Skip to main content
. 2022 Sep 22;14(4):784–803. doi: 10.3390/neurolint14040065

Table 1.

Basic characteristics of the 28 included studies.

Authors, Year of Publication Biomarker Type of Study Type of Stroke Number of Participants/Mean Age Time of Blood Sampling Scale of Stroke Severity and
Prognosis/Clinical Outcome		 Cut-Off Values; (Specificity); [Sensitivity] Main Results
1. Montaner et al. 2012 [44] BNP Longitudinal IS and HS 896 patients/72 (SD 12) Upon admission (within 24 h from symptom onset)

  • NIHSS (on admission and at discharge)

  • For neurological deterioration: BNP > 56.7 ng/L; (47.9%); [68.8%]

  • For death after stroke: BNP > 65.3 ng/L; (51.2%); [73.5%]

 For both IS and HS, elevated
BNP levels were associated with early neurological deterioration and mortality.
2. Maruyama et al. 2013
[45]		 BNP Longitudinal IS 231 patients/71 ± 12 Upon admission

  • NIHSS (on admission),

  • mRS (at discharge or 2 months after stroke onset)

 Types of IS:

  • SVO: 29 pg/mL (13–91); (N.A.); [N.A.]

  • LAA: 54 pg/mL (30–101); (N.A.); [N.A.]

  • CE: 202 pg/mL (120–385); (N.A.); [N.A.]

  • Other: 12 pg/mL (7–57); (N.A.); [N.A.]

 High BNP levels might serve as a useful biomarker to predict
cardioembolism (CE) and its clinical outcome as well as the size of cerebral infarct and the risk for stroke in AF patients.
3. Tu et al. 2013 [46] BNP Longitudinal IS 189 patients/66 (IQR 58–75) The first morning after admission

  • NIHSS (on admission and on day 90),

  • mRS (at discharge or within 90 days)

  • 100 pg/mL; (N.A.); [N.A.]

 Increased BNP levels were associated with IS clinical severity and unfavorable short-term outcomes.
4. Nigro et al. 2014 [47] BNP Longitudinal IS and TIA 441 patients/74.6 (IQR 62.6–81.9) Upon admission
(within 72 h from
symptom onset)

  • NIHSS (on admission),

  • mRS (3 and 12 months after stroke onset)

 N.A. Increased BNP levels can be used to predict unfavorable clinical outcomes and mortality within 90 days as
well as in the first year after
stroke. In addition, BNP levels were higher in patients with a cardioembolic stroke or TIA.
5. Chaudhuri et al. 2015 [30] BNP Longitudinal IS 270 patients, 110 healthy controls/patients: 59 (21–87), controls: 58 (23–85) Upon admission

  • NIHSS and mRS (on admission and 3 months after stroke onset)

 89 pg/mL; (62.2%); [83.9%] A significant association was noticed between elevated
BNP levels and cardioembolic stroke.
6. Maruyama et al. 2017
[48]		 BNP Longitudinal IS 168 NVAFpatients with
cardioembolic stroke, 157 were eligible for analysis/76.3 ± 10.2		 Upon admission

  • NIHSS (on admission),

  • mRS (3 months after stroke onset)

 Poor functional outcome: BNP > 115 pg/mL; (N.A.); [N.A.] A positive correlation between BNP levels on admission and the
mRS score at 3 months in patients with NVAF after AIS was detected.
7. Otaki et al. 2019 [49] BNP Longitudinal IS 282 patients, 138 controls/patients: 71 ± 12, controls: 67 ± 13 Blood samples were obtained
before TEE
(transesophageal
echocardiography)

  • NIHSS

  • For cardiogenic stroke: 58.2 pg/mL; (N.A.); [N.A.]

  • For MACCE: 73.4 pg/mL; (N.A.); [N.A.]

 BNP can be used as a biomarker to predict cardiogenic stroke.
8. Xiong et al. 2015 [32] GFAP Longitudinal HS
(ICH) and IS		 43 ICH and
65 IS patients/ICH patients: 68.7 ± 11.2, IS patients: 70.9 ± 9.6		 Upon admission

  • NIHSS (on admission),

  • mRS (3 months after stroke onset)

  • Differentiation between ICH and IS: 0.7 ng/mL; (76.9%); [86.0%]

  • Poor functional outcome: 1.04 ng/mL; (80.0%); [95.7%]

 Differences in serum concentrations of GFAP
between ICH and IS can be
used to differentiate strokes. In patients with ICH, GFAP levels were higher.
9. Liu et al.
2018 [50]		 GFAP Longitudinal IS 286 patients/Q1 3: 61 (50–72), Q4: 67 (56–78) On the first day of admission

  • NIHSS (on admission),

  • mRS (one year after stroke onset)

 0.25 [0.16–0.34] ng/mL in patients with moderate-to-high clinical severity; (N.A.); [N.A.] GFAP levels on admission may predict clinical and functional outcomes after IS.
10. Kim et al. 2012 [51] RDW Longitudinal IS 847/65.88 ± 12.45 Upon admission

  • NIHSS (on admission),

  • mRS (3 months after stroke onset)

  • Poor outcome: RDW > 13.37 ± 1.41; (N.A.); [N.A.]

