Dziedziczne mutacje genetyczne a wyniki operacyjnego leczenia epilepsji: analiza danych 272 pacjentów
Germline Genetic Variants and Epilepsy Surgery Response: Individual Participant Pooled Analysis of 272 Patients
W skrócie
Badacze przeanalizowali wyniki operacyjnego leczenia epilepsji u pacjentów z wrodzonymi mutacjami genetycznymi. Okazało się, że operacje były najskuteczniejsze u pacjentów z zaburzeniami naczyniowymi i pewnymi zmianami metabolicznymi (ponad 65% uzyskało kontrolę padaczki), natomiast znacznie mniej skuteczne u pacjentów z mutacjami kanałów jonowych i zaburzeniami synaptycznymi (zaledwie 20-30% bez napadów). Wyniki sugerują, że skuteczność operacji zależy od typu genetycznego zaburzenia i potrzebne są dalsze badania, aby lepiej wybrać pacjentów do leczenia chirurgicznego.
Oryginalny abstract (angielski)
BACKGROUND AND OBJECTIVES: Genetic testing is increasingly used in presurgical evaluation, but the yield of resection and ablation across germline genetic epilepsies remains uncertain. METHODS: We conducted a systematic review of MEDLINE (PubMed) and Scopus and added cases from 3 institutional cohorts and the Pediatric Epilepsy Research Consortium (PERC) databases, including individuals with pathogenic/likely pathogenic germline variants besides tuberous sclerosis who underwent resection or laser ablation. Etiologies were grouped into biologically informed categories (GATORopathies, vascular, overgrowth, copy number variants (CNVs), channelopathies, synaptopathies, and other). Primary outcome was seizure freedom (Engel I) at the last follow-up. Group comparisons used Fisher exact and Kruskal-Wallis tests (α = 0.05; Bonferroni when applicable). Prespecified sensitivity analyses stratified by lesional status, excluded GATORopathies, and restricted to literature-only cases. RESULTS: We included 224 literature cases (65 studies), 36 institutional cases, and 12 PERC cases (n = 272). The median follow-up was 24 months (interquartile range 12-48.0). Seizure freedom was achieved in vascular disorders 14/19 (73.6%), GATORopathies 79/120 (65.8%), CNVs 18/31 (58.0%), overgrowth 9/16 (56.6%), channelopathies 13/43 (30.0%), synaptopathies 4/18 (22.2%), and other 11/25 (44.0%) (overall < 0.001). Among cases with available imaging results, 208/253 (82.2%) had epileptogenic MRI lesions, including 64% of channelopathies and 80% of the synaptopathies. In univariate contrasts (each category vs all others), odds of seizure freedom were higher for vascular disorders (2.64-fold, 95% CI 0.87-9.65) and GATORopathies (2.41-fold, 95% CI 1.44-4.09), and lower for synaptopathies (∼4.2-fold lower, OR 0.23, 95% CI 0.05-0.77) and channelopathies (∼4.5-fold lower, OR 0.22, 95% CI 0.09-0.48). Direction and magnitude were consistent across prespecified sensitivity analyses (lesional only, literature only, exclusion of GATORopathies). DISCUSSION: Resective surgeries can be effective in germline genetic epilepsies, but outcomes vary by pathway. Disorders with discrete, lesional substrates (GATORopathies, vascular) show the highest likelihood of seizure freedom, whereas channelopathies and synaptopathies, despite the presence of MRI lesions, have substantially lower yields even in lesional cases. Prospective, genotype-aware surgical registries with standardized reporting (EEG, imaging, and pathology) and time-to-event outcomes are needed to refine the selection of surgical candidates and quantify seizure and non-seizure-related outcomes.