Intracranial
Hemorrhage in
Herpes Simplex
Encephalitis: An
Unusual Presentation
Guliz Erdem, MD*,
Paula A. Vanderford, MD†, and
Robert D. Bart, Jr, MD*‡
We describe a 14-month-old patient with atypical presentation of herpes simplex encephalitis. She initially presented with fever, lethargy, seizures, and large hemorrhages in the right parietal lobe, and clinical findings
suggestive of a hypercoagulable state. The etiology of
coagulation abnormality was not identified, although it
was suggested as a possible causative factor in severe
bleeding along with acute neuronal lysis as a result of
infection. Although large intracerebral hemorrhages are
occasionally described with systemic herpes infection, this
presentation is unusual beyond the infant period.
© 2002 by Elsevier Science Inc. All rights reserved.
Erdem G, Vanderford PA, Bart Jr RD. Intracranial hemorrhage in herpes simplex encephalitis: An unusual presentation. Pediatr Neurol 2002;27:221-223.

Introduction
Herpes simplex virus (herpesvirus) is the most frequent
agent causing sporadic viral encephalitis [1]. Typically,
herpesvirus produces hemorrhagic necrotizing encephalitis in the medial temporal and frontal lobes [2]. A
14-month-old infant who presented with bilateral large
hemorrhages in the right parietal lobe and clinical findings
suggestive of a hypercoagulable state is described in this
study. The diagnosis of herpes simplex encephalitis was

From the *Department of Pediatrics, the †Division of Pediatric
Intensive Care, and the ‡Department of Internal Medicine; University
of Hawaii John A. Burns School of Medicine; Honolulu, Hawaii.

© 2002 by Elsevier Science Inc. All rights reserved.
PII S0887-8994(02)00428-9 ● 0887-8994/02/$—see front matter

confirmed late in the hospital course with a positive
herpesvirus polymerase chain reaction. Large areas of
hemorrhage in herpes simplex encephalitis are reported in
infants with disseminated herpesvirus infection and infrequently in adults, although hemorrhage has not been
previously described in other pediatric patients [3,4].
Case Report
A 14-month-old female was admitted to the Kapiolani Medical Center,
Honolulu, Hawaii, with generalized seizures. She had developed fever and
irritability 4 days before admission, which was followed by drooling,
decreased oral intake, lethargy, and generalized seizures. A computed
tomography scan of her head performed in an outlying hospital revealed a
large hemorrhage in the right parietal parenchyma with surrounding edema,
three smaller lesions with surrounding edema in the same area, and similar
smaller symmetric lesions on the left side. There was no midline shift or
meningeal enhancement. She had no history of trauma or ill contacts and no
previous history of bleeding. Her past medical history was significant with
premature delivery at 29 weeks of gestation to a 17-year-old mother with no
history of complications. The infant had intermittent apneas and bradycardias during the first week of life. She had several head ultrasound studies,
which were reported to be normal. She was able to walk and say a few words
before her illness. She was in foster care for social reasons.
At the time of her admission she was lethargic. Her weight was 11 kg
(ninety-fifth percentile corrected for gestation). The deep tendon reflexes
were decreased in the lower extremities. She had no focal neurologic
findings. The results of the remainder of her physical examinations were
within normal limits. The initial biochemistry and coagulation studies
could not be performed because several blood samples obtained from
arterial and venous lines clotted. After several attempts the coagulation
studies including prothrombin time (11.6 seconds, normal ⫽ 10.5-12.5
seconds), partial thromboplastin time (33 seconds, normal ⫽ 27-35
seconds), fibrinogen (234 mg/dL, normal ⫽ 200-400 mg/dL), antithrombin III (103%, normal ⫽ 85%-122%), protein C (94%, normal ⫽
60%-138%), protein S levels (53%, normal ⱖ 60%, the result considered
to be not significantly low) were obtained. However, fresh-frozen plasma
was administered empirically while waiting for the protein C and protein
S levels, because she appeared to have a hypercoagulable state. Several
laboratory tests were performed to find the etiology of intracranial
hemorrhage, testing for causes such as infections, blood disorders,
cardiac disorders, trauma, vasculitis, and several metabolic diseases. Her
complete blood count, electrolytes, and transaminases were at normal
levels. Her reticulocyte count was normal, and sickle test was negative.
Her arterial blood gas measurements did not reveal acidosis. Anticardiolipin antibodies and coagulation factor II and factor V mutations were
absent. She was noted to be heterozygous for 5,10-methylenetetrahydrofolate reductase. Results of influenza, Cytomegalovirus, echovirus, Coxsackie, varicella virus, and mycoplasma serologies were negative. Her
neuroimaging findings were not reported to be consistent with vasculitis.
An echocardiogram result was normal. Her lumbar puncture at the time
of admission revealed 700/␮L red blood cells and 33/␮L white blood
cells with lymphocyte predominance. The cerebrospinal fluid protein and

