Purine Metabolism Profiling Reveals Distinct Associations of Uric Acid, Xanthine, and Hypoxanthine with Neurological Severity and Functional Outcome After Acute Ischemic Stroke

Purine metabolism and oxidative stress are increasingly recognized as important contributors to ischemic brain injury following acute ischemic stroke (AIS). Although uric acid has been extensively investigated because of its dual antioxidant and pro-oxidant properties, comparatively limited data exist regarding the prognostic relevance of upstream purine metabolites such as xanthine and hypoxanthine. The present study aimed to evaluate the association between serum uric acid, xanthine, and hypoxanthine concentrations and neurological severity and functional outcome following AIS. We performed a prospective observational cohort study including 143 consecutive patients admitted with acute ischemic stroke in a tertiary neurological center. Neurological severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), while functional outcome was evaluated using the modified Rankin Scale (mRS) at discharge and at 3-month follow-up. Plasma xanthine and hypoxanthine concentrations were quantified using validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) methodology. Distribution normality was assessed using Shapiro–Wilk and Kolmogorov–Smirnov testing. Comparative analyses were performed using Student’s t-test, the Mann–Whitney U test, and the Kruskal–Wallis test, according to the distribution and measurement scale of the variables. Correlations were assessed using Spearman’s rank correlation coefficient and visualized using a heatmap. Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression models were additionally performed in order to evaluate the predictive performance of purine metabolism biomarkers for unfavorable functional outcome. Numerically lower serum uric acid concentrations were observed in patients with poorer functional outcomes at discharge and at 3 months, although these differences were not statistically significant. Hypoxanthine concentrations varied significantly according to admission NIHSS severity categories (p = 0.022), with lower values observed among patients presenting severe neurological deficits. Plasma xanthine concentrations demonstrated significant association with unfavorable long-term functional outcome (p = 0.033) and exhibited the highest predictive performance in ROC analysis (AUC = 0.614). In the adjusted multivariable logistic regression model, admission NIHSS remained the main independent predictor of unfavorable 3-month functional outcome, whereas xanthine and the other purine biomarkers did not retain statistically significant independent associations. Purine metabolism biomarkers showed exploratory associations with neurological severity and functional outcome, but the underlying biological mechanisms were not directly assessed. Simultaneous assessment of uric acid together with xanthine and hypoxanthine may provide additional insight into stroke severity and neurological recovery, supporting the potential role of purine metabolism profiling as a complementary biomarker approach in acute ischemic stroke.