Table 1 Biomarker specific tables for selected biomarkers: S100B, tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), and ubiquitin C-terminal hydrolase—L1 (UCH-L1)
Reference | Study type | Design | Setting | Sport | Athlete group | Control group | Exposure | Source | Sample times | Findings | Bias | QA |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
S100B | ||||||||||||
Arslan et al. [54] | Acute | Cohort study | Field | Wrestling | 15 male Greco-Roman wrestlers, median age (range) 19.0 (19–30); 16 male Free style wrestlers, aged 20.0 (19–26) | N/A | Wrestling competition (3 × 2 min) | Serum | Before and 20 min post | Significant findings | Serious | C (1) |
Asken et al. [55] | Chronic | Observational cohort study | Other | Soccer, diving, wrestling, ice hockey, Am. football | 415 (256 M, 159 F) collegiate athletes, aged 19.0 ± 1.2 | N/A | Cumulative exposure to collision sports in years (and modified CHII) | Serum | Off-season | No significant findings | Moderate | B (4) |
Bouvier et al. [56] | Acute | Prospective cohort study | Field | Rugby | 39 professional rugby players, aged 28.6 ± 3.98 (27 non-concussed, 5 concussed) | N/A | Rugby match (collisions) | Serum | 3 basal levels during the season (> 48 h from competition) and within 2 and 36 h after a match | Significant findings | Moderate | B (4) |
DiBattista et al. [57] | Chronic | Cross-sectional study | Other | Ice hockey, football, rugby, lacrosse | 41 (39 M, 2 F) collision sport athletes; aged (including all participants): M (n = 60) 19.5 ± 2.0, F (n = 27) 19.5 ± 1.8 | 46 (21 M, 25 F) non collision sport athletes (inadvertent contact: soccer, basketball) | Collision sport participation | Plasma | Before the start of varsity season | No significant findings | Moderate | B (4) |
Dorminy et al. [58] | Acute | Randomized controlled trial | Laboratory | Soccer | 16 (10 M, 6 F), aged 20.4 ± 0.2 | N/A | 5 linear standing headers | Serum | Before and 1–1.5 h post | No significant findings | Serious | B (4) |
Graham et al. [59] | Acute | Retrospective cohort study | Field | Boxing | 8 male amateur boxers, aged 17.6 ± 5.3 (PTH – punches to the head and body) | 8 male amateur boxers, aged 19.1 ± 3.2 (PTB – punches to the body) | 5 × 2-min boxing rounds | Serum | 1 h before and after 5 min of cessation | Significant findings | Moderate | C (2) |
Graham et al. [60] | Acute | Cohort study | Field | Karate | 12 males, aged 30.4 ± 6.7 (KTH – kicks to the head and body) | 12 males, aged 28.2 ± 6.5 (KTB – kicks to the body) | 4 × 3-min karate round | Serum | Before and immediately after | Significant findings | Moderate | C (1) |
Hoffman et al. [61] | Acute | Cohort study | Field | Am. football | 15 Israel national football team players, aged 26.2 ± 5.3 | N/A | Am. football match | Serum | 1 week before, immediately (< 30 min) and 24 h post | No significant findings | Moderate | C (2) |
Huibregtse et al. [62] | Acute | Randomized controlled trial | Laboratory | Soccer | 37 (19 M, 18 F), median age (IQR) 21 (19–22) | 31 (14 M, 17 F), median age (IQR) 21 (20–22) | 10 linear headers; controls: 10 kicks | Plasma | Before and 0, 2 and 24 h post | No significant findings | Low | A (5) |
Kawata [63] | Semi-acute | Prospective longitudinal cohort study | Field | Am. football | 22 male Division I collegiate footballers, aged 20.6 ± 1.5 | N/A | Am. football season | Plasma | Pre- and post-season, and before and after 5 practices (1 non-contact, 4 full contact) | No significant findings | Moderate | A (6) |
Kawata et al. [64] | Acute | Prospective longitudinal cohort study | Field | Am. football | 22 male Division I collegiate footballers, aged 20.6 ± 1.5 | N/A | Pre-season Am. football practices | Plasma | Baseline, before and after 5 pre-season practices (1 non-contact, 4 full contact) | Significant findings (both in contact and no contact). Impacts correlated with the increase | Moderate | A (5) |
Marchi et al. [65] | Acute and semi-acute | Cohort study | Field | Am. football | Acute: 27 collegiate players, aged ~ 21 Semi-acute: 10 collegiate players | N/A | Am. football matches and season | Serum | Acute: baseline (prior to any football related activity), 24 h before, 1 and 24 h post Semi-acute: pre- and post-season | Acute: significant findings in players that had frequent head impacts. Increase correlated with head impact index Semi-acute: anti-S100b Ab increased in 5 out of 10 players | Serious | B (4) |
Mussack et al. [40] | Acute | Non-randomized experimental study | Laboratory | Soccer | 61 male amateur players, median age (IQR) 15.3 (14.8—16.4) | 58 male amateur players, median age (IQR) 15.9 (15.0—16.8); 81 mTBI controls: 20 CCT + 41.8 (32.3—61.1), 61 CCT- 37.1 (27.6—53.5) | Controlled soccer heading aimed at the forehead performed for a median: 55 min; control: 61 min of exercise | Serum | Baseline and 1 and 6 h post | No significant findings. Significant findings in the mTBI group | Moderate | B (3) |
