Clinical application of HMGB1-TLR4 signaling pathway-mediated neuroinflammatory markers in infantile epileptic spasms
Hui Chen1, Jianmin Zhong1, Yong Chen1
1Department of Neurology, Children's Hospital of Jiangxi Province, Nanchang, China.
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 ΔPre-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 ΔPre-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.
