Hypomyelinating disorders

Time-course of myelination and atrophy on MRI in PLP1-related disorders


We studied the natural time-course of hypomyelinating PLP1-related disorders on cerebral MRI in 35 patients followed over 7 years. Patients were classified according to best motor function acquired before 5 years into 5 categories. We determined myelination and atrophy scores, corpus callosum area, volumes of cerebellum, white matter (WM) and grey matter (GM) on 63 MRI. Severe patients had higher severity atrophy scores and smaller corpus callosum area than mild and moderate patients. Myelination increased until 12 years and was correlated with clinical severity in anterior regions. Atrophy worsened in most patients whereas GM and WM compartments did not change with aging.


Fig. 1: MRI of PMD/SPG2 patients; severe (PMD0; top row), intermediate (PMD2; intermediate row) and mild (PMD4; bottom row) forms. T1- weighted (a-c), T2-weighted (d-f), and FLAIR (g-i) axial slices, showing different degrees of hypomyelination according to clinical severity. CC segmentation on midline FLAIR (j-k) and T1- weighted (l) sagittal slices. Segmentation of cerebellum on FLAIR axial slices (m-o) through the middle cerebellar peduncle.



Fig. 2: Inter- and intra-individual MRI evolution over time in the subgroup of 17 patients with successive MRIs. Atrophy scores (A; y-axis; from 0, no atrophy, to 21, maximal atrophy) and myelination score (B; y-axis; from 0, no myelination to 60, achieved myelination) according to age (x-axis; years); atrophy tends to increase over time, and myelination tends to increase until 12 years before stabilizing as patients get older. CC area/TIV ratios (C; y-axis) according to the age (x-axis; years); note inter- and intra- individual progressive CC atrophy over time. Cerebellum volume/TIV ratios (D; y-axis) according to age (x-axis; years); note inter- and intra-individual progressive cerebellum atrophy over time. Blue squares: PMD0-1; orange diamonds: PMD2; green triangles: PMD3-4. Several patients are represented with empty symbols for visibility.