A panel of biomarkers including caspase-3 and D-dimer may differentiate acute stroke from stroke-mimicking conditions in the emergency department

Background and aims. At present, a rapid and widely available diagnostic test for stroke remains elusive. The aim of this study was to examine the predictive value of a panel of blood-borne biochemical markers for stroke diagnosis. Design. Consecutive patients with strokes or stroke mimicking conditions (mimics) were evaluated within 24 h from symptom onset (915 strokes and 90 mimics). Blood samples were analysed by enzyme-linked immunosorbent assay for C-reactive protein, D-dimer, soluble receptor for advanced glycation end products (sRAGE), metalloproteinase 9 (MMP-9), S100B, brain natriuretic peptide, caspase-3, neurotrophin-3, chimerin and secretagogin. Results. The main independent predictors of stroke versus mimics were caspase-3 > 1.96 ng mL(-1) [odds ratio (OR) = 3.32; 95% confidence interval (CI) 1.88-5.88, P < 0.0001], D-dimer > 0.27 mu g mL(-1) (OR = 2.97; 95% CI 1.72-5.16, P = 0.0001), sRAGE > 0.91 ng mL(-1) (OR = 2.19; 95% CI 1.26-3.83, P = 0.006), chimerin < 1.11 ng mL(-1) (OR = 0.4; 95% CI 0.19-0.81, P = 0.011), secretagogin < 0.24 ng mL(-1) (OR = 0.51; 95% CI 0.27-0.97, P = 0.041) and MMP-9 > 199 ng mL(-1) (OR = 1.66; 95% CI 1.01-2.73, P = 0.046). The model's predictive probability of stroke when the six biomarkers are above/below these cut-off levels was 99.01%. The best combination of biomarkers in the model was caspase-3 and D-dimer. Moreover, a model developed for samples obtained within the first 3 h showed high sensitivity (Se) and specificity (Sp) (threshold at 25th percentile: Se 0.87, Sp 0.55; threshold at 75th percentile: Se 0.28, Sp 0.99). Conclusions. A combination of biomarkers including caspase-3 and D-dimer appears to be the most promising to achieve a rapid biochemical diagnosis of stroke. If replicated, this approach could be used as a tool for urgent referral of stroke patients to hospitals in which acute treatments are available.