Non-periodic acoustic stimulation: preliminar reports of an alternative therapeutic for epilepsy

Abstract

Being refractory is a significant challenge for one third of patients with epilepsy, and there is a need for new treatments. Non-periodic Stimulation (NPS) has shown promise in animal models, but it involves invasive technology. Consequently, non-invasive non-periodic Acoustic Non-periodic Stimulation (ANPS) has been developed based on NPS, with the hope that it could offer anticonvulsant effects. However, it is essential to ensure the safety of ANPS, particularly in individuals with refractory epilepsy, before it can be used in a specific application. To this end, this study aimed to assess the safety of ANPS in patients with refractory epilepsy (n=14; 8 women; 18-49 years old) using Electroencephalographic (EEG) recording and side effect evaluations over a period of five days. A questionnaire was administered immediately following the ANPS exposure and 30 days later. The study also aimed to investigate whether ANPS could trigger electrographic seizure events by counting epileptiform interictal spikes and sharp waves before and after ANPS. Additionally, the effects of ANPS on overall EEG signal properties and synchronicity were studied by calculating entropy and Phase Lock Value (PLV). Results indicate that ANPS did not trigger seizures or side effects after acute exposure or 30 days later. Rather, an improvement in quality of life and a reduction of interictal peaks and sharp waves in the EEG were observed, indicating possible anticonvulsant effects of ANPS. ANPS also increased EEG signal entropy and induced changes in brain synchrony, as evidenced by increased PLV values in some neural networks and decreased PLV values in others. Overall, these findings suggest that ANPS is well-tolerated and safe in patients with refractory epilepsy and may have anticonvulsant properties. Further investigation of its effects on neurophysiology and refractory epilepsy is warranted.