Early Inflammatory Biomarkers Associated With Functional Outcomes in Acute Cerebral Venous Thrombosis: CLOT-VENUS Substudy

BACKGROUND: Inflammatory serum biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are associated with outcomes in acute cerebrovascular diseases. However, their prognostic role in cerebral venous thrombosis remains uncertain. We aimed to assess the prognostic value of these biomarkers in acute cerebral venous thrombosis by identifying optimal thresholds and internally validating their predictive performance. METHODS: This retrospective observational cohort study included adults diagnosed with acute cerebral venous thrombosis from the international CLOT-VENUS registry (Collaboration on Cerebral Venous Thrombosis Study; 2004–2024), including 2 comprehensive stroke centers in the United States and Mexico. Biomarkers of interest (NLR, MLR, PLR, SII) were calculated from admission complete blood counts. The primary outcome was functional status at 6 months, measured by the modified Rankin Scale dichotomized as 0 to 2 versus 3 to 6. Secondary outcomes included modified Rankin Scale score at discharge and mortality. Associations were tested with multivariable logistic regression adjusted for clinically relevant covariates. Optimal biomarker cutoffs were identified using stratified bootstrap receiver operating characteristic analysis and internally validated with out-of-bag testing. RESULTS: Of 432 patients, 394 met the inclusion criteria, and complete data were available for 339 of those patients. Median age was 40 years [interquartile range, 27–45], and 65.2% were female. Elevated biomarkers at admission were associated with modified Rankin Scale score 3 to 6 at discharge and 6 months. At 6 months, optimal cutoff values for NLR ≥4.88 (adjusted odds ratio [aOR], 2.19; P =0.044), MLR ≥0.54 (aOR, 2.32; P =0.027), PLR ≥161.04 (aOR, 3.33; P =0.003), and SII ≥1388.58 (aOR, 2.03; P =0.049). Similar associations occurred at discharge using the same thresholds. PLR and SII notably predicted mortality at discharge (PLR aOR, 6.33; P =0.008, and SII aOR, 3.93; P =0.031) and at 6 months (PLR aOR, 7.19; P =0.004, and SII aOR, 4.69; P =0.010). CONCLUSIONS: Elevated admission levels of NLR, PLR, MLR, and SII are independently associated with poor discharge and 6-month outcomes in patients with acute cerebral venous thrombosis. These accessible biomarkers may aid early risk stratification. Further studies should validate and explore its usefulness in clinical models for personalized management.