Neselius et al. [46] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) Olympic boxers, mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing bout | CSF | 1–6 days post and after ≥ 14 days rest | Acute: significant findings Semi-acute: no significant findings | Moderate | C (2) |
Neselius et al. [66] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) amateur boxers (competing at elite level), mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing | Serum | 1–6 days post and after ≥ 14 days rest | No significant findings | Serious | C (2) |
O'Connell et al. [67] | Acute and semi-acute | Prospective longitudinal cohort study | Field | Rugby | 38 professional male rugby players, aged 26.6 ± 4.4 | 15 rowers, median age (IQR) 22.0 (20.0—24.0) | Rugby training and games | Serum | Pre- and post-season, ≤ 2 h post-games Controls: pre- and post-80 min of training | Acute: significant findings Semi-acute: no significant findings | Moderate | C (1) |
O'Keeffe et al. [68] | Acute and semi-acute | Cohort study | Field | Rugby | 8 rugby university team players, mean age (range) 22.1 (18–23); 11 male rugby school team players, mean age 17.4 | 27 non-contact sport athletes, median age (range) 28 (18–36); 26 healthy non-athlete controls, median age (range) 30 (18–40) | Rugby match (university team) and season (school and university team) | Plasma | University team: pre-season, ≤ 2 h post-match, 2 months post-season School team: pre- and post-season | Acute: significant findings Semi-acute: significant findings (decrease) | Moderate | B (3) |
Otto et al. [69] | Acute | Cohort study | Field, laboratory | Boxing, soccer | 25 male amateur boxers: competitive fights n = 10, sparring fights n = 15 (13 with head protector), aged 17–40; heading: 12 sportsmen, aged 20–52 | 35 male runners (sprinters, 10 and 25 km), aged 20–52. 12 male cyclists, aged 23–52 | (1) 5 × 2-min competitive boxing rounds (2) 3 or 5 × 2-min sparring fights (3) 20 standing soccer headers (ball dropped from 7.5 m) | Serum | Before and ≤ 15 min post | Mixed findings (boxing: significant; soccer: not significant) | Serious | C (1) |
Puvenna et al. [70] | Acute | Cohort study | Field | Am. football | 15 athletes | 406 positive controls with mTBI and 465 negative controls | 2 Am. football games | Serum | Baseline (day before) and post (< 1 h) (positive controls: < 6 h of injury) | Significant findings | Serious | B (3) |
Rogatzki et al. [71] | Acute | Cohort study | Field | Am. football | 17 male Division III collegiate footballers, aged 19.5 ± 0.9 | N/A | Am. football game | Serum | 2 days before and 1 h post | Significant findings | Moderate | C (2) |
Rogatzki et al. [72] | Acute and semi-acute | Cohort study | Field | Am. football | 16 male Division III collegiate footballers, age range 18 to 22 | 32 controls, age range 18–22 [control groups: resistance exercise n = 18 (10 M, 8 F); treadmill running n = 8 (5 M, 3 F); treadmill walking n = 6 (3 M, 3 F)] | Am. football game | Serum | Baseline (prior to training camp); before (day before, ≤ 30 min post-practice) and ≤ 30 min post-4 games Controls: immediately before and ≤ 30 min post | Acute: significant findings for experimental and 2 control groups Semi-acute: no significant findings Number of hits and plays correlated with S100B | Moderate | B (3) |
Soriano et al. [52] | Semi-acute | Cohort study | Field | Am. football | 33 male collegiate players, aged 19.3 ± 1.4 | N/A | Am. football season (games and training) | Serum | Mid-season, post-season and off-season (after a rest period) | No significant findings | Serious | B (4) |
Stålnacke and Sojka [73] | Acute | Randomized controlled trial | Laboratory | Soccer | 10 male amateur players, aged 22 ± 8 (age for entire sample n = 19) | 9 male amateur players | 5 headers in 15–20 min (ball dropped from 18 m, velocity 63.6 km/h) | Serum | Before and 0.5, 2 and 4 h post | No significant findings | Moderate | B (3) |
Stålnacke et al. [74] | Acute | Cohort study | Field | Ice hockey | 26 male elite ice hockey players, aged 28 ± 4 | 18 elite basketball players, aged 25 ± 4 | Ice hockey game (body checkings, falls, collisions, boardings); basketball game (jumps, collisions, falls) | Serum | 1–2 h before and ≤ 1 h post | Significant findings in all conditions | Serious | C (2) |
Stålnacke et al. [75] | Acute | Cohort study | Field | Soccer | 28 male elite players, aged 26 ± 5 | N/A | Headers, jumps, falls and collision during a competitive soccer game | Serum | 1–5 h before and immediately post | Significant findings | Moderate | B (3) |
Stålnacke et al. [38] | Acute | Cohort study | Field | Soccer | 44 female elite players, aged 23 ± 3 | N/A | Headers, jumps, falls and collisions during a competitive soccer game | Serum | Before and immediately post | Significant findings (changes correlated with headers and jumps, collisions, and falls) | Moderate | B (3) |
