Pathological Correlation of Inflammatory Cytokines with Neurocognitive Impairment in Pediatric Epilepsy. A Clinical Cross-Sectional Study

Background: Pediatric epilepsy is a common neurological condition characterized not only by recurrent seizures but also by notable disruptions in cognitive development during key stages of brain maturation. Recent studies have increasingly implicated neuroinflammatory processes—particularly those involving pro-inflammatory cytokines—as major contributors to both seizure activity and cognitive deterioration. Despite this, limited clinical evidence exists regarding the relationship between systemic inflammation and cognitive outcomes in epileptic children. Objective: This study aimed to investigate the association between serum levels of key inflammatory cytokines (IL-6, TNF-α, and IL-1β) and cognitive performance in children diagnosed with epilepsy. Methods: Between January 2022 and March 2023, 100 pediatric epilepsy patients, ages 5 to 16, were selected from two tertiary healthcare institutions in Pakistan for a cross-sectional analysis. The Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) was used to assess cognitive ability. TNF-α, IL-1β, and IL-6 serum concentrations were measured by the enzyme-linked immunosorbent assay (ELISA). Multivariate linear regression and Pearson's correlation were used in the statistical analysis to find correlations between cytokine levels and cognitive scores. Results: Serum levels of IL-6 (6.2 ± 1.1 pg/mL), TNF-α (7.9 ± 1.5 pg/mL), and IL-1β (5.0 ± 1.3 pg/mL) were substantially greater in participants with impaired cognitive function (Full Scale IQ < 85) than in those with normal cognitive function (p < 0.001). IL-6 and Full-Scale IQ showed a considerable negative connection (r = –0.65, p < 0.001), with the Processing Speed Index being most affected. While IL-1β was particularly associated with working memory problems, multivariate regression revealed that IL-6 and TNF-α were independent predictors of worse cognitive scores. Conclusion: Systemic inflammation, marked by elevated cytokine levels, is significantly associated with cognitive impairment in pediatric epilepsy, independent of seizure frequency or antiepileptic medication. These findings underscore the importance of inflammatory biomarkers in predicting neurocognitive outcomes and suggest potential benefits of integrating cytokine assessment into routine clinical evaluation to identify high-risk patients and explore anti-inflammatory treatment strategies.