Communications should be addressed to:
Dr. Bart; Professor of Pediatrics and Internal Medicine; Division
Chief, Neurology; University of Hawaii John A. Burns School of
Medicine; Kapiolani Medical Center for Women and Children; 1319
Punahou Street, Suite 999; Honolulu, HI 96826.
Received March 22, 2001; accepted April 8, 2002.

Erdem et al: HSV with Cerebral Bleeding After Infancy 221

Figure 1. (A) Initial T2-weighted axial image reveals heterogenous
hemorrhage in the right temporal lobe and bilateral temporal edema
(TR ⫽ 3,716, TE ⫽ 129). (B) Follow-up scan reveals the right-sided
hemorrhage and progressive edema on T2-weighted image (TR ⫽
3,716, TE ⫽ 93.7). (C) Decreasing edema and hemorrhage and
frontal atrophy on T2-weighted image is indicated (TR ⫽ 3,750,
TE ⫽ 92.5).

glucose were 38 mg/dL and 60 mg/dL, respectively. She was empirically
begun on intravenous acyclovir (20 mg/kg/dose every 8 hours).
On her second hospitalization day, she became comatose. She continued to have occasional seizures despite fosphenytoin and subsequently
phenobarbital. Her cranial magnetic resonance imaging on the second
day of hospitalization revealed a large right temporoparietal hemorrhage
with surrounding edema and additional symmetric areas of edema
involving both temporoparietal lobes and both posterior frontal lobes,
thalami, and insular regions (Fig 1A). Magnetic resonance angiography
for both cerebral arteries and veins were normal.
She continued to have fevers up to 103°F for 3 days. A repeat magnetic
resonance imaging on the third day of hospitalization revealed evolving
hemorrhage with increasing edema of both temporoparietal lobes, parasagittal area, thalami, and bilateral insular regions, as well as increasing
areas of T1 signal along the gyral surfaces (Fig 1B). She developed
hepatosplenomegaly along with elevated liver enzymes during the first
week of hospitalization. She continued to receive intravenous acyclovir.
The herpesvirus polymerase chain reaction was reported as positive. Her

222

PEDIATRIC NEUROLOGY

Vol. 27 No. 3

cerebrospinal fluid and blood viral cultures remained negative. She
received 21 days of acyclovir treatment with improvement in magnetic
resonance imaging findings beginning from the eighth day of treatment
with resolving hemorrhages and subsiding bilateral temporoparietal
edema (Fig 1C). A repeat herpesvirus polymerase chain reaction, which
was performed after 7 days of acyclovir treatment, was negative. Her
level of consciousness improved, and she was successfully extubated
after 10 days. She continued to have severe bulbar dysfunction but no
seizures on antiepileptic drugs at the time of her discharge from the
hospital. She has continued to be a spastic quadriparetic child but was
feeding by mouth 9 months after her discharge.

