Abstracts

Rationale: Neurostimulation devices are widely used to treat seizures in patients with medically-refractory epilepsy. The effect of these therapies on sleep is only beginning to be explored. For example, vagus nerve stimulation can contribute to sleep apnea, and thalamic deep brain stimulation can cause sleep disruption (Romero-Osorio et al., Seizure 2018). Clinical trials demonstrated that brain-responsive neurostimulation with the RNS® System (NeuroPace, Inc.) is well-tolerated and acceptably safe (Skarpaas et al., Epilepsy Res 2019), but its potential effects on sleep have not been investigated. Methods: Six adults with medically refractory focal epilepsy treated for at least 6 months with the RNS System underwent a single night of standard polysomnography (PSG) extended by modified 10-20 system scalp electroencephalography (EEG). RNS System lead locations included mesial temporal and neocortical targets. Sleep stages and arousals were scored according to AASM Guidelines. An arousal is defined as an abrupt shift of EEG frequencies, including alpha, theta, and/or frequencies greater than 16 Hz (but not spindles) that last at least 3 sec, with at least 10 sec of stable sleep preceding the change. Stimulations delivered in response to epileptiform activity were identified by artifacts on scalp EEG (Giraldez et al., Neurology 2017). The distribution of arousals relative to stimulation was analyzed to test for possible causal relationships. Results: In 5 subjects, stimulation artifacts were identifiable in the EEG, and stimulation-aligned arousal histograms were generated (see Figure). There was no evidence of a consistent peak in arousals after stimulation; instead, unexpectedly, all 5 subjects showed a significant peak in arousals just before stimulation. In one subject (S2), the arousal peak began before stimulation and extended to ~1 sec post-stimulation. These pre- and peri-stimulation arousal peaks are consistent with (1) the fact that epileptiform activity is detected by the RNS System and triggers stimulation at variable latencies across subjects, and (2) the well-described phenomenon that epileptiform activity itself is often followed by arousals (Malow et al., Sleep 2000). Conclusions: Our findings in this small cohort of subjects support a model in which epileptiform activity can both cause arousals and trigger stimulation, and/or a model in which arousals themselves trigger stimulation. However, no subjects demonstrated arousals consistently peaking only after stimulation, suggesting that brain-responsive neurostimulation itself does not disrupt sleep. If confirmed in larger studies, this could represent a potential clinical advantage of brain-responsive neurostimulation relative to other neuromodulation modalities. Funding: No funding