Differential prognostic value of circulating biomarkers across small ischemic stroke subtypes

Circulating biomarkers reflecting inflammation and endothelial dysfunction have been proposed as indicators of cerebral small vessel disease; however, their relevance during the hyperacute phase of ischemic stroke remains uncertain. We aimed to determine whether circulating biomarkers measured on admission differ between small ischemic stroke subtypes and whether they provide prognostic information beyond conventional predictors. We conducted a retrospective analysis of 168 patients with acute ischemic stroke treated with intravenous thrombolysis within 4.5 h of onset, classified by MRI as having recent small subcortical infarcts (RSSI; n = 84) or small cortical or cortico-subcortical infarcts (non-RSSI; n = 84). We measured admission blood levels of interleukin-1β, interleukin-6, matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), neurofilament light chain (NfL), C-reactive protein (CRP), and leukocyte ratios, and evaluated their associations with 3‑month functional outcomes using the modified Rankin Scale. Our findings showed that RSSI patients were younger (66 vs. 74 years, p < 0.001) and had smaller infarcts (0.68 vs. 2.55 mL, p < 0.001). Higher NfL (OR 2.07, p < 0.001) and VCAM‑1 levels (OR 1.84, p = 0.034) were associated with poorer outcomes. Notably, the prognostic contribution of CRP, MMP‑9, and VCAM‑1 was more pronounced in patients with RSSI. These findings suggest that circulating biomarkers may offer additional prognostic value, with patterns varying across small ischemic stroke subtypes, though their clinical utility warrants further investigation.