Infantile Multiple
Sclerosis with
Extensive White
Matter Lesions
Yasufumi Maeda, MD*,
Ikuko Kitamoto, MD*,
Toru Kurokawa, MD*, Kohji Ueda, MD*,
Kanehiro Hasuo, MDt, and
Katsuyoshi Fujioka, MD§

onset before the age of 3 years [2-5]. Shaw and Alvord
reported the youngest known MS patient who manifested
relapsing neurologic symptoms at 10 months of age [5].
Characteristic computed tomographic (CT) findings in
MS are low-density areas in the deep white matter, optic
nerves, periventricular regions, and brainstem [6]. Magnetic resonance imaging (MRI) is a more sensitive procedure than CT for detecting MS lesions [7].
We report an MS patient with onset at 13 months of age;
the diagnosis was definitely established at 23 months of
age. Although he experienced the second youngest onset
reported, our MS patient was diagnosed at a younger age
than any previous patient. CT and MRI, unlike typical MS
findings, revealed extensive white matter lesions.

Case Report
A boy developed a right hemiparesis at 13 months of
age which disappeared spontaneously at 19 months.
Computed tomography and magnetic resonance imaging revealed extensive low-density areas with left-sided
predominance in the white matter at age 17 months.
The flash visual evoked potential revealed abnormal
findings of wave V. At 20 months of age, paraplegia
developed; as it receded 3 months later, a left hemiparesis developed. At that time, computed tomography
demonstrated a new low-density area in the right
centrum semiovale which disappeared at 28 months of
age concomitant with the recovery of the left hemiparesis. Overall, he had experienced 3 independent
episodes, 2 of which corresponded to each of the lesions
depicted by computed tomography and magnetic resonance imaging. Multiple sclerosis was diagnosed at 23
months of age which is earlier than in any previously
reported patient. Unlike most typical findings of multiple sclerosis on computed tomography and magnetic
resonance imaging studies, our patient demonstrated
extensive white matter lesions.
Maeda Y, Kitamoto I, Kurokawa T, Ueda K, Hasuo K,
Fujioka K. Infantile multiple sclerosis with extensive
white matter lesions. Pediatr Neurol 1989;5:317-9.

Introduction
Childhood multiple sclerosis (MS) is rare and onset
before the age of 10 years occurs in only 0.2-0.4% of all
patients [1]. Only 4 MS patients have been reported with

From the Departments of *Pediatrics and tRadiology; Faculty of
Medicine; Kyushu University; Fukuoka, Japan; ~Division of Special
Education; Joetsu University of Education; Niigata, Japan;
§Department of Pediatrics; Karatsu Red Cross Hospital; Saga, Japan.

This 18-month-old boy was admitted to Kyushu University Hospital
because of a right hemiparesis and for the evaluation of peculiar CT
findings.
Patient history, early developmental milestones, and family history
were noncontributory. He had been well until 13 months of age when
he began to have difficulty using his right hand. One month later, he
began to walk with no pre-existing hemiparesis. No preceding infection
had occurred during the month prior to symptom onset. Further walking difficulties developed at 15 months of age; 2 months later, he was
admitted to the Karatsu Red Cross Hospital. The physical examination
was normal. Neurologic examination demonstrated a right hemiparesis.
CT disclosed low-density areas with left-sided predominance in the
white matter (Fig 1A).
He was admitted to Kyushu University Hospital at 18 months of age.
Neurologic examination confirmed a right hemiparesis, with hyperactive deep tendon reflexes, increased muscle tone, decreased muscle
strength, Babinski sign, and ankle clonus on the right side. Cranial
nerves were normal, including ocular fundi. No bowel or bladder disturbance was observed. His intelligence and emotional state appeared
appropriate for age.
Complete blood cell count, electrolytes, blood gas analysis, and
blood chemistry (i.e., creatine kinase, blood glucose, free fatty acid,
copper, ceruloplasmin, lactate, pyruvate, and ammonia) were all within
normal limits. Plasma and urine quantitative amino acid analysis was
normal. Antinuclear factor was not detected. Antibody titers for measles, rubella, and herpesvirus were not elevated. Lymphocyte reactions
of monoclonal antibodies for CD4 and CD8 were normal. The cerebrospinal fluid (CSF) revealed 1 lymphocyte/mm3, protein 25 mg/dl,
glucose 48 mg/dl, lactate 8.7 mg/dl, and pyruvate 0.69 mg/dl. Leukocyte lysosomal enzyme assay revealed normal values of D-galactosidase, arylsulfatase A, and galactosylceramidase. C22-C26 long-chain
fatty acid concentrations were normal in the plasma and erythrocyte
membranes. Electron microscopic examination of the skin revealed no
abnormal findings. MRI demonstrated the site and extent of cerebral
lesions which were compatible with CT findings at 17 months of age
(Fig IB). Electroencephalography, brainstem evoked potentials, and
motor nerve conduction velocity were normal. Flash visual evoked
potentials (VEP) revealed abnormality of wave V. At 19 months of age,
the right hemiparesis gradually disappeared without any specific
therapy.

Communications should be addressed to:
Dr. Maeda; Department of Pediatrics; Faculty of Medicine;
Kyushu University; 3-l-l, Maidashi, Higashi-ku;
Fukuoka gl2, Japan.
Received May 1, 1989; accepted August 14, 1989.

