Clínica y diagnóstico de la enfermedad de Pelizaeus-Merzbacher: descripción de cinco casos / Clinical features and diagnosis of Pelizaeus-Merzbacher disease: five case reports

Introducción. La enfermedad de Pelizaeus-Merzbacher es un trastorno hipomielinizante raro debido a alteraciones en el gen PLP1, que lleva a un fallo de la mielinización axonal de los oligodendrocitos en el sistema nervioso central. Existen dos formas descritas según la gravedad de su presentación: connatal y clásica. Se caracteriza por hipotonía neonatal, retraso del desarrollo psicomotor, espasticidad progresiva de predominio en los miembros inferiores y nistagmo, con signos y síntomas piramidales y extrapiramidales, y la forma connatal es mucho más grave. La resonancia magnética muestra leucoencefalopatía hipomielinizante difusa, los potenciales evocados usualmente se alteran y la confirmación se realiza mediante estudio molecular del gen PLP1. Casos clínicos. Se presentan cinco pacientes pediátricos afectados, cuatro con la forma clásica y uno con la forma connatal; se describen las características clínicas, los estudios complementarios y se realiza una revisión concisa de la bibliografía. Conclusión. Esta enfermedad tiene una evolución progresiva y casi invariable, lo cual es la clave clínica para diferenciarla de otras entidades como la parálisis cerebral infantil, neuropatías periféricas, esclerosis múltiple, entre otras, además de los hallazgos característicos en las neuroimágenes. Es necesario sospechar este diagnóstico y confirmar alteraciones en el gen PLP1 con el fin de obtener una incidencia real de esta entidad, probablemente subestimada, como otras leucodistrofias (AU)

Introduction. Pelizaeus-Merzbacher disease is an infrequent hypomyelinating disorder caused by alterations in the PLP1 gene, which leads to a fault in the axonal myelination of the oligodendrocytes in the central nervous system. Two forms have been reported, according to the severity of the presentation: connatal and classic. It is characterised by neonatal hypotonia, delayed psychomotor development, progressive spasticity predominantly in the lower limbs and nystagmus, with pyramidal and extrapyramidal signs and symptoms; the connatal form is far more severe. Magnetic resonance imaging shows diffuse hypomyelinating leukoencephalopathy, evoked potentials are usually altered and confirmation is obtained through a molecular study of the PLP1 gene. Case reports. We present the cases of five paediatric patients, four of whom had the classic form and one with the connatal form. The clinical characteristics and complementary studies are described, and a concise review of the literature is carried out. Conclusion. This disease has a progressive and almost unvarying course, which is the clinical key to be able to differentiate it from other entities such as infantile cerebral palsy, peripheral neuropathies or multiple sclerosis, among others, in addition to the characteristic neuroimaging findings. It is necessary to suspect this diagnosis and confirm alterations in the PLP1 gene with the aim of obtaining a real incidence of this entity, which is probably underestimated, like other leukodystrophies (AU)

Time-course of myelination and atrophy on cerebral imaging in 35 patients with PLP1-related disorders.

AIM: Brain magnetic resonance imaging (MRI) motor development score (MDS) correlations were used to analyze the natural time-course of hypomyelinating PLP1-related disorders (Pelizaeus-Merzbacher disease [PMD] and spastic paraplegia type 2). METHOD: Thirty-five male patients (ranging from 0.7-43.5y at the first MRI) with PLP1-related disorder were prospectively followed over 7 years. Patients were classified according to best motor function acquired before 5 years (MDS) into five categories (from PMD0 without motor acquisition to PMD4 with autonomous walking). We determined myelination and atrophy scores and measured corpus callosum area, volume of cerebellum, white matter and grey matter on 63 MRI. RESULTS: Age-adjusted multivariate analysis revealed that patients with PMD0-1 had higher-severity atrophy scores and smaller corpus callosum area than did patients with PMD2 and PMD3-4. Myelination score increased until 12 years. There was evidence that the mean myelination differed in frontal white matter, arcuate fibres, and internal capsules among the groups. Most patients showed worsening atrophy (brain, cerebellum, corpus callosum), whereas grey matter and white matter proportions did not change. INTERPRETATION: Brain atrophy and myelination of anterior cerebral regions appear to be pertinent biomarkers of motor development. The time-course of inter- and intra-individual cerebral white matter and grey matter atrophy suggests that both oligodendrocytes and neurons are involved in the physiopathology of PLP1-related disorders.

[Congenital cerebral hypomyelination---Pelizaeus-Merzbacher disease and associated disorders].

Congenital cerebral hypomyelination includes a group of genetic disorders, such as Pelizaeus-Merzbacher disease (PMD), and is characterized by hypomyelination of the cerebral white matter. Until recently, no classification system was available for congenital hypomyelination disorders that are clinically and genetically excluded for PMD. However, the establishment of new disease entities with gene discoveries has generated a clinical need for a new classification and diagnostic criteria for this group of disorders. Here, we review the recent findings on congenital cerebral hypomyelination, which includes 11 diseases, with a novel disease classification and diagnostic criteria with flow charts.