Purpose Temporal lobe epilepsy (TLE) is increasingly conceptualized as a network disorder, with the piriform cortex as an implicated region. We characterized postoperative contralateral piriform cortex–cortical amygdala (PCA) structural and perfusion-related changes in a small seizure-free TLE cohort. Methods Nine patients with drug-resistant TLE who underwent epilepsy surgery and achieved postoperative seizure freedom were included in this single-center pre–post pilot study. Bilateral PCA was manually delineated on 3D T1-weighted MRI using ITK-SNAP, and volumes were normalized to total intracranial volume derived from CAT12 segmentation. Eight atlas-derived contralateral temporal lobe regions were examined as exploratory regional-specificity comparisons. In patients with available pulsed arterial spin labeling (PASL), piriform and putaminal signal intensities were measured by region-of-interest analysis. Non-parametric paired tests were used; secondary and exploratory analyses were corrected using the Benjamini–Hochberg false discovery rate (FDR) procedure. Results Normalized to total intracranial volume (TIV) contralateral PCA volume decreased postoperatively (Wilcoxon Z = −2.073, exact two-tailed p = 0.039; r = 0.69). None of the eight atlas-derived contralateral temporal regions showed a significant pre–post volume change. Contralateral putamen-normalized piriform signal intensity did not change significantly (Z = −0.105, p = 0.917), and no secondary or exploratory analysis remained significant after FDR correction. Conclusions In this hypothesis-generating pilot cohort, contralateral PCA volume decreased after epilepsy surgery, whereas the PASL-derived signal-intensity measure did not show a corresponding group-level change. These observations do not establish a surgery-induced network mechanism and require confirmation in larger controlled longitudinal cohorts.
Background Cannabidiol (CBD) has emerged as an important adjunctive treatment option for pediatric drug-resistant epilepsies (DREs), particularly in developmental and epileptic encephalopathies (DEEs) such as Dravet syndrome and Lennox–Gastaut syndrome. However, the current literature remains heterogeneous and predominantly focused on seizure outcomes, with limited evaluation of broader neurodevelopmental domains. Methods A systematic review with meta-analysis of proportions was conducted according to PRISMA 2020 recommendations. PubMed/MEDLINE was searched for studies evaluating CBD treatment in pediatric epilepsies (search updated to October 1st 2026), supplemented by citation searching. Randomized controlled trials and observational studies were included; secondary reports of the same cohort (extensions, post hoc and sub-analyses) were linked to their parent study. Extracted variables included study design, epilepsy syndrome, follow-up duration, seizure outcomes, cognitive outcomes, and behavioral outcomes. The primary outcome was the proportion of patients achieving ≥ 50% seizure reduction at the earliest stable post-titration timepoint, pooled across all studies with ≥ 10 assessed patients using a random-effects model (logit transformation, DerSimonian–Laird estimator). Results Sixty-three studies (92 reports) were included, predominantly observational (56/63, 88.9%). The meta-analysis included 37 studies (3439 assessed patients; 1610 responders) and yielded a pooled ≥ 50% responder rate of 48.4% (95% CI 44.5–52.3), with substantial heterogeneity (I²=76.4%; 95% prediction interval 29.4–67.8%). Responder rates were lower in the CBD arms of randomized trials (41.3%) than in observational studies (49.8%), and higher at long-term than at short-term assessments (57.4% vs 42.8%). Seizure outcomes were reported in 98.4% of included studies, whereas cognitive and behavioral outcomes were reported in only 7.9% and 27.0% of studies, respectively. Conclusions Approximately half of children with drug-resistant epilepsies treated with adjunctive cannabidiol achieve a ≥ 50% seizure reduction in the available, predominantly observational literature; randomized trials suggest a somewhat lower proportion, and long-term estimates are likely inflated by selective retention. The literature remains strongly seizure-centered, while cognitive and behavioral outcomes are inconsistently assessed and poorly standardized. Future pediatric CBD studies should incorporate harmonized longitudinal follow-up and standardized neurodevelopmental outcome measures alongside seizure outcomes.
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.
