AJR 2000; 174:1651-1655
© American Roentgen Ray Society
MR Imaging of Herpes Simplex Type I Encephalitis in Infants and Young Children
A Separate Pattern of Findings
Jeffrey R. Leonard1,
Christopher J. Moran2,
DeWitte T. Cross, III2,
Franz J. Wippold, II2,3,
Yechiel Schlesinger4 and
Gregory A. Storch4
1
Department of Neurological Surgery, Washington University School of Medicine,
660 S. Euclid Ave., St. Louis, MO 63110.
2
Mallinckrodt Institute of Radiology, Washington University Medical Center, 510
S. Kingshighway Blvd., St. Louis, MO 63110.
3
Department of Radiology and Nuclear Medicine, Uniformed Services University of
the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814.
4
Department of Pediatrics, Washington University School of Medicine, St. Louis,
MO 63110.
Received December 14, 1998;
accepted after revision November 12, 1999.
The opinions and assertions contained herein are the private views of the
authors and are not to be construed as official or as reflecting the views of
the Department of Defense.
Address correspondence to C.J. Moran.
Abstract
OBJECTIVE. We sought to identify the initial MR findings of herpes
simplex encephalitis in infants and young children.
CONCLUSION. MR imaging findings of herpes encephalitis in infants
and young children appear to differ from those seen in neonates, older
children, and adults. Appreciation of this MR imaging pattern coupled with a
strong clinical suspicion of herpes helps to ensure the correct diagnosis is
made.
Introduction
Herpes encephalitis is the most common sporadic encephalitis in the United
States and other industrialized countries
[1]. Occurring as either a
primary infection with herpes simplex virus or as a reactivation of latent
virus, herpes encephalitis causes significant morbidity and mortality
[2]. Early intervention with
acyclovir significantly improves outcome; therefore, recognition of the MR
imaging pattern of herpes encephalitis is imperative
[1,
3].
Herpes encephalitis has been divided into two distinct entities on the
basis of the presenting age (neonatal versus children and adults). Neonatal
herpes encephalitis typically presents after being contracted during vaginal
delivery. Symptoms include seizure, fever, and lethargy
[4]. Neonatal herpes
encephalitis is usually associated with herpes simplex virus type 2
[5]. Neonatal herpes
encephalitis causes widespread MR imaging signal abnormalities that are
hypointense on T1-weighted sequences and hyperintense on T2-weighted
sequences. Neonatal herpes usually involves the periventricular white matter
and spares the medial temporal and inferior frontal lobes. Additionally,
meningeal enhancement occasionally occurs after IV contrast material
administration [3]. In children
and adults, herpes encephalitis usually presents with nonspecific symptoms
including behavioral changes, fever, focal neurologic deficits, and headaches
[2,
6]. Herpes encephalitis in
children and adults is usually associated with herpes simplex virus type 1
[1]. MR imaging usually shows a
hemorrhagic process, which often involves the medial temporal lobes, inferior
frontal lobes, and insula. Early in the course of the disease, these areas can
be isointense with the normal brain on T1-weighted sequences and hyperintense
on T2-weighted sequences [2,
3,
6]. We describe three infants
and one child, ages 4-13 months, with herpes encephalitis, whose MR imaging
findings differ from the classic findings in neonates as well as in children
and adults.
Subjects and Methods
In the last decade at our institution, four patients, 4-13 months old, have
been diagnosed with herpes simplex type 1 encephalitis. All were included in
this study. Each had herpes simplex type 1 viral DNA in the cerebrospinal
fluid detected by a polymerase chain reaction. Our polymerase-chain-reaction
methodology has been described in detail
[7], and results from these
four patients were confirmed by a second method
[8].
Initial MR imaging was performed on all our patients 1-12 days after
symptom onset. Spin-echo T1-weighted sequences were obtained in the axial and
sagittal planes. T2-weighted sequences were obtained in the axial and coronal
planes. Three of the four patients underwent imaging with a 1.0-T magnet and
the other was scanned with a 1.5-T magnet. T1-weighted sequences were obtained
in axial and coronal planes on three of the four patients 10-15 min after IV
administration of 0.1 mmol/kg of gadopentetate dimeglumine (Magnevist; Berlex
Laboratories, Wayne, NJ). A contrast-enhanced T1-weighted sequence for the
4-month-old infant was not obtained because of contrast material
extravasation. These images were reviewed for signal intensity, extent of
cortical and white matter involvement, presence of hemorrhage, and presence of
contrast enhancement in the brain or meninges.
Results
Clinical Findings
All patients presented with seizures. Two patients experienced generalized
tonic—clonic seizures, and the other two suffered focal motor seizures.
