Journal article
Lower limb muscle MRI fat fraction is a responsive outcome measure in CMT X1, 1B and 2A
Annals of clinical and translational neurology, Vol.11(3), pp.607-617
03/2024
DOI: 10.1002/acn3.51979
PMCID: PMC10963306
PMID: 38173284
Abstract
With potential therapies for many forms of Charcot-Marie-Tooth disease (CMT), responsive outcome measures are urgently needed for clinical trials. Quantitative lower limb MRI demonstrated progressive calf intramuscular fat accumulation in the commonest form, CMT1A with large responsiveness. In this study, we evaluated the responsiveness and validity in the three other common forms, due to variants in GJB1 (CMTX1), MPZ (CMT1B) and MFN2 (CMT2A).
22 CMTX1, 21 CMT1B and 21 CMT2A patients and matched controls were assessed at a 1-year interval. Intramuscular fat fraction (FF) was evaluated using three-point Dixon MRI at thigh and calf level along with clinical measures including CMT examination score, clinical strength assessment, CMT-HI and plasma neurofilament light chain.
All patient groups had elevated muscle fat fraction at thigh and calf levels, with highest thigh FF and atrophy in CMT2A. There was moderate correlation between calf muscle FF and clinical measures (CMTESv2 rho = 0.405; p = 0.001, ankle MRC strength rho = -0.481; p < 0.001). Significant annualised progression in calf muscle FF was seen in all patient groups (CMTX1 2.0 ± 2.0%, p < 0.001, CMT1B 1.6 ± 2.1% p = 0.004 and CMT2A 1.6 ± 2.1% p = 0.002). Greatest increase was seen in patients with 10-70% FF at baseline (calf 2.7 ± 2.3%, p < 0.0001 and thigh 1.7 ± 2.1%, p = 0.01).
Our results confirm that calf muscle FF is highly responsive over 12 months in three additional common forms of CMT which together with CMT1A account for 90% of genetically confirmed cases. Calf muscle MRI FF should be a valuable outcome measure in upcoming CMT clinical trials.
Details
- Title: Subtitle
- Lower limb muscle MRI fat fraction is a responsive outcome measure in CMT X1, 1B and 2A
- Creators
- Nick Zafeiropoulos - National Hospital for Neurology and NeurosurgeryKatherine J Stephens - Roy and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa, USATiffany Grider - University of IowaShawna M E Feely - University of Washington School of MedicinePeggy Nopoulous - University of IowaMariola Skorupinska - National Hospital for Neurology and NeurosurgeryEvelin Milev - Great Ormond Street HospitalEmma Nicolaisen - University of IowaMagdalena Dudzeic - National Hospital for Neurology and NeurosurgeryAmy McDowell - National Hospital for Neurology and NeurosurgeryNuran Dilek - University of RochesterFrancesco Muntoni - Great Ormond Street HospitalAlexander M Rossor - National Hospital for Neurology and NeurosurgerySachit Shah - National Hospital for Neurology and NeurosurgeryCarolynne M Doherty - National Hospital for Neurology and NeurosurgeryMatilde Laura - National Hospital for Neurology and NeurosurgeryJasper M Morrow - National Hospital for Neurology and NeurosurgeryTarek A Yousry - National Hospital for Neurology and NeurosurgeryRiccardo Zuccarino - University of IowaDaniel Thedens - University of IowaPaige Howard - University of IowaJohn Thornton - National Hospital for Neurology and NeurosurgeryStephen Wastling - National Hospital for Neurology and NeurosurgeryMichael E Shy - University of IowaMenelaos Pipis - National Hospital for Neurology and NeurosurgeryMary M Reilly - National Hospital for Neurology and Neurosurgery
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.11(3), pp.607-617
- DOI
- 10.1002/acn3.51979
- PMID
- 38173284
- PMCID
- PMC10963306
- NLM abbreviation
- Ann Clin Transl Neurol
- eISSN
- 2328-9503
- Grant note
- Muscular Dystrophy Association
- Language
- English
- Electronic publication date
- 01/03/2024
- Date published
- 03/2024
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Electrical and Computer Engineering; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984539755702771
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