Can Blood Biomarkers Predict Recovery From Concussion?
Shahim P, Tegner Y, Wilson DH, et al
JAMA Neurol. 2014;71:684-692
Counseling athletes about when it is safe to return to play after a sports-related concussion is difficult owing to the lack of objective biomarkers for brain damage. The goals of this multicenter, prospective cohort study were to examine whether biochemical markers of central nervous system injury increase in sports-related concussion and to determine whether plasma levels of these biomarkers could help predict safe return to sports participation.
The study sample consisted of 288 professional ice hockey players from all 12 teams of the Swedish Hockey League playing during the 2012-2013 season. Before the season began, all participants underwent clinical baseline testing including concussion assessment measures, and 47 players from 2 teams also had blood tested for total tau, S-100 calcium-binding protein B, and neuron-specific enolase concentrations in plasma and serum. From September 13, 2012, to January 31, 2013, of a total of 35 players who had a concussion, 28 had repeated blood tests at 1, 12, 36, and 144 hours after concussion and upon returning to play.
Compared with preseason values, levels of the axonal injury biomarker total tau increased after concussion (preseason median, 10.0 pg/mL; range, 2.0-102 pg/mL vs postconcussion median, 4.5 pg/mL; range, 0.06-22.7 pg/mL; P < .001). There was a similar increase in S-100 calcium-binding protein B, a biomarker of astroglial injury (preseason median, 0.075 μg/L; range, 0.037-0.24 μg/L vs postconcussion median, 0.045 μg/L; range, 0.005-0.45 μg/L; P < .001).
Levels of both of these biomarkers peaked immediately after concussion and declined during rehabilitation. In contrast, levels of neuron-specific enolase did not measurably change from preseason (median, 6.5 μg/L; range, 3.45-18.0 μg/L) to postconcussion (median, 6.1 μg/L; range, 3.6-12.8 μg/L; P = .10).
Levels of total tau (the biomarker with the greatest diagnostic accuracy) declined during the first 12 hours, with a second peak at 12-36 hours. Total tau levels 1 hour after concussion predicted the number of days to resolution of concussion symptoms and safe return to play. Moreover, high T-tau levels at 144 hours after concussion were associated with persistence of postconcussion syndrome.
Limitations of this study include a relatively small sample size, precluding subgroup analysis on the basis of concussion form and severity, a relatively short follow-up, and lack of access to preseason samples for all ice hockey players, which would have facilitated evaluation of longitudinal change in biomarker levels after concussion.
Nonetheless, these findings highlight the association of sports-related concussion with acute axonal and astroglial injury, which can be monitored using blood biomarkers. These biomarkers may be developed into clinical tools assisting sport physicians in counseling athletes about return-to-play decisions. In fact, this study used an innovative digital immunoassay technology, which is 3000-fold more sensitive than standard immunoassays.
Blood Biomarkers for Brain Injury in Concussed Professional Ice Hockey Players
Shahim P, Tegner Y, Wilson DH, et al
JAMA Neurol. 2014;71:684-692
Study Summary
Counseling athletes about when it is safe to return to play after a sports-related concussion is difficult owing to the lack of objective biomarkers for brain damage. The goals of this multicenter, prospective cohort study were to examine whether biochemical markers of central nervous system injury increase in sports-related concussion and to determine whether plasma levels of these biomarkers could help predict safe return to sports participation.
The study sample consisted of 288 professional ice hockey players from all 12 teams of the Swedish Hockey League playing during the 2012-2013 season. Before the season began, all participants underwent clinical baseline testing including concussion assessment measures, and 47 players from 2 teams also had blood tested for total tau, S-100 calcium-binding protein B, and neuron-specific enolase concentrations in plasma and serum. From September 13, 2012, to January 31, 2013, of a total of 35 players who had a concussion, 28 had repeated blood tests at 1, 12, 36, and 144 hours after concussion and upon returning to play.
Compared with preseason values, levels of the axonal injury biomarker total tau increased after concussion (preseason median, 10.0 pg/mL; range, 2.0-102 pg/mL vs postconcussion median, 4.5 pg/mL; range, 0.06-22.7 pg/mL; P < .001). There was a similar increase in S-100 calcium-binding protein B, a biomarker of astroglial injury (preseason median, 0.075 μg/L; range, 0.037-0.24 μg/L vs postconcussion median, 0.045 μg/L; range, 0.005-0.45 μg/L; P < .001).
Levels of both of these biomarkers peaked immediately after concussion and declined during rehabilitation. In contrast, levels of neuron-specific enolase did not measurably change from preseason (median, 6.5 μg/L; range, 3.45-18.0 μg/L) to postconcussion (median, 6.1 μg/L; range, 3.6-12.8 μg/L; P = .10).
Levels of total tau (the biomarker with the greatest diagnostic accuracy) declined during the first 12 hours, with a second peak at 12-36 hours. Total tau levels 1 hour after concussion predicted the number of days to resolution of concussion symptoms and safe return to play. Moreover, high T-tau levels at 144 hours after concussion were associated with persistence of postconcussion syndrome.
Viewpoint
Limitations of this study include a relatively small sample size, precluding subgroup analysis on the basis of concussion form and severity, a relatively short follow-up, and lack of access to preseason samples for all ice hockey players, which would have facilitated evaluation of longitudinal change in biomarker levels after concussion.
Nonetheless, these findings highlight the association of sports-related concussion with acute axonal and astroglial injury, which can be monitored using blood biomarkers. These biomarkers may be developed into clinical tools assisting sport physicians in counseling athletes about return-to-play decisions. In fact, this study used an innovative digital immunoassay technology, which is 3000-fold more sensitive than standard immunoassays.