Time, frequency and information domain analysis of short-term heart rate variability before and after focal and generalized seizures in epileptic children

Objective: In this work we explore the potential of combining standard time and frequency domain indexes with novel information measures, to characterize pre- and post-ictal heart rate variability (HRV) in epileptic children, with the aim of differentiating focal and generalized epilepsy regarding the autonomic control mechanisms. Approach: We analyze short-term HRV in 37 children suffering from generalized or focal epilepsy, monitored 10 s, 300 s, 600 s and 1800 s both before and after seizure episodes. Nine indexes are computed in time (mean, standard deviation of normal-to-normal intervals, root mean square of the successive differences (RMSSD)), frequency (low-to-high frequency power ratio LF/HF, normalized LF and HF power) and information (entropy, conditional entropy and self-entropy) domains. Focal and generalized epilepsy are compared through statistical analysis of the indexes and using linear discriminant analysis (LDA). Main results: In children with focal epilepsy, early post-ictal phase is characterized by significant tachycardia, depressed HRV, increased LF power and LF/HF, and decreased complexity, progressively recovered across time windows after the episodes. Children with generalized seizures instead show significant tachycardia, lower RMSSD, higher LF power and LF/HF ratio before the seizure. These different behaviors are exploited by LDA analysis to separate focal and generalized epilepsy up to an accuracy of 75%. Results suggest a shift of the sympatho-vagal balance towards sympathetic dominance and vagal withdrawal, noticeable just after the termination of seizure episodes and then reverted in focal epilepsy, and persistent during inter-ictal and pre-ictal periods in generalized epilepsy. Significance: Our analysis helps in elucidating the pathophysiology of inter-ictal HRV autonomic control and the differential diagnosis of generalized and focal epilepsy. These findings may have clinical relevance since altered sympatho-vagal control can be related to a higher danger of morbidity and mortality, may reduce thresholds for life-threatening arrhythmias, and could be a biomarker of risk for sudden unexpected death in epilepsy.