Identification of PMD subgroups using a myelination score for PMD.
Hypomyelination
MRI
Myelination
PLP1
Pelizaeus-Merzbacher disease
Score
Journal
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
ISSN: 1532-2130
Titre abrégé: Eur J Paediatr Neurol
Pays: England
ID NLM: 9715169
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
12
07
2022
revised:
18
09
2022
accepted:
24
10
2022
pubmed:
12
11
2022
medline:
7
12
2022
entrez:
11
11
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 36368233
pii: S1090-3798(22)00144-1
doi: 10.1016/j.ejpn.2022.10.003
pii:
doi:
Substances chimiques
Myelin Proteolipid Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-79Subventions
Organisme : NINDS NIH HHS
ID : U54 NS115052
Pays : United States
Informations de copyright
© 2022 The Author(s). Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Déclaration de conflit d'intérêts
Declaration of competing interest IH, SFG, SDR, AM, OS: none. AV is an investigator in clinical trials, mechanistic studies, and natural history studies for leukodystrophies (Ionis, Takeda, Homology, Passage Bio, Biogen, Eli-Lilly, Illumina, SynaptixBio) without personal payment. NIW is advisor and/or co-investigator for trials in Pelizaeus-Merzbacher disease and other leukodystrophies (Shire/Takeda, Orchard, Ionis, PassageBio, VigilNeuro, Sana Biotech), without personal payment.