Post-Ictal Heart Rate Oscillations in Partial Epilepsy 1.0.0

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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

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This article originally appeared in <i>Neurology</i> <b>53</b>(7):1590-1592,
1999 (October 22).  Please cite this publication when referencing this
material.  The data on which this article is based may be found <a


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.


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

<h2>Subjects and Methods</h2>

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

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].


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.


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.

<h2>Figure Legends</h2>

<p><em>[Sorry, the figures are not currently available.]</em>

<em>Figure 1:</em> 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.

<em>Figure 2:</em> 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

<em>Figure 3:</em> 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,

Please address correspondence to:

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

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