Elsevier

Pediatric Neurology

Volume 18, Issue 4, April 1998, Pages 334-337
Pediatric Neurology

Original Articles
An MRI and MRS Study of Pelizaeus-Merzbacher Disease

https://doi.org/10.1016/S0887-8994(97)00212-9Get rights and content

Abstract

Earlier reports on T2-weighted magnetic resonance imaging (MRI) in the classical form of Pelizaeus-Merzbacher disease seemed to divide the patterns of the high-intensity lesions in the white matter into three subtypes: type I, diffusely hemispheric and corticospinal; type II, diffusely hemispheric without brainstem lesions; and type III, patchy in the hemispheres. The four boys presented in our study, between 10 and 17 years of age, with classical Pelizaeus-Merzbacher disease, who all had a duplicated proteolipid protein gene, invariably manifested type I despite their various clinical severities. Follow-up MRI after an interval of 5 years and proton magnetic resonance spectroscopy was performed in three of the patients. The white matter on the last MRI was unchanged in volume and the distribution of high-intense areas. Proton magnetic resonance spectroscopy revealed no abnormal peaks. These results were consistent with the lack of definite neurologic regression in the last 5 years and with the pathologic characteristics of well-preserved axons and the absence of sclerosis. Further study is required to precisely determine whether the patterns of MRI findings can be divided into subtypes corresponding to those of proteolipid protein gene abnormalities.

Introduction

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked disorder in which the pathogenesis involves dysmyelination rather than demyelination of the central nervous system (CNS) 1, 2. In most patients with the classical form of PMD the development of symptoms is almost complete early in life: they manifest hypotonicity and spontaneous nystagmus with onset in the initial months after birth. Spasticity appears in late infancy. Mental retardation, athetosis, and motor ataxia are recognized by early childhood. However, the subsequent clinical course is most commonly stable or slowly progressive. The proteolipid protein (PLP) gene is the sole candidate gene for PMD. It encodes PLP and DM20, the major structural myelin proteins of the CNS that presumably contribute to early oligodendrocyte development and maintain the intraperiod line of compact myelin 3, 4. The various point mutations have been reported since the 1980s, and duplication has recently been revealed 5, 6.

There have been many case reports concerning the characteristics of magnetic resonance imaging (MRI) of classical PMD in the past decade 7, 8, 9, 10, 11, 12, 13, 14. However, the findings have not been entirely identical in all cases. The abnormal patterns seemed to be divisible into three subtypes, according to the distribution of the white matter lesions: type I, diffuse alteration in the hemispheres and corticospinal tracts 7, 8; type II, diffuse alteration in the hemispheres with intact corticospinal tracts 9, 10, 11, 12; and type III, patchy changes in the hemispheres [13]. In this report, because all four patients with classical PMD previously reported on by us were recently determined to have a PLP gene duplication 6, 15, we present their MRI findings with follow-up evaluation and proton magnetic resonance spectroscopy (1H-MRS). Which differences in the clinical or genetic factors are related to ones in the MRI subtypes is also discussed.

Section snippets

Methods

The detailed clinical features of our four patients with sporadic classical PMD, between 10 and 17 years of age, were previously reported elsewhere [15]. All the patients had manifested spontaneous pendular nystagmus and hypotonia since the initial months after birth. Developmental milestones were variously delayed because of mental retardation, spastic contractures of the lower limbs, ataxia, and athetotic movements of the upper extremities. Their neurologic status was almost stable for more

Results

In all patients the white matter of the cerebral and cerebellar hemispheres exhibited diffuse iso-intensity compared with the cortex in T1-weighted images, except for the mildly high intensity of the internal capsules and the optic radiations. T2-weighted images revealed diffusely high intensity not only in the hemispheric white matter but also throughout the corticospinal tracts. Axial images at the pontine level thus showed a couple of circular high-intense lesions in the pontine nuclei (Fig.

Discussion

Compared with the connatal form of PMD attributed to the complete or subtotal absence of myelination in the CNS, classical PMD is neuropathologically characterized by the patchy absence of myelin with persistent myelinated islands, especially in the hemispheres of the cerebrum and cerebellum. This finding has been traditionally described as the “tigroid pattern of myelin defects” 2, 16. However, patchy lesions demonstrating such a tigroid pattern are a minority on MRI [13]. In most cases of

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