibly common worldwide  – particularly in younger people – and we need to have a much better appreciation of how such injuries can lead to long term problems. And for whom.”

 

Prof Tim Griffiths, Professor of Cognitive Neurology, Newcastle University, said:

“The work used brain imaging to measure white-matter tract damage to the brain in over 40 professional rugby players, half of whom had a recent mild traumatic brain injury, and sporting and non-sporting controls. 7 had evidence of white matter tract damage and 3 had tiny haemorrhages. Analysis showed lower white-matter volume in the players than would be expected at their age.

“The study supports a plausible mechanism by which rugby can cause brain damage: based on damage to white-matter tracts, which is well established in other forms of brain trauma. The work highlights a need for larger studies. These might also use new chemical measures of brain damage in the brain fluid and blood. Assessment using blood tests, in particular, would allow the study of much larger populations than the one that underwent sophisticated imaging here.

“The comparison between players with and without recent mild head injury was inconclusive, and requires a larger study. This is important to clarify further because an effect driven by obvious mild injury would indicate further measures to prevent this. An effect that was related to participation in the sport irrespective of defined mild head injuries would be an equal (or possibly greater) concern.”

 

 

White matter abnormalities in active elite adult rugby players’ by Karl A. Zimmerman et al. was published in Brain Communications at 00:05 UK time on Thursday 22 July.

 

 

Declared interests

Dr Virginia Newcombe: “I hold a grant with ROCHE on a health economic assessment of the use of biomarkers after traumatic brain injury.”

Prof Derek Hill: “No conflicts of interest.”

Prof Tim Griffiths: “No COI.”

None others received

 

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