Straume-Naesheim et al. [76] | Acute | Prospective cohort study | Field | Soccer | Professional soccer players: heading exercise n = 46, mean age 26.1; head impacts during a match n = 69, 28.1 | Professional soccer players: high intensity exercise n = 48, 26.1; match control n = 56, 26.2 | Heading exercise (90 min), head impacts (some concussive) during match play Controls: 90 min exercise, match w/o head trauma | Serum | Baseline, 1 and 12 h post | Significant findings in all conditions | Serious | B (3) |
Zetterberg et al. [48] | Acute | Non-randomized experimental study | Laboratory | Soccer | 23 male amateur soccer players, median age (range): 10 headers n = 10, 26 (19–32); 20 headers n = 13, 23 (20–28) | 9 male non athletes, median age (range) 24 (22–27) | 10 or 20 standing headers from a corner kick (kicked from 30 m) | CSF and serum | 7–10 days post | No significant findings | Serious | B (3) |
Zetterberg et al. [77] | Chronic | Observational case–control study | Other | Boxing | 44 male amateur boxers, median age (range) 19 (17–28) | 23 healthy males w/o contact sport history, median age (range) 28 (19–50) | Boxing participation (boxing debut, boxing duration in yr, number of bouts) | Serum | After a 2-month period of nonparticipation in boxing | No significant findings | Moderate | C (1) |
Zonner et al. [41] | Acute and semi-acute | Longitudinal prospective cohort study | Field | Am. football | 15 high school footballers, aged 16.4 ± 0.5 | N/A | Am. football games and season | Serum | Semi-acute: pre- and post-season; acute: 4–5 h before and ≤ 1 h after 5 games | Acute: significant findings Semi-acute: no significant findings | Low | A (5) |
Tau | ||||||||||||
Alosco et al. [78] | Chronic | Cross-sectional study | Other | Am. football | 96 male symptomatic former NFL players, aged 55.2 ± 7.9 | 25 asymptomatic controls w/o contact sport history, aged 57.0 ± 6.6 | Am. football (NFL) career | Plasma | N/A | Mixed | Moderate | C (2) |
Alosco et al. [43] | Chronic | Cross-sectional study | Other | Am. football | 68 male symptomatic former NFL players, aged 54.4 ± 8.0 | 21 asymptomatic controls w/o contact sport history, aged 57.6 ± 7.1 | Am. football (NFL) participation (CHII) | CSF | N/A | Tau: mixed P-tau: no significant findings | Moderate | C (2) |
Asken et al. [55] | Chronic | Observational cohort study | Other | Soccer, diving, wrestling, ice hockey, Am. football | 415 (256 M, 159 F) collegiate athletes, aged 19.0 ± 1.2 | N/A | Cumulative exposure to collision sports in yr (and modified CHII) | Serum | Off-season | No significant findings | Moderate | B (4) |
Bernick et al. [79] | Acute, semi-acute, and chronic | Longitudinal cohort study | Other | Boxing, MMA | 52 (50 M, 2 F) retired professional boxers, aged 48.0 ± 10.3 117 (110 M, 7 F) active professional boxers, aged 30.4 ± 6.9 169 (152 M, 17 F) active professional MMA fighters, aged 29.6 ± 4.8 | 79 (69 M, 10 F) controls w/o contact sport history, aged 30.8 ± 10.0 | Fights and sparring (martial arts or boxing) | Plasma | Baseline and ≥ 2 measurements over 1.6 years (average) (range 1–5 years); active fighters: ≥ 45 days from a sanctioned fight | Acute and chronic: no significant findings Semi-acute: significant findings | Serious | C (1) |
Di Battista et al. [80] | Chronic | Cross-sectional study | Other | Ice hockey, football, rugby, lacrosse | 41 (39 M, 2 F) collision sport athletes; aged (including all participants): M (n = 60) 19.5 ± 2.0, F (n = 27) 19.5 ± 1.8 | 46 (21 M, 25 F) non collision sport athletes (inadvertent contact: soccer, basketball) | Collision sport participation | Plasma | Before the start of varsity season | Significant findings | Moderate | B (4) |
Hoffman et al. [61] | Acute | Cohort study | Field | Am. Football | 15 Israel national football team players, aged 26.2 ± 5.3 (range 18–35) | N/A | Am. football match | Serum | 1 week before, immediately (< 30 min) and 24 h post | No significant findings | Moderate | C (2) |
Joseph et al. [42] | Acute and semi-acute | Prospective observational cohort study | Field | Am. football | 16 male high-school varsity footballers, aged 16.9 ± 0.2 (pre- and post-season sample n = 12) | N/A | Am. football games, practices and season | Serum | Semi-acute: pre- and post-season; acute: 1–2 h post | Significant findings | Moderate | B (3) |
Kawata et al. [81] | Acute | Prospective longitudinal cohort study | Field | Am. football | 23 male Division I collegiate footballers, aged 20.5 ± 1.3 | N/A | Pre-season Am. football practices | Plasma | Pre-season baseline, immediately before and ≤ 1 h after 4 practices (1 non-contact) | Significant findings | Moderate | A (5) |
Kawata et al. [82] | Semi-acute | Cohort study | Field | Ice hockey | 8 male professional players (including 2 concussed athletes), aged 26.6 ± 1.6 | N/A | Ice hockey season | Plasma | Pre- and post-season | No significant findings | Critical | C (1) |
