title: Autonomic changes following generalized tonic clonic seizures: An analysis of adult and pediatric patients with epilepsy.
abstract: OBJECTIVE
  Sudden unexpected death in epilepsy (SUDEP) is the most common cause of mortality directly related to epilepsy. Its incidence is higher in adult patients and its pathophysiology remains poorly understood, but likely involves autonomic dysregulation following generalized tonic clonic seizures (GTCS). In the current study, we aimed to analyze post-ictal autonomic changes following GTCS in adult and pediatric patients.
  
  
  METHODS
  Patients admitted to the epilepsy monitoring unit were prospectively recruited, and wore an electrodermal activity (EDA) wrist sensor that continuously measured sympathetic activity while being monitored with EEG and EKG electrodes. Peri-ictal EDA parameters were assessed as a measure of sympathetic activity. Peri-ictal parasympathetic activity was determined through the high frequency component (HF) analysis of heart rate variability (HRV). The duration of post-ictal generalized EEG suppression (PGES) was also documented.
  
  
  RESULTS
  Twenty patients with GTCS were included in the study on whom 30 GTCS were recorded. PGES duration strongly correlated with age (r=0.62, p=0.004) and measures of the EDA response. After controlling for PGES duration, we found pediatric patients had greater sympathetic activation measured as log rising portion of the area under the curve of the EDA response (β=+0.67, p=0.034) and a higher degree of vagal suppression measured as maximal percentage change of HF power (β=-12.65, p=0.0036).
  
  
  CONCLUSIONS
  Sympathetic activity can be measured in the peri-ictal period, and directly correlates with PGES duration. Age is a significant determinant of the sympathetic and parasympathetic response following a GTCS; given the same PGES duration, pediatric patients demonstrate stronger sympathetic activation and higher vagal suppression. However, the increase in PGES duration with age and the associated autonomic dysregulation may provide clues as to why there is a variable vulnerability to SUDEP across age groups.
authors.affiliation: Department of Neurology, Edward B. Bromfield Epilepsy Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: rsarkis@partners.org.
authors.forename: Rani A
authors.initials: RA
authors.lastname: Sarkis
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Sigride.Thome@childrens.harvard.edu.
authors.forename: Sigride
authors.initials: S
authors.lastname: Thome-Souza
authors.affiliation: MIT Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: zher@mit.edu.
authors.forename: Ming-Zher
authors.initials: MZ
authors.lastname: Poh
authors.affiliation: Department of Neurology, Edward B. Bromfield Epilepsy Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: nllewellyn@partners.org.
authors.forename: Nichelle
authors.initials: N
authors.lastname: Llewellyn
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Jacquelyn.Klehm@childrens.harvard.edu.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Klehm
authors.affiliation: Department of Neurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Joseph.Madsen@childrens.harvard.edu.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Madsen
authors.affiliation: MIT Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA; Empatica, Inc., Cambridge, MA, USA. Electronic address: picard@media.mit.edu.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Picard
authors.affiliation: Department of Neurology, Edward B. Bromfield Epilepsy Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ppennell@partners.org.
authors.forename: Page B
authors.initials: PB
authors.lastname: Pennell
authors.affiliation: Department of Neurology, Edward B. Bromfield Epilepsy Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: bdworetzky@partners.org.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Dworetzky
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Tobias.Loddenkemper@childrens.harvard.edu.
authors.forename: Tobias
authors.initials: T
authors.lastname: Loddenkemper
authors.affiliation: Department of Neurology, Edward B. Bromfield Epilepsy Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Institute of Sports Medicine, University of Paderborn, Paderborn, Germany. Electronic address: creinsberger@partners.org.
authors.forename: Claus
authors.initials: C
authors.lastname: Reinsberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D002648:Child; D004562:Electrocardiography; D004569:Electroencephalography; D004829:Epilepsy, Generalized / Q000503:physiopathology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D011446:Prospective Studies; D012640:Seizures / Q000503:physiopathology*; D013997:Time Factors; D055815:Young Adult
keywords: Autonomic nervous system; Electrodermal activity; Generalized tonic clonic seizures; Post-ictal generalized EEG suppression; Sudden unexpected death in epilepsy