| Summary: | Abstract The RNS System is not approved in patients under 18, although a critical need for novel treatment modalities in this vulnerable population persist. We present two pediatric patients with drug‐resistant epilepsy secondary to Lennox‐Gastaut Syndrome (LGS) and autism spectrum disorder (ASD) treated with the RNS System. Both patients have experienced 75–99% clinical seizure reductions in >1 year of follow‐up. We illustrate that children with diffuse onset, multifocal epilepsy, including frontal and thalamic circuits thought to exist in the generation of LGS seizures, can be treated with responsive neurostimulation safely and effectively, targeting thalamic networks, and avoiding palliative disconnections and resections.
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