Clinical Neurophysiology 110 (1999) 1036±1040

Asynchronous pentobarbital-induced burst suppression with corpus
callosum hemorrhage
L.M. Lazar, L.M. Milrod, G.E. Solomon, D.R. Labar*
Comprehensive Epilepsy Center, The New York Hospital-Cornell University Medical Center, New York, NY 10021, USA
Accepted 17 February 1999

Abstract
Objective: We describe the electroencephalographic (EEG) ®ndings in a 9-year-old girl, who presented with generalized tonic-clonic
status epilepticus requiring pentobarbital anesthesia, and correlate these ®ndings with clinicoradiologic evidence of a ruptured AVM with
hemorrhage into the body of the corpus callosum.
Methods: EEG analysis accompanied by clinical assessment, CT and MRI scans, and cerebral angiography were performed.
Results: With pentobarbital coma, the EEG showed burst suppression with prominent interhemispheric asynchrony. Suppression epochs
.2 s in duration and with amplitude ,20 mV in all channels were identi®ed. In 12 min of the EEG analyzed, 6 unilateral and 20 bilateral
epochs occurred. Of the 20 bilateral suppression epochs, interhemispheric asynchrony of .1 s was noted at onset for 5 epochs and at offset
for one. Chi-square analysis revealed an equal tendency for unilateral suppressions to occur over either hemisphere, and for suppression in
one hemisphere to begin before the other.
Conclusions: We conclude that the corpus callosum plays a critical role in interhemispheric synchronization of cortical neuronal electrical
activity and propose that: (1) normally, the corpus callosum modulates interhemispheric synchronization of cortical inhibition; and (2) with
corpus callosal disruption, cortical areas are `released' from such synchronization. q 1999 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Pentobarbital; Burst suppression; Corpus callosum; Status epilepticus

1. Introduction
As increasing doses of barbiturates are given, the EEG
shows an orderly progression of changes: increased fast
activity, attenuation of the background amplitude, greater
activity in the theta and delta frequency ranges, burst
suppression, and ®nally complete suppression of all EEG
activity.
The burst portion of a burst suppression pattern is generally de®ned as a bilateral, high amplitude, synchronous, and
diffuse `paroxysm' of activity of delta and theta frequencies.
Sharp waves and spikes are usually present. As its name
implies, the suppression period (also known as the interburst
interval) electroencephalographically consists of absent or
severely attenuated activity of delta and theta frequency
(Chatrian, 1990). In diseases diffusely affecting cerebral
cortical function, the bursts are bilaterally synchronous
and the degree of attenuation during the suppression
symmetrical.

Whether the burst suppression pattern occurs as a result
of hypoxia, ischemia, encephalitis, or administration of
anesthetic agents, deafferentation of the cortex from thalamic projections is thought to be the underlying pathophysiologic explanation (Fisch, 1991). Barbiturates, then, may
effectively disconnect the cortex from the subcortical
regions.
Pharmacologically-induced asynchronous interhemispheric burst suppression has not been reported. Spontaneously occurring asynchronous burst suppression has
been noted with Aicardi's syndrome, a condition of female
infants characterized by the clinical triad of chorioretinal
lacunae, infantile spasms, and partial or complete agenesis
of the corpus callosum (Fariello et al., 1977; Ohtsuka et al.,
1993). Brenner and Schaul (1990) conclude that `relatively
little is known regarding the mechanism of periodic EEG
discharges' but concede that a `mechanism of synchrony
and timing' must exist. Our report suggests that the corpus
callosum provides such a mechanism.
1.1. Case report

* Corresponding author. Comprehensive Epilepsy Center, The New
York Hospital-Cornell Medical Center, 525 East 68th Street K-619 New
York, NY 10021; Tel.: 1 1-212-746-2359; fax: 1 1-212-746-8984.

