OBJECTIVE
Epilepsy duration is a modifiable risk factor in the outcome of definitive epilepsy surgery; however, an analogous effect in palliative procedures has not been shown. We reviewed the Pediatric Epilepsy Surgery Database data for an association between epilepsy duration and seizure reduction in palliative procedures.
METHODS
Patients enrolled between January 2018 and April 2025 who underwent their first epilepsy surgery with palliative intent with 6 months of follow-up were included. Procedures included neuromodulation, corpus callosotomy, hemispherotomy, lesionectomy, and lobectomy where surgical intent was not seizure freedom. Outcomes of seizure freedom, 90% seizure reduction, and 50% seizure reduction were considered at 6-12 months and >12 months from surgery. Duration from epilepsy onset to surgery was compared for patients above and below each outcome threshold at each time point. Logistic regression analysis for the association between epilepsy duration and seizure reduction adjusted for potential confounders including procedure type, etiology, and other clinical factors. Logistic regression analysis was performed on the overall cohort and subgroups of patients with each procedure.
RESULTS
A total of 588 patients were included. Initial univariate analysis suggested that epilepsy duration at time of surgery was significantly associated with seizure freedom and 90% seizure reduction at both 6-12 months and >12 months. After adjusting for confounders, only seizure freedom at >12 months was significantly associated with duration of epilepsy. When individual procedures were considered, only lobectomy was sensitive to duration of epilepsy in multivariate analysis, with significant impacts on >50% and >90% seizure reduction at >12 months. Lesional epilepsy predicted seizure freedom at >12 months. Neuromodulation and corpus callosotomy were less likely to achieve seizure reduction than other procedures.
SIGNIFICANCE
We did not find an association between early epilepsy surgery and seizure reduction. This reflects the heterogeneity of our population, including different types of surgical procedures and lesional and nonlesional epilepsies.
Robert M Crutcher, David E. Horvat, A. Caraway et al.· Epilepsia· 0 citations
BACKGROUND
Epilepsy of infancy with migrating focal seizures (EIMFS) is among the most severe developmental and epileptic encephalopathies (DEEs), marked by intractable multifocal seizures migrating across both hemispheres, profound developmental arrest, and high early mortality. Advances in next-generation sequencing have revealed a heterogeneous genetic architecture dominated by KCNT1 gain-of-function variants across more than 30 implicated genes, creating opportunities for precision therapeutics.
OBJECTIVE
To systematically map published evidence on the clinical, electrophysiological, neuroimaging, genetic, and therapeutic landscape of EIMFS, and to delineate critical knowledge gaps and future research priorities.
METHODS
A scoping review was conducted following the Arksey and O'Malley framework, searching PubMed, Ovid MEDLINE, Embase, Cochrane Library/CENTRAL, and ClinicalTrials.gov.
RESULTS
Of 643 articles screened, 89 met inclusion criteria. Beyond confirmation of the canonical electroclinical phenotype, several gaps emerged: neonatal versus post-neonatal onset stratification by genetic etiology remains largely uncharacterized; genotype-specific EEG biomarkers are lacking except for a single small KCNT1 study; and the clinical significance of atypical EEG features-including burst suppression and hypsarrhythmia-is undefined. Neuroimaging literature documents progressive cerebral atrophy and myelination abnormalities without quantitative volumetry, diffusion tractography markers, or attribution to seizure burden, medication effects, or underlying etiology. Genetic diagnostic yield was 70-80%, with KCNT1 accounting for 30-50% of solved cases; however, genotype-outcome stratification is limited. Seizures were broadly refractory; potassium bromide, ketogenic diet, cannabidiol, and quinidine (in KCNT1-confirmed cases) showed partial efficacy. Emerging precision approaches include sodium channel blockers for SCN2A gain-of-function variants, novel small molecules, fluoxetine, antisense oligonucleotides, and divalent siRNA targeting KCNT1. Systemic-to-pulmonary collateral circulation causing severe cardiopulmonary complications was reported across multiple cases, yet no consensus screening protocol exists.
CONCLUSIONS
EIMFS remains one of the most refractory epilepsy syndromes of infancy. Precision genetic diagnosis is essential to guide targeted therapy. International collaborative registries, standardized outcome measures, genotype-stratified biomarker studies, and rapid point-of-care genomic testing are urgently needed to advance evidence-based care for this highly vulnerable population.
Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.
Debopam Samanta· Brain & development (Tokyo....· 0 citations
Similar children evaluated at different institutions had significant differences in the odds of not being recommended surgery, suggesting that institutional decision-making contributes importantly to surgical candidacy.
A. Caraway, Nancy A Mcnamara, Andrew T. Knox et al.· Epilepsia· 0 citations
Delays from DRE diagnosis were independently associated with reduced seizure freedom, supporting presurgical evaluation within 1 year as an evidence-based quality benchmark, and DRE-to-evaluation interval, not total epilepsy duration, predicted outcomes.
Debopam Samanta, A. Caraway, Andrew T. Knox et al.· Neurology Clinical Practice· 0 citations
A comprehensive narrative review of studies indexed in PubMed/MEDLINE, Embase, Cochrane Library, ClinicalTrials.gov, and American Epilepsy Society proceedings through January 2026 positions STXBP1-RD as a leading test case for precision medicine in DEEs.
A rapidly advancing precision-therapy pipeline-including antisense oligonucleotides to upregulate the intact allele, AAV-based gene replacement, CRISPR-mediated transcriptional activation, epigenetic modulators, and rational pathway-targeted small molecules-offers realistic prospects for disease modification.