Table 6.

Biomarkers for traumatic brain Injury

Authors/year	Study design	Population	N	Bio-marker	Sample source	Findings
Molecules of CNS origin
Okonkwo/2013/[180]	Pro	Mild, moderate & severe TBI	215	GFAP-BDP	Blood	Levels of GFAP-BDP were related to number of CT scan lesions and to neurological recovery A level of 0.68 μg/L was associated with a 21.61 OR for a positive CT and a 2.07 OR for failure to return to pre-injury baseline
Metting/2012/[170]	Pro	Mild TBI	94	s100β. GFAP	Blood	Levels of GFAP but not s100β were related to outcome, but the PPV was not high (<50 %)
Vos/2010/[178]	Pro	Moderate & severe TBI	79	s100β, GFAP	Blood	Levels of si00P and GFAP on admission were associated with poor outcome at 6 months and with mortality at 6 months even after adjusting for injury severity
Vos/2004/[172]	Pro	Severe TBI	85	s100β, NSE, GFAP	Blood	s100β, NSE, and GFAP were all higher in non-survivors and in those with poor 6-month outcome. s100β >1.13 μg/L predicted death with 100 % discrimination.
Wiesmann/2009/[167]	Pro	Mild, moderate, & severe TBI	60	s100β, GFAP	Blood	levels of s100β and GFAP were correlated with 6 month GOS Levels of s100β at 24 h post injury had the highest correlation
Pelinka/2004/[168]	Pro	TBI within 12 h	92	s100β, GFAP	Blood	GFAP and s100β were higher in non-survivors and predicted mortality
Nylen/2008/[167]	Pro	Severe TBI	59	s100β, s100a1b, s100βb	Blood	Levels of s100β, s100a1b, and s100βb were all related to 1 year GOS
Nylen/2006/[179]	Pro	Severe TBI	59	GFAP	Blood	Levels of GFAP were independently associated with 1-year outcome
Olivecrona/2009/[171]	Pro	Severe TBI	48	s100β, NSE	Blood	Levels of NSE and s100β were not significantly related to outcome at 3 or 12 months
Topolovec-Vranic/2011/[175]	Pro	Mild TBI within 4 h	141	s100β, NSE	Blood	s100β predicted poor cognitive outcome at 1 week NSE is independently associated with poor cognitive outcome at 6 weeks post injury
Rainey/2009/[165]	Pro	Severe TBI within 24 h	100	s100β	Blood	s100β at 24 h post injury were higher in patients with unfavorable outcome. s100β >0.53 μg/L predicted poor outcome (>80 % sensitivity; 60 % specificity)
Thelin/2013/[166]	Retro	Severe TBI	265	s100β	Blood	Levels of s100β between 12 and 36 h of injury were correlated with 6–12 month GOS and remained significantly related to outcome after adjustment for injury severity factors
Rodriguez-Rodriguez/2012/[159]	Pro	Severe TBI	55	s100β	Blood urine	Blood and urine s100β at 24 h postTBI were significantly higher in non-survivors Serum s100β >0.461 μg/L (88.4 % specificity) and urine s100β >0.025 μg/L (62.8 % specificity) predicted mortality
Kay/2003/[81]	Case control	TBI with GCS < 8	27 TBI, 28 CTRL	ApoE, s100β	CSF	s100β is elevated and ApoE is decreased in TBI compared with controls
Mondello/2012/[183]	Case control	severe TBI	95	UCH-L1	Blood, CSF	Blood and CSF levels of UCH-L1 were higher in patients with lower GCS, in patients who died, and in patients with unfavorable outcome. Levels at 6 h had the highest correlation Cumulative serum UCH-L1 >5.22 μg/L predicted death with OR = 4.8
Brophy/2011/[184]	Pro	Severe TBI GCS ≤8	86 (blood), 59 (CSF)	UCH-L1	Blood, CSF	Non-survivors had higher median serum and CSF UCH-L1 levels in the first 24 h
Papa/2009/[181]	Pro	TBI GCS ≤8 with EVD	41 TBI, 25 CTRL	UCH-L1	CSF	UCH-L1 was higher in TBI compared with controls at all time points up to 168 h Levels of UCH-L1 were higher in patients with a lower GCS at 24 h, post-injury complications, in those died within 6 weeks, and in those with poor outcome at 6 months
Papa/2012/[185]	Pro	Mild & moderate TBI GCS 9–15	96 TBI, 199 CTRL	UCH-L1	Blood	UCH-L1 within 4 h of injury distinguished TBI from uninjured controls (AUC = 0.87 [0.82–0.92]) UCH-L1 was associated with severity of injury in TBI
Liliang/2010/[177]	Pro	severe TBI	34	Tau	Blood	Tau levels were significantly higher in patients with a poor outcome Remained significant when adjusted for injury severity factors
Pineda/2007/[186]	Pro	Severe TBI	41	SBDP145, SBDP150	CSF	SBDP145 and 150 levels were significantly related to outcome at 6 months
Brophy/2009/[187]	Case control	Severe TBI	38	SBDP145, SBDP150	CSF	SBDP145 and 150 levels were higher in patients with worse GCS and longer ICP elevation
Mondello/2010/[188]	Pro	Severe TBI	40 TBI, 24 CTRL	SBDP145, SBDP120	CSF	SBDP145 >6 μg/L (OR = 5.9) and SBDP 120 > 17.55 μg/L (OR = 18.34) predicted death SBDP145 within 24 h of injury correlated with GCS score
Inflammatory markers
Schneider Soares/2012/[195]	Pro	mild, moderate, & severe TBI	127	IL-10, TNFα	Blood	Levels of IL-10 but not TNFα were related to mortality, even when adjusted for injury severity characteristics
Stein/2012/[194]	Pro	severe TBI	68	IL-8, TNFα	Serum	High levels of both IL-8 and TNFα predicted subsequent development of intracranial hypertension (specificity was high but sensitivity was low)
Tasci/2003/[196]	Pro	mild, moderate, & severe TBI	48	IL-1	Blood	IL-1 levels within 6 h correlated with the initial injury severity (GCS) and with GOS, but timing of the GOS is not described
Antunes/2010/[197]	Pro	TBI with hemorrhagic contusions	30	IL-6	Blood	IL-6 levels at 6 h were higher in patients who would subsequently clinically deteriorate due to evolving contusions
Combinations of markers
Diaz-Arrastia/2013/[189]	Pro	mild, moderate, & severe TBI	206	UCH-L1, GFAP	Blood	Levels of UCH-L1 were higher with moderate-severe than with mild TBI UCH-L1 levels were poorly predictive of complete recovery but better at predicting poor outcome For predicting complete recovery, UCH-L1 in combination with GFAP was not better than GFAP alone. For predicting favorable vs. unfavorable outcome, UCH-L1 is marginally better than GFAP and both together are better than either alone
Czeiter/2012/[190]	Pro	severe TBI	45	GFAP, UCH-L1, SBDP145	Serum, CSF	GFAP, UCH-L1, and SBDP145 all had at least one measure that was significantly related to unfavorable outcome When included in a model with IMPACT predictors of outcome, serum GFAP during first 24 h and the first CSF UCH-L1 value obtained were significantly related to mortality and only serum GFAP during first 24 h was significantly related to unfavorable outcome In combination, the IMPACT core model with the first CSF GFAP value, the first serum GFAP value, and the first CSF SBDP145 value performed the best

Pro prospective, PPV positive predictive value, Retro retrospective, CTRL control subjects, GOS Glasgow outcome scale, OR odds ratio, PPV positive predictive value