Table 1.

Clinical studies investigating the effect of extracranial injury (ECI) on traumatic brain injury (TBI)

Studies reporting effects of ECI on TBI
Author	Subjects	Major Relevant Findings	Limitations
Kumar et al., 2015	114 TBI patients TBI: GCS ≤ 8, AIS ≥ 3 and evidence of damage by CT PT: TBI + AIS ≥ 3 at least one ECI	- Weekly average patient serum IL-6 and IL-10 higher in PT compared to isolated TBI group - No difference in GOS scores between TBI and PT patients	–TBI group older than PT (Mean age 39 v 30) –PT group higher incidence of skull fractures –Low numbers
Leitgeb et al., 2013	767 TBI patients TBI: AIS 2–5 (Mean 4) MT: TBI + AIS > 2 at least one ECI	–Mortality higher in mild TBI (AIS = 2) patients with ECI, however overall mortality comparable between groups –Favourable outcome (GOS 4/5) reported in more MT patients	–TBI group older than MT (Mean age 61 v 46) –Orthopaedic interventions common (25% MT had ECI surgery) but not accounted for
Lingsma et al., 2013	508 TBI patients TBI: GCS 9–13 (moderate), 3–8 (severe) MT: TBI + ECI (Median ISS = 4)	–Unfavourable outcome (GOS = 2/3) and mortality higher for patients with moderate TBI and ECI than for isolated moderate TBI	–Missing patients in follow up –Variability in ECI severity
Leong et al., 2013	100 TBI patients TBI: mild (GCS 13–15), moderate (9–12), severe (3–8) MT: TBI + AIS ≥ 3 at least one ECI	–Fewer mild TBI patients with ECI made ‘good recovery’ (GOS = 5) compared with those with isolated mTBI	–Low numbers
Van Leeuwen et al., 2012	39,274 TBI patients (IMPACT, CRASH, TARN databases) TBI: GCS 13–15 (mild), 9–12 (moderate), 3–8 (severe) MT: TBI + AIS ≥ 3 (or requiring hospital admission) at least one ECI	–IMPACT/CRASH pooled adjusted OR: Effect of ECI on mortality = 2.14 in mild-, 1.46 moderate-, 1.18 severe-TBI. –TARN adjusted OR higher in MT patients (2.81 mild-, 2.18 moderate-, 2.14 severe-TBI).	–Missing values in databases –Variability in ECI severity –No functional outcomes
Lefering et al., 2008	21,356 trauma patients Various combinations of TBI and/or ECI to extremity or torso (AIS 0–6)	–Non-significant increase in mortality in MT versus TBI only overall, but significant difference at all TBI severities when ECI AIS ≥ 4	–No GCS used –No functional outcomes
Hensler et al., 2002	125 trauma patients TBI: GCS ≤ 8 or AIS ≥ 3 PT with TBI: TBI + AIS ≥ 3 for one ECI PT without TBI: AIS ≥ 3 for two ECI	–Serum levels of IL-6, IL-10, 55- and 75-kDa soluble tumor necrosis factor receptors, polymorphonuclear neutrophil elastase all lower in patients with TBI only compared with PT (with and without TBI)	–Low numbers –TBI group older than PT (Mean age 42 v 36) –Only pathological changes reported
Siegel et al., 1991	1709 TBI patients TBI: GCS 13–14 (mild), 9–12 (moderate), 7–8 (moderately severe), 4–6 (severe), 3 (near fatal) MT: TBI + ECI separated by location (no defined AIS)	–Overall mortality rate (all GCS) almost tripled in blunt TBI patients with pelvis or femur fracture (similar results for lung-, liver-, bowel-, major vessel- injury). –Increase in mortality most substantial in mild to moderate TBI.	–Variability in ECI severity –No functional outcomes
Gennarelli et al., 1989	16,524 TBI patients TBI: AIS 2–6 MT: TBI + AIS 1–6 at least one ECI	–Synergistic effect on mortality when moderate head injuries (AIS 3–4) combined with severe ECI (AIS 4–6). –No additive effect on mortality when ECI AIS ≤ 3	–No GCS used
Studies reporting no/inconclusive effects of ECI on TBI
Author	Subjects	Major Relevant Findings	Limitations
Stulemeijer et al., 2006	299 TBI patients TBI: GCS 13–15 MT: TBI + AIS ≥ 2 for one ECI	–Mild TBI patients with ECI had worsened GOS-E scores, however no differences in post-concussion symptoms at 6 months –Acute symptoms (headache, dizziness, nausea) lower in MT group	–TBI slightly more severe in MT patients –Symptoms masked by frequent use of analgesic in MT patients?
Sarrafzadech et al., 2001	119 trauma patients TBI: GCS 3–7, Mean total ISS = 25 MT: TBI + AIS other 1–6, Mean total ISS = 39.5 ECI only: AIS other 1–6, Mean ISS = 29	–No difference in physiological variables between patients with isolated TBI or MT with TBI between days 1–12 post-injury –No differences in GOS score at 6 and 12 months between TBI and MT patients, higher GOS scores in extracranial injury only patients.	–TBI group older than MT (Mean age 36 v 28) –Low numbers –Wide range of injury severities and locations
Baltas et al., 1998	386 TBI patients TBI: GCS 3–8 MT: TBI + ECI (no defined AIS)	–No difference in mortality in MT versus TBI only groups.	–No defined AIS for extracranial injury –No functional outcomes

ECI extracranial injury, MT multitrauma, PT polytrauma