| Studies | N* | Inclusion criteria | Age, yr | No. of patients (F/M) | Severity scales | Assay | Main outcome |
|---|---|---|---|---|---|---|---|
| Al Nimer et al.30 | 182 | Patients with NF-L sample in Traumatic Brain Injury Database of Karolinska Institute | Median (range) 55 (15-79) | 45/137 | Mean ± SD GCS 7 ± 4; Median (IQR) ISS 25 (19-29) | IRMA, Liaison (DiaSorin) | GOS at 6 and 12 mo 1-3 unfavourable 4-5 favourable |
| Baker et al.31 | 64 | GCS ≤ 8; coma or loss of consciousness because of isolated blunt TBI | Mean (range) 41.4 (18.3-87.9) | 23/41 | Mean ± SD GCS 5.7 ± 2.7 | Mortality, GOSE and GOS at hospital discharge (or 30 d) 1-3 unfavourable 4-5 favourable | |
| Böhmer et al.32 | 20 | GCS ≤ 8 with abnormal brain CT scan on admission; ventriculostomy installed | Mean ± SD 29 ± 13 | 2/18 | NR | Elecsys (Roche Diagnostics) | Mortality |
| Chabok et al.33 | 28 | GCS ≤ 8; Severe diffuse axonal injury (exclusion of intra- and extracranial hematoma on CT); age ≥ 16 yr; no severe systemic injury; no intoxication; no pre-existing disease | Mean ± SD 31 ± 19 | 2/26 | Mean admission ± SD GCS 6.7 ± 1.3 | ELISA (Can Ag Diagnostics) | |
| Dauberschmidt et al.34 | 9 | Cerebral coma after severe head trauma | Mean ± SD 39.7 ± 16.9 | 1/8 | NR | RIA | Mortality at 1 mo |
| Di Battista et al.35 | 85 | GCS < 13; on-head abbreviated injury score (AIS) ≤ 2 | Mean ± SD 45.8 ± 21.9 | 19/66 | Median (range) GCS 5 (3-8); Mean ± SD ISS 23.6 ± 11; Mean ± SD AISh 4.2 ± 1.1 | ELISA, SECTOR Imager (Meso Scale Diagnostics) | Mortality and GOS at 6 mo1-3 unfavourable 4-5 favourable |
| Gatson et al.36 | 18 | GCS ≤ 8; ventriculostomy installed | Mean ± SD 32.1 ± 12.3 | 7/11 | Mean ± SD GCS 3.75 ± 1.2 | ELISA (USCN Life Science) | GOSE1-4 unfavourable 5-8 favourable |
| Gradisek et al.37 | 84 | GCS ≤ 8 after reanimation or deterioration to GCS < 8 after the first 24 hr; isolated TBI (no extracranial injury with AIS ≥ 3); no neurologic disease | Mean ± SD 46 ± 21 | 11/73 | Median (IQR) GCS 6 (4-8); Median (IQR) ISS 24 (16-25) | ELISA, Liaison (Sangtec Medical) | All-cause mortality and GOS at 12 mo 1-3 unfavourable 4-5 favourable |
| Guan et al.38 | 41 | Admission within 6 hr after injury; closed TBI; no history of disease of vital organs such as heart, kidney and brain | Mean (range) 44 (5-92) | NR | NR | NR | GOS at 6 mo 1-3 unfavourable 4-5 favourable |
| Kuroiwa et al.39 | 47 | NR | Mean 35.1 | 12/35 | NR | RIA | Mortality and GOS |
| Li et al.40 | 40 | GCS ≤ 8; no severe systemic injury; no heart or renal failure; no severe CNS infection | NR | NR | NR | RIA (Sangtec Medical) | GOS at 6 mo 1-3 unfavourable 4-5 favourable |
| Luo et al.41 | 24 | TBI | NR | NR | GCS ≥ 13 = 9; GCS 9-12 = 17; GCS ≤ 8 = 24 | Custom | GOS 1-3 unfavourable 4-5 favourable |
| McKeating et al.42 | 21 | TBI admitted to ICU | Median (range) 35 (17-69) | 4/17 | Median (range) GCS 6 (3-13); Median (range) ISS 25 (9-38) | RIA (Sangtec Medical) | GOS at 6 mo 1-3 unfavourable 4-5 favourable |
| Meissner et al.43 | 20 | NR | NR | NR | NR | NR | Mortality |
| Meric et al.44 | 40 | ≥ 18 yr of age; presenting to ED within 24 hr after trauma | Median (range) 31 (18-88) | 28/12 | GCS ≤ 13 | ECLIA (Roche Diagnostics) | Mortality and GOS at 1 mo |
| Olivecrona et al.45 | 48 | GCS ≤ 8; 15-70 yr of age; first recorded CPP > 10 mm Hg; arrival < 24 hr after TBI | Median (range) 31 (15-63) | 17/31 | Median (range) ISS 29 (9-50); Median (range) APACHE II 21 (12-32) | LIA (DiaSorin Diagnostica) | GOS at 3 and 12 mo 1-3 unfavourable 4-5 favourable |
| Persson et al.46 | 4 | NR | NR | NR | NR | Custom | GOS at hospital discharge 1-3 unfavourable 4-5 favourable |