A 9-year-old, left-handed girl presented with generalized
tonic-clonic status epilepticus upon rupture of an AVM. CT

1388-2457/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved.
PII: S13 88-2457(99)0004 6-2

CLINPH 98089

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1037

Fig. 1. (A) Transverse view of head CT scan performed on hospital admission demonstrates a 3 cm hematoma in the body of the corpus callosum.
Intraventricular hemorrhage is also seen. Additional axial sections (not shown) revealed hydrocephalus with dilatation of the lateral ventricles and its temporal
horns. (B) Axial view of T1 weighted MRI scan of the brain obtained on hospital day 18, demonstrates a large residual hemorrhage of mixed signal intensity in
the corpus callosum. The punctate hyperintensities seen in the left frontal region (and in right frontal white matter, left basal ganglia, and right thalamus which
are not shown) are attributed to ventriculostomy catheter placements. (C) Sagittal view of T1 weighted MRI scan of the brain obtained on hospital day 18,
demonstrates the anatomical localization of the hemorrhage in the body of the corpus callosum.

and MRI scans revealed a 3 cm hematoma in the body of the
corpus callosum, extensive intraventricular hemorrhage,
and hydrocephalus (Fig. 1). Administration of mannitol,
hyperventilation, left ventriculostomy catheter placement,
and pentobarbital coma were instituted. Cerebral angiography revealed a 3 £ 1:5cm AVM involving the left pericallosal artery (Fig. 2).
Intermittently, increased intracranial pressure occurred
requiring repositioning of the ventriculostomy catheter in

alternate hemispheres. Pentobarbital coma was discontinued
on hospital day 9. Seizures did not recur.
After 1 week of mutism, the patient recovered language
function but exhibited a mild left hemiparesis, left upper
extremity dysmetria, and decreased short-term memory.
Neuropsychological testing 7 months later indicated normal
callosal transfer of tactile information as measured by the
ability, with eyes closed, to choose by hand the same object
simultaneously palpated by the other hand.

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L.M. Lazar et al. / Clinical Neurophysiology 110 (1999) 1036±1040

Suppression epochs were de®ned as those periods with
duration .2 s and amplitude ,20 mV, in all channels of a
given hemisphere. Both visual and statistical (Chi-square)
analyses of the EEG were performed.
3. Results
Portions of the patient's initial EEG performed on hospital day 2 are shown in Fig. 3. Burst suppression with prominent interhemispheric asynchrony is evident. This EEG was
performed prior to repositioning of the ventriculostomy
catheter into the right hemisphere. The patient's serum
level of pentobarbital at this time was 34.3 mg/l.
Visual analysis of 12 min of the initial EEG revealed 26
suppression epochs, with 6 occurring unilaterally and 20
occurring bilaterally. Of the 20 bilateral suppression epochs,
interhemispheric asynchrony of .1 s was noted at onset for
5 of the epochs and at offset for 1. Chi-square analysis
revealed an equal tendency for unilateral suppressions to
occur over either hemisphere as well as for suppression in
one hemisphere to begin before the other. Suppression
epochs which met the above duration and amplitude criteria
in all but one channel, commonly demonstrated persistence
of activity in the frontopolar regions.
A repeat EEG performed 1 week following initial presentation continued to reveal burst suppression, but now with
less prominent asynchrony. Serum levels of pentobarbital
and phenobarbital at this time were 11.7 mg/l and 24.2 mg/l,
respectively.
At 1 month follow-up, the EEG was normal in the awake
and drowsy states (Fig. 4). At 10 months follow-up, an EEG
performed in the sleep state revealed synchronous and
symmetric sleep spindles.
4. Discussion

Fig. 2. (A) Rapid sequence digital AP cerebral angiogram reveals an AVM
within the body of the corpus callosum supplied via the left pericallosal
artery. (B) Lateral view of cerebral angiogram demonstrates a relatively
hypovascular region in the central aspect of the AVM which may correspond to the hematoma noted in Fig. 1. The AVM measures 3 £ 1:5 cm.

EEGs were recorded 2 days, 1 week, 1 month and 10
months after initial clinical presentation.
2. Materials and methods
EEGs were recorded with silver cup electrodes in longitudinal and transverse bipolar montages employing the
International 10±20 system of electrode placement. A longitudinal bipolar montage was used for quantitative measurements.

