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Brain & Development 1995; 17:280-2

Case report

A sporadic case of very slow progressive leukodystrophy
involving the cerebellar peduncles
Seiichi Sugama *, Kaoru Kusano
Department of Pediatrics, Tokyo Metropolitan Kita Medical Rehabilitation Centerfor the Handicapped, Tokyo, Japan
Received 5 December 1994; accepted 11 April 1995

We describe a patient with infantile onset ieukodystrophy involving the cerebeilar peduncles. She had mild
mental retardation, spastic diplegia and mild cerebellar ataxia. The peripheral nerves seemed to be normal. The
characteristic MRI findings in this case were extensive lesions of the white matter involving the cerebellar
peduncles. In addition there was ventricular enlargement with a markedly decreased volume of the white matter and
a hypoplastic corpus callosum. The clinical and laboratory findings imply that the white matter lesions in this
patient were the result of delayed myelination rather than demyelination. The patient was evaluated for known
metabolic and degenerative diseases, but no abnormalities were observed. Her symptoms and neuroimaging findings
did not fit the criteria for any defined ieukod.ystrophy.
Keywords: Leukodystrophy; C e r e b e l l a r p e d u n c l e ; Hypoplastic corpus callosum

1. I N T R O D U C T I O N
The myelin disorders of childhood are rare diseases that
clinically involve increasingly severe neurological and psychological impairment. There are a number of unclassified
leukodystrophies [1-3]. We present a patient who showed
very slow progression of neurological symptoms with infantile
onset and diffuse white matter lesions involving the cerebellar peduncles. The progression of her symptoms and neuroimaging findings were clearly different from those of known
leukodystrophies.

2. CASE R E P O R T
A female infant was born to healthy nonconsanguineous
parents after a 32-week gestation period with an uneventful
pregnancy. Her birth weight was 1780 g and she had no
asphyxia. She exhibited a mild respiratory distress sign which
required oxygenation for 1 day. She had severe jaundice

* Corresponding author at: Department of Pediatrics, Tokyo Jikei
University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku,
Tokyo 105, Japan. Fax: (81) (20) 3-3435-8665.
0387-7604/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved

SSDI 0387-7604(95)00037-2

which needed phototherapy and exchange blood transfusion.
She did not have a severe hypoxic episode during this period.
Otherwise, the course was uneventful. Her mother has no
history of spontaneous abortion or still birth. One older
healthy male sibling was aged 21 years. There was no history
of epilepsy, a neurodegenerative disease or other neurological disease in the extended family.
Limitation of hip joint motion was noticed at age 2 months.
Her development had been delayed since the infantile period. She could sit with support at age 10 months, started to
walk at age of 2 years and uttered meaningful words at age 2
years. Examination by an orthopedist did not reveal any
abnormalities. She had been trained at a special institution
because of her psychomotor developmental delay from 3
years of age. She first visited our hospital at age 14 because
of increasing difficulty in walking. She was found to have
spasticity of the legs and left equinovarus. CT-scanning
demonstrated periventricular hypodensity. At age 18, she was
admitted for an Achilles tendon elongation operation because of the exacerbated equinovarus. There was no sign of
cognitive deterioration. She had never convulsed.
When examined at age 18, her head circumference was
54.5 cm (50th percentile), her weight 46 kg (50th percentile),
and her height 155 cm (75th percentile). She was nondysmorphic and no abnormalities were found on general examination. She was mentally slow, her full scale IQ being 62 (PIQ

Seiichi Sugama, Kaont Kusano ~Brain & Development 1995; 17:280-2
62, VIQ 72). Cranial nerve functions were normal and eye
movements were slightly saccadic. Funduscopy revealed normal optic discs. Her hearing was normal. Dysarthria was not
present. She was spastic and hypertonic in the lower extremities. The tone in the arms was normal. The left lower
extremity was slightly weak. Tendon reflexes were increased
in the legs, with sustained clonus at the ankles. Bilateral
extensor plantar responses were present. Light touch and
pinprick sensation were normal and she could sense vibration. The finger to nose test revealed terminal oscillation.
The heel to knee test caused dysmetria that was predominant
in the left leg. Fine movement of the fingers was almost
normal. Her tandem gait was poor. There was no abnormal
involuntary movement.
The following blood parameters were measured and found
to be normal: complete blood cell count, electrolytes, glucose, blood gases, lactate, pyruvate, liver enzymes, ammonia,
creatine kinase, cholesterol, triglycerides, iipoproteins, vitamins E and B12, immunoglobulins, copper, ceruloplasmin,

