Elsevier

Epilepsy Research

Volume 79, Issue 1, March 2008, Pages 49-54
Epilepsy Research

Effects of antiepileptic drug therapy on heart rate variability in children with epilepsy

https://doi.org/10.1016/j.eplepsyres.2007.12.020Get rights and content

Summary

Impaired cardiac autonomic function may contribute to the risk of sudden unexpected death in epilepsy. Heart rate variability (HRV) is a useful tool for the detection of sympathetic–parasympathetic balance of autonomic nervous system. In the present study, epilepsy patients who had never received antiepileptic medication and those whose seizures have been successfully controlled with antiepileptic drugs were compared with each other and a control group in order to investigate the effects of epilepsy and various antiepileptic drugs on HRV. HRV were tested via 5 min ECG monitoring in 92 patients and 83 controls. Time domain parameters including SDNN, RMSSD and the frequency domain parameters including HF (reflects parasympathetic activity) and LF (reflects sympathetic activity) were assessed. In this group, 78 patients were using antiepileptic drugs including valproic acid (n = 33), oxcarbazepine (n = 19), phenobarbital (n = 11), combined regimens (n = 10) and other drugs (n = 5), while 14 patients had never received antiepileptic medication. For both of the epilepsy patients groups with or without treatment, time domain parameters were found to be significantly suppressed. In addition, parasympathetic activity was found to be decreased (HF was decreased, LF/HF ratio was increased) in epilepsy patients without antiepileptic drug therapy.

Our results indicate that seizure control with antiepileptic drugs may help to improve the cardiac autonomic function impairment in epilepsy patients.

Introduction

Sudden unexplained death is an important cause of mortality in patients with epilepsy (Ryvlin et al., 2006). Previous studies have shown that epilepsy can lead autonomic dysfunction which may indicate one of the main causes of sudden unexplained death (SUDEP) (Devinsky, 2004, Leung et al., 2006).

Heart rate variability (HRV) is a useful tool for the detection of sympathetic–parasympathetic balance of autonomic nervous system. Autonomic nervous system involvement in patients with epilepsy has been investigated by some authors, but the effects of antiepileptic drugs on HRV in patients with epilepsy have rarely been studied and have shown conflicting results (Berilgen et al., 2004, Evrengul et al., 2005). In the present study, epilepsy patients who had never received antiepileptic medication and those whose seizures have been successfully controlled with antiepileptic drugs were compared with each other and control group in order to investigate the effects of epilepsy and various antiepileptic drugs on HRV.

Section snippets

Patients and methods

This study included 98 consecutive pediatric patients admitted to the pediatric neurology outpatient clinic in whom we established the diagnosis of epilepsy, and 83 age and sex matched healthy controls.

Fourteen patients were newly diagnosed epilepsy and did not receive any antiepileptic drug therapy, while other 84 patients were using various types of antiepileptic drugs. Of patients under antiepileptic drug treatment, six subjects in whom seizure control could not be achieved were excluded;

Time domain measures of HRV

HRV measurement is based on the sequence of RR intervals. SDNN is the standard deviation of all normal RR intervals (those measured between consecutive sinus beats). The RMSSD (units in ms) or the root-mean-square successive difference, calculates the square root of the mean of the squared differences between successive RR intervals. All HRV indices described above are measures of variability in RR interval (Bilchick and Berger, 2006). Among time domain parameters; average heart rate, SDNN,

Frequency domain measures of HRV

HRV may similarly be broken into the frequency components that compose the overall variability. Frequency domain analysis is performed by taking a series of numbers along the axis and computing the Fourier transform (Bilchick and Berger, 2006). Akselrod et al. showed that low frequency (LF) band (0.04–0.15 Hz) is related to both sympathetic and parasympathetic modulation, and the high frequency (HF) band (0.15–0.40 Hz) is related to parasympathetic effects. The ratio of LF to HF power is often

Results

A short period analysis of HRV was performed for both the frequency and time domain in 92 epilepsy patients and 83 age and sex matched controls. Comparison of clinical and HRV characteristics between epilepsy patients with/without treatment and control subjects are shown in Table 1. Of 27 symptomatic epilepsy patients with treatment, 16 had CT/MRI abnormalities including cortical–subcortical atrophy (n = 8), left frontal and/or temporal encephalomalacia (n = 4), corpus callosum hypoplasia (n = 3),

Discussion

Measurement of HRV gives information on the degree of vagal modulation of heart rate. Reduced HRV is a powerful and independent predictor of an adverse prognosis in patients with heart disease and also in healthy subjects from the general population. There are some considerations about how might impaired cardiac vagal control influence prognosis. The most obvious beneficial effect of cardiac vagal activity is to decrease cardiac work by reducing resting heart rate and contractility.

Acknowledgement

We thank to Oznur Tuncer (technical assistant) for her help in obtaining HRV recordings.

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