  • Mortality at 3 months: RDW > 14.04 ± 1.71; (N.A.); [N.A.]

 Higher values of RDW were associated with poor functional outcomes and higher mortality.
11. Ye et al. 2020 [52] RDW Longitudinal IS 480/71 (IQR 16) Upon admission

  • NIHSS (on admission and at discharge),

  • mRS (at discharge and one year after stroke onset)

 14.65; (88.3%); [42%] RDW before thrombolysis could be used as a predictor of one-year mortality but
not for stroke severity prognostication.
12. Cong et al. 2020 [53] RDW Longitudinal IS 196/64.22 ± 12.45 Upon admission

  • NIHSS (on admission, 24 h after stroke onset, and at discharge),

  • mRS (on admission, at discharge, and 3 months after stroke onset)

 Poor prognosis ≥ 13.15; (60.7%); [64.0%] An elevated RDW value was associated with poor
prognosis in patients who received rtPA thrombolysis.
13. Cui et al. 2020 [54] RDW Longitudinal HS (ICH) 235/64.6 ± 14.5 Upon admission

  • mRS (30 days after stroke onset)

  • Nonsurvivors: 14.7 ± 1.2; (N.A.); [N.A.]

  • Unfavorable outcome: 14.2 ± 1.3; (N.A.); [N.A.]

 High RDW values were correlated with
poor clinical outcomes in patients with ICH.
14. Brooks et al. 2014 [55] NLR Longitudinal IS 116/67 (18–93) Upon admission

  • NIHSS (on admission),

  • mRS (3 months after stroke onset)

  • Poor outcome: NLR ≥ 5.9; (N.A.); [N.A.]

  • Functional independence: NLR < 3.2; (N.A.); [N.A.]

 In patients with IS who underwent endovascular treatment, NLR > 5.9 predicted poor outcomes and death and NLR < 3.2 predicted an outcome of functional independence.
15. Sun et al. 2016 [56] NLR Longitudinal HS (ICH) 352/64.2 ± 13.8 Upon admission

  • NIHSS (on admission),

  • mRS (3 months after stroke onset)

 NLR ≥ 7.85; (N.A.); [N.A.] Patients with higher admission NLR values had larger hematoma volumes and
higher baseline NIHSS scores.
16. Tao et al. 2016 [57] NLR Longitudinal HS (ICH) 336/58.5 ± 13.0 Upon admission

  • mRS (3 months after stroke onset)

  • For predicting poor 90-day outcome: NLR > 6.28; (57.4%); [73.3%]

  • For predicting 90-day mortality: NLR > 6.62; (N.A.); [N.A.]

 Elevated levels of NLR can predict poor 90-day outcomes after ICH.
17. Malhotra et al. 2018 [58] NLR Longitudinal IS 657/64 ± 14.4 Within
12 h from admission

  • NIHSS (on admission),

  • mRS (3 months after stroke onset)

 For 3-month favorable functional outcome and functional independence: NLR < 2.2; (63.1%); [51.4%] In AIS patients treated with
IVT, lower NLR levels were associated with favorable clinical outcomes at 3 months.
18. Pikija et al. 2018 [59] NLR Longitudinal HS (ICH) 187/74 (IQR 60–81) Upon admission

  • NIHSS (on admission and at discharge),

  • mRS (3 months after stroke onset)

 3.89; (73.0%); [67.0%] Patients who developed ICH after EVT had higher admission NLR values.
19. Pektezel et al. 2019 [60] NLR Longitudinal IS 142/69 ± 13 Upon admission
and after 24 h

  • NIHSS (on admission, at 24 h after IV tPA, and at discharge),

  • mRS (3 months after stroke onset)

  • NLR ≤ 3.2 indicates IV tPA effectiveness; (84%); [48%]

  • NLR ≤ 3.6 indicates favorable prognosis; (73%); [65%]

  • NLR ≤ 7.4 indicates absence of symptomatic cerebral hemorrhage; (76%); [100%]

 Increased NLR values during the first 24 h were associated with poor
prognosis. Pretreatment
NLR values seemed to have no connection with the IV tPA response.
20. Fonseca et al. 2019 [61] NLR Longitudinal HS (ICH) 135/73 (64–80) Upon admission

  • GCS (on admission),

  • NIHSS (on admission),

  • ICH score (on admission),

  • FUNC score (on admission),

  • mRS (3 months after stroke onset)

  • Independence at 90 days (mRS 0 to 2): NLR < 2.3; (N.A.); [N.A.]

  • Mortality at 30 days: NLR > 4.4; (N.A.); [N.A.]