Our patient's clinical presentation with mutism and leg
weakness coincides with descriptions of behavior following
anterior corpus callosum section for intractable seizures
(Roberts, 1991). The anatomic basis for such mutism has
been attributed to a `disconnection' of white matter tracts
which originate in the anterior cingulate and supplementary
motor areas of the frontal lobe and traverse the body of the
corpus callosum (the location of the lesion in our patient)
(Pandya and Rosene, 1985).
Roles for the corpus callosum in interhemispheric integration and synchronization of neuropsychological and
neurophysiological processes follows from analyses of
EEG abnormalities which accompany callosal disruption.
For example, asynchrony of EEG sleep spindles and
decreased coherence at frequencies less than 4 Hz have
been noted in patients with callosal agenesis (Lynn et al.,
1980; Kuks et al., 1987). Following total carpus callosum
section, desynchronization of the ictal onset of bilateral
hemispheric discharges is electrographically seen (Spencer

L.M. Lazar et al. / Clinical Neurophysiology 110 (1999) 1036±1040

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Fig. 3. EEG performed on hospital day 2 showing burst suppression with prominent interhemispheric asynchrony. Occasional multifocal sharp wave
discharges are noted within the asynchronous and synchronous bursts.

Fig. 4. Normalization of EEG performed 1 month following clinical
presentation.

et al., 1993) supporting a role for the corpus callosum in the
secondary generalization or synchronization of epileptic
activity.
The persistence of bilaterally synchronous interictal EEG
discharges following partial or complete corpus callosum
section suggests that the corpus callosum is not the sole
pathway for hemisphere synchronization. Experimental
evidence suggests that a pathway between ipsilateral and
contralateral cortex relayed via thalamic and mesencephalic
subcortical structures may also contribute to secondary
bilateral synchrony (Spencer et al., 1985).
Developmentally, the trace discontinu and trace alternant
patterns of premature and full-term infants are analogous to
burst suppression, in that bihemispheric suppression of
activity occurs. Hahn et al. (1989) have postulated that the
decrease in duration of interburst intervals with increasing
gestational age is due to `the loss of presumed subcortical
systems responsible for the abrupt bihemispheric inhibition
of cortical activity.'
Human and animal data demonstrate an increase in focal
EEG abnormalities and focal seizures following callosal
section. These ®ndings lend support to the corpus callosum's contribution toward inhibition of cerebral activity,
potentially through relay of inhibitory signals toward the
ictal focus (Spencer et al., 1985).
In the clinical and experimental settings, the typical bilaterally synchronous burst suppression EEG pattern is thought

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L.M. Lazar et al. / Clinical Neurophysiology 110 (1999) 1036±1040

attributable to cortical isolation from afferent input originating in subcortical nuclei (Chatrian, 1990). In our patient, it
could be argued that such functional `deafferentation' was
produced by barbiturate anesthesia. Our ®ndings of asynchronous burst suppression with corpus callosum hemorrhage suggest that the corpus callosum plays a
fundamental role in the synchronization of EEG activity
in the two hemispheres, even under the extreme conditions
of burst suppression due to barbiturates. When the corpus
callosum was severed by hemorrhage, the burst suppression
pattern became asynchronous. The association of asynchronous burst suppression with Aicardi's syndrome (which
includes partial or complete agenesis of the corpus callosum) supports such a role for the corpus callosum in interhemispheric synchrony (Fariello et al., 1977).
We might speculate that burst suppression does not derive
from discharges arising in subcortical structures, but is in
fact of cortical origin. One might propose that a burst
suppression pattern secondary to cortical suppression with
release of subcortical activity would likely be synchronous.
Thus, asynchronous bursts would suggest that the primary
pacemaker of the burst suppression pattern is cortical in
origin.
In conclusion, we propose that asynchronous burst
suppression under pentobarbital anesthesia in our patient
with a corpus callosum hemorrhage occurred because: (1)
normally, the corpus callosum modulates interhemispheric
synchronization of cortical inhibition; and (2) cortical areas
were `released' from such synchronization due to disruption
of the corpus callosum.

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