AJR 2000; 175:826-828
© American Roentgen Ray Society
MR Imaging of Vanishing White Matter
Utku 
enol1,
enay Haspolat2,
Kamil Karaali1 and
Ersin Lüleci1
1
Department of Radiology, Faculty of Medicine, Akdeniz University, 07070
Antalya, Turkey.
2
Department of Pediatric Neurology, Faculty of Medicine, Akdeniz University,
07070 Antalya, Turkey.
Received October 6, 1999;
accepted after revision February 8, 2000.
Address correspondence to U. enol
Introduction
After MR imaging, important features of various white matter diseases have
been observed and a definition of new white matter diseases has been possible.
One of these newly defined disorders is vanishing white matter. MR imaging and
MR spectroscopy features of the disorder were noticed in 1993
[1]. In 1997, the
"disease" was named "vanishing white matter disease"
and diagnostic criteria were described
[2]. No diagnostic laboratory
tests for the disorder exist, and the diagnosis is based on clinical and MR
imaging findings [2,
3]. We present clinical and
radiologic findings of a patient with vanishing white matter. After vanishing
white matter was described in 1993 as a distinct entity
[1], five studies about this
disorder were carried out by two different author groups. Three groups are
from The Netherlands
[2,3,4],
and two are from the United States
[5,
6].
Case Report
A 5-year-old girl was admitted to the children's neurology department for
slowly progressive ataxia after a motor vehicle crash that occurred 18 months
before presentation. After the accident, in which she was in the vehicle but
was not injured, she developed an unsteady gait. The patient's perinatal
period and infancy were uneventful. She attained normal developmental
milestones up to 4 years old. Neurologic examination revealed normal
orientation and cooperation. She had normal cranial nerves, eye movements,
fundi, muscle tone, and strength. Tendon reflexes were brisk, with bilateral
Achilles' clonus. The patient had a severe gait ataxia, dysarthria, and a
bilateral intention tremor. Her head circumference was normal. No nerve fiber
involvement was seen on electromyography. Serum immunoglobulins,
-fetoprotein, ammonia, lactate, pyruvate, vitamin B12 and
folic acid levels, and urine and plasma amino acids were normal.
On MR imaging, diffuse white matter hyperintensity involving arcuate fibers
was noted on T2-weighted images. Hypointense areas, which have signal
intensity values close to that of cerebrospinal fluid (CSF), were interspersed
within the hyperintense white matter on fluid attenuated inversion recovery
(FLAIR) images (Fig.
1A,1B,1C,1D).
Basal ganglia and internal and external capsules were spared. Corpus callosum
involvement was seen on T2-weighted images as hyperintensity, mainly in the
splenium.
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Fig. 1B. —5-year-old girl with vanishing white matter. T2-weighted MR image
shows diffuse white matter hyperintensity involving arcuate fibers. Basal
ganglia and internal and external capsules are spared.
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Fig. 1C. —5-year-old girl with vanishing white matter. Fluid attenuated
inversion recovery MR image shows hypointense (similar to cerebrospinal fluid
intensity) areas interspersed within diffuse white matter hyperintensity.
|
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Cerebral atrophy was not present. Slight atrophic changes in cerebellar
hemispheres and the vermis were found, but cerebellar white matter was not
involved.
Discussion
Clinical and radiologic properties are similar in reported cases of
vanishing white matter; therefore, diagnostic criteria have been established.
The initial reports suggested that the disorder is seen in early childhood,
but adolescent onset was reported later
[3]. Clinical presentation is
nearly the same in all patients: a minor head trauma or infection triggers the
disorder, and remarkable deterioration begins. Recovery is usually slow and
incomplete. These symptoms are repeated in episodes, and the result is severe
neurologic disability. Mental functions are usually spared but are not
completely intact. Unexplained coma status may be seen in patients at early
ages [2,
3]. Some cases in the
histopathologic literature were identified as cavitary leukoencephalopathy.
Clinical and histopathologic features of these cases were consistent with
vanishing white matter disease but their MR imaging findings were not
available [3]. According to
these reports, death occurred in a few months to 14 years. Histopathologic
findings are rarefaction of the white matter, which is more severe in the
deeper portions, microcystic changes in the white matter close to the lateral
ventricles, and spongiform changes in the arcuate fibers and the corpus
callosum. Severe loss of myelin with spongy alterations occurs, but neuronal
loss is not present [2,
3]. Research on the disorder
has mainly concentrated on its genetic aspects
[7]. Genetic features are not
clearly understood, but some clues suggest autosomal recessive inheritance
[3]. A recent report revealed
that the gene for this disorder is located on chromosome 3q27
[4]. No information about its
relation to enzyme defects exists.
MR imaging features have been previously described
[2,
3]. White matter, including
arcuate fibers, is diffusely involved. As the disorder progresses, white
matter is replaced by CSF and vanishes. Involved regions are seen as
low-signal-intensity areas close to CSF on proton density-weighted and FLAIR
sequences. Sometimes the intensity of the involved areas is not as low as the
intensity of CSF. This difference is explained as rarefaction, not complete
vanishing of the white matter. Eventually, fluid-filled cavities form in the
white matter. MR spectroscopy gives important additional information. The
spectrum of the nonaffected gray matter is near normal but a small amount of
lactate and glucose is present. Affected white matter shows decrease of all
metabolites but only lactate and glucose peaks
[2,
3].
Clinical and radiologic diagnostic criteria of the disorder were proposed
by Van der Knaap et al. [2] in
1997 and were revised in 1998
[3]. According to these
criteria, initial psychomotor development is normal or mildly delayed.
Neurologic deterioration shows a chronic, progressive, and episodal course.
These episodes may follow minor head trauma or infection. Deterioration may
lead to lethargy or coma. The main neurologic symptoms are cerebellar ataxia
and spasticity. Optic atrophy is not a rule but may be seen. Epilepsy may be
present but is not a predominant feature. Mental functions may be influenced
but not as severely as motor functions. On MR imaging, symmetric involvement
is present within the hemispheres. The affected parts show signal intensity
similar to that of CSF on FLAIR, proton density-weighted, T1-weighted, and
T2-weighted sequences. White matter may be involved completely. Cerebellar
atrophy may be mild or severe, and the vermis is primarily involved.
A few disorders showing diffuse white matter involvement including arcuate
fibers may be considered in the differential diagnosis. These disorders can be
differentiated from the vanishing white matter on the basis of clinical and MR
imaging characteristics. Infantile leukoencephalopathy, which is also known as
Van der Knaap's disease, may have a similar MR imaging appearance. Age of
onset, presence of macrocephaly, and temporal and frontal cysts are important
clues for its diagnosis. Canavan's disease also shows diffuse white matter
involvement, but infantile onset, presence of macrocephaly, and severe delay
of mental and motor development is a distinguishing feature. Also, no areas
showing signal intensity values equal or close to that of CSF are found within
the white matter on MR imaging. MR spectroscopy features are also diagnostic
for Canavan's disease. Alexander's disease may be another disorder that could
be considered in the differential diagnosis, but its age of onset, clinical
course, and presence of macrocephaly exclude it
[2,
8].
The clinical presentation of our patient was typical for vanishing white
matter. On MR imaging, FLAIR sequence revealed diffuse white matter
hyperintensity and interspersed areas of low signal intensities similar to CSF
(Fig.
1A,1B,1C,1D).
These findings suggested that the disorder had progressed enough to show
diagnostic MR features.
In conclusion, despite being rare and a recently reported disorder,
vanishing white matter may be confidently diagnosed by its clinical and MR
imaging findings.
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Introduction
Case Report
