Table 3
Author, country, datePatient groupStudy typeOutcomesKey resultsStudy weaknesses
Waterloo K et al, 2005, Norway7 patients with high S-100b after mild head injury matched with 7 patients with no detectable S-100bCase control studyOverall cognitive functionNo difference
Reaction timeIncreased in raised S-100b group
AttentionReduced in raised S-100b group
Rothoerl et al, 1998, Germany30 patients with a severe head injury (GCS< = 9) and 11 with minor head injury (GCS 13-15) admitted to a neurosurgical unitDiagnostic Cohort study (4)Glasgow Outcome Scale on discharge (Mean day 19 in severe group and mean day 1.3 in minor head injury group)Patients with GOS 3-5 S-100 level mean 1.2mcg SD 1.8Non-independent gold standard
S-100 levels measured mean 2.5 hrs after injuryDetectable level of S-100 (>0.5mcg/l)Patients with GOS 1-2 (unfavourable) S-100 level mean 4.9mcg/l SD 5.3Small, selected cohort of patients
P = 0.0025
25 of 27 Elevated S-100 levels were found in the minor head injury group
Raabe A et al, 1999, Germany82 patients after severe head injury (GCS< = 8)Diagnostic cohort study (2b)Glasgow outcome score at 6 monthsFor S-100 level of >2.5mcg/l, unfavourable outcome was predicted withNo confidence intervals presented
s-100 taken at admission and every 24 hoursUnfavourable outcome defined as severe disability or vegetative stateSensitivity 44%Non-consecutive
Specificity 97%
Woertgen et al, 1999, Germany44 patients after severe head injury (GCS score < = 8)Diagnostic cohort study (3b)Glasgow outcome score calculated at mean 11 months after trauma (GOS 1-3 unfavourable)For S-100 level of >2mcg/l, PCS symptoms predicted withTables 2, 3 and 4 are incorrect, with erratum printed in a later edition
S-100 taken 1-6 hrs after injurySensitivity 95%
Specificity 70%
Ingebrigtsen et al, 1999, Sweden50 patients with minor head injury and LOC (GCS 13-15) referred to Neurosurgery dept after CT scanDiagnostic Cohort study (3b)Neuropsychological testing at 3 months (for attention, psychomotor speed, trail-making test, memory, digit span) In 36 patients11/36 patients had S-100 >0.2mcg/lVery small study with no sample size estimates
S-100 taken hourly up to 12 hoursMRI and CT scan findings within 48hrsThere were non significant trends to reduced impairment in the S-100 negative groupNon consecutive
4 of 5 patients with brain contusion had S-100 >0.4mcg/lOnly 36 of 50 patients followed up at 3 months
Sensitivity 80% (p = 0.035)
Ingebrigsten et al 2000 Scandinavia (3 centres Sweden, Denmark, Norway)182 patients from 3 centres with GCS 13-15 and brief Loss of Consciousness.Diagnostic Cohort Study (2b)Rivermead postconcussion symptoms questionnaire score (RPQ)Patients with a positive S-100 had mean RPQ 6.0 vs 4.0 in S-100 negative group p = 0.07No sensitivities or specificities given for prediction of long term disability
S-100 taken on admissionIntracranial Pathology on CT scan at <24 hoursDetectable S-100 predicted intracranial pathology with: Sensitivity 90%, Specificity 65%
Mussack T et al, 2000, Germany80 patients presenting with a history of minor head trauma (GCS 13-15)Diagnostic study (4)S-100 in Minor Head Trauma ptsPatients discharged < = 6hrs 0.29 +/- 0.11 ng/mlNo gold standard outcome measures
Also 10pts with severe head injury (GCS<8)Patients with Severe head Injury GCS<8Patients discharged > =  24hrs 0.70 +/- 0.19 ng/mlNon consecutive
S-100 taken at 0h, 6h and 24hrs post admissionPatients subsequently admitted to ICU 5.03 +/- 3.18 ng/mlResults not clearly presented
50 patients GCS 13-15 after normal CT scan5.26 +/- 1.56ng/mlNon significant findings between groups
Low number of patients
Herrmann et al, 2001, Germany69 patients admitted to a neurosurgical unit (mostly GCS >13)Diagnostic study (3b)Intracranial pathology on CT scan at 2 weeks and 6 months, or focal neurologyAt 2 weeks, S-100 of >0.14mcg/l predicted positive outcome:Inclusion criteria for patients unclear
S-100 taken at 1, 2 and 3 daysSensitivity 69%Only 29 patients followed up to 6 months
Specificity 90%
At 6 month, S-100 of >0.14mcg/l predicted positive outcome:
Sensitivity 65%
Specificity 89%
Chatfield DA et al, 2002, UK20 patients with severe head injury (GCS< = 8) admitted to neurosurgical unitDiagnostic cohort study (4)Glasgow outcome score at 6 months after trauma (GOS 1-3 unfavourable)Patients with GOS 1-3 S-100 mean level 2.46 +/-0.32mcg/lData not clearly presented
s-100 on admissionPatients with GOS 3-5 S-100 mean level 0.6 +/-0.1mcgSmall study
P<0.05No cut off points or ROC curves calculated
Townend WJ et al, 2002, UK148 adult head injury patients (GCS 4-15) in 4 hospitals. Most had a minor head injuryDiagnostic study (2b)Extended Glasgow outcome score at 1 monthS-100>0.32mcg/l predicted severe disability (15 patients with GOSE<5):Wide confidence intervals
S-100 levels taken within 6 hours of head injurySensitivity 93% (63%-100%)Non consecutive
Specificity 72% (54%- 79%)Wide definition of head injury (including no LOC)
NPV 99% (93%-100%)80% follow up rate
Spinella et al, 2003, USA27 children (<18yrs) with traumatic brain injuryDiagnostic cohort study (3b)Pediatric Cerebral performance category score (PCPC) assessed at discharge and 6 monthsFor s-100 level of >2.0mcg/l, unfavourable outcome was predicted withVery small study
S-100 taken within 12 hoursSensitivity 86%Confidence intervals not given
Specificity 95%Non consecutive
Savola O & Hillbom M, 2003, Finland172 consecutive patients with mild head injury (GCS 13-15)Diagnostic cohort study (2b)Post concussional symptoms defined by Rivermead Post-Concussion Symptoms Questionnaire at 2–6 weeksFor s-100 level of >0.50mcg/l, PCS symptoms predicted withNo confidence intervals or sample size calculations
Sensitivity 27%
Specificity 93%