Herpes simplex virus is a leading cause of sporadic encephalitis. While seizures are a common feature of Herpes simplex virus encephalitis, and periods of asystole have been reported in Herpes simplex virus patients, there have been no prior reports of ictal asystole secondary to such an infection

B Schaller

BK Smith

F Colivicchi

FJ Rugg-Gunn

G Rubboli

JW Britton

KL Tyler

MJ Stone

MM Alsolaiman

P Auyeung

R Rocamora

Robert Gooch

SL Tokgozoglu

SM Oppenheimer

SU Schuele

English

PubMed

Crossref

Ictal asystole secondary to suspected herpes simplex encephalitis: a case report

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BioMed CentralCases Journal
ssOpen AcceCase Report
Ictal asystole secondary to suspected herpes simplex encephalitis: a 
case report
Robert Gooch
Address: Schulich School of Medicine and Dentistry, The University of Western Ontario, 61 Gunn Street, London, ON N6G 1C6, Canada
Email: Robert Gooch - rgooch2010@meds.uwo.ca
Abstract
Herpes simplex virus is a leading cause of sporadic encephalitis. While seizures are a common
feature of Herpes simplex virus encephalitis, and periods of asystole have been reported in Herpes
simplex virus patients, there have been no prior reports of ictal asystole secondary to such an
infection.
This case report describes a 33 year old, previously healthy, gentleman of Malaysian descent, with
new onset seizures resulting in a twenty-one second period of ictal asystole. In hospital the patient
developed focal neurological symptoms. A diagnosis of Herpes simplex virus encephalitis was made,
although this diagnosis was not confirmed by lumbar puncture, magnetic resonance imaging or
biopsy.
Literature is reviewed regarding ictal asystole as well as clinical features and cardiac complications
of Herpes simplex virus encephalitis. Given the link between ictal asystole and Herpes simplex virus
encephalitis, cardiac monitoring would be recommended for Herpes simplex virus encephalitis
patients having seizures. The use of anticonvulsants with cardiac side effects should be carefully
considered.
Introduction
Herpes simplex virus (HSV), usually type 1, is a leading
cause of sporadic encephalitis, with an annual incidence
of between 1 in 250 000 and 1 in 1 000 000 [1,2]. Com-
mon presenting symptoms and signs include headache,
altered level of consciousness, focal neurologic symp-
toms, fever, aphasia, and seizures. The seizures associated
with HSV infection are most often focal.
Cerebrospinal fluid (CSF) analysis tends to show pleocy-
tosis, as well as increased protein and erythrocytes. Mag-
netic resonance imaging (MRI) is recommended if there is
suspicion of HSV infection [1]. T2 weighted scans often
show temporal lobe hyperintensity. HSV patients occa-
sionally have normal scans. Auyeung and Dunn report a
case of confirmed HSV encephalitis with normal MRI and
no CSF leukocytosis [3]. Computed tomography (CT) is
useful to rule out other causes for neurologic symptoms,
such as mass lesions, and is recommended if a patient is
unable to undergo MRI. Electroencephalogram (EEG)
tends to show nonspecific findings, including periodic lat-
eralising epileptiform discharges. Single photon emission
computed tomography (SPECT) scans can be used as an
adjunct; in HSV patients, the common finding is unilat-
eral temporal lobe hypoperfusion [1].
The gold standard for HSV encephalitis diagnosis is
polymerase chain reaction (PCR) detection of HSV DNA
in the CSF. Sensitivity is 98% and specificity is 94% [2].
Brain biopsy is another option for diagnosis. However,
Published: 22 December 2009
Cases Journal 2009, 2:9378 doi:10.1186/1757-1626-2-9378
Received: 6 November 2009
Accepted: 22 December 2009
This article is available from: http://www.casesjournal.com/content/2/1/9378
© 2009 Gooch; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
Cases Journal 2009, 2:9378 http://www.casesjournal.com/content/2/1/9378virus distribution may not be uniform, leading to false
negative results, and the procedure is invasive. It has a role
when CSF is not available.
In addition to neurologic complications, HSV encephali-
tis has also been associated with cardiac arrythmias. Smith
et al. report a case of a patient with HSV encephalitis con-
firmed by PCR who had short episodes of unconscious-
ness [4]. Electrocardiogram (ECG) monitoring showed
that these were associated with bradycardia and periods of
asystole lasting up to 7 seconds. Alsolaiman et al. report
the case of a woman who presented with syncope and,
while asleep in hospital, had asymptomatic asystolic peri-
ods of 4 to 8 seconds [5]. Findings of CSF analysis and
MRI were consistent with HSV encephalitis. Proposed
causes for such asystole include herpes simplex myositis
and central nervous system (CNS) causes. There is no evi-
dence that HSV has ever been found in the heart [5]. A
central cause for the asystole in these cases, which may
involve parasympathetic stimulation or sympathetic inhi-
bition, would be in accordance with proposed mecha-
nisms for ictal asystole (IA).
Asystole is a rare complication of focal seizures, but it is
concerning, given its hypothesized link to sudden unex-
plained death in epilepsy (SUDEP). A study in a large sur-
gical epilepsy centre found IA in 5 out of 1244 patients
(0.4%); asystolic periods were as long as 60 seconds [6].
As patients with IA do not have asystole with every sei-
zure, it is quite possible that this study did not record asys-
tole in some patients with IA; the prevalence may, indeed,
be significantly higher. In a group of 19 patients with
intractable focal seizures, 4 had asystolic periods [7,8].
IA can present as a sudden loss of tone and a fall during a
partial seizure. It is important, but may be clinically diffi-
cult, to differentiate IA from convulsive syncope or tem-
poral lobe syncope. In convulsive syncope, the loss of
consciousness and the fall tend to occur simultaneously,
while in temporal lobe syncope a loss of tone is seen at the
beginning of seizure activity. Atonia in IA patients occurs
later in the seizure, and usually after an asystolic period of
about 8 seconds [7]. The best method to differentiate
between these entities seems to be simultaneous video/
EEG/ECG monitoring [9].
The etiology of IA may be a result of seizure spread to
autonomic centres resulting in sympathetic inhibition or
parasympathetic stimulation. Attempts have been made
to localize these centres. Experimenting on rats, Oppenhe-
imer et al. found that stimulation of the rostral posterior
insular cortex resulted in tachycardia while more caudal
stimulation caused bradycardia, heart block, ventricular
ectopics, and death [10,11]. In experiments on presurgical
lobectomy patients, stimulation of the left insular cortex