Major et al. [83] | Chronic | Cross-sectional study | Other | Au. football | 81 (50 M, 31 F) amateur footballers (no-mTBI history n = 42; mTBI history n = 39), aged ~ 24 | 42 (23 M, 19 F) age-matched non-contact sport athletes | Au. football participation | Serum | Pre-season | Tau: no significant findings P-tau: no significant findings | Moderate | A (5) |
Muraoka et al. [44] | Chronic | Cross-sectional study | Other | Am. football | 15 male symptomatic former NFL players, aged 56.3 ± 7.3 | 16 asymptomatic males w/o contact sport history, aged 57.1 ± 7.0 | Am. football career | CSF | N/A | Tau: no significant findings P-tau: no significant findings | Moderate | B (3) |
Muraoka et al. [84] | Chronic | Cross-sectional study | Other | Am. football | 27 male symptomatic former NFL players, aged 56.6 ± 7.6 | 25 asymptomatic males w/o contact sport history, aged 57.0 ± 6.6 | Am. football career | Plasma | N/A | Tau: significant findings P-tau: significant findings | Moderate | B (3) |
Neselius et al. [46] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) Olympic boxers, mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing bout | CSF | 1–6 days post and after ≥ 14 days rest | Tau: Acute: significant findings Semi-acute: no significant findings P-tau: no significant findings | Moderate | C (2) |
Neselius et al. [66] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) amateur boxers (competing at elite level), mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing bout | Plasma | 1–6 days post and after ≥ 14 days rest | Acute: significant findings Semi-acute: no significant findings | Serious | C (2) |
Nowak et al. [85] | Acute | Case–control study | Laboratory | Soccer | 17 (6 M, 11 F) soccer players with ADHD, aged 20.2 ± 0.2; 17 (10 M, 6 F) w/o ADHD, aged 21.1 ± 0.1 | 17 (7 M, 10 F) soccer players with ADHD, aged 20.5 ± 0.1 | 10 linear headers; controls: 10 kicks | Plasma | Baseline, 2 and 24 h post | No significant findings | Low | A (5) |
Oliver et al. [86] | Semi-acute | Longitudinal observational cohort study | Field | Am. football | 19 (11 starters, 8 non-starters) Division I footballers, aged 20 ± 1 | 19 NCAA swimmers, aged 20 ± 1 (baseline sample only) | Am. football season | Plasma | T1: after 9 weeks of non-contact; T2: after training camp; T3: following pre-season camp (highest concentration of impacts); T4 through T8 mid-season, 36–48 h post-games | No significant findings | Moderate | B (3) |
Oliver et al. [87] | Semi-acute | Prospective longitudinal cross-sectional study | Field | Am. football | 35 (20 starters, 15 non-starters) Division III footballers, aged 21 ± 1 | N/A | Am. football season | Plasma | T1: after 14-weeks of non-contact; T2: end of camp (period with most impacts); T3: 72 h post-full-contact practice, T4 and T5: ~ 36 h following a game; T6 and T7: post-season | Significant findings (decrease) | Moderate | B (3) |
Sandmo et al. [88] | Acute and chronic | Prospective cohort study | Field | Soccer | Male premier league players: heading exercise group n = 47, head impacts during a match n = 35 | Male premier league players: high intensity exercise n = 47 | (1) heading exercise (90 min), (2) head impacts (some concussive) during match play | Serum | Baseline, 1 and 12 h post | No significant findings | Serious | B (2) |
Soriano et al. [52] | Semi-acute | Cohort study | Field | Am. football | 33 collegiate athletes, aged 19.3 ± 1.4 | N/A | Am. football season (games and training) | Serum | Mid-season, post-season and off-season (after a rest period) | Not detectable | Serious | B (4) |
Stern et al. [89] | Chronic | Case–control study | Other | Am. football | 78 male symptomatic former NFL players, aged 54.5 ± 8.0 | 16 male asymptomatic non-contact sport athletes, 56.9 ± 7.2 | Am. football career | Plasma | N/A | Significant findings | Moderate | C (2) |
Symons et al. [53] | Chronic | Cross-sectional study | Other | Au. football | 95 (69 M, aged 23.3 ± 0.4; 26 F, aged 23.2 ± 0.9) amateur players | 49 (28 M, aged 22.5 ± 0.4; 21 F, aged 23.1 ± 0.8) amateur basketball, tennis, cricket, track and field athletes | Au. football participation | Serum | N/A (pre-season) | Tau: significant findings P-tau: significant findings | Moderate | B (4) |
Wallace et al. [90] | Acute | Prospective controlled cohort study | Laboratory | Soccer | 11 male collegiate players, aged 23.7 ± 3.9 | N/A | 40 headers; sham condition: contact with ball using hands, chest or thigh | Plasma | Immediately before and 1 h and 3 weeks post | No significant findings | Critical | C (2) |
Zetterberg et al. [47] | Acute and chronic | Longitudinal cohort study | Field | Boxing | 14 (11 M, 3 F) amateur boxers, aged 22 ± 3.8 | 10 male nonathletic controls, aged 30 ± 6.3 | Boxing bout | CSF | 7–10 days post and after 3 months of rest | Tau: Acute: significant findings Chronic: no significant findings P-tau: no significant findings | Moderate | C (0) |
