Brain & Development 1996; 18: 150-152

ELSEVIER

Case report

Diffuse white matter lesions associated with herpes simplex
encephalitis as observed on magnetic resonance imaging
Tadahisa Tamura "~*, Akihiro Morikawa b, Kenji Kikuchi c
a Department of Pediatrics. Hoshi General Hospital Epilepsy Center. 2-1-16 Omachi Koriyama, Fukushima 963. Japan
h Department of Pediatrics, Gunma University School of Medicine, Maebashi, Gunrna, Japan
c Department ofNeurosurgery, Akita Unit,ersity School of Medicine, Akita, Akita, Japan

Received 24 July 1995; accepted 26 October 1995

A 2-year-old boy with herpes simplex encephalitis developed diffuse brain lesions involving the white matter of
both cerebral hemispheres. These lesions in the white matter were clearly observed on magnetic resonance imaging
(MRI) with the T2-weighted sequence, and were found to have spontaneously disappeared on subsequent MRI
performed 7 weeks later. Brain lesions associated with herpes simplex encephalitis in the literature are reviewed and
the pathogenesis in the present case is discussed.
Keyword¢: Herpes simplex encephalitis; Brain lesions; White matter; Magnetic resonance imaging

1. I N T R O D U C T I O N
Herpes simplex encephalitis (HSE) is caused by the herpes
simplex virus (HSV), which selectively affects the cortex of the
brain, often with temporal lobe focality. Pathologically, HSE is a
necrotizing hemorrhagic process [1], in which there may be
contiguity with the sub-arachnoid space, and which rarely involves deeply the white matter of the brain in a diffuse manner.
Magnetic resonance imaging (MRI) is a relatively new diagnostic
modality, which may be superior to computed tomography (CT)
for delineating the lesions in HSE. We report a child who
developed diffuse lesions in the white matter of both cerebral
hemispheres, which were clearly demonstrated on MRi.

2. C A S E R E P O R T
A 2-year-old Japanese boy was admitted to a local hospital on
28 January 1989, after he suddenly developed a high fever of up
to 39.5°C and right-sided convulsive seizures. As the convulsions
became progressive and occurred in rapid succession, the patient
gradually became drowsy and confused. He was transferred to
our center 6 days later for further evaluation and treatment.
On admission, the patient was lethargic and did not properly
respond to vocal commands. There were no obvious motor or

• Corresponding author. Fax: (81) (249) 39-3141.
0387-7604/96/$15.00 (~ 1996 Elsevier Science B.V. All rights reserved
SSDI 03 87-7604(95)0014 1-7

sensory abnormalities, and his reflexes were equal bilaterally in
both the upper and lower limbs. Physical examination was unremarkable. A lumbar puncture yielded cerebrospinal fluid (CSF)
showing mononuclear pleocytosis, but no elevation of the protein
level. A hemogram, urinalysis, and other chemical studies exhibited normal results.
A plain CT scan revealed a wedge-shaped area of high density
involving the cerebral cortex of the left frontal region. This lesion
was delineated as a high-intensity area in Tl-weighted images
(spin-echo, TR = 650 ms, TE = 40 ms), and as a widespread
high-intensity area in T2-weighted images (spin-echo, TR = 2000
ms, TE = 80 ms) (Fig. la), compared with on plain CT. Serial
cerebral angiography failed to reveal definite abnormalities. An
electroencephalogram (EEG) showed abnormal, paroxysmal activity characterized by periodic lateralized epileptiform discharges (PLEDs) in the left frontocentral region.
Gradually, the patient regained consciousness and the convulsive seizures were completely controlled by means of anticonvulsant therapy. However, intravenous administration of acyclovir,
an antiherpes agent, at a daily dosage of 30 m g / k g , was then
initiated and continued for a period of 6 days, because 7 days
after admission the titers of HSV neutralizing antibodies were
found to be significantly elevated in both serum and CSF. These
increasing HSV antibody titers finally led to the diagnosis of
acute herpes simplex encephalitis. Subsequently, the patient was
again evaluated by enhanced CT and T2-weightcd MRI (Fig. lb),
on which a new focus of encephalitis was indicated in the cortex
of the right frontal region, as judged from the characteristic gyral

T. Tarnura et al./Brain & DeL'elopment 1996; 18:150-152

Fig. I. a: T2-weighted MR imaging, an axial view (spin-echo, TR = 2000
ms, TE = 80 ms) performed on admission, showing a widespread area of
high signal intensity involving the cerebral cortex of the left frontal
region, in comparison with that on plain CT. b: T2-weighted MR
imaging, a coronal view (spin-echo, TR = 2000 ms, TE = 80 ms) obtained 2 weeks after admission, showing a new focus of encephalitis in
the cortex of the right frontal region.