tended to cause bradycardia and a depressor response
[10,12]. Patients with temporal lobe and insular infarc-
tion may have decreased heart rate variability [13-15].
Schuele et al., in a study involving combined EEG/ECG
monitoring, found that there did not seem to be a distinct
lateralization [7]. Indeed, at the onset of asystole in the
patients with temporal lobe epilepsy, half the patients had
bilateral temporal involvement, a quarter of the patients
had left temporal involvement and the rest had right tem-
poral involvement. This study did, however, demonstrate
that IA tends to result from temporal lobe seizures. 8 out
of the 10 patients with IA in the study had temporal lobe
epilepsy. In the two patients without temporal lobe epi-
lepsy, the asystolic periods may have been secondary to
respiratory arrest. IA was not seen in patients with gener-
alized epilepsy [7]. Britton et al. also found that temporal
lobe seizures tended to cause bradyarrhythmias; 12 of 13
patients with ictal bradyarrhythmia had temporal lobe
seizures. A review of the literature showed that of 65
patients with ictal bradyarrhythmia, 36 had temporal sei-
zures and 15 had frontotemporal seizures [13].
Case presentation
A 33-year-old, male, right handed, realtor, of Malaysian
descent, presented to hospital following a nocturnal sei-
zure. His wife reported being awoken by a cry and found
her husband convulsing. The patient's arms were flexed
and his eyes open and rolled back. This lasted for approx-
imately 1 minute and was followed by restless thrashing
movements and awkward attempts to get up. There was
some foaming at the mouth.
On admission there was some residual disorientation but
no lateralizing symptoms or signs. The patient had been
previously well, although one week prior he had had flu-
like symptoms, including loss of appetite and general
myalgia, as well as a swelling on the right side of his neck
which had resolved on its own.
There was no history of previous seizures, meningitis,
encephalitis, blackouts, loss of consciousness, head inju-
ries, or febrile seizures. The patient reported no use of rec-
reational drugs. Neither the patient nor his family
members had a history of tuberculosis. The patient's most
recent travel was an Alaskan cruise. There were mosqui-
toes but the patient had not been bitten. He had not been
bitten by any ticks or animals. There were no exposures to
sick people. The patient denied any history of sexually
transmitted infections or other relevant past illnesses.
In hospital, the patient was started on phenytoin but con-
tinued to have further nocturnal seizures with post ictal
periods of approximately 30 minutes. During the third
seizure there was a twenty-one second period of asystolePage 2 of 4
(page number not for citation purposes)
Cases Journal 2009, 2:9378 http://www.casesjournal.com/content/2/1/9378and a permanent pacemaker was placed the following
day.
Prior to the placement of the pacemaker, the patient was
afebrile and had no headache, vision changes, or difficulty
speaking or swallowing. There was no abnormality in
bowel or bladder function. Gait was normal, and the
patient's neurological exam was unremarkable except for
gaze evoked nystagmus, thought to be a side effect of the
phenytoin. Following the procedure, the patient reported
feeling better and his wife reported that conversation with
him was more normal, although he had forgotten details
of events up to a week prior.
The same morning, however, the patient had a fourth sei-
zure from sleep. The patient's phenytoin was optimized.
Lumbar puncture (LP) showed WBC 7 cells/μL, RBC 1
cell/μL, protein 428 mg/L, and glucose 4.1 mmol/L. CT
head with contrast was normal. The placement of the
pacemaker precluded MRI.
Levetriacetam was added, but the patient continued to
have recurrent seizures. He developed additional symp-
toms. There was a right sided headache, right ear pain and
tenderness, and an unusual sound in the right ear, which
evolved into a hallucination of music. The patient also
developed complex partial seizures; these involved speech
arrest, leftward head and eye turning, as well as left arm
posturing. The focal neurologic symptoms and focal sei-
zures suggested a diagnosis HSV encephalitis, despite the
normal LP results. A course of acyclovir was started and
further investigations were carried out.
Results of a second LP were also normal. PCR for Herpes
simplex was negative. Cytology was negative, and repeat
CT head with contrast was normal. SPECT showed a slight
decrease in perfusion of the left side compared to the
right. Repeat EEG showed nonspecific abnormality of the
right temporal lobe. A biopsy was not done as there was a
lack of a definable area to target.
Over the first week of acyclovir therapy the patient
showed significant improvement, and the headache and
seizures resolved. The hallucination of music persisted for
several days. The patient was discharged to complete a 3
week course of acyclovir. Tapering of the anticonvulsants
resulted in breakthrough seizures, so the patient remains
on levetriacetam and phenytoin.
Discussion
In the literature there are no reported cases of ictal asystole
secondary to HSV encephalitis. The patient in the case pre-
sented here had a negative PCR and CSF analyses, and an
MRI was unavailable due to the implantation of a pace-
maker. However, the seizures, focal neurologic symp-
toms, evolution of focal seizures, and rapid improvement
with initiation of acyclovir therapy strongly suggest a diag-
nosis of herpes simplex encephalitis.
HSV tends to affect the temporal lobes, which is also the
localization of the majority of seizures associated with IA.
Given that HSV has been associated with periods of asys-
tole in patients without seizures, IA associated with HSV
infection should not be entirely unexpected. The mecha-
nism of the asystole in this case may indeed be a result of
involvement of temporal autonomic centres. The trigemi-
nocardiac reflex is also a consideration, as it describes a
pathway wherein central stimuli can effect bradyarrhyth-
mia and asystole [16,17]. Regardless of mechanism, car-
diac monitoring may be warranted in HSV encephalitis
patients, especially those having seizures. The use of anti-
convulsants with cardiac side effects in such patients
should be considered carefully.
Competing interests
The author declares that he has no competing interests.
Consent
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Acknowledgements
The author would sincerely like to thank Dr. Gordon Mackie and Dr. Shan-
non Venance for their generous help and support with this paper.
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A: Atypical case of herpes simplex encephalitis.