281

thyroid function and very long chain fatty acids. The serum
anti-titers of cytomegalovirus, herpes virus, HTLV-1 and
toxoplasmosis were normal. The following urine parameters
were measured and found to be normal: amino acids, organic
acids and N-acetylaspartic acid. The patient was found to
have the normal 46 XX female karyotype. The activities of
lysosomal enzymes, including galactocerebroside-/3-galactosidase, /3-hexosaminidase and arylsulfatase A, in leukocytes
were all within normal range. CSF examinations were all
normal, i.e., protein concentration, lactate, pyruvate, IgG,
myelin basic protein (MBP), neuron specific enolase (NSE),
and virus titers. No oligoclonal bands were detected. Motor
and sensory nerve conduction velocities were normal. The
brainstem auditory evoked potential (BAEP) and EEG were
normal. Visual evoked potentials were not examined. CTscanning demonstrated ventricular dilatation without cortical
atrophy, and hypodensity of the periventricular white matter,
centrum semiovale and cerebellar peduncles (Fig. la). No
further deterioration of the brain parenchyma was observed

Fig. 1. Head CT-scan at age 18 years (a). Magnetic resonance imaging at age 18 years, 1.5-T, Tlrweighted image (TR 60/TE 15), sagittal (b),
axial (D. T2-weighted image (TR 2000/TE 80), axial (e-e). a: The white matter of the cerebrum shows abnormal areas of decreased density, b:
The corpus callosum is complete but diffusely diminished in size (arrows). c: Marked, diffuse, rather symmetrical areas of abnormal intensity in
the white matter of the cerebrum is seen. The subcortical U-fiber seems to be affected as well (small arrows), d: The periventricular white matter
adjacent to the frontal and occipital horns shows abnormal areas of high intensity. The internal capusule is spared, e: Symmetrical areas of
abnormal intensity is seen in the bilateral cerebellar peduncles (arrows). f: The volume of the white matter is severely diminished.

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Seiichi Sugama, Kaoru Kusano / Brain & Development 1995; 17:280-2

on serial CT-scanning (1990 and 1994). MRI demonstrated
diffuse abnormal high intensity in almost all of the white
matter and bilateral cerebellar peduncles, in a T-2 weighted
image. The U-fiber seemed to be involved as well. The
corpus callosum was diffusely diminished in size (Fig. lb-f).

3. D I S C U S S I O N
The patient was evaluated for known metabolic and degenerative diseases. Major leukodystrophies, such as
adrenoleukodystrophy, metachromatic leukodystrophy,
globoid cell leukodystrophy and Canavan disease, were ruled
out by measurement of very long chain fatty acids, arylsulfatase A, galactocerebroside-/3-galactosidase and N-acetylaspartic acid, respectively. The patient did not present macrocephaly, which is characteristic of Alexander disease [4].
Other metabolic and infectious diseases which could represent leukodystrophy, such as mitochondrial disease [5],
phenylketonuria, subacute sclerosing panencephalitis, postinfectious encephalopathy [4] and well-defined lysosomal storage diseases, were ruled out by the characteristic clinical
symptoms and blood exam results.
The patient presented a very slow progressive or static
course. She had mild mental retardation, spastic diplegia and
mild cerebellar ataxia. There was no peripheral nerve involvement. These clinical findings are somewhat reminiscent
of those in Pelizaeus-Merzbacher disease (PMD). PMD is
considered to be a deficiency of proteolipid protein, a constituent of the myelin sheath, and representative of congenital hypomyelination of the central nervous system [6]. Although PMD is primarily an X-linked recessive disorder, the
clinical course is slow and there is an apparent lack of
progression with onset during the first year of life, as in our
case. However, PMD involves rotatory nystagmus and more
profound cerebellar ataxia, and BAEP reveals characteristic
abnormality [4,7].
The characteristic MRI findings in our case were extensive lesions of the white matter involving the cerebellar
peduncles. In addition, there was ventricular enlargement
with a markedly decreased volume of the white matter and a
hypoplastic corpus callosum. Dys-or de-myelination mainly
affects the long myelinated tracts such as the pyramidal and
spinocerebeUar fascicles in leukodystrophies [4]. Some
leukodystrophies affect the white matter of the cerebellum,
but no reports have mentioned involvement of the cerebellar
peduncles [1-4,8-10]. A complete but atrophic corpus callosum results from an insult to the cortex or white matter after
formation of the corpus callosum is complete (18-20 weeks).
Patients with dysmyelinating diseases, Alexander disease and
PMD have been reported to have marked atrophy of the
corpus callosum because of poor myelin development [11]. In
conjunction with the findings of very slow progression of the

clinical course and a decreased volume of the white matter
with a hypoplastic corpus callosum, our case is possibly
suggestive of developmental disturbance of myelin rather
than a myelinoclastic process. The normal value of protein,
IgG, NSE and MBP in CSF are also consistent with delayed
myelination rather than demyelination.
Patients with progressive white matter diseases which do
not fit the criteria for any defined leukodystrophy is not
extraordinary. However, we could not find reports of a similar clinical presentation and similar neuroimaging to those in
our case. Although we present only one case, the current
report will hopefully lead to the accumulation of similar
cases and thereby new findings in the future.
ACKNOWLEDGEMENTS We are grateful to Drs. Akira Akatsuka,
Yukikatsu Ochiai and Shigenobu Tsuzura, Tokyo Metropolitan Medical and Rehabilitation Center Hospital, and Dr. Kihei Maekawa,
Tokyo Jikei University School of Medicine, for their helpful comments.

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