Efficacy of Lactobacillus reuteri as an adjunctive therapy for seizure control and quality of life in pediatric drug-resistant epilepsy: A prospective interventional study.

BACKGROUND

Drug-resistant epilepsy (DRE) remains a critical challenge in pediatric neurology, profoundly impacting cognitive development and health-related quality of life (HRQOL). Given the role of the gut-microbiota-brain axis in neuromodulation, probiotics have emerged as a potential adjunctive therapy. This study assessed changes in seizure frequency and HRQOL and evaluated the safety of Lactobacillus reuteri supplementation on seizure frequency and HRQOL in children with DRE.

METHODS

In this prospective, single-arm, before-after interventional trial, 75 children (aged 3-18 years) with confirmed DRE were enrolled. Participants received daily oral L. reuteri (1 ×109 CFU) for 12 weeks alongside their stable anti-seizure medication (ASM) regimens. The primary outcome was HRQOL measured by the Persian-validated QOLCE-55 questionnaire. Secondary outcomes included seizure frequency, recorded prospectively using standardized caregiver seizure diaries. Statistical analyses utilized paired-sample t-tests and Wilcoxon signed-rank tests, with effect sizes calculated to quantify the magnitude of within-participant changes.

RESULTS

Seventy-one patients completed the study (mean age 7.26 ± 3.33 years; 53.5% male). The cohort showed heterogeneous seizure phenotypes and underlying etiologies. Total HRQOL scores increased from 33.75 ± 4.92 at baseline to 34.23 ± 4.97 after the intervention (absolute change, 0.48 points; p < 0.001), with a small-to-moderate standardized effect size (d = 0.40). However, this change was substantially below the 10-13-point MCID range used in the sample-size rationale. Median seizure frequency changed from 32 (IQR: 15-84) to 30 (IQR: 14-80) episodes per 3 months (p = 0.001; r = 0.39). Four patients (5.6%; 95% CI, 1.6-13.8%) experienced a reduction of more than 50% in seizure frequency. Adverse events were reported in 11.3% of participants and were mild and transient, with no treatment discontinuations.

CONCLUSIONS

In this single-arm before-after study, statistically significant within-participant changes in HRQOL and seizure frequency were observed during the 12-week period following adjunctive L. reuteri supplementation. However, the absolute magnitude of these changes was modest and their clinical significance remains uncertain. Because there was no concurrent placebo control group, the observed changes cannot be attributed specifically to L. reuteri supplementation. Larger, adequately powered placebo-controlled randomized trials are needed to determine whether L. reuteri provides a clinically meaningful benefit in pediatric drug-resistant epilepsy.