Intracranial and Peripheral Inflammatory Biomarkers Predict Futile Recanalization after Endovascular Treatment

BACKGROUND: Futile recanalization (absence of functional independence despite successful endovascular treatment [EVT]) remains a limitation in the treatment of large vessel occlusion stroke. Inflammation has emerged as a key contributor to brain reperfusion injury. Leveraging EVT, we quantified a large panel of immunologic biomarkers in the intracranial and peri-procedural peripheral blood samples and probed their association with futile recanalization. METHODS: We conducted a prospective single-center cohort study of patients with anterior-circulation large vessel occlusion, successful EVT (modified Thrombolysis in Cerebral Infarction ≥2b), and no reocclusion. We sampled intracranial blood distal to the thrombus before recanalization and collected peripheral blood immediately before and after EVT, and at 24 hours post-EVT. We measured 37 immune-vascular biomarkers selected a priori, using immunoassays, and tested their associations with futile recanalization (90-day modified Rankin Scale score, 3-6) using rank-based tests with false discovery rate control. Biomarkers meeting a prespecified effect-size threshold (≥0.5) entered multivariable logistic regression models adjusted for age, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, intravenous thrombolysis use, and time from last known well to groin puncture. RESULTS: Among 177 enrolled patients, 139 patients were included (median age, 77 years; 41% women), and 64 (46%) had futile recanalization. Six biomarkers showed at least a medium effect size at ≥1 timepoints: IL (interleukin)-6 (pre-EVT, intracranial, and 24-hour post-EVT), IL-10 (pre-EVT and intracranial), IL-15 (pre-EVT), VEGFR1 (vascular endothelial growth factor receptor 1; pre-EVT and 24-hour post-EVT), VCAM-1 (vascular cell adhesion molecule-1; intracranial and post-EVT), and SAA (serum amyloid A; post-EVT). In adjusted multivariable analyses, futile recanalization remained associated with VCAM-1 intracranially (adjusted odds ratio [aOR], 1.84 [95% CI, 1.11-3.05]) and post-EVT (aOR, 2.08 [95% CI, 1.03-4.19]), IL-10 pre-EVT (aOR, 3.87 [95% CI, 1.58-9.43]) and intracranially (aOR, 4.84 [95% CI, 1.68-13.90]), IL-15 pre-EVT (aOR, 1.60 [95% CI, 1.00-2.53]), and SAA post-EVT (aOR, 7.08 [95% CI, 1.95-25.59]). CONCLUSIONS: A core set of immune-vascular mediators measured in blood, both intracranially and peripherally, after EVT predicted futile recanalization. These findings support biomarker-guided risk stratification and motivate trials targeting microvascular inflammation.