Journal of the Neurological Sciences 165 (1999) 90–93

Vacuolating leukoencephalopathy with subcortical cysts with late onset
athetotic movements
a,

b

Jun-ichi Takanashi *, Katsuo Sugita , Yoichi Kohno

a

a

b

Department of Pediatrics, Faculty of Medicine, Chiba University, 1 -8 -1 Inohana, Chuo-ku, Chiba-shi, Chiba 260 -8677, Japan
Department of Clinical Medicine, Faculty of Education, Chiba University, 1 -8 -1 Inohana, Chuo-ku, Chiba-shi, Chiba 260 -8677, Japan
Received 14 August 1998; received in revised form 1 February 1999; accepted 15 March 1999

Abstract
We reported a 10-year-old male with vacuolating leukoencephalopathy with subcortical cysts, who presented athetotic movements in
the late stage. Magnetic resonance imaging demonstrated diffuse cerebellar white matter lesions, in addition to typical cerebral white
matter abnormalities and characteristic subcortical cysts in the anterotemporal and parietal areas. Fluid-attenuated inversion recovery
images are highly sensitive for the detection of subcortical cysts, which is essential for a diagnosis. This is most likely to be a severe form
of vacuolating leukoencephalopathy with subcortical cysts, presenting with athetotic movements in the late stage. ï›™ 1999 Elsevier
Science B.V. All rights reserved.
Keywords: Valuolating leukoencephalopathy with subcortical cysts; Magnetic resonance imaging; Fluid-attenuated inversion recovery; Athetosis; Child

1. Introduction
A number of neurological disorders with onset in
infancy are characterized by a combination of progressive
neurological dysfunction, megalencephaly, and leukoencephalopathic changes on computed tomography or magnetic
resonance (MR) imaging. Among them, Canavan disease
and Alexander disease are best known. They are clinically
severe, and diagnosed based on increased N-acetylaspartate
in urine or on proton MR spectroscopy in patients with
Canavan disease [1], and increased a B-crystallin and heat
shock protein 27 in the cerebrospinal fluid in patients with
Alexander disease [2].
Recently, van der Knaap et al. [3] reported eight
children with new leukoencephalopathy, who had infantile
onset megalencephaly, followed by delayed onset relatively mild motor deterioration with ataxia and spasticity,
and typical MR imaging findings. According to the

*Corresponding author: Tel.: 181-43-226-2144; fax: 181-43-2262145.
E-mail address: jtaka@med.m.chiba-u.ac.jp (J. Takanashi)

pathological findings [4], they named this syndrome vacuolating leukoencephalopathy with subcortical cysts
(VLESC). We report the first Japanese case of VLESC
with prominent cerebellar white matter involvement, who
presented prominent athetotic movements in the late stage,
and the availability of fluid-attenuated inversion recovery
(FLAIR) images for a diagnosis.

2. Case report
A now 10-year-old male was referred to Chiba University Hospital for evaluation of megalencephaly and psychomotor deterioration at the age of eight. He was born at 42
weeks gestation without pre- or perinatal difficulties, and
his weight, height and head circumference were of the 50th
percentile at birth. There was no family history of neurological illness. His development was normal for one year,
i.e. smiling at two months, head control at three months,
sitting alone at six months, standing up at nine months,
uttering his first word at 12 months, and walking alone at
14 months. His head circumference began to increase after

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J. Takanashi et al. / Journal of the Neurological Sciences 165 (1999) 90 – 93

the age of six months. After two years, he showed an
ataxic gait and tremor with a progressive increase in
muscle tonus, and could not walk alone after six years.
Generalized tonic clonic seizures commenced at the age of
five years, and were successfully treated with valproic acid
and carbamazepine. His developmental quotient (DQ)
score was 97 at one-year-old, 53 at four-years-old, and 41
at eight-years-old.
On the first admission at eight-years-old, his height was
116.0 cm (21.5 SD), weight 21.0 kg (21.2 SD), and head
circumference 58.0 cm (14.0 SD). He could sit alone and
crawl, but could not stand up or walk alone. The cranial
nerves were intact. Cerebellar symptoms, such as truncal
ataxia, dysmetria, tremor and slurred speech, were recognized. He also exhibited athetotic movements (irregular
and writhing movements) of the distal upper limbs, and
rigospastic quadriparesis with increased deep tendon reflexes and ancle clonus. Cranial MR imaging (Fig. 1) was
performed with a 1.5 tesla superconducting imager
(SIGNA Advantage, General Electric, Milwaukee, WI),
which revealed diffuse T1 and T2 elongation in the
cerebral and cerebellar white matter with sparing of deep
white matter structures, such as the corpus callosum and
internal capsules. We performed extensive laboratory
studies, including on hematology, blood chemistry; serum
very-long-chain fatty acids, amino acids; the activities of
lysosomal enzymes, such as b-galactosidase, hexosaminidase A, galactosylceramidase, arylsulfatase-A; cell counts,
protein, glucose, lactate, pyruvate, aB-crystallin and heat
shock protein 27 in the cerebrospinal fluid; and metabolic
screening of urine for amino acids, organic acids, and
mucopolysaccharides; all of which were either within
normal limits or negative. Brainstem auditory evoked
potentials, flash-visual evoked potentials and motor nerve
conduction velocities were all normal. Electroencephalogram showed independent sharp waves in the bilateral
temporal regions.

