Table 5.

Biomarkers for intracerebral hemorrhage

Authors/year/Ref	Study design	Population	N	Bio-marker	Sample source	Findings
Molecules of CNS origin
Hu/2012/[132]	Pro	Basal ganglia ICH within 6 h of onset	176	Tau	Serum	Tau >91.4 pg/mL predicted poor 3-month outcome (83.6 % sensitivity; 75.8 % specificity) Addition of tau improved prognostic value of NIHSS for outcome but not for mortality
Hu/2010/[127]	Pro	Basal ganglia ICH	86 ICH, 30 CTRL	s100β	Plasma	s100β was significantly associated with IVH, GCS scores, and ICH volumes s100β is independently associated with mortality at 1 week (OR = 1.046) s100β >192.5 pg/mL predicted 1-week mortality (93.8 % sensitivity; 70.4 % specificity)
Delgado/2006/[126]	Pro	ICH	78	s100β	Blood	s100β was higher in patients who deteriorated early and in patients with a poor neurological outcome
Brea/2009/[129]	Pro	ICH and AIS	44 ICH, 224 AIS	NSE	Blood	NSE elevation at 24 h post ICH was independently associated with poor outcome (OR = 2.6 [1.9–15.6])
James/2009/[128]	Pro	ICH	28	s100β, BNP	Blood	s100β and BNP levels correlated with outcome at hospital discharge Inclusion of biomarkers added little to the predictive power of ICH score
Cai/2013/[133]	Case control	Basal ganglia ICH	112 ICH, 112 CTRL	pNF-H	Plasma	pNF-H is higher in ICH compared to controls pNF-H is an independent predictor of 6-month mortality (OR = 1.287), 6-month unfavorable outcome (OR = 1.265) and early neurological deterioration (OR = 1.246) Addition of pNF-H did not improve predictive value of NIHSS
Biomarkers of inflammation
Leira/2004/[137]	Pro	ICH within 12 h of onset	266	Neutrophils, fibrinogen	Blood	Higher neutrophil count (OR = 2.1) and fibrinogen >523 mg/dL (OR = 5.6) on admission were independently associated with early neurological deterioration
Di Napoli/2011/[135]	Pro	ICH	210	WBC, CRP, Glucose	Blood	Higher WBC, CRP, and glucose were significantly related to mortality Only CRP remained significantly related to mortality when adjusted for ICH score and the combination of ICH score and CRP had the best predictive ability
Agnihotri/2011/[136]	Retro	Spontaneous ICH	423	WBC	Blood	Change in WBC (difference between max WBC in first 72 h and WBC on admission) correlated with worse discharge disposition and decline in modified Barthel Index at 3 months
Zhao/2013/[149]	Pro	Basal ganglia ICH within 6 h of onset	132 ICH, 68 CTRL	pGSN	Plasma	pGSN was lower in ICH compared to controls pGSN is an independent predictor of 6-month mortality and unfavorable outcome in multivariate analysis pGSN improved prognostic value of NIHSS for poor outcome but not for mortality
Castillo/2002/[134]	Pro	ICH within 24 h of onset	124	Glutamate, TNFα	Blood	Glutamate level was an independent predictor of poor outcome TNFα correlated with volume of peri-hematoma edema
Wang/2011/[139]	Pro Posthoc analysis	ICH within 24 h of onset	60	sICAM-1, sE-selectin	Plasma	Higher levels of sICAM-1 and sE-selectin were found in patients who had a poor outcome at hospital discharge.
Li/2013/[148]	Pro	ICH within 24 h of onset	59	MMP-3, MMP-9	Plasma	Elevated MMP-3 was independently associated with peri-hematoma edema volume MMP-3 >12.4 μg/L and MMP-9 >192.4 μg/L were associated with poor outcome in multivariate analysis
Hernandez-Guillamon/2012/[140]	Pro	ICH within 48 h of onset	66 ICH, 58 CTRL	VAP-1/SSAO	Plasma	VAP-1/SSAO activity <2.7 pmol/min·mg was independent predictor of neurological improvement after 48 h (OR = 6.8)
