Download Autonomic Consequences of Cerebral Hemisphere Infarction

113
Autonomic Consequences of
Cerebral Hemisphere Infarction
Stephen A. Barron, MD; Ze'ev Rogovski, PhD; Jesaiahu Hemli, MD
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Background and Purpose Recently, supraventricular tachycardia has been reported following right hemisphere stroke,
suggesting a reduction in parasympathetic cardiac innervation
after stroke of the right hemisphere. We performed power
spectrum analysis of fluctuations in RR interval duration in
the electrocardiogram in an attempt to determine how ischemic stroke influences autonomic cardiac innervation.
Methods Power spectrum analysis of the variation in 256
consecutive electrocardiographic RR intervals was performed
using the fast-Fourier transformation. The area under the
spectral curve from 0 to 0.5 Hz and the area under that portion
of the curve produced by parasympathetically mediated respiratory variations were determined in 20 patients with righthemisphere and 20 patients with left-hemisphere ischemic
stroke confirmed by computerized tomography. Data were
compared with 40 age- and sex-matched healthy controls.
Results Total cardiac autonomic innervation was reduced
after a stroke of either hemisphere without regard to laterality.
Cardiac parasympathetic innervation was reduced after stroke
of either hemisphere with a significantly greater reduction
after stroke on the right (P=2.9xlO~5)Conclusions Power spectral analysis of heart rate variability can detect autonomic consequences of stroke. The spectral
data predict that, to the degree that cardiac arrhythmia is
produced by unbalanced cardiac autonomic activity favoring
the sympathetic system, such arrhythmias could be seen after
stroke of either hemisphere and would be more common after
cerebral infarction on the right. This is consistent with evidence from the recent literature. (Stroke. 1994;25:113-116.)
Key Words • autonomic nervous system • cerebral
infarction • electrocardiography • heart rate
T
nomic reflexes.25"8 The technique has identified reduced
cardiac autonomic innervation in diabetes mellitus,
chronic renal failure, and in familial dysautonomia.911
We have performed PSA of the heart rate variation
from the ECGs of 40 patients with stroke in an effort to
study how ischemic stroke influences cardiac autonomic
innervation.
he effect of disturbance of cerebral hemisphere
function on the autonomic nervous system has
been the focus of much investigation, particularly with reference to cardiovascular function.1-2
Evidence for cerebral hemisphere-autonomic interaction includes electrocardiographic (ECG) changes
with a variety of neurological lesions, including subarachnoid hemorrhage, intracerebral hemorrhage, and
ischemic stroke, as well as cardiac arrhythmia and even
death associated with epileptic seizures.3
Lane et al4 have recently described a differential
effect of cerebral infarction on cardiac rhythm. Supraventricular tachycardia was significantly associated with
right hemisphere stroke, whereas patients with left
hemisphere stroke tended to have more ventricular
arrhythmias. The authors suggested that parasympathetic tone was reduced ipsilateral to the side of the
cerebral infarction, thus producing a relative increase in
sympathetic tone on that side.
Power spectrum analysis (PSA) of the beat-to-beat
variation in RR interval duration in the ECG is a sensitive
tool for assessing cardiac autonomic innervation and
reflects the variability in heart rate resulting from both
sympathetic and parasympathetic cardiovascular auto-
Received June 8, 1993; final revision received August 18, 1993;
accepted September 13, 1993.
From the Laboratory of Clinical Neurophysiology, the Bruce
Rappaport Faculty of Medicine, the Technion-Israel Institute of
Technology (S.A.B., Z.R.) and the Department of Neurology, the
Rambam (Maimonides) Medical Center (S.A.B., Y.H.), Haifa,
Israel.
Correspondence to Dr Stephen A. Barron, Laboratory of Clinical Neurophysiology, Bruce Rappaport Faculty of Medicine,
Technicon-Israel Institute of Technology, Efron St, POB 9649,
Haifa 31096, Israel.
Subjects and Methods
Patients were hospitalized in the Neurology Service of the
Rambam (Maimonides) Medical Center after a first stroke. All
40 patients suffered from ischemic cerebral infarction in the
distribution of the carotid artery system, 20 having suffered
from right hemisphere infarction, and 20 from left hemisphere
infarction. Patients were studied from 4 to 11 days following
the stroke, at which time they were either neurologically stable
or improving.
