title: Circadian and ultradian patterns of epileptiform discharges differ by seizure-onset location during long-term ambulatory intracranial monitoring.
abstract: Previous studies reporting circadian patterns of epileptiform activity and seizures are limited by (1) short-term recording in an epilepsy monitoring unit (EMU) with altered antiepileptic drugs (AEDs) and sleep, or (2) subjective seizure diary reports. We studied circadian patterns using long-term ambulatory intracranial recordings captured by the NeuroPace RNS System.
  
  
  
  Retrospective study of RNS System trial participants with stable detection parameters over a continuous 84-day period. We analyzed all detections and long device-detected epileptiform events (long episodes) and defined a subset of subjects in whom long episodes represented electrographic seizures (LE-SZ). Spectrum resampling determined the dominant frequency periodicity and cosinor analysis identified significant circadian peaks in detected activity. Chi-square analysis was used to compare subjects grouped by region of seizure onset.
  
  
  
  In the 134 subjects, detections showed a strongly circadian and uniform pattern irrespective of region of onset that peaked during normal sleep hours. In contrast, long episodes and LE-SZ patterns varied by region. Neocortical regions had a monophasic, nocturnally dominant rhythm, whereas limbic regions showed a more complex pattern and diurnal peak. Rhythms in some individual limbic subjects were best fit by a dual oscillator (circadian + ultradian) model.
  
  
  
  Epileptiform activity has a strong 24 h periodicity with peak nocturnal occurrence. Limbic and neocortical epilepsy show divergent circadian influences. These findings confirm that circadian patterns of epileptiform activity vary by seizure-onset zone, with implications for treatment and safety, including SUDEP.
authors.affiliation: Oregon Health & Science University, Portland, Oregon, U.S.A.
authors.forename: David C
authors.initials: DC
authors.lastname: Spencer
authors.affiliation: NeuroPace, Inc., Mountain View, California, U.S.A.
authors.forename: Felice T
authors.initials: FT
authors.lastname: Sun
authors.affiliation: Oregon Health & Science University, Portland, Oregon, U.S.A.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Brown
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, U.S.A.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Jobst
authors.affiliation: University of Virginia, Charlottesville, Virginia, U.S.A.
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Fountain
authors.affiliation: Oregon Health & Science University, Portland, Oregon, U.S.A.
authors.forename: Victoria S S
authors.initials: VS
authors.lastname: Wong
authors.affiliation: NeuroPace, Inc., Mountain View, California, U.S.A.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Mirro
authors.affiliation: University of Virginia, Charlottesville, Virginia, U.S.A.
authors.forename: Mark
authors.initials: M
authors.lastname: Quigg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018670:Monitoring, Ambulatory; D012189:Retrospective Studies; D012640:Seizures / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants
keywords: Circadian rhythms; Epilepsy; Epileptiform; Responsive neurostimulation