Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature

Abstract

Brugada syndrome is an inherited cardiac channelopathy arising from mutations in voltage-gated cardiac sodium channels. Idiopathic epilepsy portrays a coalescent underlying pathophysiological mechanism pertaining to the premature excitation of neuronal voltage-gated ion channels resulting in the disruption of presynaptic neurons and the unregulated release of excitatory neurotransmitters. The coexistence of epilepsy and Brugada syndrome may be explained by mutations in voltage-gated ion channels, which are coexpressed in cardiac and neural tissue. Moreover, the incidence of sudden unexpected death in epilepsy has been associated with malignant cardiac arrhythmias in the presence of mutations in voltage-gated ion channels. Lamotrigine is an antiepileptic drug that inhibits neuronal voltage-gated sodium channels, thus stabilizing neural impulse propagation and controlling seizure activity in the brain. However, lamotrigine has been shown to inhibit cardiac voltage-gated sodium channels resulting in a potential arrhythmogenic effect and the ability to unmask Brugada syndrome in genetically susceptible individuals. We are reporting a case of a 27-year-old male patient with a background of presumed idiopathic epilepsy who was initiated on lamotrigine therapy resulting in the unmasking of Brugada syndrome and the onset of syncopal episodes. This case provides further evidence for the arrhythmogenic capacity of lamotrigine and highlights the relationship between epilepsy and Brugada syndrome. In this report, we aim to review the current literature regarding the associations between epilepsy and Brugada syndrome and the impact of lamotrigine therapy on such patients.

Keywords: Brugada syndrome; epilepsy; ion channels; lamotrigine; sudden cardiac death (SCD); sudden unexpected death in epilepsy (SUDEP); syncope.

FIGURE 1

Twelve-lead electrocardiogram demonstrating 2 mm ST segment elevation in leads V1 and V2 with a prominent J wave followed by negative T waves. Suggestive of a type 1 Brugada pattern.

FIGURE 2

Electrophysiological study demonstrating the induction and termination of ventricular fibrillation. (A) Twelve -lead electrocardiogram demonstrating the induction of ventricular fibrillation through triple extrastimuli at the right ventricular outflow tract. (B) Twelve-lead electrocardiogram demonstrating sustained ventricular fibrillation. (C) Twelve-lead electrocardiogram demonstrating the termination of ventricular fibrillation through a 360-J transthoracic direct current shock and subsequent return to sinus rhythm.

FIGURE 3

Twelve-lead electrocardiogram after the discontinuation of lamotrigine. The electrocardiogram demonstrates normal sinus rhythm with near resolution of the J-point elevation and type 1 Brugada pattern.