Genetic effects on sleep/wake variation of seizures

• Type of Material: Article
• Authors: Melodie R. Winawer, Columbia University; Jerry Shih, Mayo Clinic; Erin S. Beck, Columbia University; Jessica E. Hunter, Kaiser Permanente Center for Health Research Northwest; Michael Epstein, Emory University; EPGP Investigators
• Language: English
• Date: 2016-04-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1111/epi.13330
• Title of Journal or Parent Work: Epilepsia
• ISSN: 0013-9580
• Volume: 57
• Issue: 4
• Start Page: 557
• End Page: 565
• Grant/Funding Information: Supported by National Institute of Neurological Disorders and Stroke (NINDS) U01 NS 053998.
• Keywords: Genetics; SEMISTRUCTURED INTERVIEW; CHILDREN; Neurosciences & Neurology; Sleep; Seizure; Epilepsy; Life Sciences & Biomedicine; CLASSIFICATION; MUTATIONS; INTERICTAL SPIKING; MECHANISM; Circadian; FOCI; Science & Technology; FRONTAL-LOBE EPILEPSY; BENIGN EPILEPSY; Clinical Neurology
• Research Categories: Biology, Neuroscience; Biology, Genetics; Health Sciences, General

Abstract

Objective: There is a complex bidirectional relationship between sleep and epilepsy. Sleep/wake timing of seizures has been investigated for several individual seizure types and syndromes, but few large-scale studies of the timing of seizures exist in people with varied epilepsy types. In addition, the genetic contributions to seizure timing have not been well studied. Methods: Sleep/wake timing of seizures was determined for 1,395 subjects in 546 families enrolled in the Epilepsy Phenome/Genome Project (EPGP). We examined seizure timing among subjects with different epilepsy types, seizure types, epilepsy syndromes, and localization. We also examined the familial aggregation of sleep/wake occurrence of seizures. Results: Seizures in nonacquired focal epilepsy (NAFE) were more likely to occur during sleep than seizures in generalized epilepsy (GE), for both convulsive (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.59–7.52) and nonconvulsive seizures (OR 4.2, 95% CI 2.48–7.21). Seizures occurring within 1 h of awakening were more likely to occur in patients with GE than with NAFE for both convulsive (OR 2.3, 95% CI 1.54– 3.39) and nonconvulsive (OR 1.7, 95% CI 1.04–2.66) seizures. Frontal onset seizures were more likely than temporal onset seizures to occur during sleep. Sleep/wake timing of seizures in first-degree relatives predicted timing of seizures in the proband. Significance: We found that sleep/wake timing of seizures is associated with both epilepsy syndrome and seizure type. In addition, we provide the first evidence for a genetic contribution to sleep/wake timing of seizures in a large group of individuals with common epilepsy syndromes.