Fig. 1. MR imaging at eight-years-old. T2 weighted images revealed
diffuse T2 elongation in the cerebral white matter with sparing of deep
white matter structures, such as the corpus callosum and internal capsules.

91

On the second admission at 10 years, he showed truncal
ataxia and progressive athetotic movements of the upper
limbs. Tremor or dysmetria was not recognized. T1 and T2
weighted images showed T1 and T2 elongation in the
cerebral and cerebellar white matter without obvious
interval changes. FLAIR (Fig. 2A,B) revealed subcortical
cysts in the left temporal and parietal regions, which could
not be detected on T1 and T2 weighted images (Fig. 2C).
From the laboratory data, we could rule out disorders
with megalencephaly and leukoencephalopathy, such as
Alexander disease, Canavan disease, L-2-hydroxyglutaric
aciduria, glutaric aciduria type 1, sphingolipidosis,
mucopolysaccharidosis and mitochondrial encephalopathy.
Because of the infantile onset megalencephaly, delayed
onset of motor dominant deterioration, and typical MR
imaging findings, we diagnosed him as having VLESC.

3. Discussion
van der Knaap et al. [3] reported eight children with
megalencephaly and leukoencephalopathy, and a delayed
onset of slowly progressive neurological dysfunction as
‘‘leukoencephalopathy with swelling and a discrepantly
mild clinical course’’. The disorder probably has an
autosomal recessive mode of inheritance, but no basic
biochemical defect has not been identified. The histopathological findings revealed a spongiform leukoencephalopathy without cortical involvements [4]. Most vacuoles were covered by single five-layered membranes,
representing single myelin lamella. The histopathological
findings place the disease among the vacuolating
myelinopathies, the possible pathophysiological mechanism being splitting of the outermost myelin lamella at the
intraperiod line or disturbance of compaction of the
outermost myelin lamella at the intraperiod line. Based on
the pathological findings, they named the disorder VLESC
[5].
In the original eight children with VLESC, the neurological findings were initially normal or near normal,
despite megalencephaly with onset within one year. Slowly
progressive ataxia and spasticity developed, while intellectual functioning was preserved for years after onset.
Athetotic movements, which were observed in the late
stage of this patient, i.e. six years after onset, were not
described in the originally reported eight cases, although
three of them had suffered for more than 10 years.
Recently, Mejaski-Bosnjak et al. [6] also reported a case of
VLESC, who presented choreoathetosis at 6 years of age.
Athetotic movements are recognized in disorders with
damage to striatal regions, such as Wilson disease and
Hallervorden-Spatz disease, in which MR imaging revealed striatal lesions. However, the MR images in the
present case demonstrated no abnormal signal intensity in
the caudate nucleus or putamen. In Pelizaeus-Merzbacher

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J. Takanashi et al. / Journal of the Neurological Sciences 165 (1999) 90 – 93

Fig. 2. MR imaging at 10-years-old. (A, B) FLAIR images revealed subcortical cysts in the left temporal and parietal regions (arrows), and high intensity
lesions in the cerebellar white matter. (C) Subcortical cysts could not be recognized on T2 weighted images.

disease (a rare dysmyelinating disorder affecting the
central nervous system), in which MR images demonstrate
diffuse white matter abnormality and no abnormal lesions
in the striatal regions, choreiform or athetotic movements
begin to appear later than abnormal eye movements in
early infancy. Although the pathophysiological mechanism
is uncertain, this case could be considered as a severe form
of VLESC, presenting with athetotic movements in the late
stage.
The MR imaging abnormalities that are characteristic of
VLESC are the discrepant severity in comparison with the
clinical picture [3]. MR imaging revealed supratentorial,
hemispheral white matter involvement with relative sparing of central white matter structures, the absence of any
gray matter involvement, and the presence of subcortical
cysts in the anterotemporal, fronto-parietal areas [3,5].
MR images of this patient demonstrated obvious bilateral cerebellar white matter lesions, in addition to typical

cerebral white matter lesions and subcortical cysts. The
cerebellar lesions, which were none or slight in the original
eight cases [3], may explain more prominent cerebellar
symptoms, such as truncal ataxia, dysrmetria, tremor, and
slurred speech in our patient.
FLAIR images, with which the signal from the cerebrospinal fluid is reduced and there is high T2 weighting
for the brain, are reported to be more sensitive for
detecting abnormal lesions than conventional T1 and T2
weighted images in many neurological disorders [7,8]. In
the present case, subcortical cysts could not be recognized
on conventional T1 and T2 weighted images at eight and
10 years because of the prominent T1 and T2 elongation in
the surrounding white matter and contamination of the
cerebrospinal fluid signal. Since subcortical cysts are
radiologically essential for the diagnosis of VLESC,
FLAIR images are strongly recommended for patients with
diffuse leukodystrophy in order not to miss this disorder.

J. Takanashi et al. / Journal of the Neurological Sciences 165 (1999) 90 – 93

Acknowledgements
We wish to thank van der Knaap, MD for valuable
radiological comments, and Fuminori Morita and
Yoshitada Nakano for their excellent technical support.

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