Germline Genetic Variants and Epilepsy Surgery Response: Individual Participant Pooled Analysis of 272 Patients

This individual participant pooled analysis combines 224 literature cases (65 studies), 36 cases from 3 institutional cohorts and 12 cases from the Pediatric Epilepsy Research Consortium, totalling 272 patients with pathogenic or likely pathogenic germline variants, excluding tuberous sclerosis, who underwent resection or laser ablation. With a median follow-up of 24 months, seizure freedom (Engel I) varied by etiological category: 73.6% for vascular disorders, 65.8% for GATORopathies, 58.0% for CNVs and 56.6% for overgrowth syndromes, versus 30.0% for channelopathies and 22.2% for synaptopathies (p < 0.001). Odds of seizure freedom were higher for GATORopathies (OR 2.41; 95% CI 1.44-4.09) and lower for channelopathies (OR 0.22) and synaptopathies (OR 0.23). An epileptogenic MRI lesion was present in 82.2% of patients with available imaging, including 64% of channelopathies and 80% of synaptopathies, and results were consistent across prespecified sensitivity analyses (lesional only, literature only, exclusion of GATORopathies).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Directly useful for presurgical discussion: a GATORopathy or vascular cause carries a rather favourable surgical outlook, whereas a channelopathy or synaptopathy should temper expectations, even with an MRI lesion. The result argues for having the genetic diagnosis before the surgical decision. Data remain mostly literature-derived, exposed to publication bias and heterogeneous follow-up, hence the authors' call for prospective genotype-aware registries.

Analysis by Dr Thibaut Benquey