TY - JOUR
T1 - Identification of PMD subgroups using a myelination score for PMD
AU - Harting, Inga
AU - Garbade, Sven F.
AU - Rosendaal, Stefan D.
AU - Mohr, Alexander
AU - Sherbini, Omar
AU - Vanderver, Adeline
AU - Wolf, Nicole I.
N1 - Funding Information: A. Vanderver received support by a grant from the PMD Foundation and from the Rare Disease Clinical Research Network ( U54TR002823 ). Funding Information: I. Harting and N.I. Wolf were supported by a grant of the PMD Foundation.A. Vanderver received support by a grant from the PMD Foundation and from the Rare Disease Clinical Research Network (U54TR002823). Publisher Copyright: © 2022 The Author(s)
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Background: The clinical spectrum of Pelizaeus-Merzbacher disease (PMD), a common hypomyelinating leukodystrophy, ranges between severe neonatal onset and a relatively stable presentation with later onset and mainly lower limb spasticity. In view of emerging treatment options and in order to grade severity and progression, we developed a PMD myelination score. Methods: Myelination was scored in 15 anatomic sites (items) on conventional T2-and T1w images in controls (n = 328) and 28 PMD patients (53 MRI; n = 5 connatal, n = 3 transitional, n = 10 classic, n = 3 intermediate, n = 2 PLP0, n = 3 SPG2, n = 2 female). Items included in the score were selected based on interrater variability, practicability of scoring and importance of scoring items for discrimination between patients and controls and between patient subgroups. Bicaudate ratio, maximal sagittal pons diameter, and visual assessment of midsagittal corpus callosum were separately recorded. Results: The resulting myelination score consisting of 8 T2-and 5 T1-items differentiates patients and controls as well as patient subgroups at first MRI. There was very little myelin and early loss in severely affected connatal and transitional patients, more, though still severely deficient myelin in classic PMD, ongoing myelination during childhood in classic and intermediate PMD. Atrophy, present in 50% of patients, increased with age at imaging. Conclusions: The proposed myelination score allows stratification of PMD patients and standardized assessment of follow-up. Loss of myelin in severely affected and PLP0 patients and progressing myelination in classic and intermediate PMD must be considered when evaluating treatment efficacy.
AB - Background: The clinical spectrum of Pelizaeus-Merzbacher disease (PMD), a common hypomyelinating leukodystrophy, ranges between severe neonatal onset and a relatively stable presentation with later onset and mainly lower limb spasticity. In view of emerging treatment options and in order to grade severity and progression, we developed a PMD myelination score. Methods: Myelination was scored in 15 anatomic sites (items) on conventional T2-and T1w images in controls (n = 328) and 28 PMD patients (53 MRI; n = 5 connatal, n = 3 transitional, n = 10 classic, n = 3 intermediate, n = 2 PLP0, n = 3 SPG2, n = 2 female). Items included in the score were selected based on interrater variability, practicability of scoring and importance of scoring items for discrimination between patients and controls and between patient subgroups. Bicaudate ratio, maximal sagittal pons diameter, and visual assessment of midsagittal corpus callosum were separately recorded. Results: The resulting myelination score consisting of 8 T2-and 5 T1-items differentiates patients and controls as well as patient subgroups at first MRI. There was very little myelin and early loss in severely affected connatal and transitional patients, more, though still severely deficient myelin in classic PMD, ongoing myelination during childhood in classic and intermediate PMD. Atrophy, present in 50% of patients, increased with age at imaging. Conclusions: The proposed myelination score allows stratification of PMD patients and standardized assessment of follow-up. Loss of myelin in severely affected and PLP0 patients and progressing myelination in classic and intermediate PMD must be considered when evaluating treatment efficacy.
KW - Hypomyelination
KW - MRI
KW - Myelination
KW - PLP1
KW - Pelizaeus-Merzbacher disease
KW - Score
UR - http://www.scopus.com/inward/record.url?scp=85141506548&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejpn.2022.10.003
DO - https://doi.org/10.1016/j.ejpn.2022.10.003
M3 - Article
C2 - 36368233
SN - 1090-3798
VL - 41
SP - 71
EP - 79
JO - European journal of paediatric neurology : EJPN
JF - European journal of paediatric neurology : EJPN
ER -