Discussion
Herpesvirus is the most common identifiable cause of
encephalitis in the United States [5]. Herpes simplex
encephalitis is well recognized in adolescents and adults,

and a high index of suspicion is usually present in patients
presenting with acute onset of encephalopathy, focal
seizures, and neurologic deficits. The cerebrospinal fluid
findings, including the presence of erythrocytes and lymphocytes and especially the presence of focal temporal or
frontal abnormalities on magnetic resonance imaging
scans, also supported the decision to treat with intravenous
acyclovir [6]. There are few clinical descriptions of herpes
simplex encephalitis except in the infant and adolescent
periods in the pediatric literature. Our patient was admitted
for evaluation of acute onset of seizures. She had fevers
and cerebrospinal fluid pleocytosis suggestive of an infectious process. However, her clinical presentation with
seizures, unilateral parietal hemorrhage, bilateral parietal
edema, and recurrent clotting of arterial blood samples
during the first hours of her hospitalization seemed more
consistent with a hypercoagulable state that was induced
by an infectious agent.
Vascular changes that have been reported in herpes
simplex encephalitis include areas of hemorrhagic necrosis and perivascular cuffing [1]. Although petechial hemorrhages and smaller lesions have been described in herpes
simplex encephalitis, large areas of hemorrhage and
edema, as described in our patient, are unusual and may
delay the diagnosis and treatment [3,4]. It may be argued
that the magnetic resonance imaging abnormalities observed in this patient are in the distribution of middle
cerebral arteries and they may represent bilateral infarctions with hemorrhage. However; infarction with hemorrhagic transformation is unlikely in the presence of such
dense hemorrhages that are also observed in the initial
computed tomography scans of the head.
A coagulopathy and bleeding at a variety of sites including
the brain are known to complicate severe perinatal herpesvirus infections and perinatal herpesvirus sepsis [7]. Bleeding
in infants may reflect a combination of disseminated intravascular coagulation, hepatocellular damage with consequent
insufficient production of clotting factors, and viral-induced
thrombocytopenia [7]. Although disseminated herpesvirus
infection with coagulopathy cannot be excluded as the
preceding or co-existing event, the etiology of the coagulation dysfunction remains unclear. One week after her initial
presentation with irritability and fevers and after the hypercoagulable state, our patient developed hepatosplenomegaly
and a mild increase in her liver enzymes. These findings were
thought to be a result of the use of high doses of acetaminophen and clindamycin and spontaneously resolved. Her
blood viral cultures remained negative, and she had no
further bleeding. To our knowledge, this is the first pediatric
patient with herpes simplex encephalitis presenting with large
areas of intracranial hemorrhage beyond the neonatal period.
Although our patient’s presentation was atypical, her
hospital course was characteristic for herpes simplex
encephalitis. She initially lacked the temporal lobe involvement considered characteristic of herpes simplex
encephalitis beyond the neonatal period. The signs of
inflammation and petechial hemorrhages appeared after

the initial presentation with intracranial bleeding and a
possible coagulopathic stage. The early presentation with
severe bilateral intracranial hemorrhages in this patient
may be a result of the co-existence of this coagulation
abnormality with acute intense neuronal lysis after viral
replication [8]. Acyclovir treatment was instituted on the
first day of admission primarily because of the fevers and
cerebrospinal fluid pleocytosis. There were no data on the
expected cerebrospinal fluid findings of herpes simplex
encephalitis at our patient’s age, although the mildly
elevated cerebrospinal fluid lymphocyte counts were
within the reported range for infants [9]. The diagnosis of
herpes simplex encephalitis was confirmed with a positive
herpesvirus polymerase chain reaction.
We believe that this patient illustrates several important
points about pediatric herpes simplex encephalitis. The
polymerase chain reaction detection of DNA in the cerebrospinal fluid proved to be a sensitive and specific tool
for the diagnosis of herpes simplex encephalitis; however,
the most important factor in the diagnosis herpesvirus
infection in our patient was the consideration of the
diagnostic possibility [10,11]. This report also illustrated
that herpes simplex encephalitis can present with large
intracerebral hemorrhage.

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