Blood Biomarker for Concussion Identified

March 26, 2014

Blood levels of total-tau — a protein signalling axonal damage in the brain — could be used as a biomarker to gauge severity of concussions in athletes and to assess when it is safe to return to play, a new study shows.

The study was conducted by a team led by Pashtun Shahim, MD, Sahlgrenska University Hospital, Molndal, Sweden.

"T-tau is a promising biomarker for the diagnosis and prognosis of concussion in athletes," Dr. Shahim commented to Medscape Medical News. "I would say if you suspect concussion, you could measure blood levels of T-tau, and then repeat the test every few days to gauge whether it is safe to go back to play."

He added: "Our data are very promising but they need to be replicated in a larger sample size before we can recommend this approach for routine use. But in future, there could be a point-of-care test that could be used at the side of the pitch."

The study showed that the plasma levels of T-tau increased in ice hockey players with sports-related concussion. The highest concentrations of T-tau were measured immediately after the injury, and the levels declined during the first 12 hours, followed by a second peak between 12 and 36 hours. Importantly, T-tau concentrations at 1 hour after concussion predicted the number of days it took for the concussion symptoms to resolve and the players to return to play safely.

Their findings were published online March 13 in JAMA Neurology.

In an accompanying editorial, Joshua Gatson, PhD, University of Texas Southwestern Medical Center, Dallas, and Ramon Diaz-Arrastia, MD, Uniformed Services University of the Health Sciences, Bethesda, Maryland, point out that T-tau at 1 hour had high diagnostic accuracy for discriminating players who had a concussion from those who had played in a friendly game and were not concussed, and it had even better prognostic accuracy for identifying players who had concussion symptoms lasting longer than 6 days.

T-tau Increased Up to 10-Fold in Concussion

The researchers measured serum levels of 3 biomarkers, all of which have been previously associated with brain injury: neuron-specific enolase (NSE), S-100 calcium-binding protein B (S-100B), and T-tau.

The study included 288 professional ice hockey players. Of these, 47 underwent blood tests for the 3 biomarkers at the start of the season before playing a game. These results would act as the control values for the study. Half of these players were tested again after a friendly game in which there were no concussions to assess the effect of exercise. Results showed that levels of 2 of the biomarkers — S100B and NSE — increased after the friendly match, but there was no change in total tau.

In the 28 players who sustained concussions during the season, T-tau was measured at 1 hour, 12 hours, 36 hours, and 6 days and when the athlete returned to play. It was raised in cases of concussion, with levels about 5 to 10 times higher than at preseason in age-matched players who didn't have concussion. In addition, tau levels immediately after concussion correlated with the number of days of symptoms, and tau returned to preseason levels when concussion symptoms resolved.

Dr. Shahim noted that T-tau is usually found only in the cerebral spinal fluid (CSF), but may get into the blood after concussion if the blood-brain barrier is damaged. It is a protein secreted by the axons of unmyelinated nerve cells when they are injured, and raised levels are a marker of cortical injury. It is increased in the CSF in Alzheimer's disease, but measuring blood levels after head injury is a new concept.

This is an ongoing study. These results are for the first half of the season. The researchers are including more athletes with concussion as the season progresses and continuing to add data.

In their editorial, Dr. Gatson and Dr. Diaz-Arrastia say that this study casts serious doubts on the usefulness of NSE and S-100B as biomarkers for mild traumatic brain injury. The NSE concentration was not elevated after a concussion compared with the preseason baseline. The S-100B concentration was elevated immediately after a concussion but normalized by 12 hours after injury.

More importantly, they point out, levels of both NSE and S-100B were elevated after a friendly match that did not result in concussion (presumably a consequence of exertion and bruising of muscles and peripheral tissues), indicating a lack of specificity for brain injury.

The editorialists add that longer-term follow-up of players is needed in future studies to assess how long it takes for plasma total tau levels to normalize, and whether persistently elevated plasma tau identifies athletes who have sustained multiple concussions and are at risk of developing chronic traumatic encephalopathy.

They also note that concussion is a heterogeneous disorder affecting all cell types, and it is likely that biomarker panels measuring tau as well as other proteins that reflect damage to other types of brain cells, will ultimately be required.

JAMA Neurol. Published online March 13, 2014. Abstract Editorial


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