Revisiting the concept that interictal implies asymptomatic: Pulse wave amplitude drops uncover autonomic responses...

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.

We retrospectively analyzed 511 GPFA events during sleep from 21 patients undergoing polysomnography. We characterized GPFA events and their association with PWAD.

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.

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.