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Sudden unexpected death in epilepsy (SUDEP) is the leading seizure-related cause of death in epilepsy patients. There are no validated biomarkers of SUDEP risk. Here, we explored peri-ictal differences in topological brain network properties from scalp EEG recordings of SUDEP victims. Functional connectivity networks were constructed and examined as directed graphs derived from undirected delta and high frequency oscillation (HFO) EEG coherence networks in eight SUDEP and 14 non-SUDEP epileptic patients. These networks were proxies for information flow at different spatiotemporal scales, where low frequency oscillations coordinate large-scale activity driving local HFOs. The clustering coefficient and global efficiency of the network were higher in the SUDEP group pre-ictally, ictally and post-ictally ( p  &amp;lt; 0.0001 to  p  &amp;lt; 0.001), with features characteristic of small-world networks. These results suggest that cross-frequency functional connectivity network topology may be a non-invasive biomarker of SUDEP risk.

A Peri-Ictal EEG-Based Biomarker for Sudden Unexpected Death in Epilepsy (SUDEP) Derived From Brain Network Analysis