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Identification of PMD subgroups using a myelination score for PMD
Inga Harting1, Sven F Garbade2, Stefan D Rosendaal3
1Department of Neuroradiology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 60120, Heidelberg, Germany.
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.
Insights
A new Pelizaeus-Merzbacher disease (PMD) myelination score effectively differentiates patient subgroups and controls. This tool aids in assessing disease severity and monitoring treatment efficacy for hypomyelinating leukodystrophy.
Area of Science:
- Neurology
- Radiology
- Genetics
Background:
- Pelizaeus-Merzbacher disease (PMD) is a hypomyelinating leukodystrophy with a broad clinical spectrum.
- Emerging treatments necessitate standardized methods for grading PMD severity and progression.
Purpose of the Study:
- To develop and validate a novel myelination scoring system for Pelizaeus-Merzbacher disease.
- To enable accurate stratification of patients and objective assessment of disease progression.
Main Methods:
- A myelination score was developed using 15 anatomic sites on T2- and T1-weighted MRI scans.
- The score was validated in 328 controls and 28 PMD patients across various subtypes.
- Interrater variability, scoring practicality, and discriminatory power were key selection criteria for score items.
Main Results:
- The developed score, comprising 8 T2- and 5 T1-weighted imaging items, successfully distinguished between PMD patients and controls, and among patient subgroups.
- Severely affected patients (connatal, transitional) showed minimal myelin and early loss, while classic PMD patients had deficient myelin.
- Ongoing myelination was observed during childhood in classic and intermediate PMD cases, with atrophy increasing with age.
Conclusions:
- The proposed PMD myelination score facilitates patient stratification and standardized follow-up assessments.
- The score is crucial for evaluating treatment efficacy, considering myelin loss in severe/PLP0 cases and myelination progression in classic/intermediate PMD.
