My thanks to Rik Hagen for the heads up on this article on a trial of brain injury biomarkers; specifically neuron-specific enolase (NSE), S100 calcium-binding protein (S100-B) nad total tau protein (T-tau).

Now, I can hear your eyelids closing already, but stick with me on this because it may be an indicator of future directions, both in terms of how we approach concussion in sport and perhaps for the level of expectation that is placed on the abilities of medics providing cover at sporting events.

The article was published in JAMA:Neurology (formerly the Archives of Neurology) and the full text article can be found here:

Blood Biomarkers for Brain Injury in Concussed Professional Ice Hockey Players.
Pashtun Shahim, MD, et al. JAMA Neurol. Published online March 13, 2014. doi:10.1001/jamaneurol.2014.367

What they looked at:

The authors measured the blood and plasma levels of T-tau, S100-B and NSE in a selected group of Swedish ice hockey players, as well as a physical examination and a Standardised Assessment of Concussion, during the pre-season as a baseline. They then measured these same serum and blood levels at 1, 12, 36, 48 and 144 hours in any player who sustained a head injury or suspected concussion, along with a guideline approved concussion assessment as the reference (gold) standard. They then sought to identify the pattern of serum levels of these markers in players with suspected concussion versus those without and determine any correlation with severity and duration of concusion.

What they found:

The authors report that t-tau levels were significantly elevated within an hour of injury and, though they fell off within 12 hours, they remained elevated above baseline up to 6 days after injury. T-tau was not significantly elevated in pre-season players without concussion or head injury. The peak of the 1 hour post-injury T-tau level correlated with symptom severity and duration until safety of return to play was clinically determined.

S100-B also rose within an hour of injury but had returned to baseline by 12 hours regardless of ongoing symptoms. It also had apparent poor specificity, being elevated in players without suspected head injury or concussion.

NSE did nothing at all, regardless of the player's activity or injury.

So what does all of this mean?

Well to be honest, probably not too much at this stage. It suggests a direction for investigation, but it's not practice changing yet, as there are some clear flaws.

The actual sample size is very small. Although the authors state an initial screening of 288 ice hockey players, they really only looked at the 24 pre-season baseline players and the 28 concussed players.

Additionally, it would seem that those who were assessed following concussion (28 players from all 24 teams) were not necessarily the same population that were assessed at pre-season baseline (all 24 members of 2 selected teams).

35 players were recorded as having sustained a possible concussion, but 7 dropped out due to refusal of consent or "an uncertain diagnosis of concussion". This is a 20% drop-out rate, which is big for such a small trial, with potential for biasing the results. Also, we don't know what happened to the 7 who were not included, which may have shifted the results significantly.

Blinding was probably not adequate, as only those players with suspected head injury or concussion during the competitive season had blood samples drawn, so immediately there may be a bias built in to the outcomes.

There are declared conflicts of interest of the study authors, having ties to the patented blood sampling technology, but these are openly declared.

Even recognising these flaws, this was probably a tricky trial to do logistically and the authors tick a lot of boxes for reasonable trial design.

There are some additional concerns. The big one for me is trying to reconcile these two statements from the paper and if anyone can point out whatever it is that I've missed, I'd be grateful:

"We graded the players with concussion into 4 categories: (1) those who were free from symptoms and had safe RTP within 6 days after a concussion (n = 12), (2) those who had safe RTP 7 to 10 days after concussion (n = 9), (3) those who had safe RTP more than 10 days after concussion (n = 7), and (4) those who also had loss of consciousness due to the head impact (n = 3). The level of T-tau 1 hour after concussion was not statistically significantly different between the concussion categories"


"The concentration of T-tau 1 hour after concussion correlated with the number of days it took for concussion symptoms to resolve (ρ = 0.60; 95% CI, 0.23 to 0.90; P = .002)"

To my reading of these two statements, the first says that t-tau level at 1 hour post injury didn't differ enough between the various recovery period groups, yet the second statement says it did. Not sure how to interpret that!

It also appears that there is a mixing of terms when the authors discuss TBI (traumatic brain injury - a physical pathology) and concussion (functional impact), making it a little blurry when it comes to discussing their conclusions. T-Tau may correlate with concussion severity and duration but given its source and physiology, it probably reflects physical brain injury. The difference may only matter if your central concern is outright physical injury versus functional impact. Perhaps it is the actual injury that is related to the more controversial of the concussive syndromes such as chronic traumatic encephalopathy or second impact syndrome, for which we also use concussion as simply a marker. Maybe what we should be doing is keeping a competitor from play as long as there is evidence of physical brain injury (T-tau level), regardless of the presence or absence of concussive features. Unfortunately this trial doesn't tell us how long the T-tau stays elevated beyond the 6 days (144 hours).

And of course, finally, the results don't necessarily extrapolate to our target population in motorsport.

Interesting, but not practice changing yet. Hopefully there will be a bigger follow-up trial.

Feel free to comment below, or on the Motorsport Medicine and Rescue community on Google

References and resources