The Epileptic Heart Syndrome: Epidemiology, pathophysiology and clinical detection.

Population studies report elevated incidence of cardiovascular events in patients with chronic epilepsy. Multiple pathophysiologic processes have been implicated, including accelerated atherosclerosis, myocardial infarction, altered autonomic tone, heart failure, atrial and ventricular arrhythmias, and hyperlipidemia. These deleterious influences on the cardiovascular system have been attributed to seizure-induced surges in catecholamines and hypoxemic damage to the heart and coronary vasculature.

Individuals with chronic epilepsy have elevated P-wave heterogeneity comparable to patients with atrial fibrillation.

Objective: Identification of epilepsy patients with elevated risk for atrial fibrillation (AF) is critical given the heightened morbidity and premature mortality associated with this arrhythmia. Epilepsy is a worldwide health problem affecting nearly 3.4 million people in the United States alone.

Reprint of: A brief history of Epilepsy & Behavior.

This article is part of a Special 15th Anniversary Issue.

Targeting NMDA Receptor Complex in Management of Epilepsy.

-methyl-D-aspartate receptors (NMDARs) are widely distributed in the central nervous system (CNS) and play critical roles in neuronal excitability in the CNS. Both clinical and preclinical studies have revealed that the abnormal expression or function of these receptors can underlie the pathophysiology of seizure disorders and epilepsy. Accordingly, NMDAR modulators have been shown to exert anticonvulsive effects in various preclinical models of seizures, as well as in patients with epilepsy.

The Epileptic Heart and the Case for Routine Use of the Electrocardiogram in Patients with Chronic Epilepsy.

A dire complication associated with chronic epilepsy is abrupt premature death, currently referred to as sudden unexpected death in epilepsy (SUDEP). Although the traditional view has been that SUDEP is due primarily to peri-ictal respiratory failure leading to cardiac asystole, mounting evidence implicates accelerated heart disease, leading to an "epileptic heart" condition, especially after age 40, as another potential cause of abrupt premature death, although cardiac death is specifically excluded by the standard definition of SUDEP. Sudden cardiac death in epilepsy carries a 2.

Epileptic seizures and Epilepsy Monitoring Unit admission disclose latent cardiac electrical instability.

Background: Sudden cardiac arrest results from cardiac electrical instability and is 3-fold more frequent in patients with chronic epilepsy than in the general population. We hypothesized that focal to bilateral tonic-clonic seizures (FTBTCS) would acutely impact T-wave alternans (TWA), a marker of cardiac electrical instability linked to an elevated risk for sudden cardiac death, more than focal seizures (FS) [focal aware seizures (FAS) and focal with impaired awareness seizures (FIAS)], due to their greater sympathetic stimulation of the heart. Since stress has been shown to cause significant TWA elevations in patients with heart disease, we also hypothesized that the early days of an inpatient admission to an epilepsy monitoring unit (EMU) would be associated with higher TWA levels compared to later hospital days in patients with chronic epilepsy, presumably due to stress.

T-wave heterogeneity crescendo in the surface EKG is superior to heart rate acceleration for seizure prediction.

We examined whether T-wave heterogeneity (TWH) on the surface electrocardiographic (EKG) could predict epileptic seizure onset. Patients with electroencephalography-confirmed generalized tonic-clonic seizures (GTCS) (n = 6) exhibited abnormal elevations in TWH (>80 µV) at baseline (105 ± 20.4 µV), which increased from 30 min prior to seizure without heart rate increases > 2 beats/min until 10 min pre-seizure.

Genetic Variation in on 1p36.13 Is Associated with Common Forms of Human Generalized Epilepsy.

We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance ( ≤ 5 × 10) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls.

Epileptic heart: A clinical syndromic approach.

Prevention of premature death in patients with chronic epilepsy remains a major challenge. Multiple pathophysiologic factors have been implicated, with intense investigation of cardiorespiratory mechanisms. Up to four in five patients with chronic epilepsy exhibit cardiovascular comorbidities.

New technologies and future trends.

Numerous technologies have been introduced for the diagnosis, treatment, and management of patients with neurologic disorders, offering the promise of early diagnosis, tailored and individualized interventions, improvement in quality of life, and restoration of neurologic function. Many of these technologies have become available commercially without having been evaluated by rigorous clinical trials and regulatory reviews, or at the least by peer review of results submitted for publication. A subset is intended to assess, assist, and monitor cognitive functions, motor skills, and autonomic functions and as such may be applicable to persons with developmental disabilities.

The Epileptic Heart: Concept and clinical evidence.

Sudden unexpected death in epilepsy (SUDEP) is generally considered to result from a seizure, typically convulsive and usually but not always occurring during sleep, followed by a sequence of events in the postictal period starting with respiratory distress and progressing to eventual cardiac asystole and death. Yet, recent community-based studies indicate a 3-fold greater incidence of sudden cardiac death in patients with chronic epilepsy than in the general population, and that in 66% of cases, the cardiac arrest occurred during routine daily activity and without a temporal relationship with a typical seizure. To distinguish a primarily cardiac cause of death in patients with epilepsy from the above description of SUDEP, we propose the concept of the "Epileptic Heart" as "a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction.

Cardiac electrical instability in newly diagnosed/chronic epilepsy tracked by Holter and ECG patch.

Objective: We hypothesized that cardiac electrical instability and abnormal autonomic tone result from cumulative cardiac injury sustained in recurrent seizures. We tested this hypothesis by comparing T-wave alternans (TWA) and heart rate variability (HRV), both established markers of sudden cardiac death (SCD) risk, in patients with chronic as compared to newly diagnosed epilepsy.

Methods: In this prospective, observational cohort study, patients (newly diagnosed epilepsy, n = 6, age 41.

Repeated generalized seizures can produce calcified cardiac lesions in DBA/1 mice.

Studies suggest that cardiorespiratory dysfunction likely contributes to sudden unexpected death in epilepsy (SUDEP). Seizures result in autonomic and respiratory dysfunction, leading to sympathetic hyperactivity and respiratory distress, including apnea. While the heart is vulnerable to catecholamine surges and hypoxia, it remains unknown if repetitive generalized seizures lead to cardiac damage.

Psychiatric comorbidities go unrecognized in patients with epilepsy: "You see what you know".

Patients with epilepsy (PWE) have a significantly higher prevalence of psychiatric comorbid disorders involving depression, anxiety, psychotic, and attention-deficit disorders compared with the general population or patients with other chronic medical conditions. Currently, there is no systematic approach in the evaluation and management of psychiatric comorbidities in these patients. In addition, neurologists are not trained to recognize these disorders, and consequently, they remain undertreated.