Authors :
First Author: Justin Ryan, PhD – SUNY Upstate Medical University
Presenting Author: David Auerbach, PhD – SUNY Upstate Medical University
Amir Aschner, PhD – University of Toronto Hospital for Sick Children; Elizabeth Donner, MD, M.Sc., FRCPC – University of Toronto Hospital for Sick Children; David Auerbach, PhD – SUNY Upstate Medical University
Rationale:
Dravet syndrome (DS) is a severe form of epilepsy in which over 80% of cases have a variant in the
SCN1A gene.
SCN1A encodes a protein that forms the α subunit of a voltage-gated Na
+ channel that is expressed in both the brain and heart. In an
Scn1a-mutant mouse model of DS, there is cardiac hyperexcitability, ECG abnormalities, and ventricular fibrillation was the mechanism for a case of sudden death. Increased cardiac Na
+ current and hyperexcitability were also observed in iPSC-myocytes from people with DS. We aim to determine if cardiac electrical function differs in people with DS compared to another severe form of epilepsy without cardiac genetic variants (Lennox-Gastaut syndrome, LGS), particularly surrounding seizures.
Methods:
Continuous EEG/ECG recordings were obtained and annotated for seizures by a board certified epileptologist. ECG signals were analyzed in the five minutes leading up to seizure onset, five minutes following seizure end, and during a 10-minute non-seizure period. Dynamic ECG measures of cardiac conduction, repolarization, and autonomic function were evaluated at each timepoint.
Results:
There is a pre-to-post-ictal decrease in heart rate surrounding DS seizures. There are significant changes in ECG waveform morphology surrounding both DS and LGS events. Fifteen to twenty five percent of recordings from each group exhibit ECG abnormalities. ECG measures are not pathological in either group and changes surrounding events do not differ in DS and LGS.
Conclusions:
People with DS and LGS exhibit ECG changes surrounding seizures that could provide a substrate for cardiac-mediated sudden death. Continued analysis is required to determine specific abnormalities associated with
SCN1A variants.
Funding:
Dravet Syndrome Foundation, JAM For Dravet