Epilepsy associated with periventricular nodular heterotopia (PVNH) frequently begins in childhood and often proves refractory to medication. Surgical management is challenging, as lesions are frequently deep-seated or bilateral, and seizure onset often involves networks extending beyond the heterotopic tissue itself, with the precise contribution of the nodules varying between patients. This systematic review synthesises all available evidence on neurosurgical and invasive interventions for childhood-onset PVNH-associated epilepsy, focusing on outcomes and prognostic factors. We conducted a PRISMA 2020-compliant systematic review searching PubMed/MEDLINE, Scopus, and Web of Science from inception to 13 December 2025. Eligible studies reported neurosurgical interventions in patients with MRI- or histopathology-confirmed PVNH whose epilepsy began before age 18, with outcomes reported using Engel or ILAE classification. Two reviewers independently screened and extracted data. Methodological quality was appraised using GRADE. Findings were synthesised narratively due to the inherent heterogeneity of the included studies. Thirty studies comprising 134 patients met our inclusion criteria. Excellent outcomes, defined as seizure freedom or auras only, were achieved in 50.7% (n = 68), with 76.9% (n = 103) experiencing meaningful benefit, defined as at least a 50% reduction in seizure frequency. Outcomes were better in unilateral than bilateral PVNH (75.9%vs 33.8%, p < 0.001) and with complete rather than incomplete nodule removal (72.9%vs 25.0%, p < 0.001). Permanent morbidity was 10.4% (n = 14), predominantly visual field deficits. Invasive EEG-guided approaches can achieve seizure freedom in around half of children with PVNH-related epilepsy, with outcomes strongly predicted by laterality. As with all subgroup comparisons in this review, reported p-values reflect effect size across pooled retrospective cohorts rather than formal hypothesis testing. Minimally invasive ablation appears effective and safe, while neuromodulation offers palliation where curative treatment is not feasible. Evidence remains limited by retrospective study designs and small sample sizes, and prospective multicentre data are needed.
Srishruthi Thirumalai, D. Champsas, M. L. Bianco et al.· Seizure· 0 citations
Paediatric drug-resistant epilepsy (DRE) is associated with IQ deficits only partially explained by clinical seizure variables (for example, age of onset, seizure burden, seizure location). Given that intelligence depends on efficient large-scale brain networks, structural connectomics provides a complementary mechanistic framework for explaining residual IQ variance. We tested whether brain-network architecture explains additional IQ variance using global and network-averaged graph-theoretic metrics derived from streamline-count weighted diffusion MRI connectomes. Seventy-one children with DRE (50 focal epilepsy; 21 multifocal epilepsy) and 15 control participants underwent diffusion and T1-weighted MRI. For each participant, a 253 × 253 structural connectome was constructed, edge weights were defined as the number of streamlines, and graph metrics were computed using the Brain Connectivity Toolbox. Nodal metrics were averaged within Yeo's seven functional networks plus a Subcortical network. Associations with IQ were examined using correlations and general linear models (single-network and eight-predictor models). Finally, mediation analyses tested whether network metrics explained IQ differences between controls and children with DRE. Global metrics were not associated with IQ (all p > 0.05). Regionally, higher Salience-network betweenness centrality showed a nominal negative association with IQ in the multifocal subgroup (p = 0.040*, adjusted R2 = 0.142). In the eight-network GLM, higher nodal efficiency within the Default Mode Network (DMN) was positively associated with IQ (B = 122.406, p = .013), whereas higher nodal efficiency within the Subcortical Network was negatively associated with IQ (B = -51.942, p = .012). These regional associations did not survive Bonferroni correction. Exploratory mediation analyses suggested that opposing DMN and Subcortical Network effects partially accounted for the observed group difference in IQ. These findings are hypothesis-generating, as the regional associations with IQ were nominal and did not survive family-wise correction. Nevertheless, the mediation effects survived correction, highlighting opposing regional, rather than global, network alterations as candidate correlates of IQ variability in paediatric DRE.
Prithviraj Tawde, D. Velanoski, R. Piper et al.· Epilepsy & Behavior· 0 citations
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