Blood biomarkers as an alternative to imaging in diagnosing acute ischaemic stroke
| Author, date , country | Patient group | Study type (level of evidence) | Outcomes | Key results | Study weaknesses |
| Steigleder et al,
2 2012, Germany | 42 patients admitted with AIS defined clinically had blood collected within 6 hours after symptom onset and different time points afterwards to measure GPBB | Prospective cohort study | Difference in AIS plasma GPBB compared with controls: 68.0±40.5 vs <10 ng/mL | Sensitivity, specificity and AUC not included | Conference paper Sample size calculation not included Small sample size CSF GPBB levels not measured |
| Long et al
3 2013, China | 197 patients with first-ever AIS defined by ICD-9 had blood samples collected at different time points after stroke onset to measure levels of miR-30a, miR-126 and let-7b | Cross-sectional study | Difference in large-vessel atherosclerosis AIS plasma let-7b compared with controls: 70%–75% (p<0.05) | Sensitivity 79.6% Specificity 72.1% AUC 0.801 | Sample size calculation not included Small sample size Reasons behind varying expressions of let-7b among various types of AIS were not investigated CSF miRNAs levels not measured |
| Difference in other types of AIS plasma let-7b when compared with controls: 3.51–14.42 fold increase (p<0.05) | Sensitivity 92% Specificity 84% AUC 0.93 | ||||
| Tian et al,
4 2015, China | 442 patients with first-ever AIS defined according to WHO criteria and with symptom onset within 24 hours had fasting venous blood collected on day of admission to measure serum levels of PCT | Prospective cohort study | Difference in AIS serum PCT when compared with controls: 1.04 vs 0.25 ng/mL (p<0.0001) | Sensitivity 79.6% Specificity 72.1% AUC 0.801 | Did not record data on when and for how long PCT levels were elevated No follow-up data collected CSF PCT levels in CSF not measured |
| Qi et al,
5 2015, China | 312 patients with first-ever AIS defined according to WHO criteria and with symptom onset within 24 hours had blood collected a day after admission to measure serum thioredoxin levels | Prospective cohort study | Difference in median AIS serum TRX compared with controls: 15.03 vs 8.95 ng/mL (p<0.0001) | Sensitivity 80.3% Specificity 73.7% AUC 0.87 | Igs in serum might have affected results of immunoassays by binding to reagent antibodies CSF TRX levels not measured Serial measurements of TRX levels not done TRX measurements may not accurately reflect prestroke exposure |
| Peng et al,
6 2015, China | 72 patients admitted with clinical history and MRI results supporting diagnosis of first-ever AIS had blood and CSF samples collected at different time points after stroke onset to measure let-7e levels | Prospective cohort study | Difference in AIS serum let-7e compared with controls 1.5 vs 0.88 (p=0.0001) | Sensitivity and specificity not included AUC 0.86 | Sample size calculation not included Small sample size Let-7e target proteins not measured Did not match cardiovascular comorbidities of the patients Method used required time |
| Li et al,
7 2016, China | 206 patients admitted with first-ever AIS defined according to WHO criteria with symptoms within 72 hours had their blood collected at 06:00 after admission to measure IL-33 levels | Prospective cohort study | Difference in AIS serum IL-33 compared with control: 57.68 vs 45.00 ng/L (p<0.001) | Sensitivity, specificity and AUC not included | Circulating IL-33 levels were only measured once, that is, no serial measurements CSF and IL-33 levels not measured |
| Optimal cut-off value of serum IL-33 levels as an index to diagnose AIS: 47.92 ng/L | Sensitivity 69.9% Specificity 44.4% AUC 0.706 | ||||
| Ormstad et al,
8 2016, Norway | 45 patients admitted with first-ever AIS defined according to ICD-10 had their blood collected at different time points to measure serum PHE and TYR levels | Prospective cohort study | Difference in AIS serum TYR compared with control: 74.3 vs 83.8 1¼m (p=0.035) | Sensitivity 76% Specificity not included AUC 0.82 | Sample size calculation not included Small sample size with significant inclusion bias Did not include haemorrhage or stroke-mimics CSF TYR and PHE levels not measured |
| Difference in AIS serum PHE compared with control: 124 vs 101 1¼m (P<0.001) | Sensitivity 85% Specificity N/A AUC 0.88 | ||||
| Walsh et al,
9 2016, USA | 14 patients admitted with AIS diagnosed clinically and by neuroimaging had blood collected within 12 hours of symptom onset to measure Apo A-I and Po-1 levels | Prospective cohort study | Difference in AIS serum Apo A-I compared with control: 140 vs 175 mg/dL (no p value) | Sensitivity, specificity and AUC not included | Small sample size Only recruited patients at a single site Did not draw samples within an even shorter time range (ie, within 12 hours vs within 3 hours of symptom onset) Serial measurements were not taken CSF Apo A-I and Po-1 levels not measured |
| Difference in AIS serum Po-1 compared with control: 2 50 500 vs 3 45 500 mg/dL (no p-value) | Sensitivity, specificity and AUC not included | ||||
| Ranga et al,
10 2016, India | 60 male patients admitted with AIS diagnosed by CT brain or MRI brain had blood collected within 24 hours of stroke onset to measure CEA | Cross-sectional study | Difference in AIS serum CEA compared with control: 5.26 vs 1.38 ng/mL (p=0.001) | Sensitivity, specificity and AUC not included | Small sample size Only men were included Inability to determine presence of a causal relationship between rise in CEA and AIS due to the nature of the study CSF CEA levels not measured |
| AIS, acute ischaemic stroke; Apo, apolipoprotein ; AUC, area under the curve; CEA, carcinoembryonic antigen; CSF, cerebrospinal fluid; GPBB , glycogenphosphorylase isoenzyme BB; ICD, International Classification of Diseases; IL, interleukin; PCT, procalcitonin; PHE, phenylalanine; Po-1, paraoxonase-1; TYR, tyrosine. | |||||