Insights from stereoelectroencephalography in KCNT1-related focal epilepsy suggest a multifocal and migrating epileptogenic network

Abstract

The most characteristic syndrome related to KCNT1 is epilepsy of infancy with migrating focal seizures. Unifocal epilepsies have also been reported, the most common being sleep-related hypermotor epilepsy (SHE) of frontal origin. Only 10 cases of focal extrafrontal epilepsies with an insulo-opercular or temporal origin have been reported. Among these patients suffering from focal epilepsy, only seven underwent stereoelectroencephalography (S-EEG) describing focal or multifocal ictal onsets. We performed three S-EEGs and one S-EEG in two unrelated patients suffering from refractory magnetic resonance imagining-negative SHE with insulo-opercular seizures. None of the patients had any familial history of epilepsy or intellectual disability. They suffered from nocturnal seizures with stereotyped ictal symptoms suggestive of insulo-opercular SHE (IO-SHE). The four S-EEGs revealed multifocal, bilateral, and migrating ictal activity, whereas clinical ictal semiology remained stereotyped. These S-EEG findings led us to carry out genetic analysis, and a pathogenic missense variant of KCNT1 was found in each patient (p.Arg928Cys and p.Arg933His). Considering these two new patients, IO-SHE represents the second most frequent type of KCNT1-related focal epilepsy, and these S-EEG findings, never described before, suggest that migrating ictal activity might be a common feature of KCNT1-related epilepsy despite different syndromic presentations.

Keywords: KCNT1; SHE; S‐EEG; insulo‐opercular seizures; migrating focal seizures.