Objective: Sudden and unexpected deaths in epilepsy (SUDEP) pathophysiology may involve an interaction between respiratory dysfunction and sleep/wake state regulation. We investigated whether patients with epilepsy exhibit impaired sleep apnea-related arousals.

Methods: Patients with drug-resistant (N=20) or drug-sensitive (N=20) epilepsy and obstructive sleep apnea, as well as patients with sleep apnea but without epilepsy (controls, N=20) were included. We explored (1) the respiratory arousal threshold based on nadir oxygen saturation, apnea-hypopnea index, and fraction of hypopnea among respiratory events; (2) the cardiac autonomic response to apnea/hypopnea quantified as percentages of changes from the baseline in RR intervals (RRI), high (HF) and low (LF) frequency powers, and LF/HF.

The respiratory arousal threshold did not differ between groups. At arousal onset, RRI decreased (-9.42%) and LF power (179%) and LF/HF ratio (190%) increased. This was followed by an increase in HF power (118%), p<0.05. The RRI decrease was lower in drug-resistant (-7.40%) than in drug-sensitive patients (-9.94%) and controls (-10.91%), p<0.05. LF and HF power increases were higher in drug-resistant (188%/126%) than in drug-sensitive patients (172%/126%) and controls (177%/115 %), p<0.05.

Conclusions: Cardiac reactivity following sleep apnea is impaired in drug-resistant epilepsy.

Significance: This autonomic dysfunction might contribute to SUDEP pathophysiology.

1. The respiratory arousal threshold does not differ between apneic patients with and without epilepsy 2. The arousal related heart rate increase after obstructive apnea is less pronounced in patients with drug-resistant epilepsy 3. Late post-arousal parasympathetic activation is increased in patients with drug-resistant epilepsy