Clinical subtypes and sleep-wake evolution pattern in epilepsy manifesting as sleep-related seizures

Epilepsy manifesting as sleep-related seizures (EpSRS) represents a common but heterogeneous group. This study aimed to identify distinct clinical subtypes of EpSRS and explore alterations in sleep-wake seizure rhythms over the disease course.

EpSRS is defined by seizures occurring ≥80% during sleep. We conducted a cross-sectional study of 550 patients with EpSRS. Patients were classified as current EpSRS if ≥80% of their seizures occurred during sleep over the past year, or as previous EpSRS if they had a prior history of EpSRS but no longer met this 80% threshold during the past year. A two-step cluster analysis was applied to the current EpSRS cohort, and disease trajectories were evaluated across both cohorts.

Cluster analysis classified the current EpSRS cohort (n = 447) into two distinct subtypes. The sleep tonic-clonic seizure (TCS) subtype (n = 218) featured later onset (18.0 years), infrequent (<1 seizure/month, 73.9%) TCSs (99.5%), an unknown etiology (78.0%), and a favorable drug response (2.8% drug-resistant epilepsy [DRE]). The sleep non-TCS subtype (n = 229) featured early onset (11.0 years), frequent (≥1 seizure/month, 52.0%) focal preserved/impaired consciousness seizures (FPCSs/FICSs, 96.9%), an association with etiology of malformations of cortical development (27.9%), and a high rate of DRE (62.9%). Furthermore, an evolution pattern was found in the previous EpSRS cohort (n = 103), marked by a transition from the sleep TCS subtype into awake FPCS/FICS pattern (52.5% were diagnosed as temporal lobe epilepsy), with the DRE proportion surging from 5.2% to 39.0%. This phenotypic evolution could be predicted by later age at epilepsy onset, female sex, and a history of febrile seizures.

This study establishes a practical framework for classifying EpSRS, which is useful for predicting prognosis and evaluating etiology. It should be noted that among patients with the sleep TCS subtype, a transition into an awake FPCS/FICS pattern is associated with an increased risk of DRE.