Magnetic resonance imaging and spectroscopic analysis in 5 cases of Pelizaeus-Merzbacher disease: metabolic abnormalities as diagnostic tools

Abstract

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestations such as nystagmus, developmental delays, and spasticity, and genetic analysis can confirm the diagnosis. Further diagnostic manifestations of the disease include a lack of myelination on brain magnetic resonance (MR) imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that reflect axonal and myelination abnormalities on phroton MR spectroscopy. We report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2 patients. Brain MR analyses and MR spectroscopy were performed for all the patients. The brain MR images showed white matter abnormalities typical of PMD, and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and choline concentrations. We propose that MR spectroscopic analysis of metabolic alterations can aid the PMD diagnosis and can contribute to a better understanding of the pathogenesis of the disease.

Heterogeneidad clínica y mutacional en pacientes colombianos con Pelizaeus Merzbacher

“…Although clinical manifestations are heterogeneous 5 , 6 , the most relevant neurological signs are nystagmus, developmental delay, spasticity, along with neuroimaging supporting aberrant myelination of the Central Nervous System (CNS) compromising primarily the periventricular white matter, with a tigroid striation pattern that responds to the conservation of myelinated islets, and also an alteration of the N-acetyl aspartate and choline profiles on the brain magnetic resonance spectroscopy 5 , 7 .…”

“…Aunque las manifestaciones clínicas son muy heterogéneas 5 , 6 , los signos clínicos primarios neurológicos incluyen nistagmo, retardo global del desarrollo, espasticidad, acompañados de características radiológicas vistas por Resonancia Nuclear Magnética cerebral (RM) como una mielinización del sistema nervioso central (SNC) aberrante de predominio periventricular sin afectación subcortical, junto a la presencia de islotes mielinizados que dan una apariencia ‘tigroide’ a la sustancia blanca, así como alteración de los patrones de N-acetil aspartato y colina en la espectroscopía que reflejan anomalías mielínicas axonales 5 , 7 .…”