BACKGROUND. Idiopathic epilepsy is a neuronal disorder and involves abnormal ion channel function. As compared to the general population, people with epilepsy have an increased risk of sudden cardiac death (SCD) due to ventricular tachycardia (VT) or fibrillation (VF) irrespective of traditional cardiovascular risk factors.
J-wave syndromes, including the early repolarization syndrome (ERS) and Brugada syndrome (BrS), are genetically-determined cardiac ion channelopathies. ERS and BrS portend a risk of polymorphic VT and VF leading to SCD in young adults with no apparent structural heart disease.
Pathophysiological mechanisms that underlie the increased risk of SCD in epilepsy (SUDEP) remain unknown. However, ion channels co-expressed in heart and brain may have a role, supporting the emerging concept of a genetically determined cardiocerebral channelopathy. Overlapping aetiologies might putatively explain at least in part the increased risk of SCD in patients with idiopathic epilepsy.
STUDY AIMS. The present research proposal aims to:
1. assess whether the prevalence of Brugada and ERP syndromes are increased in people with generalized idiopathic epilepsy,
2. investigate whether family screening of affected probands helps to identify (a) previously unrecognized asymptomatic BrS/ERP subjects, and (b) genotype-positive subjects with incomplete expression of either the epileptic or the arrhythmic phenotype.
STUDY PROTOCOL. Cases will consist of patients with confirmed idiopathic generalized epilepsy aged >14 years and normal brain MRI. Controls of comparable age will be enrolled within the same geographical area.
In all, medical history and resting 12-lead ECG will be recorded. Further assessment involving 12 lead Holter ECG and genetic testing will be performed according to the results of baseline ECG and the presence of familial history of SCD. Family members of newly identified ERP/BrS patients will be screened with ECG and genetic testing.
This study aims at explaining why people with epilepsy carry an increased risk of sudden death. Routine performance of a 12-lead ECG in adults with suspected epilepsy is recommended. However, active search of J-wave syndromes in probands with epilepsy and family members has never been attempted, and its diagnostic yield has not yet been determined. In people with epilepsy and J-wave syndrome or familial history of sudden death, family screening might reveal subjects at high risk for sudden cardiac death that deserve protection with an implantable cardioverter defibrillator.