Vagus nerve stimulation: anti-inflammatory effects in epilepsy

Introduction: Vagus Nerve Stimulation (VNS) is an established standard of care for drug-resistant epilepsy; however, the biological mechanisms underlying its cumulative therapeutic effect remain incompletely understood. This study aims to evaluate the monitoring value of neuroinflammation and neurodegeneration biomarkers to objectify the therapeutic response. Methods: In this prospective longitudinal study, we evaluated 40 pediatric patients (20 receiving active VNS therapy and 20 age-matched controls). Plasma levels of UCHL-1, HMGB1, and NSE were investigated as potential indicators of blood-brain barrier status, neuroinflammation, and metabolic stress, respectively. Measurements were performed at baseline and after 3, 6, and 12 months of treatment. Clinical efficacy was defined by the reduction in seizure frequency. Results: = 0.63). Notably, NSE levels exhibited no significant longitudinal changes during the observation period. Conclusion: VNS efficacy appears to be associated with a complex, multi-phasic biological response. The temporal dynamics of peripheral biomarkers may reflect a potential early stabilization of the blood-brain barrier, followed by delayed systemic immunomodulation. While blood-based analysis precludes direct conclusions regarding central neuroinflammation, the delayed reduction of circulating inflammatory signals points to a systemic anti-inflammatory effect that likely contributes to the cumulative therapeutic benefits. Thus, dynamic assessment of these accessible neuroimmune proteins provides an objective systemic correlate of clinical improvement. This biomarker panel may serve as a valuable supportive tool for monitoring VNS therapeutic response and guiding personalized neuromodulation parameters.