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Computed tomography in late-infantile metachromatic leukodystrophy.

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Computed Tomography in LateInfantile Metachromatic Leukodystrophy
Ferdinando S . Buonanno, MD, Marshall R. Ball, MD, D. Wayne Laster, MD,
Dixon M. Moody, MD, and William T. McLean, MD
Computed tomography of 2 patients with late-infantile metachromatic leukodystrophy (MLD) demonstrated generalized white matter lucency and moderate ventricular enlargement. CAT scan findings in other white matter diseases
likely to be confused clinically with MLD are sufficiently dissimilar to allow differentiation.
Buonanno FS, Ball MR, Laster DW, et al: Computed tomography in lateinfantile metachromatic leukodystrophy. Ann Neurol 4:43-46, 1978
Metachromatic leukodystrophy (MLD) is the m o s t
c o m m o n of the hereditary leukodystrophies, diseases
characterized by extensive dysmyelination of nervous system white matter. We have recently performed computed tomography in 2 patients with
proved late-infantile MLD. T h e reports presented
here include the second proved case of MLD in a
black child.
Case Reports
Patient 1
A white girl 2 years 9 months old had developed difficulty
walking and irritability five to six months prior to evaluation. The product of a premature labor and delivery at 39
weeks, the patient weighed 2.38 kg at birth and required a
ten-day incubation. She is the only child of a healthy 38year-old mother. Although she was able to speak single
words at 1 year of age and spoke relatively well by lY2
years, her motor development was retarded, clumsy walking beginning at l$$years of age. After she had achieved a
reasonably normal gait by 2 years, the patient’s walking
ability regressed. Six months prior to evaluation she became irritable, stopped walking, and tended to hold her left
leg stiffly and her arms in a flexed posture; these findings
were accentuated by crying. Although no spontaneous seizure activity was observed, the patient demonstrated
stimulus-sensitive myoclonus in the months preceding
hospitalization. There is no family history of degenerative
neurological disorder.
Examination revealed a small, thin, pale, irritable child
with a normal head circumference of 49 cm (sixty-fifth percentile) who was unable to support her weight in a standing
or sitting position. Scissoring was present in suspended position. All four limbs were hypertonic, left greater than
right, predominating in the flexor muscle groups in the
arms and the extensor groups in the legs. Reflexes were
From the Department of NeuroIogy and the Section of
Neuroradiology, Bowman Gray School of Medicine of Wake
Forest University, Winston-Salem, NC.
normal in the upper extremities and increased in the lower;
plantar responses were extensor bilaterally. There were no
obvious sensory deficits. Except for a mild left exotropia
dating from birth and a nasal character to the speech and
cry, there were no cranial nerve deficits, retinal abnormalities, or nystagmus.
Automated serum biochemical profile, complete blood
count with differential, and urinalysis were within normal
limits. Arylsulfatase-A determinations revealed no detectable activity on one occasion and 0.3 U per liter (N> 5) on
a second testing. Chest and sku11 radiographs were normal.
Roentgenograms demonstrated a dextroconcave scoliosis
of the thoracolumbar spine and an exaggerated thoracic
kyphosis.
The electroencephalogram was abnormal, with independent left and right high-voltage theta and delta activity,
maximum in the posterior head regions; photic stimulation
produced little discernible driving response. Peripheral
nerve conduction velocities were markedly slowed, being
13, 25, and I1 m/sec at the right median, ulnar, and
peroneal nerves, respectively.
The findings on CAT scan are demonstrated in Figure 1.
There is marked generalized lucency of the white matter.
Patient 2
A black girl 2 years 4 months old was evaluated for a gait
disturbance of five months’ duration. She is the second
child, born after a full-term, uncomplicated pregnancy and
delivery to a healthy 25-year-old mother. Birth weight was
2.38 kg. The child’s early development was normal: she sat
at 7 months, walked at 10 months, and talked and was toilet
trained at 1 year. At 2 years she began complaining of pain
in her feet and knees. H e r gait became broad based and
stiff legged; initially her walk improved during the day, but
later the gait difficulty persisted at all times. No changes in
behavior, speech, or consciousness were observed.
Family history revealed that her father is asthmatic and
Address reprint requests to Dr Ball, Department of Radiology,
Bowman Gray School of Medicine of Wake Forest University, 300
S Hawthorne Rd, Winston-Salem, NC 27103.
Accepted for publication Jan 24, 1978.
0364-5134/78/0004-0lO7$01.25 @ 1978 by Ferdinando S. Buonanno 43
F i g I . Computed tomography (three adjacent 1.I cm scans) of
Patient 1 demonstrates marked lucency of the white matter
without lobar or r,asrulardrstribiition. There is moderate i'entrirular enlargement with normal cortex. (EM1 Mark 1 Sranner. 140 KVP, +L 28, WW40, no contra.rt infusion.)
