Abstracts

Rationale: Epilepsy patients often suffer from poor sleep, which may present as sleep fragmentation, apnea, and other phenomena. These effects are sometimes directly related to seizure occurrence; thus, seizures can disrupt sleep and poor sleep can precipitate seizures. Here, we speculate that improved sleep quality could reduce seizure likelihood. It is well known that the thermoregulatory response to ambient temperature (Ta) change alters sleep. It is therefore plausible that deliberate manipulation of Ta could alter sleep patterns in a way that alleviates the seizure burden, if correctly implemented. As a step in this direction, this study assesses the effect of Ta on sleep dynamics and seizure yield in the pilocarpine mouse model of chronic temporal lobe epilepsy. Methods: Four adult male C57BL/6J mice, 6-8 weeks old, were injected with pilocarpine to induce acute seizures. After a latent period, spontaneously recurring seizures indicative of chronic epilepsy were observed, and each animal was implanted with a tethered EEG/EMG headmount. All procedures were performed with IACUC approval. A thermostatic chamber was used to control cage temperature within the thermoneutral zone for mice. After a recovery period, each mouse was exposed to elevated Ta of 30C from 7 a.m ?" 9 p.m on alternate days, with reversal to baseline room temperature (Ta ~ 22C) at all other times. Continuous recording of EEG, EMG, motion, Ta, and video was performed for an average of 12 days in each mouse. Seizures were detected and counted based on simple features of the EEG, namely the signal line length and Teager energy. Metrics associated with different vigilance states (Wake, NREM, and REM) were estimated and compared statistically for the light period on days of elevated Ta versus baseline. Results: Mice spent more time in NREM sleep (p = 0.0003) and less time in Wake (p = 0.02) at elevated Ta. The mean number of NREM bouts increased significantly with Ta (p = 0.008). Daily seizure rates pooled for all animals were not significantly different during elevated Ta (p = 0.91). There was some variability in the effect on seizure yield: the mean seizure rate increased in two animals and decreased for the others with elevated Ta but the effects were not significant (p > 0.05). The two animals in which seizure rate decreased at elevated Ta also experienced a significant reduction in % Wake coupled with an increase in % REM. Conclusions: Experiments showed that sleep metrics change significantly with Ta; though changes in seizure yield were observed, the effect was not as clear and needs to be characterized in a larger sample. Manipulation of Ta could be a simple and relatively unobtrusive means for improving sleep in epilepsy patients and complement other therapies for seizure control. To test this possibility, we have devised a simple strategy for dynamic sleep modulation that we are currently testing in our mouse model. Funding: Supported in part by National Institutes of Health grant NS083218 and by a seed grant from EpiC, the University of Kentucky Epilepsy Research Center. A. Ajwad received scholarship support from the Higher Committee of Education in Iraq.