Effect of Auditory Stimulation on Spike Waves in Sleep

Study Overview
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Brief Summary
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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.

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

Conditions
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Epilepsy, Sleep

Intervention / Treatment
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* Device: Acoustic pulses


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acoustic pulses<br>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. | Device: Acoustic pulses<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spike wave index | 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 baseline (without) and with acoustic pulses in the same NREM period: 45 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spike wave amplitude | 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 baseline (without) and with acoustic pulses in the same NREM period: 45 minutes | 
| Spike wave spreading | 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 baseline (without) and with acoustic pulses in the same NREM period: 45 minutes | 
| Spike wave index in the NREM (2) period following the NREM (1) period with acoustic pulses | 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 baseline (NREM 1) and NREM 2: expected average of 1 hour | 
| Spike wave amplitude in the NREM (2) period following the NREM (1) period with acoustic pulses | 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 baseline (NREM 1) and NREM 2: expected average of 1 hour | 
| Spike wave spreading in the NREM (2) period following the NREM (1) period with acoustic pulses | 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. | Change baseline (NREM 1) and NREM 2: expected average of 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Benign epilepsy with centro-temporal spikes, Continuous spike waves in slow wave sleep, Electroencephalography, Sleep, slow wave