Cardiac autonomic derangement and arrhythmias in right-sided stroke with insular involvement. Stroke

Cascino GD: The ictal bradycardia syndrome: localization and lateralization. Epilepsia

DL: Sinus node arrest secondary to HSV encephalitis.

Elger CE: Cardiac asystole in epilepsy: clinical and neurophysiologic features. Epilepsia

Foldvary-Schaefer N: Video-electrographic and clinical features in patients with ictal asystole. Neurology

Hachinski VC: Cardiovascular effects of human insular cortex stimulation. Neurology

Hawkins CP: A medical overview of encephalitis. Neuropsychol Rehabil

Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's. Herpes 2004, 11(Suppl 2):57A-64A.

JS: Cardiac arrhythmias in focal epilepsy: a prospective long-term study. Lancet

Oto A: Effects of stroke localization on cardiac autonomic balance and sudden death. Stroke

SJ: Epileptic cardiac asystole.

The trigemino-cardiac reflex: an update of the current knowledge.

Tinuper P: Sudden falls due to seizure-induced cardiac asystole in drug-resistant focal epilepsy. Neurology

Trigeminocardiac reflex: a clinical phenomenon or a new physiological entity?

Viral encephalitis associated with reversible asystole due to sinoatrial arrest.

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Ictal asystole secondary to suspected herpes simplex encephalitis: a case report

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