Abstracts

Rationale: The goal of this study was to evaluate seizure outcomes of cortical responsive neurostimulation therapy for the treatment of genetic generalized epilepsy (GGE) in a natural nonhuman primate model. Methods: The RNS® System (Neuropace, Inc.), FDA approved for the treatment of medically refractory focal epilepsies in adult humans, was used for this research. A 10 year-old male baboon with GGE was implanted with two 1*4 contact strip leads, bridging the medial central sulcus bilaterally. Electrocorticography data was downloaded daily. Ictal patterns were correlated with video-recordings early on. Pre-treatment and post-treatment electrographic seizures (ES) were quantified over 2 and 6 months, respectively. Results: 46 ES were recorded. The ES rates decreased from 8/month at baseline to 5/month with treatment. In the pre-treatment period, 85% of ES occurred between 22:00 and 10:00; in the treatment period this rate was 58%.  The spike- and frequency-dependent seizure detections occurred predominantly over the parietal lobe contacts, but frontal propagation was almost spontaneous. The onset of spike-and-wave activity was preceded by generalized fast activity by about 7-10 seconds. At least two suspected episodes of nonconvulsive status epilepticus were included in the pre-treatment period. The underlying parietally-predominant generalized discharges were characterized by 2-3 Hz bursts of 40-50 Hz activity and lasting 100-200 ms. Interictal epileptiform discharges were generalized or distributed multiregionally, both pre- and post-treatment. Conclusions: Responsive neurostimulation, as applied cortically, moderately reduced electrographic seizure frequency in the baboon GGE model.  The predominance of the parietal lobes in seizure generation is consistent with recent intracranial EEG recordings in baboons. The diurnal seizure pattern was altered with therapy. Further studies using additional recording/stimulation sites, such as other parietal cortical sites or the thalamus, may improve electrographic seizure detection and stimulation and will further explore the effect on the frequency of primarily generalized tonic-clonic, absence and myoclonic seizures. Funding: UT BRAIN 365136, Livanova