Generalized tonic-clonic seizures are accompanied by changes of interrelations within the autonomic nervous system

•Unimodal ANS modality recording changes predominantly occur after seizures, bimodal changes are detectable before GTCS.•Interactions of different ANS modality recordings are lower in patients with GTCS than in controls.•Multimodal interactions may provide a peripheral marker of centrally driven ANS activity. A seizure is a strong central stimulus that affects multiple subsystems of the autonomic nervous system (ANS), and results in different interactions across ANS modalities. Here, we aimed to evaluate whether multimodal peripheral ANS measures demonstrate interactions before and after seizures as compared to controls to provide the basis for seizure detection and forecasting based on peripheral ANS signals. Continuous electrodermal activity (EDA), heart rate (HR), peripheral body temperature (TEMP), and respiratory rate (RR) calculated based on blood volume pulse were acquired by a wireless multi-sensor device. We selected 45 min of preictal and 60 min of postictal data and time-matched segments for controls. Data were analyzed over 15-min windows. For unimodal analysis, mean values over each time window were calculated for all modalities and analyzed by Friedman’s two-way analysis of variance. Twenty-one children with recorded generalized tonic-clonic seizures (GTCS), and 21 age- and gender-matched controls were included. Unimodal results revealed no significant effect for RR and TEMP, but EDA (p = 0.002) and HR (p