Abstracts

Rationale: Sleep and epilepsy share a close reciprocal relationship. Sleep disturbances are common in epilepsies and are associated with poor seizure control and several of the disease comorbidities. Despite their profound effects on the clinical manifestations, sleep disruptions are not often addressed in the therapeutic managements of drug refractory epilepsies. Like Dravet syndrome (DS) patients, DS mice experience both circadian and homeostatic sleep deficits like DS patients. Correcting sleep disturbances may help alleviate the prevalence of seizures and sudden unexpected death in epilepsy (SUDEP).We examined the effect of non-pharmacological sleep manipulations on the sleep architecture and epileptic phenotype in our mouse model of DS. Methods: DS mice, carrying a heterozygous Knock-out of Scn1a, were divided into three groups and subjected to food restriction to dark phase, activity restriction to dark phase, or combination of both routines. Video/EEG/EMG recordings were obtained from freely behaving animals pre- and post-manipulation. The sleep states of the mice were classified as Wake, NREM, or REM based on video observations as well as EEG and EMG analysis. Results: Comparison of Video/EEG/EMG recordings pre and post food restriction, activity restriction, or combination of the two routines exhibited significant increase in the total sleep duration. The duration and power density of REM sleep were not influenced by the manipulations. The number of brief wakes, an indicator of sleep fragmentation, was reduced by each manipulation, but more significantly with the combination treatment. Similarly, the number of interictal spikes, the hallmark of an epileptic brain, was also slightly reduced by individual treatment, but more significantly by the combination treatment.  Conclusions: Our findings suggest that modulation of sleep by restricting both food and activity to dark phase exhibited a trend toward improving sleep disruptions and alleviating epileptic phenotype in DS mice. Further studies with increased treatment duration may further improve the therapeutic outcome.  Funding: CURE Sleep and Epilepsy Grant 2017NIH R01 NS 1022796