Diffusion-weighted magnetic resonance imaging findings in a case of metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is caused by insufficiency of arylsulfatase A resulting in impaired myelination. Diffusion magnetic resonance (MR) imaging features of this disease have been rarely reported. We report diffusion MR imaging of MLD in a 12-month-old male who presented with regression of milestones and progressive spasticity.

Introduction

Metachromatic leukodystrophy (MLD) (Scholz's disease) is an autosomal recessive lysosomal storage disease caused by the lack of arylsulfatase A (ASA). This enzyme is essential for the normal metabolism of sulfatides which are vital elements of the myelin sheath. In MLD, sulfatides accrue in many organs comprising brain, peripheral nerves, kidneys, liver, and gallbladder. Sulfatide collects in white matter of the central nervous system and peripheral nerves and causes progressive demyelination and lethal neurological symptoms. MLD is diagnosed biochemically by finding low levels of arylsulfatase in peripheral white blood cells and urine. MLD is classified into three main clinical forms on the basis of the age of onset. The most common and lethal form is the late-infantile form, which begins before 4 years of age typically presenting between 12 and 18 months of age, and patients die by the end of the first decade. The juvenile form of MLD comprises age onset between 4 and 16 years, whereas symptoms of adult MLD begin after puberty. The patients usually present with signs and symptoms of peripheral neuropathy and alterations in intelligence, speech, and coordination. The disorder is progressive with gait disturbance, quadriplegia, decerebration, and mortality by the age of 6 months to 4 years. Magnetic resonance (MR) imaging findings of the brain, especially T2-weighted imaging findings in the form of symmetric T2 hyperintense signal in the periventricular white matter, have been commonly reported in previous reports.[12] However, diffusion-weighted imaging (DWI) findings have been sparsely reported and we present MR imaging, especially DWI findings in a 12-month-old patient of MLD.

Case Report

A 12-month-old male presented with regression of milestones and progressive spasticity. MR imaging examination was performed and T2-weighted images revealed symmetrical hyperintensities, predominantly involving the deep white matter, corpus callosum with sparing of subcortical U-fibers [Figure 1]. The tigroid and “leopard skin” patterns of demyelination, which imply sparing of the perivascular white matter, were evident in the periventricular white matter and centrum semiovale [Figure 2]. The corpus callosum (genu and splenium) was also involved. Using the transverse single-shot echo planar diffusion-weighted MR imaging, diffusion MR images were acquired. On b = 1000 mm2/s images (heavily DWIs), hyperintensities were apparent in the deep white matter and corpus callosum with a signal intensity pattern the same as that of cytotoxic edema. On apparent diffusion coefficient (ADC) maps, the corresponding ADC values were low appearing hypointense [Figure 3]. Low levels of arylsulfatase in peripheral white blood cells and urine confirmed the diagnosis of MLD.

Figure 1

(a and b) Bilateral symmetrical butterfly-shaped T2 hyperintensities of the periventricular and deep white matter with relative sparing of the subcortical U-fibers

Figure 2

Sagittal T2-weighted image showing tigroid pattern of due to hypointense linear bands against the background of hyperintense white matter

Figure 3

The corresponding lesions showing restricted diffusion with high diffusion-weighted (a and b) and low apparent diffusion coefficient signal (c and d)

Discussion

Symmetric confluent areas of T2 hyperintense signal in the periventricular white matter with sparing of the subcortical U-fibers and with no enhancement in postcontrast images are the most frequent reported MR imaging findings of MLD. The tigroid and “leopard skin” patterns of demyelination are basically due to sparing of perivascular white matter and are visualized as dark spots or dark linear areas against a background of hyperintense white matter, giving the appearance of the skin of a leopard. The disease process also commonly affects the corpus callosum, internal capsule, and corticospinal tracts. The cerebellar white matter may also be affected and appears bright on T2-weighted images. In the advanced stage of MLD, diffuse cerebral atrophy frequently occurs, especially when the subcortical white matter is involved. It has been reported that the diminished activity of ASA leads to dysmyelination (failure of myelin breakdown and reutilization).[13] The corresponding distribution of the lesions on T2-weighted image and DWI in the present case strongly implied that the lesions on DWI were directly linked to the disease process. Restricted diffusion (cytotoxic edema) was seen on the echo planar sequence as hyperintensities on heavily DWIs (b = 1000 s/mm2 ) and low ADC values on ADC maps [Figure 3]. Sener[4] reported a similar diffusion MR imaging pattern on echo planar diffusion images of a patient with MLD with unchanged pattern on 6-month follow-up. Phillips et al.[5] also reported a similar pattern of restricted diffusion in patients of phenylketonuria which was hypothesized to be due to impaired myelination leading to reduced mobility of protons. Hence, in the present case of MLD, the restricted diffusion pattern perhaps was consistent with some breakdown of the white matter secondary to impaired myelination, which results in restricted mobility of protons leading to a diffusion MR imaging pattern similar to that of cytotoxic edema. To conclude, we report diffusion MR imaging of MLD done using the echo planar sequence which has been sparsely reported. More diffusion MR imaging studies of dysmyelinating disorders might improve our interpretation of the imaging features of these diseases.

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Nil.

Conflicts of interest

There are no conflicts of interest.