Zetterberg et al. [48] | Acute | Non-randomized experimental study | Laboratory | Soccer | 23 male amateur soccer players, median age (range): 10 headers n = 10, 26 (19–32); 20 headers n = 13, 23 (20–28) | 9 male non athletes, median age (range) 24 (22–27) | 10 or 20 standing headers from a corner kick (kicked from 30 m) | CSF | 7–10 days post | No significant findings | Serious | B (3) |
NfL | ||||||||||||
Antonio et al. [39] | Chronic | Cross-sectional study | Other | Soccer | 8 female Division II soccer players, aged 22 ± 6 | 17 female non-contact sport athletes, aged 25 ± 8 | Soccer participation | Plasma | N/A | Significant findings | Serious | C (2) |
Austin et al. [91] | Acute | Randomized controlled trial | Laboratory | Soccer | 36 males (12 in each heading group), aged 23.7 ± 4.8 | 8 males, aged 23.7 ± 4.8 | 10, 20 and 40 linear headers | Serum | Baseline, 6 h, 24 h, 7 days | No significant findings | Low | A (5) |
Bernick et al. [79] | Acute, semi-acute, and chronic | Longitudinal cohort study | Other | Boxing, MMA | 52 (50 M, 2 F) retired professional boxers, aged 48.0 ± 10.3 117 (110 M, 7 F) active professional boxers, aged 30.4 ± 6.9 169 (152 M, 17 F) active professional MMA fighters, aged 29.6 ± 4.8 | 79 (69 M, 10 F) controls w/o contact sport history, aged 30.8 ± 10.0 | Fights and sparring | Plasma | Baseline and ≥ 2 measurements over 1.6 years (average) (range 1–5 years); active fighters: ≥ 45 days from a sanctioned fight | Acute: significant findings (boxers) Semi-acute and chronic: not significant | Serious | C (1) |
Heileson et al. [92] | Semi-acute | Non-randomized controlled trial | Field | Am. football | 66 male NCAA Am. football players | N/A | Am. football games and practices | Serum | Baseline: following > 14-week period of non-contact, after pre-season camp and throughout season | Significant findings | Moderate | C (2) |
Joseph et al. [42] | Acute and semi-acute | Prospective observational cohort study | Field | Am. football | 16 male high-school varsity footballers, aged 16.9 ± 0.2 (pre- and post-season sample n = 12) | N/A | Am. football games, practices and season | Serum | Semi-acute: pre- and post-season; acute: 1–2 h post | No significant findings | Moderate | B (3) |
Kawata et al. [82] | Semi-acute | Cohort study | Field | Ice hockey | 8 male professional players (including 2 concussed athletes), aged 26.6 ± 1.6 | N/A | Ice hockey season | Plasma | Pre- and post-season | Significant findings | Critical | C (1) |
Major et al. [83] | Chronic | Cross-sectional study | Other | Au. football | 81 (50 M, 31 F) amateur footballers (no-mTBI history n = 42; mTBI history n = 39), aged ~ 24 | 42 (23 M, 19 F) age-matched non-contact sport athletes | Au. football participation | Serum | Pre-season | No significant findings | Moderate | A (5) |
Neselius et al. [46] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) Olympic boxers, mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing bout | CSF | 1–6 days post and after ≥ 14 days rest | Significant findings | Moderate | C (2) |
Nowak et al. [85] | Acute | Case–control study | Laboratory | Soccer | 17 (6 M, 11 F) soccer players with ADHD, aged 20.2 ± 0.2; 17 (10 M, 6 F) w/o ADHD, aged 21.1 ± 0.1 | 17 (7 M, 10 F) soccer players with ADHD, aged 20.5 ± 0.1 | 10 linear headers; controls: 10 kicks | Plasma | Baseline, 2 and 24 h post | Significant findings (in w/o ADHD group) | Low | A (5) |
Oliver et al. [93] | Semi-acute | Observational cohort study | Field | Am. football | 116 Division I American footballers (baseline), aged 20 ± 1 (of whom 19 were sampled over the season; 9 non-starters, 11 starters) | 19 male NCAA Division I swimmers, aged 20 ± 1 (baseline sample only) | Am. football season | Serum | T1: after 9 weeks of non-contact; T2: after training camp; T3: following pre-season camp (highest concentration of impacts); T4 through T8 mid-season, 36–48 h post-games | Significant findings | Moderate | C (2) |
Oliver et al. [87] | Semi-acute | Prospective longitudinal cross-sectional study | Field | Am. football | 35 (20 starters, 15 non-starters) Division III footballers, aged 21 ± 1 | N/A | Am. football season | Serum | T1: after 14-weeks of non-contact; T2: end of camp (period with most impacts); T3: 72 h post-full-contact practice, T4 and T5: ~ 36 h following a game; T6 and T7: post-season | Significant findings | Moderate | B (3) |
Rubin et al. [94] | Acute | Cohort study | Field | Am. football | 18 Division I college footballers, median age (IQR) 20.5 (20–22) | N/A | Am. football pre-season practices | Plasma | Baseline: 2 months prior to any practices; < 1 h before and < 1 h post-practices | Significant findings | Moderate | A (6) |
Sandmo et al. [88] | Acute and chronic | Prospective cohort study | Field | Soccer | Male premier league players: heading exercise group n = 47, head impacts during a match n = 35 | Male premier league players: high intensity exercise n = 47 | (1) heading exercise (90 min), (2) head impacts (some concussive) during match play | Serum | Baseline, 1 and 12 h post | No significant findings | Serious | B (2) |
