Clinical Markers Associated with Sudden Unexpected Death in Epilepsy in Dravet Syndrome
Abstract number :
2.444
Submission category :
4. Clinical Epilepsy / 4D. Prognosis
Year :
2022
Submission ID :
2232928
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:28 AM
Authors :
Melissa Baltuano, MD – University of Oklahoma Health Sciences Center, OU Children's Hospital; Veronica Hood, MS, PhD – Scientific Director, Dravet Syndrome Foundation; Abigail Van Nuland, MS – Research Scientist, Epilepsy Center, Ann and Robert H. Lurie Children’s Hospital of Chicago; Mary Anne Meskis, - – Executive Director, Dravet Syndrome Foundation; Linda Laux, MD – Associate Professor of Pediatrics (Neurology and Epilepsy), Pediatrics, Division of Neurology, Epilepsy Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine
This is a Late Breaking abstract
Rationale: Dravet syndrome (DS) is a rare genetic epileptic encephalopathy characterized by multiple seizure types and recurrent status epilepticus1 associated with mutations in the SCN1A gene. These patients have significant mortality rates, with up to 15-56% secondary to sudden unexpected death in epilepsy (SUDEP) described.2 Major risk factors for SUDEP in general include frequency of convulsive seizures and failure to control treatment resistant seizures,4 both of which occur frequently in DS. However, to this date no study has identified specific characteristics in these patients associated with an increased risk of developing SUDEP. This study aims to identify clinical markers associated with SUDEP in DS.
Methods: This was a retrospective study that gathered information on patients with DS, specifically those who developed SUDEP. Participants had to be least 18 years old and be a parent, caregiver or guardian of a child or adult with DS and agree to participation in the study. Information was obtained by using an online survey distributed by email to potential participants by the Dravet Syndrome Foundation. The survey contained questions regarding demographics, clinical and genetic characteristics of patients as well as cause of death when applicable.
Results: There were a total of 113 survey responses and after data cleaning, 68 controls and 7 cases (n=75) were included in the final analysis. The mortality rate in our case sample was 9.3%, with status epilepticus (SE) being the main cause of death (5.3%) followed by probable SUDEP cases (4.0%). This group was predominantly male (71%), white, non-hispanic, with a mean age of death 9.9 years, peaking before age 5 and over age 20, all with confirmed SCN1A mutations. Mean age of seizure onset was at 5.6 months, with 85.7% presenting in SE and 71.4% with convulsive seizures. In terms of phenotype severity, all of the patients had convulsions, 71% had at least one lifetime episode of SE and all were on average, on 3.4 anti-seizure medications around the time of death. Most patients had abnormal breathing and gasping after seizures with 85.7% of parents reporting this finding and 57% reporting cyanosis during seizures. None of the patients were reported to have cardiac issues and cardiac testing done including echocardiogram and EKG were normal.
Conclusions: Our findings show a high mortality rate in the DS population, similar to what has been previously described. Preliminary descriptive findings showed the majority of patients who died were male, below the age of 5 and above the age of 20. Phenotype severity showed high rates of SE, convulsive seizures and early intractability. Most patients had abnormal breathing and cyanosis during seizures however none had evidence of cardiac issues. The main limitation of this study was the low number of cases in our cohort, however it provided important information on mortality and characteristics in this group. Next steps will include identifying more cases to compare with controls and finding potentially modifiable risk factors to prevent this outcome in patients with DS.
Funding: None
Clinical Epilepsy