Post-Ictal Heart Rate Oscillations in Partial Epilepsy

IC Al-Aweel, B.S., KB Krishnamurthy, M.D., JM Hausdorff, Ph.D., JE Mietus, B.S., JR Ives, B.Sc., AS Blum, M.D., Ph.D., DL Schomer, M.D., AL Goldberger, M.D.

Departments of Neurology and Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215

Abstract

We report post-ictal heart rate oscillations in a heterogeneous group of patients with partial epilepsy. This pattern is marked by the appearance of transient but prominent low-frequency heart rate oscillations (0.01 - 0.1 Hz) immediately following five of 11 seizures recorded in five patients. This finding may be a marker of neuroautonomic instability, and, therefore, may have implications for understanding perturbations of heart rate control associated with partial seizures.

Introduction

Seizures may be associated with cardiac arrhythmias [1], prominent arterial oxygen desaturations [2], and sudden death [3]. In the course of analyzing cardiac dynamics in patients with partial epilepsy, we noted transient but prominent low-frequency heart rate oscillations immediately following seizures in some patients. We describe the features of this pattern that may have implications for understanding cardiac and neuroautonomic instability in epilepsy.

Subjects and Methods

This preliminary report is based upon analysis of data from 11 partial seizures recorded in five women patients during continuous electroencephalographic (EEG)/electrocardiographic (ECG)/video monitoring [2]. The patients ranged in age from 31 to 48 years old, were without clinical evidence of cardiac disease, and had partial seizures with or without secondary generalization from frontal or temporal foci. Recordings were made under a protocol approved by Beth Israel Deaconess Medical Center's Committee on Clinical Investigations.

Data were analyzed off-line using customized software. Onset and offset of seizures were visually identified to the nearest 0.1 second by an experienced electroencephalographer (DLS) blinded with respect to the heart rate variability analysis. Continuous single-lead ECG signals were sampled at 200 Hz. From the digitized ECG recording, a heartbeat annotation file (a list of the type and time of occurrence of each heartbeat) was obtained using a version of our commercially available arrhythmia analysis software [4]. To remove higher order nonstationary fluctuations in heart rate that could mask low-frequency oscillations, the time series were detrended using a least squares fitted 4th degree polynomial. Power spectral density estimates were then calculated using standard fast Fourier transform techniques with a rectangular window [5].

Results

Five patients had a total of 11 recorded seizures, lasting from 15-110 seconds. (Two of the subjects had multiple recorded seizures.) Low-frequency post-ictal heart rate oscillations, two to six minutes in duration, were observed on one occasion in each of the five patients. Examples are shown in Figures 1-3. These oscillations had a well-defined spectral peak in the 0.01 to 0.10 Hz frequency band. Te peak-to-trough amplitude of these oscillations ranged from 15 to 41 beats per minute (bpm). The oscillations were not observed in the pre-ictal period for these seizures. The increase in heart rate during the seizures ranged from 28 to 88 bpm for the events with post-ictal oscillations (n=5), and 3 to 68 bpm for those seizures without the oscillations (n=6). Two of the five seizures with post-ictal oscillations were associated with secondary generalization, the remaining three were complex partial. Patients with and without oscillations were either asleep (Stage II or III) or resting quietly before the seizures.

Discussion

Two features of the post-ictal cardiac oscillation (PICO) pattern described here are notable. First, these oscillations are clearly distinct from the higher frequency (usually 0.2 - 0.4 Hz), physiologic oscillations associated with breathing (respiratory sinus arrhythmia). Second, these post-ictal oscillations may be of extremely high amplitude (up to 40 bpm from peak-to-trough) (Figs. 1-3), further distinguishing them from very short-term physiologic changes associated with activity or posture.

The mechanism underlying these fluctuations in heart rate remains to be determined. The transient post-ictal dynamics differ from the relatively low-frequency, but typically more sustained oscillations in heart rate that have been reported in a number of settings associated with cardiopulmonary instability, including congestive heart failure and sudden cardiac death syndromes [6] (0.015 - 0.025 Hz), obstructive sleep apnea [7] (0.017 - 0.035 Hz), and high altitude exposure [8] (0.04 - 0.06 Hz). Whether the PICO phenomenon is mechanistically related to transient Mayer-like waves [9] (0.07 - 0.09 Hz), such as those seen with orthostatic challenge or related stressors is uncertain. The prominent increase in heart rate that occurred during the seizures prior to the oscillations suggests a possible role for sympathetic activation. The accompanying decrease in vagally-mediated, higher frequency oscillations, evident in some of the cases (Figs. 1 and 3), supports the notion of sympathetic activation and concomitant decreased vagal tone [10]. This type of ``ringing'' effect, regardless of mechanism, may be important because of its possible association with unstable cardiopulmonary dynamics. None of the subjects in the small, heterogeneous group reported here exhibited cardiac arrhythmias. However, to the extent that such heart rate oscillations may be a marker of profound fluctuations in ionic or neuroautonomic variables, such alterations could be arrhythmogenic in susceptible individuals [6]. Further prospective study is warranted to determine the prevalence of these oscillations in specific epilepsy syndromes, to study their possible relation to systemic blood pressure and respiratory dynamics, and to define their mechanism and clinical significance.

Figure Legends

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Figure 1: Example of post-ictal heart rate oscillations in a 37-year-old woman with generalized tonic-clonic seizures originating from the right temporal region. For this and the other figures, the top panel shows a continuous sinus rhythm heart rate time series. Bottom panels show the Fourier spectra of selected portions of data pre- and post-seizure. The pre-seizure spectrum shows a broad low-frequency peak (< 0.05 Hz), and a higher peak at about 0.3 Hz, which is consistent with physiologic respiratory sinus arrhythmia. Immediately after the seizure, the heart rate increases and then falls below the pre-seizure values, followed by a secondary increase, after which the prominent low-frequency oscillations occur. The post-seizure spectrum shows a large, sharp spectral peak at about 0.03 Hz, with a decrease in the amplitude of the higher frequency peak compared to pre-seizure.

Figure 2: Example of post-ictal heart rate oscillations in a 48-year-old woman with partial epilepsy, with the seizure originating from the right frontal temporal region. Prior to the seizure, there are relatively high-frequency heart rate oscillations consistent with respiratory sinus arrhythmia at about 0.3 Hz. During the seizure, heart rate increases markedly. Following the seizure, transient prominent oscillations at about 0.13 Hz are noted.

Figure 3: Example of post-ictal heart rate oscillations in a 46-year-old woman with partial epilepsy, with the seizure originating from the left perisylvian region. Before the seizure, the heart rate fluctuates in a complex manner, with a broad low-frequency peak, and a high-frequency peak at 0.3 Hz corresponding to respiration. A transient increase in heart rate occurs during the seizure, followed by the appearance of low-frequency oscillations with a sharp spectral peak at about 0.07 Hz and a decrease in higher frequency power compared to pre-seizure.

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This study was supported by grants from the National Aeronautics and Space Administration, Washington, DC; The G. Harold and Leila Y. Mathers Charitable Foundation, Mt. Kisco, New York; and the National Institute on Aging, Bethesda, MD

Please address correspondence to:

Ary L. Goldberger, M.D.
Cardiovascular Division, GZ-435
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA 02215
Phone: 617-667-4267
Fax: 617-667-7268