Abstracts

Rationale: SCN8A channelopathies have been recently recognized as a cause of epileptic encephalopathy in infants. We describe a case of an infant with refractory epilepsy who experienced ictal aystole, a new phenotypic feature. Though traditionally sodium channel inhibitors are avoided in epileptic encephalopathies, especially when a sodium channelopathy is suspected, our patient responded to pharmacologic blockade of sodium channels with improvement in his seizure burden and cardiac arrhythmia.Methods: We retrospectively reviewed the history of a 13 month old male who initially presented at two months old with paroxysmal spells of apnea, tonic extension, flexion of the extremities, and facial grimacing. The events were confirmed on EEG to be seizures. During the seizures he experienced episodes of asystole lasting up to four seconds followed by ventricular bradycardia, then sinus tachycardia. He was tried on multiple medications including phenobarbital, levetiracetam, and clobazam with minimal response. Sodium channel blocking medications were initially withheld given the concern for provoking cardiac arrhythmias. Pacemaker placement was discussed but ultimately not undertaken.Results: A trial dose of intravenous fosphenytoin led to an improvement in seizure frequency and level of alertness. His seizure burden decreased and the episodes of asystole shortened during breakthrough seizures. He was ultimately discharged on oral phenytoin, oxcarbazepine, levetiracetam, and clobazam. An attempted outpatient wean of oxcarbazepine resulted in an ICU admission for increased seizure frequency, which again responded to sodium channel blockade. Whole exome sequencing revealed a novel de novo SCN8A mutation resulting in c.4408C>G substitution. Similar mutations in other patients have been linked to an increase in function of the SCN8A sodium channel subtype.Conclusions: Our case expands the phenotype of SCN8A channelopathies to include cardiac arrhythmias and ictal asystole. Other case series have found a higher rate of SUDEP in these patients, which may be related to undetected cardiac conduction abnormalities. Moreover, in a subset of patients with an epileptic encephalopathy due to sodium channelopathies, sodium channel blocking medications may be beneficial. The improvement observed in our patient is thought to result from pharmacologic modulation of the abnormal increase in function of the SCN8A channels. This experience highlights the increasing importance of pharmacogenomics and utility of whole exome sequencing.