Table 1 shows the age and sex distribution of the patients in
each of the two groups.
Consecutive patients were admitted to the study if they
fulfilled the following criteria: (1) the time of onset of the
stroke was precisely known; (2) computerized tomography
scan of the brain confirmed a single cerebral infarct consistent
with the clinical localization of the stroke; (3) they did not have
a coexisting condition known to affect the PSA of heart rate
variability: diabetes mellitus,9 active cardiac ischemia,12-13 congestive heart failure,14 or renal insufficiency10; (4) they were
not receiving medications known to affect the autonomic
nervous system; and (5) the stroke was in the distribution of
the carotid artery. Although respiratory pattern was not a
criterion for either entrance or exclusion from the study, all
the patients herein reported had a clinically normal respiratory pattern with no evidence of respiratory distress.
PSA was performed at the bedside from an ECG acquired
on-line through a personal computer from chest leads oriented
to approximate frontal plane lead I. All patients were in sinus
rhythm. Two hundred fifty-six consecutive RR intervals were
identified and analyzed in each recording, which was made
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Stroke
Vol 25, No 1 January 1994
TABLE 1. Age and Sex of Patients With
Right-Hemisphere and Left-Hemisphere Infarction
Sex
Age, y
Side
Mean
Range
Men
Right
69.2
41-79
11
9
Left
68.4
44-83
10
10
Women
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with the patient lying supine. This time series of intervals was
prepared for analysis by subtracting the mean interval of the
array from each individual interval and passing the resulting
series through a detrend filter and a Hanning window. Spectral
analysis of the series was performed using the fast-Fourier
transformation.
The power spectrum displays three areas of concentration of
spectral power between 0 to 0.5 Hz, each attributed to a
different autonomic cardiovascular control mechanism.5-7 Fig
1 shows a spectral curve from a normal subject. The area
under the spectral curve from 0 to 0.5 Hz is the total spectral
power (TSP). Of the three indicated areas of power density,
the best characterized is that appearing at the highest frequency, generally above 0.2 Hz, labeled " 1 " in Fig 1. This
spectral region reflects heart rate changes associated with
respiration and we term this area of spectral density, indicated
by the arrows in Fig 1, the respiratory related activity (RRA).
The RRA is the expression in the frequency domain of the
respiratory sinus arrhythmia, a purely parasympathetic phenomenon.15 It is totally blocked by atropine.7 The area of the
RRA is thus a quantified expression of the parasympathetic
vagal innervation of the heart.
A midfrequency zone of spectral density, labeled "2" in Fig
1, reflects heart rate variability resulting from baroreceptor
regulation of blood pressure and is a mixed sympatheticparasympathetic control system. It is significantly but incompletely blocked by atropine.7
The low-frequency peak, labeled " 3 " in Fig 1, has been the
least well studied. It reflects heart rate changes involved in
thermoregulation but is also influenced by the renin-angiotensin system.57 The unlabeled peak in Fig 1 represents slow
trends in heart rate variation and is not considered further.
Normal values for TSP and RRA were determined from the
PSA of 40 healthy age- and sex-matched volunteers.
Results
The significance of differences in means was determined by Student's / test for unmatched pairs, a=0.05.
msec 2
Hz
Fig 2 shows a representative PSA from a patient after
stroke. The patient, a 64-year-old man, had a stroke of
the right hemisphere. Note the absence of an obvious
high-frequency peak, labeled " 1 " in Fig 1.
Table 2 shows the mean TSP in normal subjects and
in the patients with stroke. There was a marked reduction in TSP after infarction in either hemisphere in
comparison to normal subjects. There was no significant
difference in TSP between the two patient groups,
P=.O92.
Table 2 also shows the RRA in normal subjects and
the patients with stroke. There was a significant reduction in RRA after infarction in either hemisphere in
comparison to normal subjects, with the reduction after
right hemisphere stroke significantly greater than after
left hemisphere stroke, P=2.9xlO~ 5 .
There was no difference in mean respiratory rate
after right- and left-hemisphere strokes (19 breaths per
minute in both groups).
