The author: Professor Yasser Metwally
http://yassermetwally.com
INTRODUCTION
November 8, 2009 — Metachromatic leukodystrophy is caused by deficiency of the enzyme arylsulfatase A, which hydrolyzes sulfogalactosylceramide, a lipid component of the myelin sheath. There is resultant sulfatide accumulation in the oligodendrocytes of the central and Schwann cells of the peripheral nervous system in patients of all ages and additional lipopigment deposition in neurons in older patients. Some nerve cell loss does occur in the deep gray nuclei. Like other lysosomal disorders, clinical presentation differs according to age of onset, and there may be clinical heterogeneity even within families. In the late-infantile form presenting between 1 and 2 years of age, symptoms include hypotonia from muscle weakness, peripheral neuropathy, deterioration in speech and coordination, and eventual hypertonia, decerebrate posturing, quadriparesis, and blindness. Patients with juvenile-onset disease that presents between 3 and 21 years of age may have difficulties with learning and concentration, emotional lability, and motor impairment, followed by dementia, bulbar abnormalities, ataxia, and seizures. Adults may present with a multiple sclerosis–like syndrome, dysarthria, progressive dementia, motor disturbance, or peripheral nerve symptoms. Psychiatric disturbances are extremely common in older patients, occurring in 53% of those with adolescent- and adult-onset disease.
Neuroimaging findings may precede symptoms. On MR imaging, involved white matter with prolonged T1/T2 relaxation times is interspersed with variable areas of normal myelination, and there is usual sparing of U-fibers on pathology and imaging studies. Preserved radiating myelinated fibers are present in the demyelinated centrum semiovale, leading to the appearance of “tiger stripes” on MR imaging (Fig. 1). Marked loss of myelin is seen in the cerebrum, corpus callosum, corticospinal tracts, and, to a lesser degree, in the cerebellum. Demyelination is symmetrical and confluent. There is also sparing of a thin rim of periventricular white matter. White matter unmyelinated at birth is the most severely affected. Demyelination is noted to spread peripherally and ventrally in patients in whom early serial imaging is performed. Diffuse involvement, however, is usual at presentation of the late-infantile variant. Adult-onset patients may have more focal or periventricular involvement of the white matter. Although there are rare imaging reports of cerebellar involvement and brainstem atrophy, relative sparing probably results from the earlier myelination of these regions. Progressive atrophy occurs, and ventricular size on pathologic and radiographic evaluation depends on the stage of the disease. MRS reveals an increase in myo-inositol, a decrease in NAA, and the presence of lactate peaks[1,2].
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Figure 1. Metachromatic leukodystrophy. Axial T2-weighted MR image shows stripes (arrow) in the centrum semiovale (Click to enlarge figure)
References
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Kim TS, Kim I-O, Kim WS, et al. MR of Childhood metachromatic leukodystrophy. AJNR Am J Neuroradiol. 1997;18:733-738
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Kruse B, Hanefeld F, Christen HJ, et al. Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance in vivo. J Neurol. 1993;241(2):68-74
