Revisiting the concept that interictal implies asymptomatic: Pulse wave amplitude drops uncover autonomic responses during generalized paroxysmal fast activities

OBJECTIVE: Interictal electroencephalographic (EEG) activities are generally considered asymptomatic. Pulse wave amplitude drop (PWAD) is a marker of autonomic nervous system (ANS) reactivity linked to cardiovascular risk. Generalized paroxysmal fast activity (GPFA) is a major EEG pattern in different epileptic conditions. We investigated whether GPFA, even when clinically silent, triggers ANS activation measured by PWAD. METHODS: We retrospectively analyzed 511 GPFA events during sleep from 21 patients undergoing polysomnography. We characterized GPFA events and their association with PWAD. RESULTS: Among 511 GPFA events, 26.4% were clinically asymptomatic without PWAD (Group 1), 40.5% were clinically silent with PWAD ≥ 30% as the only detected sign (Group 2), and 33.1% were clinically symptomatic (Group 3). Compared to Groups 1 and 2, Group 3 events had longer duration (p = .007 and p < .0001), had higher heart rate variation (p < .001), and were more often symmetric (p < .001). Group 3 GPFA occurred more often in N1 sleep compared to Group 2 (32.1 vs. 18.1%, p = .004). Unexpectedly, PWAD was poorly correlated with GPFA duration (r = .068). Finally, Group 2 GPFA-associated PWADs more closely resembled microarousal-associated PWADs than apnea/hypopnea-associated PWADs in temporal profile. SIGNIFICANCE: PWAD uncovers autonomic responses in most GPFA, challenging the concept that "interictal" implies asymptomatic. This repetitive ANS activation raises questions about its potential long-term clinical consequences. These findings support the use of pulse oximetry during video-EEG to detect subclinical autonomic changes, although further studies are needed to determine their clinical significance and whether they should influence the management of interictal activities.