Shahim et al. [95] | Acute and chronic | Prospective cohort study | Field | Boxing | 14 (11 M, 3 F) amateur boxers, median age (IQR) 21.5 (20–26) | 14 healthy nonathletic controls, 23.5 (23–26); 12 gymnasts, 19 (18–22) | Boxing bout | Serum | 7–10 days post and after 3 months of rest | Significant findings | Serious | C (1) |
Soriano et al. [52] | Semi-acute | Cohort study | Field | Am. football | 33 collegiate athletes, aged 19.3 ± 1.4 | N/A | Am. football season (games and training) | Serum | Mid-season, post-season and off-season (after a rest period) | No significant findings | Serious | B (4) |
Symons et al. [53] | Chronic | Cross-sectional study | Other | Au. football | 95 (69 M, aged 23.3 ± 0.4; 26 F, aged 23.2 ± 0.9) amateur players | 49 (28 M, aged 22.5 ± 0.4; 21 F, aged 23.1 ± 0.8) amateur basketball, tennis, cricket, track and field athletes | Au. football participation | Serum | N/A (pre-season) | No significant findings | Moderate | B (4) |
Wallace et al. [90] | Acute | Prospective controlled cohort study | Laboratory | Soccer | 11 male collegiate players, aged 23.7 ± 3.9 | N/A | 40 headers; sham condition: contact with ball using hands, chest or thigh | Serum | Immediately before and 1 h and 3 weeks post | Mixed | Critical | C (2) |
Wirsching et al. [96] | Acute | Randomized controlled trial | Laboratory | Soccer | 18 (7 M, 11F), aged 20.3 ± 1.5 | 16 (6 M, 10F), aged 21.2 ± 1.4 | 10 soccer headers; controls: 10 kicks | Plasma | Before and 0, 2 and 24 h post | Significant findings | Low | A (5) |
Zetterberg et al. [47] | Acute and chronic | Longitudinal cohort study | Field | Boxing | 14 (11 M, 3F) amateur boxers, aged 22 ± 3.8 | 10 male nonathletic controls, aged 30 ± 6.3 | Boxing bout | CSF | 7–10 days post and after 3 months of rest | Significant findings | Moderate | C (0) |
Zetterberg et al. [48] | Acute | Non-randomized experimental study | Laboratory | Soccer | 23 male amateur soccer players, median age (range): 10 headers n = 10, 26 (19–32); 20 headers n = 13, 23 (20–28) | 9 male non athletes, median age (range) 24 (22–27) | 10 or 20 standing headers from a corner kick (kicked from 30 m) | CSF | 7–10 days post | Not detectable | Serious | B (3) |
GFAP | ||||||||||||
Asken et al. [55] | Chronic | Observational cohort study | Other | Soccer, diving, wrestling, ice hockey, Am. football | 415 (256 M, 159 F) collegiate athletes, aged 19.0 ± 1.2 | N/A | Cumulative exposure to collision sports in yr (and modified CHII) | Serum | Off-season | No significant findings | Moderate | B (4) |
DiBattista et al. [57] | Chronic | Cross-sectional study | Other | Ice hockey, football, rugby, lacrosse | 41 (39 M, 2 F) collision sport athletes; aged (including all participants): M (n = 60) 19.5 ± 2.0, F (n = 27) 19.5 ± 1.8 | 46 (21 M, 25 F) non collision sport athletes (inadvertent contact: soccer, basketball) | Collision sport participation | Plasma | Before the start of varsity season | No significant findings | Moderate | B (4) |
Hoffman et al. [61] | Acute | Cohort study | Field | Am. football | 15 Israel national football team players, aged 26.2 ± 5.3 | N/A | Am. football match | Serum | 1 week before, immediately (< 30 min) and 24 h post | No significant findings | Moderate | C (2) |
Joseph et al. [42] | Acute and semi-acute | Prospective observational cohort study | Field | Am. football | 16 male high-school varsity footballers, aged 16.9 ± 0.2 (pre- and post-season testing n = 12) | N/A | Am. football games, practices and season | Serum | Semi-acute: pre- and post-season; acute: 1–2 h post | No significant findings | Moderate | B (3) |
Kawata et al. [82] | Semi-acute | Cohort study | Field | Ice hockey | 8 male professional players (including 2 concussed athletes), aged 26.6 ± 1.6 | N/A | Ice hockey season | Plasma | Pre- and post-season | No significant findings | Critical | C (1) |
Major et al. [83] | Chronic | Cross-sectional study | Other | Au. football | 81 (50 M, 31 F) amateur footballers (no-mTBI history n = 42; mTBI history n = 39), aged ~ 24 | 42 (23 M, 19 F) age-matched non-contact sport athletes | Au. football participation | Serum | Pre-season | No significant findings | Moderate | A (5) |
Neselius et al. [46] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) Olympic boxers, mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing bout | CSF | 1–6 days post and after ≥ 14 days rest | Significant findings | Moderate | C (2) |
Neselius et al. [66] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) amateur boxers (competing at elite level), mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing bout | Serum | 1–6 days post and after ≥ 14 days rest | GFAP not detectable | Serious | C (2) |
