Chronic vagus nerve stimulation improves alertness and reduces rapid eye movement sleep in patients affected by refractory epilepsy

Objective: Our study aimed to evaluate the existence and entity of changes in sleep structure following vagus nerve stimulation in patients with refractory epilepsy. Method: A polysomnographic study was performed on the nocturnal sleep of 10 subjects with refractory epilepsy. Subjects were recorded both in baseline conditions and after chronic vagus nerve stimulation. Sleep parameters of the entire night were evaluated. Mean power value of slow-wave activity was computed in the first non-rapid eye movement sleep cycle. A sleep-wake diary evaluated quantity of both nocturnal and daytime sleep, while visual-analog scales assessed quality of sleep and wake. The differences between the 2 conditions underwent parametric and nonparametric statistical evaluation. Results: Vagus nerve stimulation produced a significant reduction in REM sleep (in all subjects with vagus nerve stimulus intensity greater than 1.5 milliampere, but not in the only patient with a stimulus intensity less than 1.5 milliampere), along with an increase in the number of awakenings, percentage of wake after sleep onset, and stage 1 sleep. Data from a sleep-wake questionnaire show a decrease in both nocturnal sleep and daytime naps and an increased daytime alertness, while the quality of wakefulness is globally improved. Spectral analysis shows an enhancement of delta power during non-rapid eye movement sleep. Conclusions: Our data demonstrate major effects of vagus nerve stimulation on both daytime alertness (which is improved) and nocturnal rapid eye movement sleep (which is reduced). These effects could be interpreted as the result of a destabilizing action of vagus nerve stimulation on neural structures regulating sleep-wake and rapid eye movement/non-rapid eye movement sleep cycles. Lower intensity vagus nerve stimulation seems only to improve alertness;, higher intensity vagus nerve stimulation seems able to exert an adjunctive rapid eye movement sleep-attenuating effect.