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. 2021 May 28;12:638693. doi: 10.3389/fneur.2021.638693

Table 1.

Summary of the 12 articles included in the systematic review.

Biomarker panel Sample size (n)/groups Time Essays Cut off Specificity Sensitivity Area under the curve References
BNP, D-dimer, MMP-9, and S100β
ICH vs. mimics
n = 946 subjects
293 (IS), 95 (ICH), 197 (TIA), and 361 (mimics)
343 subjects for the validation cohort: 87 (IS), 64 (ICH), 40 (TIA), and 152 (mimics)
ICH vs. mimics
0–3 h
3–6 h
Triage Stroke Panel (fluorescence immunoassay) MMP-9: 25–1,300 ng/mL
D-dimer: 150–5,000 ng/mL
S100β: 100–8,000 pg/mL
BNP: 10–5,000 pg/mL
Stroke vs. mimics: 45%
ICH vs. mimics: 38%
Stroke vs. mimics: 90%
ICH vs. mimics: 88%
Stroke vs. mimics: 0.75
ICH vs. mimics: 0.81
(23)
BNP, D-dimer, MMP-9, S100β, and multimarker index (MMX) n = 139 subjects
89 (AIS), 11 (ICH), and 39 (brain disorders)
AIS vs. others (control, brain diseases)
<6 h Triage® Meter (Biosite Inc.) fluorescence immunoassay MMP-9: 25–1,300 ng/mL
D-dimer: 150–5,000 ng/mL
S100β: 100–8,000 pg/mL
BNP: 10–5,000 pg/mL
21.5% 91.0% 0.714 (24)
BNP, D-dimer, MMP-9, S100β, and multimarker index (MMX) n = 174 subjects
100 (IS), 49 (mimics), and 25 (TIA)
IS vs. mimics
<6 h Triage® Stroke Panel 33% 86% 0.59 (25)
Eotaxin, EGFR, S100A12, TIMP-4, and prolactin n = 167 subjects
57 (IS), 32 (ICH), 41 (TIA), and 37 (mimics)
IS + ICH vs. mimics
<24 h 84%
IS vs. mimics (c = 0.92)
90% 0.97 (26)
D-dimer, caspase-3, sRAGE, MMP-9 chimerin, and secretagogin n = 1,005 subjects
776 (IS), 139 (ICH), and 90 (mimics)
IS vs. mimics
<6 h ELISA immunoassays Caspase-3: 1.962 ng/mL
D-dimer: 0.275 μg/mL
sRAGE: 0.91 ng/mL
chimerin: 1.11 ng/mL
secretagogin: 0.24 ng/mL
MMP-9: 199 ng/mL
63% 84% 0.810 (0.757–0.863) (27)
S100β, MMP-9, VCAM, and vWF n = 80 subjects
44 (IS), 21 (controls), 13 (TIA), 1 (syncope), 1 other conditions
Stroke vs. controls
<6 h
6–24 h
Biosite Inc. 90% 90% (28)
S100β, BNGF, vWF, MMP-9, and MCP-1 n = 274 subjects
82 (ISCH), 65 (SAH), 38 (ICH), 38 (closed head injuries, CLH), and 51 (TIA)
AIS vs. other groups
ICH vs.other groups
<6 h ELISA-immunoassays 93% AIS: 91.7%
ICH: 80%
(29)
IMA index
IMA
n = 52 subjects
28 (IS) and 24 (No-Stroke)
IS vs. no stroke
<6 h Albumin–cobalt binding (ACB) test 91.4 U/mL 96.4% 95.8% 0.990 (0.970–1.000) (30)
AT-III
Fibrinogen
n = 198 subjects
152 (IS) and 46 (mimics)
IS vs. no stroke
4.5 h AT-III: chromogenic assay
Fib: immunoturbidimetry assay
AT-III: 210%
Fib: 4 g/L
AT-III:93.62%
F: 82.61%
AT-III: 97.37%
F: 96.05%
(31)
Ab NR2 and GFAP n = 124 subjects
49 (IS), 23 (ICH), 52 controls
IS vs. ICH
<12 h GFAP: ELISA kit
AB NR2: Gold Dot NR2 Antibody Assay kit (ELISA)
91% 94% (32)
GFAP/UCH-L1
GFAP
n = 184 subjects
45 (ICH), 79 (IS), 5 (SAH), 3 (TIA), and 57 controls
IS vs. controls
ICH vs. controls
IS vs. ICH
<4.5 h ELISA immunoassays GFAP: 0.34 ng/mL

0.875
0.71 (IS vs. C)
0.95 (ICH vs. C)
0.86 (IS vs. ICH)
(33)
ApoC-III, NT-proBNP, and FasL
(21 biomarkers)
n = 1,308 subjects
941 (IS), 193 (mimics) and 174 (hemorrhagic)
767 validation cohort
IS vs. mimics
IS vs. ICH
<6 h ELISA immunoassays IS vs. mimics 0.742 (0.686–0.797)
IS vs. ICH
0.757 (0.691–0.823)
(34)

ROC analysis includes clinical variables selected by the authors. Bold values indicate groups compared in the studies analyzed by Receiver Operating Curve analysis (ROC).