Time‐course of myelination and atrophy on cerebral imaging in 35 patients with <i><scp>PLP</scp>1</i>‐related disorders

Abstract

Aim Brain magnetic resonance imaging (MRI) motor development score ( MDS ) correlations were used to analyze the natural time‐course of hypomyelinating PLP 1 ‐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 PLP 1 ‐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 PMD 0 without motor acquisition to PMD 4 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 PMD 0‐1 had higher‐severity atrophy scores and smaller corpus callosum area than did patients with PMD 2 and PMD 3‐4. 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 PLP 1 ‐related disorders.