  • Significant early cerebral edema: NLR > 8.06; (N.A.); [N.A.]

 Higher NLR values at admission were associated with unfavorable functional outcomes.
21. Aly et al. 2021 [62] NLR Longitudinal IS 142/70 ± 16 Upon admission,
(within 3–7 days)

  • NIHSS (on admission),

  • mRS (3 months after stroke onset)

 Favorable outcome: follow-up NLR at 3–7 days < 5.3; (68.0%); [76.0%] Lower follow-up NLR at 3–7 days was associated with successful reperfusion and positive clinical outcomes.
22. Topcuoglu et al. 2021
[63]		 NLR Longitudinal IS 165/70 ± 14 Upon admission
and 24 h after
IV tPA

  • NIHSS (on admission and at 24 h after IV tPA),

  • mRS (3 months after stroke onset)

 For symptomatic PH2-type hemorrhagic transformation: NLR > 5.65; (65.7%); [71.3%] Patients who responded well to IV tPA had lower NLR
values. On the other hand, those patients who
developed symptomatic
hemorrhagic transformation after IV tPA had higher pretreatment
NLR values.
23. Chen et al. 2021 [64] NLR Longitudinal IS 257 AIS patients who
underwent
EVT/63.2 ± 12.6		 Upon admission

  • NIHSS (on admission, within 72 h),

  • mRS (3 months after stroke onset)

 N.A. Increased levels of NLR may be associated with unfavorable clinical
outcomes in stroke patients who underwent EVT.
24. Menon et al. 2021 [65] NLR Longitudinal HS (ICH) 851/58.09 ± 12.85 Upon admission

  • mRS (3 months after stroke onset)

 NLR > 8.2; (N.A.); [N.A.] NLR above the cutoff of 8.2 at admission was
associated with unfavorable functional outcomes and high mortality.
25. Chang et al. 2021 [66] NLR Longitudinal HS (SAH) 474/56 ± 16 Upon admission

  • mRS (at discharge),

  • Hunt Hess Scale (at discharge)

 Poor functional outcome at discharge: NLR > 6.48; (N.A.); [N.A.] Higher NLR values at admission corresponded to poor functional outcomes in aSAH patients.
26. Sapojnikova et al. 2014
[67]		 MMP-9 Longitudinal IS 42 patients, 32 healthy controls/patients: 69 ± 15, healthy controls: 63 ± 20 Upon admission

  • GCS (on admission),

  • GOS (at discharge, one month after IS),

  • Barthel index, mRS, and Allen scale

 N.A. A linear correlation was detected between highlevels of MMP-9 and poor functional outcomes.
27. Zhong et al. 2017 [68] MMP-9 Longitudinal IS 767/62.4 ± 10.8 Within 24 h of
hospital admission

  • NIHSS (on admission).

  • mRS (3 months after stroke onset)

 812.2 ng/mL; (N.A.); [N.A.] Elevated MMP-9 levels in the acute phase of ischemic stroke were accompanied by
increased risks of mortality and major disability.
28. Ramiro et al. 2019 [69] AQP4 Longitudinal IS 42 t-PA-treated
patients, 13 healthy controls/patients: 74 (66–78), controls: 76 (70–83)		 Upon admission

  • NIHSS (on admission, at 48 h, and at discharge),

  • mRS (3 months after stroke onset)

  • cut-off point for AQP4 associated with patients’ neurological improvement 48 h after stroke: 2.52 ng/mL; (89.9%); [54.5%]

  • cut-off point for AQP4 that was associated with neurological improvement by the time of hospital discharge: 1.72 ng/mL; (76.9%); [58.6%]

 Lower circulating AQP4 levels were associated with early neurological improvement.
In addition, an inverse correlation was found between AQP4 values and the infarct size.

Abbreviations. AF: atrial fibrillation, aSAH: aneurysmal subarachnoid hemorrhage, AQP4: aquaporin-4, BNP: brain natriuretic peptide, CE: cardioembolism, EVT: endovascular thrombectomy, FUNC: Functional Outcome in Patients with Primary Intracerebral Hemorrhage, GCS: Glasgow Coma Scale, GFAP: glial fibrillary acidic protein, GOS: Glasgow Outcome Scale, HS: hemorrhagic stroke, ICH: intracerebral hemorrhage, IQR: interquartile ranges, IS: ischemic stroke, IVT: intravenous thrombolysis, LAA: large artery atherosclerosis, MACCE: major adverse cardiovascular and cerebrovascular events, MMP-9: matrix metalloproteinase-9, mRS: modified Rankin Scale, N.A.: not applicable, NIHSS: National Institutes of Health Stroke Scale, NLR: neutrophil-to-lymphocyte ratio, NVAF: nonvalvular atrial fibrillation, RDW: red cell distribution width, SAH: subarachnoid hemorrhage, SVO: small vessel occlusion, TIA: transient ischemic attack.