| Pleines et al.47 | 13 | GCS ≤ 8 admission; isolated TBI | Mean (range) 36 (16-67) | NR | NR | ELISA (Wallac Sverige AB) | GOS between 3 and 6 mo |
| Raabe et al.48 | 44 | Severe head injury | Median (range) 41 (16-83) | 11/33 | Median (range) GCS 5 (3-8) | RIA (Sangtec Medical) | GOS at 6 mo 1-3 unfavourable 4-5 favourable |
| Raabe et al.49 | 82 | GCS ≤ 8 postresuscitation; admitted neurosurgical ICU | Median (range) 38 (16-85) | 16/66 | NR | RIA (Sangtec Medical) | GOS at 6 mo 1-3 unfavourable 4-5 favourable |
| Ross et al.50 | 9 | Admitted to ICU ≤ 24 h after TBI | Median (range) 21.5 (4-70) | 2/7 | Median (range) GCS 6 (3-9) | RIA | Mortality at ICU discharge GOS |
| Sawauchi et al.51 | 41 | Consecutive TBI | NR | NR | GCS > 8 = 30; GCS ≤ 9 = 11 | NR | GOS at 3 mo 1-3 unfavourable 4-5 favourable |
| Stein et al.52 | 24 | Age > 17 yr; admission within the first 6 hr after injury; GCS score < 9 on admission; isolated TBI (no extracranial injury with AIS ≥ 4); placement of a clinically indicated ICP monitor performed | Mean ± SD 30.7 ± 12.3; Range 19-64 | 3/21 | Mean ± SD GCS 5.8 ± 3.4 | ELISA (Biovendor Candor) | GOSE at 3, 6 and 12 mo 1-4 unfavourable 5-8 favourable |
| Vos et al.53 | 78 | GCS ≤ 8 postresuscitation admitted ≤ 36 hr after injury; closed TBI; blood sample taken; long-term follow-up | Median (range) 32 (15-81) | 24/61 | Median (range) GCS 4 (3-8); Median (range) ISS 29 (9-75) | LIA (Sangtec Medical) | Mortality and GOS at 6 mo 1-3 unfavourable 4-5 favourable |
| Wang et al.54 | 34 | Admitted to neurosurgery < 24 hr after injury | Range 15-73 | 15/19 | NR | ECLIA (Roche Diagnostics) | GOS at 3 mo 1-3 unfavourable 4-5 favourable |
| Woertgen et al.55 | 30 | GCS ≤ 8; admitted between 1 and 6 hr after injury; no spinal cord injury; no history of neurologic disease; no resuscitation or shock | Mean (range) 32 (17-73) | 7/23 | NR | ELISA (Wallac Sverige AB) | GOS at hospital discharge 1-3 unfavourable 4-5 favourable |
| Yamazaki et al.56 | 17 | No severe hypoxia or systemic hypotension | Mean (range) 45 (14-91) | 5/20 | GCS < 8 = 9; GCS ≥ 8 = 16 | NR | Mortality at hospital discharge (mean 22 d) |
| Yan et al.57 | 42 | GCS ≤ 8; extraventricular drain | Median (range) 29 (16-23) | 10/32 | Median (range) GCS 5 (3-10); Median (IQR) ISS 36 (27-43) | ELISA (CanAg Diagnostics) | GOSE at 6 mo 1-4 unfavourable 5-8 favourable |
| Zhan et al.58 | 30 | GCS ≤ 8 admission; no severe systemic injury; no severe cardiac ischemia; no renal failure; no severe CNS infection | Range 26-64 | 12/18 | NR | NR | GOS at 1 mo 1-3 unfavourable 4-5 favourable |
| Zhang et al.59 | 102 | Isolated head trauma; postresuscitation GCS ≤ 8; age ≥ 18 yr; admission time > 6 hr | Mean ± SD 40.5 ± 15.3 | 34/68 | Median (range) GCS 5 (3-8) | ELISA (Phoenix Pharmaceuticals) | GOSE at 6 mo 1-4 unfavourable 5-8 favourable |
Note: AIS = abbreviated injury score, AISh = abbreviated injury score head, APACHE II = acute physiology and chronic health evaluation II, CNS = central nervous system, CPP = cerebral perfusion pressure, CT = computed tomography, ED = emergency department, ECLIA = electrochemiluminescence immunoassay, ELISA = enzyme-linked immunosorbent assay, GCS = Glasgow Coma Scale, GOS = Glasgow Outcome Scale, GOSE = Glasgow Outcome Scale-Extended, ICP = intracranial pressure, ICU = intensive care unit, IQR = interquartile range, IRMA = immunoradiometric assay, ISS = injury severity score, LIA = luminescence immunoassay, NF-L = neurofilament light, NR = not reported, RIA = radioimmunoassay, SD = standard deviation, TBI = traumatic brain injury.
*Number of patients included in the analysis (may be different from the number of patients included in the study when data specific to our population of interest could be extracted).