Three of the four patients presented with fever. One patient had mild left
hemiparesis on initial physical examination, and the other three patients had
no focal deficits.
Neural Imaging
The cerebral hemispheres were initially involved in all four patients, the
parietal lobe in three, the occipital lobe in two, the frontal lobe in one,
the temporal lobe in two, the insula in two, and the thalami in one. More than
one lobe was infected in all patients (Figs.
1A,1B,2A,2B,3A,3B,3C,4A,4B,4C).
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Fig. 1A. —4-month-old male infant who presented with upper respiratory
symptoms and fever of 4 days duration and single focal motor seizure on day of
admission. MR imaging with 1.5-T magnet was performed 8 days after symptom
onset. Unenhanced axial T1-weighted MR image (600/14[TR/TE]) shows area of
hypointensity in white matter of left temporal—occipital region. Two
small areas of hemorrhage involve gray—white junction.
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Fig. 1B. —4-month-old male infant who presented with upper respiratory
symptoms and fever of 4 days duration and single focal motor seizure on day of
admission. MR imaging with 1.5-T magnet was performed 8 days after symptom
onset. Axial T2-weighted MR image (3500/90) shows hyperintensity in involved
white matter.
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Fig. 2A. —7-month-old female infant who presented with generalized
tonic—clonic seizure on day of admission. MR imaging with 1.0-T magnet
was performed that day. Coronal T2-weighted MR image (2400/90 [TR/TE]) shows
hyperintensity in right parietal and insular cortex and adjacent white
matter.
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Fig. 2B. —7-month-old female infant who presented with generalized
tonic—clonic seizure on day of admission. MR imaging with 1.0-T magnet
was performed that day. Enhanced coronal T1-weighted MR image (800/22) shows
mild enhancement in same areas as A.
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Fig. 3A. —11-month-old female infant who presented with fever, lethargy,
left-sided focal motor seizures, and decreased oral intake of 3 days duration.
Initial MR images on 1.0-T magnet were 7 days after symptom onset. Axial
T2-weighted MR image (3000/90 [TR/TE]) shows hyperintensity in cortex, white
matter of both parietal lobes (arrows), left insula
(arrowheads), and both thalami. Left hemispheric findings are more
apparent than those in right hemisphere.
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Fig. 3B. —11-month-old female infant who presented with fever, lethargy,
left-sided focal motor seizures, and decreased oral intake of 3 days duration.
Initial MR images on 1.0-T magnet were 7 days after symptom onset. Enhanced
coronal T1-weighted MR image (800/22) shows enhancing cortex in both parietal
lobes and insular regions.
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Fig. 3C. —11-month-old female infant who presented with fever, lethargy,
left-sided focal motor seizures, and decreased oral intake of 3 days duration.
Initial MR images on 1.0-T magnet were 7 days after symptom onset. Enhanced
axial T1-weighted MR image (800/22) shows enhancement in cortex and white
matter of both parietal lobes and insular regions and in left thalamus.
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Fig. 4A. —13-month-old female infant who presented with fever of 6 days
duration and two generalized tonic—clonic seizures. MR imaging on 1.0-T
magnet was performed 12 days after symptom onset. Unenhanced axial T1-weighted
MR image (600/22 [TR/TE]) shows hypointensity in thickened cortex of both
frontal and parietal lobes.
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Fig. 4B. —13-month-old female infant who presented with fever of 6 days
duration and two generalized tonic—clonic seizures. MR imaging on 1.0-T
magnet was performed 12 days after symptom onset. Enhanced axial T1-weighted
MR image (600/22) shows no evidence of meningeal enhancement.
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Fig. 4C. —13-month-old female infant who presented with fever of 6 days
duration and two generalized tonic—clonic seizures. MR imaging on 1.0-T
magnet was performed 12 days after symptom onset. Axial T2-weighted MR image
(2000/80) shows hyperintensity in cortex and adjacent white matter of both
frontal and parietal lobes.
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On T1-weighted sequences, the involved cortex was thicker than the adjacent
normal cortex and was slightly hypointense. The signal in the adjacent white
matter was also slightly hypointense compared with that of normal white
matter, resulting in obscuration of the normal gray—white matter
distinction. Involvement of both gray and white matter mildly compressed the
adjacent ventricles and sulci. The corresponding signal on T2-weighted
sequences in the areas of T1-weighted abnormalities was markedly increased,
especially in the white matter. After the IV administration of contrast
material, the cortex and white matter diffusely enhanced on T1-weighted
sequences in the three patients who received contrast material. The meninges
failed to enhance in any of these patients. Minimal hemorrhage was detected in
one patient (Fig.
1A,1B).
Medical temporal lobes, inferior frontal lobes, and periventricular white
matter were uninvolved in all patients.
