Pearls & Oy-sters: Harnessing New Diagnostic and Therapeutic Approaches to Treat a Patient With Genetic Drug-Resistant Focal Epilepsy.

Focal cortical dysplasia (FCD) is a congenital developmental malformation and is one of the leading causes of drug-resistant focal epilepsy (DRFE). Although focal epilepsies traditionally have been regarded as acquired disorders, increasing evidence suggests a substantial genetic contribution to the pathogenesis of focal structural epilepsies, including FCDs. Mutations in the Dishevelled, Egl-10 and domain-containing protein 5 (DEPDC5) have recently emerged as a causative gene mutation in familial focal epilepsies associated with FCD type 2a, including Bottom of sulcus dysplasia (BOSD). We present a case of a 20-year-old man with DRFE, positive for DEPDC5 c.1555C>T (p.GIn519*) heterozygous pathogenic variant. Initial 3T brain MRI was unrevealing, but subsequent 7T MRI including 7T edge-enhancing gradient echo (EDGE), revealed a left superior frontal sulcus BOSD concordant with the electroclinical data. The patient underwent treatment with MR-guided laser interstitial thermal ablation of the left frontal BOSD without intracranial EEG monitoring ("skipped candidate"), resulting in a seizure-free outcome of nine months since the last follow-up. Our case highlights the real-world application of summative information obtained through advancements in epilepsy-genetic testing, minimally invasive surgeries, and ultra-high field MRI, allowing us to provide a safe and effective treatment for a patient with a genetic DRFE.