Cardiac arrhythmias in Dravet syndrome

Dravet syndrome (DS) is a severe childhood-onset epileptic encephalopathy with
intractable seizures and developmental delay. Children with DS face a
substantial risk of early epilepsy-related death: up to 15% by age 20.Sudden
unexpected death in epilepsy (SUDEP) is the commonest cause of death in DS
accounting for up to 60% of all mortality. SUDEP is the sudden unexpected death
of a person with epilepsy in which a toxicological or anatomical autopsy is
negative for a cause of death. SUDEP is most likely a seizure-related event and
a high frequency of convulsions is the strongest risk factor. Currently, it is
not preventable. The pathophysiology of SUDEP is poorly understood, but likely
heterogeneous and multifactorial. The few available ictal recordings of SUDEP
indicate that most deaths occur in the aftermath of a convulsion. Mechanisms
including central cardiorespiratory dysfunction have been suggested. The
relative low incidence of SUDEP, limited availability of ictal-recordings even
in prospective multi-center registries14 and pathophysiological heterogeneity
are critical barriers to develop preventative measures.
We suggest that DS may constitute a homogeneous subgroup of SUDEP as (1) its
incidence is substantially higher than in other forms of severe childhood
epilepsy,8,9 (2) SUDEP in DS occurs in childhood: this contrast with SUDEP
where a older peak incidence is noted,15 (3) DS has a genetic basis: in >70% of
DS cases de novo mutations/deletions in the SCN1A gene encoding for the *-
subunit of the neuronal voltage-gated sodium channel Nav1.1 are found,6,7 (4)
Nav1.1 channels are expressed in mammalian brain and heart.16 A SCN1A mutation
may therefore confer a propensity for epilepsy and an innate vulnerability for
cardiac arrhythmias, thus leading to a higher risk of SUDEP in DS.

We aim to to record heart rate patterns during seizures with miniaturized
wearable EKG-monitors in a large cohort of DS

International observational study with historical controls

Participation does not carry risks. The sensor is miniaturised and wearable,
thus minimising discomfort. If this nevertheless may occur, the study can be
immediately terminated. This study provides specific tools to investigate the
seizure-related heart rate response. Subjects may thus benefit from
participation by identification of otherwise unknown arrhythmias. The rationale
of the study (the high SUDEP risk and the evidence in animal studies for
arrhythmic cause of sudden death), specifically applies to DS, a rare epileptic
syndrome including minors and incapacitated persons. We believe that the lack
of risks, the potential diagnostic benefit, the minimal intervention with novel
and wearable sensors and the possibility to terminate the study in case of
discomfort, justifies the study in this patient group.