F i g 2. Compilted tomography (three adjacent I . 1 rm scans! of
Patient 2 demonstrates generalized white matter ltlrenry similar
to hut less extensii,e than that in Patient I. There is moderate
I entrrrufarenfargement.(EM1 Mark 1 Scanner, 140 KVP, + L
18. WW40,no contra.rt infusion.!
44 Annals of Neurology
Vol 4 No 1 July 1978
her 8-year-old brother is normal. There is no family history
of degenerative neurological disorder.
Examination revealed a child small for age, weighing 9.4
kg with a height of 51 cm ( < third percentile). General
physical examination was otherwise within normal limits.
Neurological examination demonstrated that the gait was
broad based and spastic. Muscle strength was decreased in
the lower extremities; tone was increased in the proximal
extensor groups bilaterally. Neither atrophy nor fasciculations were present. Although reflexes were normal in the
upper extremities, the knee and ankle jerks were hyperactive. Plantar responses were extensor bilaterally. Sensory
testing was normal, as was cranial nerve function. Two and
a half months after the initial evaluation, the patient demonstrated greater spasticity of the legs but was still walking.
Peroneal nerve conduction velocities were slightly di-
minished at 40 d s e c . Urine arylsulfatase-A determinations
were 0.2, 0.6, and 0.4 U per liter ( N > 5 ) .
CAT scan demonstrated lucency of the white matter
throughout the hemispheres (Fig 2).
Discussion
MLD is inherited as an autosomal recessive disorder
[12]. Gustavson and Hagberg [7] have estimated that
the late-infantile form of MLD occurs once in 40,000
births in northern Sweden. The genetic defect results
in reduction or absence of normal arylsulfatase-A, a
lysosomal enzyme that hydrolyzes the sulfate group
from sulfatide in cell membranes. A sensitive and
accurate test for the diagnosis of MLD is demonstration of low to absent arylsulfatase-A in the urine [ 11,
leukocytes [14], or cultured fibroblasts [15].
CAT scanning in our patients with late-infantile
MLD (see Figs 1, 2 ) demonstrated a characteristic
low-density lesion involving the entire centrum ovale
and corresponding to the classically recognized loci
of histological involvement. The white matter lucency in these patients had values from l l to 19 EM1
units and was relatively homogeneous, involving the
subcortical white matter, with a scalloped lateral
perimeter. The findings indicated no vascular o r
lobar distribution but suggested the presence of
periventricular fiber sparing. There was minimal ventricular dilatation, suggesting atrophy. No contrast
enhancement was demonstrated after intravenous infusion of iodinated contrast medium. N o mass was
present.
CAT scan diagnosis of white matter disease in an
unclassified demyelinating disorder was described in
1974 by Davis and Pressman [2]. New and Scott [13]
found white matter lucency due to leukodystrophy in
a 14-month-old retarded girl with macrocephaly in
whom poor neurological development had dated
from birth. Harwood-Nash and Fitz [9]illustrated a
single CAT scan showing MLD in a patient of unspecified age.
Recently Robertson et a1 [16] reported in detail
the CAT scan findings in 3 patients with leukodystrophy. All 3 had abnormal scans. Two patients had
sudanophilic leukodystrophies and 1 had the juvenile
form of MLD. The scan in the last patient demonstrated symmetrical loss of central white matter with
a diffuse bilateral decrease in attenuation coefficients.
These findings are identical to those in the 2 patients
reported here.
While the exact cause of the decreased attenuation
in leukodystrophy is unknown, Robertson et a1
considered the accumulation of simple lipids and
demyelination. Lipid accumulation occurs in sudanophilic leukodystrophy, such as adrenoleukodystrophy, and may play a part in the decreased attenuation. In MLD, however, myelin catabolism does
not result in formation of simple lipids; the sulfatides that accumulate are distributed in both gray
and white matter [16], although the gray matter is
apparently unchanged on computed tomography.
Robertson and associates concluded that the most
important cause of low attenuation coefficients in
demyelinating disease is the loss of myelin and not
the accumulation of simple o r complex lipids.
Dubal and Wiggli [3] scanned 2 patients with MLD
using high- and low-kilovolt-peak CAT scans and calculated the effective atomic number (Z") of the white
matter. The Z" in a chronic case was increased, consistent with the two to five times' normal accumulation of sulfatides that is known to occur in MLD. In
an acute case the Z" calculations suggested edematous brain. Therefore, in addition to loss of myelin
and accumulation of simple lipids, edema may also
contribute to the CAT scan findings. Likewise, unknown alterations in protein and mineral content in
the affected areas may cause the observed abnormalities [ 161.
