Clinical subtypes and sleep–wake evolution pattern in epilepsy manifesting as sleep‐related seizures
Jinqi Zhou, Sha Xu, Lingqi Ye, Zhongjin Wang, Hong Li, Xiao Chen, Ruotong Chen, Yuyu Yang, Chenchuan Song, Lingli Hu, Pu Miao, Shan Wang, Yao Ding, Chunhong Shen, Yi Guo, Cong Chen, Shuang WangAbstract
Objective
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.
Methods
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.
Results
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.
Significance
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.