Hospital Course
Acyclovir therapy was initiated in all patients 3-9 days after symptom
onset and from 8 hr to 4 days after hospitalization. Two of the three infants
were discharged without significant neurologic deficits. The 11-month-old
infant and 13-month-old child had hospital courses marked by progressive
neurologic deterioration and seizure activity. Acyclovir therapy was started 3
days and 9 days after symptom onset, respectively, and was maintained for 20
days and 16 days, respectively. After treatment, both patients were unable to
respond to auditory or visual stimuli.
Follow-up imaging was not performed on the 4-month-old infant who recovered
completely. Follow-up examinations on the other three patients (CT in two
patients and MR imaging in one patient) revealed encephalomalacia in the areas
that were abnormal on initial MR imaging.
Discussion
Recognition of the familiar imaging pattern of herpes encephalitis
facilitates making the correct diagnosis and choosing appropriate therapy.
Familiar MR imaging patterns established early in the course of herpes
encephalitis distinguish neonatal herpes encephalitis from herpes encephalitis
in children and adults [6,
9]. The MR imaging
characteristics of neonatal herpes encephalitis vary more than that of the
disease in children and adults
[4]. The periventricular white
matter of both cerebral hemispheres is usually involved, and, occasionally,
the cerebellum may also be involved
[3,
10]. Affected areas usually
display hypointensity on T1-weighted sequences and hyperintensity on
T2-weighted sequences. Calcification, necrosis, and edema may produce areas of
abnormal signal intensity, and the meninges may enhance after contrast
material administration. Herpes encephalitis in neonates is rarely
hemorrhagic, and involvement of the medial temporal or inferior frontal lobes
rarely occurs [6].
In contrast, herpes encephalitis in children and adults is commonly
hemorrhagic with initial findings restricted to the medial temporal and
inferior frontal lobes [3,
5]. Imaging often displays
unilateral findings, but the disease can spread to the contralateral side. MR
imaging abnormalities of involved areas usually are hypointense on T1-weighted
sequences and hyperintense on T2-weighted sequences
[2,
3,
6]. Contrast enhancement of the
meninges, cortex, and white matter, though typically not prominent, may occur
[6].
The initial MR imaging findings of the four patients we have presented
resembled neither neonatal herpes encephalitis nor herpes encephalitis in
older children and adults. Although the signal characteristics of herpes
encephalitis are nonspecific, the location of the signal changes in the
appropriate age group faciliates making the diagnosis. In this small group of
infants and one young child, the signal abnormalities traced a vascular
distribution of the anterior, middle, and posterior cerebral arteries and
their perforating branches. This pattern suggests that hematogenous spread of
the viral particles could be the primary route of viral access to the central
nervous system.
The three patients who received IV contrast material did not exhibit
meningeal enhancement, which suggests that MR imaging findings in our patients
were not caused by inflammatory changes within the meninges but rather by
hematogenous spread of the viral particles to the affected areas. Furthermore,
the lack of meningeal enhancement, especially in the anterior and middle
cranial fossae (because the meninges in these areas are innervated by branches
of the trigeminal nerve), suggests that spread through the trigeminal nerve
was not responsible for this unusual MR imaging pattern. It should be noted
that meningeal enhancement does not always occur on MR imaging with meningitis
(Frei DF et al., presented at the American Society of Neuroradiology meeting,
April 1995).
The diagnosis of herpes encephalitis in this study was made using the
polymerase chain reaction for the DNA of herpes simplex virus. Other authors
have documented the excellent sensitivity and specificity of the
polymerase-chain-reaction technique for the detection of herpes simplex DNA in
cerebrospinal fluid [7,
8]. A large series showed a
sensitivity of 95% and specificity approaching 100% for the
polymerase-chain-reaction technique
[11]. In our study,
polymerase-chain-reaction products showed that the infectious agent was herpes
simplex type 1 in all four patients, suggesting that these patients may
represent the younger end of the adult spectrum. Traditionally, the gold
standard for the diagnosis of herpes encephalitis has been brain biopsy
[12]. However, the diagnosis
of herpes encephalitis by the polymerase-chain-reaction technique is a valid
diagnostic alternative to brain biopsy. It is a quick, noninvasive way of
obtaining the diagnosis, provided that strict precautions are undertaken to
avoid false-positive and falsenegative findings.
In summary, we present a new imaging pattern of herpes encephalitis in
infants and young children. In this age group, the cortex and adjacent white
matter of the cerebral hemispheres were involved, differing from the
previously reported pattern in neonates and older children and adults.
Recognition of this new finding enlarges the spectrum of imaging presentations
and alerts both clinicians and radiologists to consider the diagnosis of this
potentially devastating disease and more promptly institute acyclovir
therapy.
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Abstract
Introduction
