Effect of Auditory Stimulation on Spike Waves in Sleep (ECLASS)

Effect of Closed-loop Auditory Stimulation on Spike Waves During Slow Wave Sleep, an Open Label Pilot Study

Background: Close relationship exists between sleep slow wave (SSW) and the generation of spike wave in NREM-sleep. SSW are cortically generated oscillations alternating between excitatory depolarization ("Up-phase" of the SSW) and inhibitory hyperpolarization ("Down-phase" of the SSW). It has been shown experimentally that with increasing synchrony of slow neuronal oscillations SSW turn into spike waves. Acoustic pulses applied in correspondence to the SSW "Up-phase" enhance the amplitude of the subsequent SSW. Conversely, tones delivered at the SSW "Downphase" have a disruptive effect on the following SSW. Participants: Patients with epilepsy and spike waves in NREM-sleep. Objective: Modification of spike wave frequency, amplitude and spreading during NREM sleep by acoustic pulses applied at the "Up-" or "Down-phase" of SSW.

Benign epilepsy with centro-temporal spikes, Continuous spike waves in slow wave sleep, Electroencephalography, Sleep, slow wave

During NREM sleep: 15 minutes without acoustic pulses 15 minutes with acoustic pulses 15 minutes without acoustic pulses Two different protocols are applied: (A) tone application at the "Down-phase" of sleep slow wave (SSW) (B) tone application at the "Up-phase" of SSW. Participants with Rolandic epilepsy/BECTS or generalized spike waves: Protocol A and B alternatingly. Participants with ESES/CSWS: only Protocol A.

Acoustic pulses applied during NREM sleep slow waves "Up-phase" or "Down-phase". The acoustic stimulus will be delivered by speakers with a volume of about 50 dB.

Change of spike wave index during acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Spike wave index given in percent and calculated by number of seconds within 10 second windows with spike waves over the whole 15 minutes of the block design part.

Change of spike wave amplitude (in microvolts) during acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Amplitudes of maximum spike will be analyzed in 10 seconds periods of the first and the last 100 seconds of every part of the block design. EEG source derivation will be used for the analysis. The mean of the 3 highest amplitudes of each 10 seconds period will be determined and the mean of the 10 periods will presented in mean and SD.

Change of spike wave spreading during acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Spreading will be analyzed in 10 seconds periods of the first and the last 100 seconds of every part of the block design. EEG source derivation will be used for the analysis. Maximum spike wave spreading (number of electrodes involved) visible in 3 spike waves of each 10 second period will be determined and the mean of the 10 periods will presented in mean and SD.

Change of spike wave index in the NREM period following the NREM period with acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Over the first 15 minutes of the following NREM period: Spike wave index given in percent and calculated by number of seconds within 10 second windows with spike waves .

Change of spike wave amplitude (in microvolts) in the NREM period following the NREM period with acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Amplitudes of maximum spike will be analyzed in 10 seconds periods of the first and the last 100 seconds of the following NREM period. EEG source derivation will be used for the analysis. The mean of the 3 highest amplitudes of each 10 seconds period will be determined and the mean of the 10 periods will presented in mean and SD.

Change of spike wave spreading in the NREM period following the NREM period with acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Spreading will be analyzed in 10 seconds periods of the first and the last 100 seconds of the following NREM period. EEG source derivation will be used for the analysis. Maximum spike wave spreading (number of electrodes involved) visible in 3 spike waves of each 10 second period will be determined and the mean of the 10 periods will presented in mean and SD.

Inclusion Criteria: Participants with Rolandic epilepsy/BECTS Participants with ESES/CSWS Participants with generalized spike waves in sleep EEG within 6 months before study night consistent with the diagnosis Exclusion Criteria: Clinically significant concomitant acute or chronic disease Seizure frequency >1/week, history of convulsive status epilepticus or seizures provoked by sleep deprivation Severe sleep problems Treatment with corticosteroids, immunosuppressive or vagus nerve stimulation

Div. of Clinical Neurophysiology/Epilepsy, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich