Seizures influence sleep macrostructure and the sleep-wake circadian rhythm in Dravet syndrome

Dravet syndrome (DS) is a developmental and epileptic encephalopathy with a wide spectrum of comorbidities comprising sleep disorders, reported in up to 85% of cases. For this, a sleep study is recommended in patients with a sleep complaint. However, no data are available on sleep architecture in DS or on the impact of seizures on sleep quality and macrostructure. We aim to investigate the impact of epileptic phenomena on sleep in DS.

In this study, we report seizure type and frequency, seizures during sleep, and concomitant antiseizure medications (ASMs) of 30 patients with clinical diagnosis of DS and confirmed SCN1A pathogenic variant. We obtained 62 whole-night polygraphic sleep recordings (PSGs) and analyzed sleep stages duration, number of arousal events (AEs), arousal index (AI), and number and number/hour of AEs preceded by interictal epileptiform discharges (IEDs; IED-related arousals [IRAs]). In a subgroup of patients, actigraphic recordings and caregiver-reported Sleep Disturbance Scale for Children (SDSC) questionnaires were collected.

Mean age at PSG was 9.9 years (range = 1.2-20.8). Mean sleep efficiency was 92.9%, mean AI was 4.2, and the mean IRA index was .5. Patients with tonic seizures during sleep had shorter rapid eye movement sleep duration (p < .05), and those with convulsive seizures during sleep had shorter N3 duration (p < .05). Higher IRA index was also associated with lower total N3 duration (p < .05). In the recordings obtained during treatment with fenfluramine, IRAs were absent (p < .05) or less abundant (p < .05). The actigraphy parameters showed unstable sleep and correlated with PSG-derived data.

Our study shows a significant effect of epileptic phenomena on sleep macrostructure in DS. Motor seizures and IEDs influence slow wave sleep, which could be one of the mechanisms that sustain encephalopathy in DS. Interestingly, fenfluramine seems to have a protective effect on this mechanism, both by stabilizing sleep and as an ASM.