Rationale:
Epilepsy affects more than three million people in the US alone, with most reporting a relationship between seizures and sleep-wake patterns, and about one million having sleep disorders. Furthermore, many of the comorbidities of epilepsy, such as mood disorder, attentional and executive difficulties, memory dysfunction, and psychosis, are worsened by disrupted sleep, not to mention the association of sudden unexpected death in epilepsy and sleep. Despite this long-appreciated and robust relationship between sleep-wake and epilepsy, little is known about the underlying mechanisms of this interaction. We sought to examine sleep disruption in a model of medial temporal lobe epilepsy and found that this model recapitulates several human findings.
Method:
Mice were implanted with a pre-configured head plate that includes hippocampal electrodes, a microinjection cannula targeting the amygdala, along with dural screw and EMG electrodes for standard sleep scoring. After recovering from surgery, mice underwent continuous video-EEG recording for one week (baseline), continuing during intraamygdala kainic acid injection and for three subsequent weeks. Mice were then perfused for histology.
Results:
Sleep is significantly decreased (~15%) in both the light and dark periods in mice with spontaneous seizures after intraamygdala kainic acid (ANOVA P=0.032, n=6,6). Moreover, seizure frequency was correlated with sleep disruption (P=0.046, R2=0.37). There were significantly more transitions between sleep and wake (P=0.004). Seizure were also more frequent and longer during sleep than during wakefulness (P=0.013).
Conclusion:
These findings mirror documented human sleep disorders in epilepsy with prominent insomnia and sleep disruption. Moreover, this sleep disruption may contribute to some of the comorbidities of epilepsy, including affective and cognitive complaints. Studies continue with circuit-based manipulations that aim to normalize sleep and examine the effect on cognition and seizure frequency.
Funding:
:Research reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number K08NS105929. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
FIGURES
Figure 1