Discussion
The results indicate that autonomic cardiac innervation is reduced after ischemic infarction of either cerebral hemisphere. Factors known to affect the PSA were
specifically excluded in our patients and it is reasonable
to assert that the reduction in autonomic activity was
the result of the stroke. The greater reduction in RRA
after right hemisphere infarction is in accord with the
speculations of Lane et al,4 who anticipated a reduction
in ipsilateral parasympathetic innervation after right
hemisphere stroke. Our data show a similar but less
significant reduction of parasympathetic innervation
after left hemisphere stroke as well. To the degree that
a cardiac arrhythmia is produced under conditions of
unbalanced cardiac autonomic innervation favoring the
sympathetic nervous system, our data would predict an
increased incidence of such arrhythmias after stroke in
either hemisphere, with a greater incidence of these
arrhythmias after right hemisphere stroke than after left
hemisphere stroke. The number of patients in each
group is too small to allow meaningful stratification
according to the localization of the infarction within the
hemisphere; however, because patients with verte-
FIG 1. Graph of results of spectral analysis of
heart rate variability in a normal subject. The
spectrum of the respiratory-related activity (1),
baroregulation (2), and thermoregulation (3)
are indicated.
Barron et al
Autonomic Consequences of Stroke
115
coco
msec1
FIG 2. Graph of results of spectral analysis of
heart rate variability in a 64-year-old man after
stroke of the right hemisphere. The spectrum of
activity related to baroregulation (2) and thermoregulation (3) are indicated. Note the absence of respiratory-related activity (compare
with Fig 1).
2000
1000
005
015
02
025
O3
035
05
Hz
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brobasilar strokes were excluded from this report, no
patient had an infarction exclusively of the occipital
lobe.
The data are compatible with the reported observation that heart rate variability associated with cognitive
tasks requiring the mobilization of attention is absent in
patients after right hemisphere stroke.16
Cardiac autonomic innervation originates in brain
stem (parasympathetic) and spinal (sympathetic) nuclei.
An anatomic basis for cerebral hemispheric influences
on autonomic function is provided by projections onto
autonomic nuclei from cortical, amygdaloid, hypothalamic, and limbic structures.1-3 Cerebral infarction presumably reduces cardiac autonomic innervation by removal of ipsilateral suprasegmental stimulation of the
primary autonomic nuclei. Additional evidence for
some lateralization of function of the autonomic nuclei
themselves is the recent demonstration of a correlation
between systemic hypertension and neurovascular compression of the ninth and tenth cranial nerves only at
the left side of the medulla.17
Lateralization of peripheral autonomic innervation of
the heart is well established. In the experimental animal, ablation of the left stellate ganglion increases the
threshold of ventricular fibrillation whereas right stellate ganglion ablation produces the opposite effect.18 In
humans, before treatment with /3-blockers, the recurrent ventricular fibrillation associated with the long QT
interval syndrome was successfully treated with left
TABLE 2. Spectral Variables in Normal Subjects and
Patients With Stroke After Right-Hemisphere and
Left-Hemisphere Infarction
Variable
Normal
n=40
Right
n=20
TSP,
ms2
1.98±0.26 1.64+0.29 2x10" 5
RRA,
ms2
0.33+0.05
Left
n=20
P*
1.81 ±0.34 .038
0.21+0.06 4x10"" 0.29±0.04 .004
TSP indicates total spectral power; RRA, respiratory-related
activity. Values are mean±SD.
*Side indicated versus normal.
stellate ganglion ablation.19 It is also known that the
sinoatrial node is preferentially innervated by the right
vagus, whereas the atrioventricular node receives more
of its parasympathetic innervation from the left vagus.20-22 This latter observation might predict that parasympathetic effects of left hemisphere lesions would be
expressed less strongly at the sinoatrial node than those
of right hemisphere lesions.
We conclude that PSA of heart rate variation can
identify reduced autonomic cardiac activity after unilateral ischemic infarction. Right hemisphere infarction is
associated with a greater decrease in cardiac parasympathetic activity than is left hemisphere infarction, a
possible explanation for the reported greater incidence
of some types of cardiac arrhythmias after right hemisphere stroke. We recommend further use of the technique of PSA of heart rate variation in the investigation
of the autonomic consequences of cerebral hemisphere
infarction.
Acknowledgments
Supported by a grant from the Lester Aronberg Foundation.
Dr Shoshanna Hadar aided in the initial stage of the study.
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Autonomic consequences of cerebral hemisphere infarction.
S A Barron, Z Rogovski and J Hemli
Stroke. 1994;25:113-116
doi: 10.1161/01.STR.25.1.113
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