Sufficient cases of Schilder disease and adrenoleukodystrophy have been described to allow their
differentiation from MLD by CAT scan if white matter disease is found. Schilder disease commonly is
asymmetrical on CAT scan early in its course [ l o , 13,
161, although Lane [ l l ] reported finding usually
symmetrical, low-density lesions spreading anteriorly
from the occipitoparietal area, sometimes with a
contrast-enhanced anterior edge. In adrenoleukodystrophy, CAT scanning demonstrates large bilateral
(though not always symmetrical) low-density
periventricular lesions beginning in the occipital and
posterior parietal lobes [4-6, 161. Contrast enhancement of the advancing edge is common, and
progression to more diffuse involvement may occur
[51.
In patients with multiple sclerosis, white matter
lucencies on CAT scans have been described as circumscribed, irregular, asymmetrical areas usually located adjacent to the anterior horns, posterior horns,
and trigones of the lateral ventricles [2, 81. In contrast to the findings in multiple sclerosis, Schilder
disease, and adrenoleukodystrophy, the white matter
involvement in MLD is extensive, diffuse, and symmetrical, involving the entire centrum ovale, which
permits the presumptive CAT scan diagnosis of
MLD.
Demonstration of generalized white matter lucency and ventricular enlargement on CAT scans is
not specific for MLD. We have examined 2 teenage
sisters with proved systemic lupus erythematosus
who initially demonstrated generalized white matter
lucency and later ventricular enlargement secondary
to atrophy.
Computed tomographic examination is probably
Buonanno et al: CAT Scan in Metachromatic Leukodystrophy
45
not indicated in a patient strongly suspected of having MLD because arylsulfatase-A activity determinations are inexpensive, accurate, and specific for MLD.
In the undiagnosed patient, CAT scanning will differentiate MLD from Schilder disease or adrenoleukodystrophy. Hydrocephalus or bilateral subdural hematoma may be excluded as the cause of
symptoms. To date, all reported cases of MLD have
been abnormal on CAT scan.
Dr Ball is a James Picker Foundation Fellow.
References
1. Austin JH, Armstrong D, Shearer L, et al: Metachromatic
form of diffuse sclerosis: VI. A rapid test for the sulfatase
deficiency in MLD urine. Arch Neurol 14:259-269, 1966
2. Davis DO, Pressman GC: Computerized tomography of the
brain. Radio1 Clin North Am 12:297-313, 1974
3. Dubal L, Wiggli U: Tornochemistry of the brain. J Comput
Assist Tomogr 1:300-307, 1977
4. Duda EE, Huttenlocher PR: Computed tomography in adrenoleukodystrophy. Radiology 120:349-350, 1976
5. Eiben RM, DiChiro G: Computer assisted tomography in adrenoleukodystrophy. J Comput Assist Tomogr 1:308-3 14,
1977
46 Annals of Neurology Vol 4 No 1 July 1978
6. Greenberg HS, Halverson DEA, Lane B: CT scanning and
diagnosis of adrenoleukodystrophy. Neurology (Minneap)
27:884-886, 1977
7. Gustavson KH, Hagberg B: The incidence and genetics of
metachromatic leukodystrophy in northern Sweden. Acta
Paediatr Scand 60:585-590, 1971
8. Gyldensted C: Computed tomography of the cerebrum in
multiple sclerosis. Neuroradiology 12:33-42, 1976
9. Harwood-Nash DC, Fitz CR: Neuroradiology in Infants and
Children. St Louis, Mosby, 1976, p 501
10. Huckman MS, Fox JH, Ramsey RG: CT and degenerative
disease of the brain. Semin Roentgen01 1263-75, 1977
11. Lane B: Cerebral white matter disease on CT scanning. Lecture presented at the 14th Annual Meeting of the American
Society of Neuroradiology, Atlanta, GA, Apr 21, 1976
12. Moser H W Sulfacide lipidosis: metachromatic leukodystrophy, in Stanbury JB, Wyngaarden JB, Fredrickson DS
(eds): The Metabolic Basis of Inherited Disease. New York,
McGraw-Hill, 1972, pp 688-729
13. New PFJ, Scott WR: Computed Tomography of the Brain and
Orbit. Baltimore, Williams & Wilkins, 1975, pp 395-396
14. Percy AK, Brady RO: Metachromatic leukodystrophy: diagnosis with samples of venous blood. Science 161:594-595,
1968
15. Pilz H : Clinical, morphological and biochemical aspects of
sphingolipidoses. Neuropaediatrie 1:383-427, 1970
16. Robertson WC, Gomez MR, Reese DF, et al: Computerized
tomography in demyelinating disease of the young. Neurology (Minneap) 27:838-842, 1977
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