Nowak et al. [85] | Acute | Case–control study | Laboratory | Soccer | 17 (6 M, 11 F) soccer players with ADHD, aged 20.2 ± 0.2; 17 (10 M, 6 F) w/o ADHD, aged 21.1 ± 0.1 | 17 (7 M, 10 F) soccer players with ADHD, aged 20.5 ± 0.1 | 10 linear headers; controls: 10 kicks | Plasma | Baseline, 2 and 24 h post | Significant findings (ADHD cohort only) | Low | A (5) |
O'Keeffe et al. [68] | Acute and semi-acute | Cohort study | Field | Rugby | 8 rugby university team players, mean age (range) 22.1 (18–23); 11 male rugby school team players, mean age 17.4 | 27 non-contact sport athletes, median age (range) 28 (18–36); 26 healthy non-athlete controls, median age (range) 30 (18–40) | Rugby match (university team) and season (school and university team) | Plasma | University team: pre-season, ≤ 2 h post-match, 2 months post-season School team: pre- and post-season | GFAP not detectable | Moderate | B (3) |
Soriano et al. [52] | Semi-acute | Cohort study | Field | Am. football | 33 collegiate athletes, aged 19.3 ± 1.4 | N/A | Am. football season (games and training) | Serum | Mid-season, post-season and off-season (after a rest period) | Significant findings | Serious | B (4) |
Zetterberg et al. [47] | Acute and chronic | Longitudinal cohort study | Field | Boxing | 14 (11 M, 3 F) amateur boxers, aged 22 ± 3.8 | 10 male nonathletic controls, aged 30 ± 6.3 | Boxing bout | 7–10 days post and after 3 months of rest | 7–10 days post and after 3 months of rest | Acute: significant findings Chronic: no significant findings | Moderate | C (0) |
Zetterberg et al. [48] | Acute | Non-randomized experimental study | Laboratory | Soccer | 23 male amateur soccer players, median age (range): 10 headers n = 10, 26 (19–32); 20 headers n = 13, 23 (20–28) | 9 male non athletes, median age (range) 24 (22–27) | 10 or 20 standing headers from a corner kick (kicked from 30 m) | CSF | 7–10 days post | No significant findings | Serious | B (3) |
Zetterberg et al. [77] | Chronic | Observational case–control study | Other | Boxing | 44 male amateur boxers, median age (range) 19 (17–28) | 23 healthy males w/o contact sport history, median age (range) 28 (19–50) | Boxing participation (boxing debut, boxing duration in yr, number of bouts) | Serum | After a 2-month period of nonparticipation in boxing | GFAP not detectable | Moderate | C (1) |
NSE | ||||||||||||
DiBattista et al. [57] | Chronic | Cross-sectional study | Other | Ice hockey, football, rugby, lacrosse | 41 (39 M, 2F) collision sport athletes; aged (including all participants): M (n = 60) aged 19.5 ± 2.0, F (n = 27) aged 19.5 ± 1.8 | 46 (21 M, 25F) non collision sport athletes (inadvertent contact: soccer, basketball) | Collision sport participation | Plasma | Before the start of varsity season | No significant findings | Moderate | B (4) |
Graham et al. [59] | Acute | Retrospective cohort study | Field | Boxing | 8 male amateur boxers, aged 17.6 ± 5.3 (PTH – punches to the head and body) | 8 male amateur boxers, aged 19.1 ± 3.2 (PTB – punches to the body) | 5 × 2-min boxing rounds | Serum | 1 h before and after 5 min of cessation | Significant findings | Moderate | C (2) |
Graham et al. [60] | Acute | Cohort study | Field | Karate | 12 males, aged 30.4 ± 6.7 (KTH – kicks to the head and body) | 12 males, aged 28.2 ± 6.5 (KTB – kicks to the body) | 4 × 3-min karate round | Serum | Before and immediately after | Significant findings | Moderate | C (1) |
Horner et al. [97] | Acute | Cohort study | Field | Boxing | 8 male Olympic boxers, age range 18–28 | 17 male amateur oarsmen, age range 18–23 | 3 × 3-min boxing rounds; controls: 6-min ergometer test | Serum | Before and after | Significant findings | Moderate | C (1) |
Rogatzki et al. [71] | Acute | Cohort study | Field | Am. football | 17 male Division III collegiate footballers, aged 19.5 ± 0.9 | N/A | Am. football game | Serum | 2 days before and 1 h post | Significant findings | Moderate | C (2) |
Stålnacke et al. [74] | Acute | Cohort study | Field | Ice hockey | 26 male elite ice hockey players, aged 28 ± 4 | 18 elite basketball players, aged 25 ± 4 | Ice hockey game (body checkings, falls, collisions, boardings); basketball game (jumps, collisions, falls) | Serum | 1–2 h before and within 1 h post | No significant findings | Serious | C (2) |
Stålnacke et al. [75] | Acute | Cohort study | Field | Soccer | 28 male elite players, aged 26 ± 5 | N/A | Headers, jumps, falls and collision during a competitive soccer game | Serum | 1–5 h before and immediately post | Significant findings | Moderate | B (3) |
Stålnacke et al. [38] | Acute | Cohort study | Field | Soccer | 44 female elite players, aged 23 ± 3 | N/A | Headers, jumps, falls and collisions during a competitive soccer game | Serum | Before and immediately post | Significant findings | Moderate | B (3) |
