Clinical application of HMGB1-TLR4 signaling pathway-mediated neuroinflammatory markers in infantile epileptic spasms syndrome

Background Infantile epileptic spasms syndrome (IESS) is a severe age-specific epileptic encephalopathy with unclear pathogenesis, and neuroinflammation is involved in its progression. The HMGB1-TLR4 signaling pathway, a key neuroinflammatory mediator in various epilepsies, has not been studied for its role and clinical biomarker potential in IESS. Methods A retrospective study included 66 IESS patients treated with a modified prednisone regimen and 53 age-matched healthy controls. Serum HMGB1, TLR4, IL-1β, IL-2, IL-2R, IL-8 and TNF-α were detected by ELISA/chemiluminescent immunoassay in IESS patients (pre- and 2-week post-treatment) and controls; clinical data were collected via electronic medical records and follow-up. Results IESS patients had significantly higher serum HMGB1, TLR4, IL-2, IL-2R, IL-8 and TNF-α than controls ( P < 0.05; no IL-1β difference, P >0.05), and these elevated indicators decreased markedly post-treatment ( P < 0.05). Logistic regression showed identified etiology and focal seizures were risk factors for short-term prednisone ineffectiveness, while Δ Pre-Post HMGB1 was a protective factor ( P < 0.05). Long-term follow-up (≥18 months) found identified etiology to be a risk factor for uncontrolled epilepsy and poor neurodevelopment ( P < 0.05); early spasm remission and long-term seizure control were protective factors for neurodevelopment ( P < 0.05). Conclusions The HMGB1-TLR4 pathway mediates neuroinflammation in IESS pathogenesis and may serve as a therapeutic target. A high Δ Pre-Post HMGB1 level was identified as a protective factor against short-term treatment failure of prednisone, indicating that dynamic monitoring of HMGB1 has clinical value for predicting short-term treatment responses to prednisone, though it does not predict long-term seizure control or neurodevelopmental outcomes. Identified etiology is a common risk factor for poor IESS outcomes, highlighting the importance of early etiological screening and sustained seizure control for IESS management.