Maeda et al: Infantile Multiple Sclerosis

317

Figure 1. (A) CT at 17 months o] age revealed hypodense areas in the posterior white matter extending asymmetrically mt~
the frontal areas (arrows). (B) T2-weighted MR[ (TR = 2,000 ms. TE = 80 ms) at 18 months of age demonstrated hyperintensities at almost the same lesion on CT at 17 months (arrows). (C) CT at 23 months t~f age demonstrated the appearance
of a hypodense area in the right centrum semiovale (arrows) with a decreased white matter hypodense area compared with
the CT at 17 months of age. (D) T2-weighted MRI demonstrated hFperintense areas in the right centrum semiovale (arrows).
white matter, and periventrieular regions. (E) Ti-weighted MRI (TR = 600 ms. TE = 20 ms) revealed hypointense areas at
the bilateral anterolateral angle of the lateral ventriele (arrows), (F) At 28 months of age, CT revealed the disappearance c!/
a hypodense area in the right eentrum semiovale with the appearance ~['a right frontal hypodense area (arrow~).

About 1 month after the resolution of the right hemiparesis, flaccid
paraplegia gradually occurred without any history of trauma or infection. Thyrotropin-releasing hormone was administered (8 mg/day) with
no discernible effects. At 21 months of age, paraplegia gradually became spastic and disappeared 2 months later. CT at 21 months of age
revealed a low-density area in the white matter which decreased in size
compared to CT at 17 months of age. Upon further examination, we
were unable to detect the foci.
At 23 months of age, left hemiparesis spontaneously and gradually
developed concomitantly with the recovery of paraplegia. There was no
history of pre-existing infection or trauma. He was diagnosed with
clinically definite MS. CSF revealed normal values for protein and
glucose and normal myelin basic protein 6.1 mg/dl. Oligoclonal bands
(OB) and elevated immunoglobulin G (IgG) in CSF were not observed.
CT disclosed a new low-density area in the right centrum semiovale
(Fig IC). MRI more clearly defined the lesions observed initially on
CT, as well as the periventricular lesions at the anterolateral angle of
the lateral ventricle on both sides (Figs ID, IE). Flash VEP revealed a
distinctly split wave V. The left flaccid hemiparesis gradually became
spastic at 25 months of age and then disappeared 3 months later when
the low-density area in the fight centrum semiovale disappeared and a
new low-density area appeared in the right frontal region on CT
(Fig IF). At present, he remains asymptomatic at 37 months of age.

Discussion
Our patient suffered 3 i n d e p e n d e n t attacks w h i c h consisted o f right hemiparesis, paraplegia, and left h e m i paresis. E a c h episode was characterized by a relatively

318 PEDIATRIC NEUROLOGY Vol. 5 No. 5

rapid d e v e l o p m e n t and persistence o f findings for several
months, f o l l o w e d by spontaneous remission.
In general, the diagnosis o f M S primarily depends on
clinical criteria and additionally on the paraclinical evid e n c e of the lesions, such as in the e v o k e d response studies
and tissue i m a g i n g procedures. Laboratory e x a m i n a t i o n o f
C S F for OB and increased production of IgG is also valuable for a timely diagnosis of M S [8]. In our patient, there
were neither C T nor M R I findings suggestive o f tumor
and/or a vascular disorder. S l o w viral infections or imm u n e disorders were e x c l u d e d by clinical and laboratory
data. Hereditary degenerative disorders were e x c l u d e d according to the results o f the lysosomal e n z y m e s , longchain fatty acid analysis, and electron m i c r o s c o p i c skin
e x a m i n a t i o n [9]. Fluctuating neurologic s y m p t o m s h a v e
been reported in patients with mitochondrial encephalom y o p a t h y [10,11]; however, blood gas analysis and blood
and C S F values for lactate and pyruvate did not suggest
mitochondrial e n c e p h a l o m y o p a t h y . Our patient's clinical
pattern is c o m p a t i b l e with the MS criteria reported by
Poser et al. [8].
The cerebral hemispheric lesions o f MS are c o m m o n l y
multiple, typically situated in the deep white matter and
periventricular regions, and often a s y m p t o m a t i c [12]. At
17 months of age, C T findings in our patient r e v e a l e d

extensive white matter lesions mimicking those of leukodystrophies, such as metachromatic leukodystrophy and
adrenoleukodystrophy [6].
Compared to clinical symptoms and the foci on CT and
MRI, the right hemiparesis probably corresponded to leftsided predominance of the lesion in the white matter,
whereas the left hemiparesis corresponded to the lesion of
the fight centrum semiovale that disappeared at remission
of symptoms. No symptoms corresponded to the lesions
of other white matter and periventricular regions. We
could not detect the foci of paraplegia, although clinically
it was suggestive of the lesion in the lower spinal cord.
The usefulness of flash VEP, as well as the pattern VEP
in MS patients, is well known [13]. As for flash VEPs in
our patient, latencies and wave forms of waves III and IV
were normal but the subsequent negative wave forms
(wave V) revealed some obvious differences between
those at 18 and 23 months of age. This f'mding probably
signifies that there are some changes in the visual pathway
of each stage.
Only 4 MS patients with onset before the age of 3 years
have been reported [2-5]. Shaw and Alvord reported the
youngest MS patient who was diagnosed at autopsy; the
patient had presented with relapsing neurologic symptoms
since 10 months of age [5]. The first episode in our patient
began at 13 months of age. A diagnosis of clinically
definite MS was made at 23 months of age which was
younger than in any previously reported MS patient.

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We would like to thank Dr. Takuro Kobayashi,Departmentof Neurology, Kyushu University, for analysis of lysosomal enzymes and fatty
acids, Dr. Tsunekazu Yamano, Department of Pediatrics, Shiga Medical School, for electron microscopic skin examination, as well as
Prof. Brian T. Quinn, Kyushu University, for his comments on our
manuscript.

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