Abstracts

Rationale: The generation of epileptiform discharges (ED) in genetic generalized epilepsies (GGE) is closely linked with the sleep-wake cycle [1]. Several studies have found that EDs are more frequent during non-rapid eye movement sleep than wakefulness and rapid eye movement sleep in GGE ) [2]. However, there is little data describing the impact of sleep onset and offset on EDs in GGE. We hypothesized that sleep onset is likely to be a more potent trigger than sleep offset (awakening) to generate generalized EDs in GGE regardless of the 24-hour clock time. We tested our hypothesis using quantified data from 24-hour ambulatory EEGs recorded in a cohort of patients diagnosed with GGE. Methods: We studied 24-hour ambulatory electroencephalography (EEG) recordings of patients with GGE. We manually coded the time of occurrence and arousal state of each epileptiform discharge. Additionally, sleep onset and offset times were tabulated. Those who recorded ≥50 EDs per 24-hr period were included in the analysis. We employed mixed-effects Poisson regression modeling to study the temporal distribution of epileptiform discharges. The mean ED rate was defined as the mean number of ED count per hour per person. We used incidence-rate ratio (IRR) as the metric to express the association between mean ED rate and the hour. We calculated the IRR of each hourly block for the total cohort with sleep onset set as the 0 point followed by the same approach with sleep offset as the 0 point. To study the impact of secondary risk factors, we admitted those into the Poisson regression model and measured the outcome IRR. The secondary risk factors included: epilepsy syndrome, duration of seizure freedom, duration of epilepsy, number of antiepileptic drugs (AED), type of AED, and age. Results: A total of 39 patients with a mean age of 29.1 y (SD=10.1) were studied. Juvenile absence epilepsy was the most frequent syndrome among the patients (19) followed by juvenile myoclonic epilepsy (11), generalized epilepsy with tonic-clonic seizures only (5), and childhood absence epilepsy (4).The distribution of ED rate demonstrated a highly significant increase in the first hour after sleep onset (IRR=3.96; p<0.001) (Figure 1, Table 1a). In other words, in the first hour after sleep onset, the ED rate was four times higher than the reference defined as the hour with the lowest ED rate. Contrary to this, the ED rate significantly dropped in the first two hours after the sleep offset compared with the last hour block before sleep offset (IRR=0.39; p<0.001) (Figure 1, Table 1b). In the subgroup analysis, a similar trend was evident across all major GGE syndromes. None of the secondary risk factors demonstrated any significant impact on this pattern. Overall, the ED rate was significantly higher in sleep than in wakefulness (p<0.001). Conclusions: Sleep onset is a very significant biological trigger for the generation of EDs in GGE. Contrary to common belief, there is a significant reduction in ED rate with awakening. Our results suggest that there is a “critical zone of vigilance” in the sleep-wake boundary in which generalized EDs are more likely to emerge. This data provides further evidence for the intricate link between epileptogenicity and sleep-wake cycle. References1. Halasz P, et al. Spike-wave discharge and the microstructure of sleep-wake continuum in idiopathic generalised epilepsy. Neurophysiol Clin 2002;32:38-53.2. Pavlova MK, et al. Is there a circadian variation of epileptiform abnormalities in idiopathic generalized epilepsy? Epilepsy Behav 2009;16:461-7. Funding: No funding