Zetterberg et al. [77] | Chronic | Observational case–control study | Other | Boxing | 44 male amateur boxers, median age (range) 19 (17–28) | 23 healthy males w/o contact sport history, median age (range) 28 (19–50) | Boxing participation (boxing debut, boxing duration (yr), number of bouts) | Serum | After a 2-month period of nonparticipation in boxing | Significant findings | Moderate | C (1) |
BDNF | ||||||||||||
Bamaç et al. [98] | Acute | Non-randomized experimental study | Laboratory | Soccer | 17 male professional soccer players, aged 24.6 ± 4.4 | N/A | 15 jumping soccer headers; headed from a corner kick | Serum | Before and after | Significant findings | Serious | B (4) |
DiBattista et al. [57] | Chronic | Cross-sectional study | Other | Ice hockey, football, rugby, lacrosse | 41 (39 M, 2 F); age for all sample: M (n = 60) 19.5 ± 2.0, F (n = 27) 19.5 ± 1.8 | 46 (21 M, 25 F) non collision sport athletes (inadvertent contact: soccer, basketball) | Collision sport participation | Plasma | Before the start of varsity season | No significant findings | Moderate | B (4) |
Hoffman et al. [61] | Acute | Cohort study | Field | Am. football | 15 Israel national football team players, aged 26.2 ± 5.3 | N/A | Am. football match | Serum | 1 week before, immediately (< 30 min) and 24 h post | Significant findings | Moderate | C (2) |
Neselius et al. [66] | Acute and semi-acute | Prospective cohort study | Field | Boxing | 30 (28 M, 2 F) amateur boxers (competing at elite level), mean age (range) 22 (17–34) | 25 (20 M, 5 F) healthy controls, mean age (range) 22 (17–30) | Boxing bout | Serum | 1–6 days post and after ≥ 14 days rest | No significant findings | Serious | C (2) |
O'Keeffe et al. [68] | Acute and semi-acute | Cohort study | Field | Rugby | 8 rugby university team players, mean age (range) 22.1 (18–23); 11 male rugby school team players, mean age 17.4 | 27 non-contact sport athletes, median age (range) 28 (18–36); 26 healthy non-athlete controls, median age (range) 30 (18–40) | Rugby match (university team) and season (school and university team) | Plasma | University team: pre-season, ≤ 2 h post-match, 2 months post-season School team: pre- and post-season | Acute: no effects Semi-acute: significant findings | Moderate | B (3) |
Oztasyonar [99] | Acute | Cohort study | Field | Boxing, Tae Kwon Do | 20 male boxers, aged 20.15 ± 1.52; 20 male Tae Kwon Do fighters, aged 20.60 ± 1.65 | 20 male runners, aged 19.87 ± 1.60; 20 sedentary participants, aged 20.40 ± 1.85 | Boxing: 3 × 3-min rounds; Tae Kwon Do: 2 × 3-min rounds; controls: running | Serum | Immediately before and after | Significant findings | Moderate | C (1) |
Zetterberg et al. [77] | Chronic | Observational case–control study | Other | Boxing | 44 male amateur boxers, median age (range) 19 (17–28) | 23 healthy males w/o contact sport history, median age (range) 28 (19–50) | Boxing participation (boxing debut, boxing duration in yr, number of bouts) | Serum | After a 2-month period of nonparticipation in boxing | No significant findings | Moderate | C (1) |
UCH-L1 | ||||||||||||
Asken et al. [55] | Chronic | Observational cohort study | Other | Soccer, diving, wrestling, ice hockey, Am. football | 415 (256 M, 159 F) collegiate athletes, aged 19.0 ± 1.2 | N/A | Cumulative exposure to collision sports in yr (and modified CHII) | Serum | Off-season | No significant findings | Moderate | B (4) |
Joseph et al. [42] | Acute and semi-acute | Prospective observational cohort study | Field | Am. football | 16 male high-school varsity footballers, aged 16.9 ± 0.2 (pre- and post-season testing n = 12) | N/A | Am. football games, practices and season | Serum | Semi-acute: pre- and post-season; acute: 1–2 h post | Significant findings | Moderate | B (3) |
Major et al. [83] | Chronic | Cross-sectional study | Other | Au. football | 81 (50 M, 31 F) amateur footballers (no-mTBI history n = 42; mTBI history n = 39), aged ~ 24 | 42 (23 M, 19 F) age-matched non-contact sport athletes | Au. rules football participation | Serum | N/A | No significant findings | Moderate | A (5) |
Nowak et al. [85] | Acute | Case–control study | Laboratory | Soccer | 17 (6 M, 11 F) soccer players with ADHD, aged 20.2 ± 0.2; 17 (10 M, 6 F) w/o ADHD, aged 21.1 ± 0.1 | 17 (7 M, 10 F) soccer players with ADHD, aged 20.5 ± 0.1 | 10 linear headers; control: 10 kicks | Plasma | Baseline, 2 and 24 h post | Significant findings (for ADHD cohort only at 24 h post) | Low | A (5) |
Puvenna et al. [70] | Acute | Cohort study | Field | Am. football | 15 athletes | 406 positive controls with mTBI and 465 negative controls | 2 Am. football games | Serum | Baseline (day before) and post (< 1 h) (positive controls: < 6 h of injury) | Significant findings. No correlation with head hits | Serious | B (3) |
Soriano et al. [52] | Semi-acute | Cohort study | Field | Am. football | 33 male collegiate players, aged 19.3 ± 1.4 | N/A | Am. football season (games and training) | Serum | Mid-season, post-season and off-season (after a rest period) | UCH-L1 levels not detectable (for majority of samples) | Serious | B (4) |