Kenneth A Myers1,2,3,4, Luis E Bello-Espinosa2, Joseph D Symonds5,6, Sameer M Zuberi5,6, Robin Clegg7, Lynette G Sadleir8, Jeffrey Buchhalter2, Ingrid E Scheffer1,9,10. 1. Department of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. 2. Department of Pediatrics, Section of Neurology, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 3. Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. 4. Division of Child Neurology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada. 5. College of Medicine, Veterinary, and Life Sciences, School of Medicine, University of Glasgow, Glasgow, UK. 6. Paediatric Neurosciences Research Group, Royal Hospital for Sick Children, Glasgow, UK. 7. Department of Pediatrics, Section of Cardiology, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. 8. Department of Paediatrics and Child Health, University of Otago Wellington, Wellington, New Zealand. 9. Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Flemington, Victoria, Australia. 10. Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.
Abstract
OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a tragic and devastating event for which the underlying pathophysiology remains poorly understood; this study investigated whether abnormalities in heart rate variability (HRV) are linked to SUDEP in patients with epilepsy due to mutations in sodium channel (SCN) genes. METHODS: We retrospectively evaluated HRV in epilepsy patients using electroencephalographic studies to study the potential contribution of autonomic dysregulation to SUDEP risk. We extracted HRV data, in wakefulness and sleep, from 80 patients with drug-resistant epilepsy, including 40 patients with mutations in SCN genes and 40 control patients with non-SCN drug-resistant epilepsy. From the SCN group, 10 patients had died of SUDEP. We compared HRV between SUDEP and non-SUDEP groups, specifically studying awake HRV and sleep:awake HRV ratios. RESULTS: The SUDEP patients had the most severe autonomic dysregulation, showing lower awake HRV and either extremely high or extremely low ratios of sleep-to-awake HRV in a subgroup analysis. A secondary analysis comparing the SCN and non-SCN groups indicated that autonomic dysfunction was slightly worse in the SCN epilepsy group. SIGNIFICANCE: These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk. Wiley Periodicals, Inc.
OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a tragic and devastating event for which the underlying pathophysiology remains poorly understood; this study investigated whether abnormalities in heart rate variability (HRV) are linked to SUDEP in patients with epilepsy due to mutations in sodium channel (SCN) genes. METHODS: We retrospectively evaluated HRV in epilepsypatients using electroencephalographic studies to study the potential contribution of autonomic dysregulation to SUDEP risk. We extracted HRV data, in wakefulness and sleep, from 80 patients with drug-resistant epilepsy, including 40 patients with mutations in SCN genes and 40 control patients with non-SCN drug-resistant epilepsy. From the SCN group, 10 patients had died of SUDEP. We compared HRV between SUDEP and non-SUDEP groups, specifically studying awake HRV and sleep:awake HRV ratios. RESULTS: The SUDEP patients had the most severe autonomic dysregulation, showing lower awake HRV and either extremely high or extremely low ratios of sleep-to-awake HRV in a subgroup analysis. A secondary analysis comparing the SCN and non-SCN groups indicated that autonomic dysfunction was slightly worse in the SCN epilepsy group. SIGNIFICANCE: These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk. Wiley Periodicals, Inc.
Authors: Melissa A de la Garza; David Poldiak; Robert Shade; Felipe S Salinas; Alex M Papanastassiou; C Ákos Szabó Journal: Epilepsy Res Date: 2019-06-12 Impact factor: 3.045
Authors: Charles Ákos Szabó; Margarita Akopian; David A González; Melissa A de la Garza; Melanie A Carless Journal: Epilepsia Date: 2019-10-08 Impact factor: 5.864