An investigation of neuroinjury biomarkers after sport-related concussion: from the subacute phase to clinical recovery

Figures & data

Table 1. Athlete demographics and characteristics.

Characteristic	Concussed athletes (n = 19)	Matched healthy controls (n = 16)
Age (years)	19 (18–20)	19 (18–21)
Sex (n, % – male)	8 (42.1)	7 (43.7)
Sport (n, %)
Basketball	2 (10.5)	2 (12.5)
Football	3 (15.8)	2 (12.5)
Ice hockey	3 (15.8)	3 (18.8)
Lacrosse	3 (15.8)	1 (6.3)
Rugby	6 (31.6)	5 (31)
Soccer		1 (6.3)
Volleyball	2 (10.5)	2 (12.5)
Wrestling	–	–
Number of previous concussions n (%)
0	6 (31.6)	8 (50)
1	7 (36.8)	1 (6.3)
2	4 (21.1)	5 (31.2)
3 or more	2 (10.5)	2 (12.5)
Collision sport participation – n (%)	11 (57.9)	9 (56.3)
Medical History – n (%)
Migraines	2 (10.5)	1 (6.3)
Learning disability	1 (5.3)	1 (6.3)
Psychiatric disorders	0 (0.0)	2 (12.5)
Family history of psychiatric illness	4 (21.0)	7 (43.8)
SCAT3 symptoms at time of injury
Total symptoms	7.5 (5–16)	–
Symptom severity	12 (5.5–16)	–
SCAT3 symptoms at time of sampling
Total symptoms	5 (4–11)	3 (0.7–7)
Symptom severity	8 (4–15)	5 (0.7–9.2)
Days to sample from injury	4 (3–4.7)	–
Days to medical clearance	33 (12–95)	–

Unless otherwise stated, results are reported as the median and interquartile range (IQR).

Table 2. Biomarker values across groups.

	3-7 days post-injury				Medical clearance
Markers (pg/mL) ^a, b	Matched Healthy^c (n = 16)	Concussed (n = 19)	P	FDR	Matched Healthy (n = 16)	Concussed (n = 17)	P	FDR
s100B	599.4 (534.5 – 650.7)	570.3 (466.5 – 746.2)	1.00	No	630.3 (559.2 – 649.4)	647.3 (594.0 – 1082.0)	0.17	No
GFAP	68.1 (58.3 – 82.7)	64.9 (59.9 – 84.7)	--	--	--	--	--	--
NSE (ng/mL)	1.6 (1.4 – 1.9)	1.5 (1.3 – 1.9)	0.58	No	1.4 (1.0 – 2.0)	1.5 (1.2 – 2.4)	0.23	No
Ng (ng/mL)	16.4 (12.4 – 19.6)	11.4 (6.1 – 21.0)	0.16	No	16.4 (7.2 – 19.6)	9.2 (5.4 – 28.8)	0.79	No
CKBB	--	--	--	--	--	--	--	--
VILIP-1	--	--	--	--	--	--	--	--
Tau	16.3 (11.9 – 17.6)	13.8 (11.7 – 20.2)	0.95	No	14.4 (13.0 – 17.9)	20.4 (16.8 – 23.4)	0.01*	No
vWF (μg/ml)	40.0 (30.9 – 75.3)	41.7 (23.5 – 52.0)	0.34	No	30.4 (20.4 – 34.6)	35.7 (19.5 – 55.6)	0.35	No
BDNF (ng/ml)	1.0 (0.8 – 2.1)	1.3 (0.7 – 2.7)	0.73	No	1.3 (0.8 – 4.1)	1.7 (0.8 – 4.1)	0.84	No
PRDX-6 (ng/mL)	19.5 (16.5 – 24.2)	29.3 (21.9 – 47.6)	0.00*	Yes	20.7 (15.6 – 25.0)	24.6 (20.4 – 39.0)	0.03*	No
MCP-1	78.0 (57.2 – 89.7)	80.7 (68.2 – 116.2)	0.41	No	92.7 (78.2 – 102.3)	93.1 (75.0 – 115.7)	0.87	No

p-value, (P); false discovery rate (FDR); s100 calcium binding protein beta (s100B); glial fibrillary acidic protein (GFAP); neuron specific enolase (NSE); neurogranin (Ng); creatine kinase-BB isoenzyme (CKBB); visinin-like protein (VILIP-1); von Willebran factor (vWF); brain derived neurotrophic factor (BDNF); peroxiredoxin (PRDX) -6; monocyte chemoattractant protein (MCP) -1.

All biomarkers are expressed as the median and IQR.

* = p <0.05; FDR = 0.05

^a = Biomarkers were included if replicates had less than a 20% CV, were within the assay-specific detectable range, and had an inter-plate variance of less than 20% as measured by internal controls.

^b = pg/mL unless otherwise specified.

^c = matched for sex, sport participation, concussion history, and time of concussion.

“--” = below assay quantitation in >50% of samples analyzed.

Figure 1. Biomarker variance between concussed and healthy athletes. s100 calcium binding protein beta (s100B); glial fibrillary acidic protein (GFAP); neuron specific enolase (NSE); neurogranin (NRGN); creatine kinase-BB isoenzyme (CKBB); visinin-like protein (VILIP-1); von Willebran factor (vWF); brain derived neurotrophic factor (BDNF); peroxiredoxin (PRDX) − 6; monocyte chemoattractant protein (MCP) −1. Plots show the contributions of individual biomarkers towards class separation between concussed and healthy athletes at (a) the subacute period after injury, and (b) medical clearance, by PLS-DA analysis. Bars represent biomarker loadings and the standard error derived from bootstrapped resampling (1000 samples). red bars = FDR < 0.05.