Metachromatic leukodystrophy

Clinical History

A 22-month-old boy was hospitalized as a result of retarded neuropsychomotor development.
In the past three months he had lost the motoric skills achieved such as fluid crawling; cognitive levels had been delayed also.
MRI was performed suggesting a diagnosis which was analytically confirmed with a severe decrease of arylsulfatase A activity.

Imaging Findings

MRI showed diffuse hyperintesity in the deep periventricular white matter in FLAIR and T2-weighted images with preservation of the subcortical white matter (Fig. 1).
Mild hyperintensity in the cerebellar hemispheres was also identified (Fig. 2).
No thalamic or brainstem involvement was observed.
There was no evidence of restriction in diffusion weighted imaging (DWI) (Fig. 3).
T2W images showed the tigroid pattern on axial plane. It results from hypointense stripes within demyelinated periventricular white matter due to the sparing along venules (Fig. 4).

Discussion

Metachromatic leukodystrophy (MLD) is the most common hereditary leukodystrophy with an autosomal recessive inheritance pattern [1-4]. However, the prevalence is estimated at 1/100 000 newborns [3]. It is a lysosomal disorder, which is caused by a deficiency in the enzyme activity of arylsulfatase-A (ARSA). It is characterized by the accumulation of fats called sulfatides in myelin-producing cells. This accumulation causes symmetric demyelination of white matter in the peripheral and central nervous systems, with initial sparing of the subcortical U fibres [1-3].

Clinically, the differences in the residual enzyme activity cause a wide spectrum in the clinical course and the age of onset of the disease. It has been classified into three types depending on the age of onset: late-infantile, juvenile and adult forms.
Late-infantile is the most common form of metachromatic leukodystrophy, which accounts for 50–80% of all cases. It typically occurs between 18-24 months, gait disturbance being the first recognizable feature. Other clinical symptoms are rapid deterioration of motor and intellectual functions, impaired swallowing, loss of vision, convulsions and dementia. The diagnosis is confirmed by testing a drop of arylsulfatase activity in peripheral leukocytes or urine [1-3].

Radiographic findings are characterized by bilateral symmetrical confluent areas of signal change in the periventricular white matter and semioval centres. Particulary around the atria and frontal horns, with sparing of subcortical U fibres (butterfly pattern) [1-4]. Some studies say that demyelination is more prominent in the occipital region and the direction of the demyelinating process seems dorsofrontal [3].

On MRI, it demonstrates high signal intensity on T2W sequences, with numerous hypointense linear structures in a "tigroid pattern" axial plane (due to the sparing along venules).
On T1W sequences the affected areas are low signal intensity and absence of contrast enhancement is characteristic. However, some cases may show a linear punctate enhancement pattern within lesions. Multiple cranial nerve enhancement has been reported [4].
MR spectroscopy is a very useful technique, demonstrating elevation of myoinositol and choline with relatively preserved NAA. There are no evidence of restriction in diffusion weighted imaging.

In addition, progression of the disease can lead to cortico-subcortical atrophy and hydrocephalus ex-vacuo. Other common manifestations are lesions of the corpus callosum, internal capsule, corticospinal tract, brainstem and cerebellum white matter.

Finally these patients manifest a rapid and devastating clinical course. Death occurs within 6 months to 4 years after the onset of symptoms. Currently, feasible therapeutic options are limited to palliative and supportive treatments [1, 2].

Differential Diagnosis List

Final Diagnosis

Late-infantile metachromatic leukodystrophy

URL:	https://www.eurorad.org/case/13190
DOI:	10.1594/EURORAD/CASE.13190
ISSN:	1563-4086