Abstract Background and aims Circulating biomarkers reflecting inflammation and endothelial dysfunction have been proposed as indicators of cerebral small vessel disease. Still, their relevance during the hyperacute phase of ischemic stroke, not only in small vessel disease, remains uncertain. In this study we examine whether circulating biomarker profiles measured on admission differ between in patients with recent small subcortical infarcts (RSSI) and small cortical or cortico-subcortical stroke (non-RSSI), and whether they have prognostic value beyond conventional predictors. Methods Retrospective analysis of 168 patients with acute ischemic stroke treated with intravenous thrombolysis within 4.5 hours of onset. Patients were classified by magnetic resonance imaging as RSSI (n=84) or non-RSSI (n=84). Admission blood levels of interleukin-1β, interleukin-6, matrix metalloproteinase-9, vascular cell adhesion molecule-1, neurofilament light chain, C-reactive protein, and leukocyte count ratios were measured. Associations with 3-month functional outcomes (modified Rankin Scale) were evaluated using multivariable regression. Results RSSI patients were younger (66 vs. 74 years, p 0.001) and had smaller infarcts (median 0.68 vs. 2.55 mL, p0.001). Neurofilament light chain (OR 2.07, p0.001) and vascular cell adhesion molecule-1 (OR 1.84, p=0.034) predicted poorer outcomes in adjusted models. The prognostic value of C-reactive protein, matrix metalloproteinase-9, and VCAM-1 was more substantial in RSSI than in non-RSSI patients. Conclusions In RSSI, markers of inflammation and endothelial dysfunction improved outcome prediction, suggesting a role for microvascular pathology in recovery. The integration of biomarker profiling into early stroke assessment might help identify patients who could benefit from adjunctive therapies targeting microvascular dysfunction. Conflict of interest Dario Ramis: nothing to disclose.
Ramis et al. (2026) studied this question.