Fang/2005/[141]	Pro	ICH	43	IL-11	Plasma	samples collected in first 4 days of ICH plasma IL-11 higher in non-survivors compared to survivors
Diedler/2009/[138]	Retro	Supratentorial ICH	113	CRP	Blood	CRP is independent predictor of poor long-term functional outcome
Gu/2013/[142]	Pro	Basal ganglia ICH within 6 h of onset	85 ICH, 85 CTRL	Visfatin	Plasma	Visfatin was higher in ICH compared to controls Visfatin level was independent predictor of hematoma growth. (OR = 1.154 [1.046–3.018]) and of early neurological deterioration (OR = 1.195 [1.073–3.516])
Huang/2013/[143]	Case control	Basal ganglia ICH	128 ICH, 128 CTRL	Visfatin	Plasma	ICH patients had higher visfatin compared to controls Visfatin correlated with NIHSS and is independent predictor for 6-month mortality and unfavorable outcome
Zhang/2013/[144]	Pro	Basal ganglia ICH	92 ICH, 50 CTRL	Leptin	Plasma	Leptin higher in ICH compared to controls Leptin on admission is independent predictor of 6-month mortality and unfavorable outcome
Other biomarkers
Chiu/2012/[150]	Pro	ICH within 24 h of onset, >16 years old	170	d-dimer	Serum	d-dimer is independently associated with 30-day mortality (OR = 2.72)
Delgado/2006/[126]	Pro	ICH	98	d-dimer	Plasma	d-dimer levels were associated with presence of IVH or SAH extension d-dimer >1,900 μg/L is independently associated with early neurological deterioration (OR = 4.5) and with mortality (OR = 8.75)
Rodriguez-Luna/2011/[151]	Pro	Supratentorial ICH within 6 h of onset	108	LDL-C	Serum	Lower LDL-C levels were associated with hematoma growth, early neurological deterioration and 3-month mortality but not with NIHSS or ICH volume
Ramirez-Moreno/2009/[152]	Pro	ICH within 12 h of onset	88	LDL-C	Serum	Lipid profile measured in first hour after admission Low LDL-C levels were independently associated with death after ICH in multivariate analysis (HR = 3.07) LDL-C correlated with NIHSS, GCS, and ICH volume
Hays/2006/[153]	Retro	ICH	235	cTn1	Blood	Elevated cTn1 was independent predictor of in-hospital mortality
Chen/2011/[158]	Pro	ICH	64 ICH, 114 CTRL	Oxidative markers	Blood	Blood collected within 3 days of ICH Measured 8-OHdG, G6PD, GPx, MDA, vitamin E, vitamin A 8-OHdG elevation was independently associated with 30-day lower Barthel index but not with outcome by mRS
Wang/2012/[155]	Pro	ICH within 24 h of onset	60 ICH, 60 CTRL	Nuclear DNA	Plasma	Nuclear but not mitochondrial DNA correlated with GCS and ICH volume on presentation Nuclear DNA >18.7 μg/L on presentation was associated with poor outcome at discharge (63.6 % sensitivity; 71.4 % specificity)
Huang/2009/[154]	Pro	Basal ganglia ICH	36 ICH, 10 CTRL	Microparticles	Plasma, CSF	Plasma and CSF microparticles levels were associated with GCS score, ICH volume, IVH, and survival Controls have suspected SAH
Zheng/2012/[156]	Case control	ICH	79	miRNAs	Blood	Patients with hematoma expansion had different expression pattern of miRNAs (19 with increased expression, 7 with decreased expression)
Zhang/2012/[157]	Pro	Basal ganglia ICH	89 ICH, 50 CTRL	Copeptin	Plasma	Copeptin level is an independent predictor for 1-year mortality, poor outcome, and early neurological deterioration Copeptin did not improve prognostic value of NIHSS

Pro prospective observational, RCT randomized controlled trial, Retro retrospective, CTRL control subjects, OR odds ratio