Fig. 2. a: T2-weighted MR imaging, a coronal view (spin-echo, TR = 2000
ms, TE = 80 ms) performed 55 days after admission, demonstrating areas
of high signal intensity involving the white matter of both cerebral
hemispheres, b: T2-weighted MR imaging, an axial view (spin-echo,
TR = 2000 ms. TE = 80 ms) performed 55 days after admission, illustrating the dominance of the white matter lesions in the left cerebral
hemisphere, c: T2-weighted MR imaging, a coronal view (spin-echo.
TR = 2000 ins, TE = 80 ms) obtained 7 weeks after the white matter
lesions had been observed, showing marked regression of the white
matter lesions.

151

152

T. Tamura et al. / Brain & Det:elopment 1996; 18: 150-152

configuration of the contrast enhancement on CT and the high
intensity on MRI.
MRI performed 55 days after admission demonstrated extensive areas of high signal intensity involving the corpus callosum
and the white matter of both cerebral hemispheres in T2-weighted
images (Fig. 2a,b). Plain CT showed diffuse low-density areas
extending to the semioval centers of both hemispheres. CSF
obtained at that time showed both an increased protein content
(97 m g / m l ) and increased myelin basic protein (MBP; 12
ng/ml). Despite the presence of the diffuse lesions demonstrated
by MRI, the patient remained neurologically rather stable, exhibiting right-sided hemiparesis and moderate speech disturbance.
Seven weeks later, MRI revealed marked regression of the white
matter lesions (Fig. 2c). The CSF protein and MBP levels were
also within normal limits.
The patient gradually recovered over a period of 3 months and
was discharged, still exhibiting slight weakness of the right upper
limb and very mild speech disturbance.

white matter of both cerebral hemispheres and the corpus callosum. In addition, the CSF protein and MBP levels were found to
be significantly elevated at the time when the MRI was performed, but they gradually decreased to within the normal range
without any specific treatment. Though the mechanisms underlying these findings on both MRI and CSF remain to be elucidated,
they suggest the presence of a reversible change of the white
matter such as edema of a considerable degree associated with an
immune-mediated complication of a viral infection [1,5]. On the
other hand, the direct invasion of HSV into the white matter is
unlikely to have been the cause of the reversible process of
edema or myelin damage, because pathological changes due to
HSV infection are characterized by the irreversible process of
hemorrhagic necrosis [1].
While there have been some reports describing transitory
neurotoxicity associated with acyclovir [6,7], in the present case
no data were obtained which indicate the cause-effect relation
between the lesions of the white matter observed on MRI and
acyclovir.

3. D I S C U S S I O N
The prognosis of HSE is generally considered ominous,
whereas there are some patients who show only mild manifestations of HSE [2], and recover to the point where they can resume
an independent life. In the present case, spontaneous regression
of the neurological signs and symptoms was observed even prior
to acyclovir therapy. The mechanism underlying such spontaneous recovery has to date not been fully elucidated.
There have been some reports concerning the MRI appearance
of HSE [3,4], which described an increased water content caused
by inflammation in the affected brain cortex. In the present case,
T2-weighted MRI characteristically demonstrated widespread increased signal intensity in the left frontal lobe, which was
confirmed on contrast CT as a gyral blush pattern. MR1 was
found to play a significant role in delineating the extent of the
inflammatory process of HSE.
Of particular interest in the present case, however, were the
T2-weighted MR images obtained following acyclovir therapy, in
which diffuse increased signal intensity was observed in the

REFERENCES
I. Adams RD, Victor M. Viral infections of the nervous system. In
Principles of neurology. New York: McGraw-Hill, 1985; 545-68.
2. Klapper PE, Cleator GM, Longson M. Mild form of herpes encephalitis. J Neurol Neurosurg Psychiatry 1984; 47: 1247-50.
3. Davidson HD. Steiner RE. Magnetic resonance imaging in infections
of the central nervous system. AJNR 1985; 6: 499-504.
4. Schroth G. Gowehn J, Thron A, Vallbracht A, Voigt KL. Early
diagnosis of herpes simplex encephalitis by MRI. Neurology 1987:
37: 179-83.
5. Adams RD, Victor M. Multiple sclerosis and allied demyelinative
diseases. In Principles of neurology. New York: McGraw-Hill. 1985:
699-717.
6. Cohen SMZ. Mincove JA, Zebley 111 JW, Mulholland JH. Severe but
reversible neurotoxicity from acyclovir. Ann Intern Med 1984: 100:
920.
7. Wade JC. Meyers JD. Neurologic symptoms associated with parenteral
acyclovir treatment after marrow transplantation. Ann Intern Med
1983; 98: 921-5.