Tracking muscle wasting and disease activity in facioscapulohumeral muscular dystrophy by qualitative longitudinal imaging.
Biomarkers
FSHD
Facioscapulohumeral muscular dystrophy
Muscle MRI
Muscle wasting
STIR hyperintensity
Journal
Journal of cachexia, sarcopenia and muscle
ISSN: 2190-6009
Titre abrégé: J Cachexia Sarcopenia Muscle
Pays: Germany
ID NLM: 101552883
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
23
12
2018
revised:
14
05
2019
accepted:
12
06
2019
pubmed:
2
11
2019
medline:
28
7
2020
entrez:
1
11
2019
Statut:
ppublish
Résumé
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent late-onset muscular dystrophies, characterized by progressive fatty replacement and degeneration involving single muscles in an asynchronous manner. With clinical trials at the horizon in this disease, the knowledge of its natural history is of paramount importance to understand the impact of new therapies. The aim of this study was to assess disease progression in FSHD using qualitative muscle magnetic resonance imaging, with a focus on the evolution of hyperintense lesions identified on short-tau inversion recovery (STIR+) sequences, hypothesized to be markers of active muscle injury. One hundred genetically confirmed consecutive FSHD patients underwent lower limb muscle magnetic resonance imaging at baseline and after 365 ± 60 days in this prospective longitudinal study. T1 weighted (T1w) and STIR sequences were used to assess fatty replacement using a semiquantitative visual score and muscle oedema. The baseline and follow-up scans of each patient were also evaluated by unblinded direct comparison to detect the changes not captured by the scoring system. Forty-nine patients showed progression on T1w sequences after 1 year, and 30 patients showed at least one new STIR+ lesion. Increased fat deposition at follow-up was observed in 13.9% STIR+ and in only 0.21% STIR- muscles at baseline (P < 0.001). Overall, 89.9% of the muscles that showed increased fatty replacement were STIR+ at baseline and 7.8% were STIR+ at 12 months. A higher number of STIR+ muscles at baseline was associated with radiological worsening (odds ratio 1.17, 95% confidence interval 1.06-1.30, P = 0.003). Our study confirms that STIR+ lesions represent prognostic biomarkers in FSHD and contributes to delineate its radiological natural history, providing useful information for clinical trial design. Given the peculiar muscle-by-muscle involvement in FSHD, MRI represents an invaluable tool to explore the modalities and rate of disease progression.
Sections du résumé
BACKGROUND
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent late-onset muscular dystrophies, characterized by progressive fatty replacement and degeneration involving single muscles in an asynchronous manner. With clinical trials at the horizon in this disease, the knowledge of its natural history is of paramount importance to understand the impact of new therapies. The aim of this study was to assess disease progression in FSHD using qualitative muscle magnetic resonance imaging, with a focus on the evolution of hyperintense lesions identified on short-tau inversion recovery (STIR+) sequences, hypothesized to be markers of active muscle injury.
METHODS
One hundred genetically confirmed consecutive FSHD patients underwent lower limb muscle magnetic resonance imaging at baseline and after 365 ± 60 days in this prospective longitudinal study. T1 weighted (T1w) and STIR sequences were used to assess fatty replacement using a semiquantitative visual score and muscle oedema. The baseline and follow-up scans of each patient were also evaluated by unblinded direct comparison to detect the changes not captured by the scoring system.
RESULTS
Forty-nine patients showed progression on T1w sequences after 1 year, and 30 patients showed at least one new STIR+ lesion. Increased fat deposition at follow-up was observed in 13.9% STIR+ and in only 0.21% STIR- muscles at baseline (P < 0.001). Overall, 89.9% of the muscles that showed increased fatty replacement were STIR+ at baseline and 7.8% were STIR+ at 12 months. A higher number of STIR+ muscles at baseline was associated with radiological worsening (odds ratio 1.17, 95% confidence interval 1.06-1.30, P = 0.003).
CONCLUSIONS
Our study confirms that STIR+ lesions represent prognostic biomarkers in FSHD and contributes to delineate its radiological natural history, providing useful information for clinical trial design. Given the peculiar muscle-by-muscle involvement in FSHD, MRI represents an invaluable tool to explore the modalities and rate of disease progression.
Identifiants
pubmed: 31668022
doi: 10.1002/jcsm.12473
pmc: PMC6903444
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1258-1265Informations de copyright
© 2019 The Authors Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.
Références
Hum Mol Genet. 2016 Oct 15;25(20):4419-4431
pubmed: 28171552
Hum Mol Genet. 2015 Sep 1;24(17):4817-28
pubmed: 26041815
Muscle Nerve. 2018 Jun;57(6):905-912
pubmed: 29236297
J Clin Invest. 2017 Apr 3;127(4):1531-1545
pubmed: 28263188
Mol Neurobiol. 2018 Apr;55(4):2959-2966
pubmed: 28456937
Neurology. 1997 Jan;48(1):38-46
pubmed: 9008491
J Neuromuscul Dis. 2019;6(1):1-30
pubmed: 30714967
J Cachexia Sarcopenia Muscle. 2019 Dec;10(6):1258-1265
pubmed: 31668022
PLoS Genet. 2010 Oct 28;6(10):e1001181
pubmed: 21060811
PLoS One. 2014 Feb 28;9(2):e90377
pubmed: 24587344
Mol Ther. 2016 Mar;24(3):527-35
pubmed: 26527377
J Clin Immunol. 2011 Apr;31(2):155-66
pubmed: 21063901
Neurology. 2014 Sep 23;83(13):1178-83
pubmed: 25142899
Neurology. 2014 Sep 16;83(12):1056-9
pubmed: 25122204
Neuromuscul Disord. 2016 Feb;26(2):181-6
pubmed: 26627872
PLoS One. 2014 Jan 14;9(1):e85416
pubmed: 24454861
Science. 2010 Sep 24;329(5999):1650-3
pubmed: 20724583
J Cachexia Sarcopenia Muscle. 2017 Dec;8(6):1081-1083
pubmed: 29098794
Neuromuscul Disord. 2014 Jan;24(1):79-85
pubmed: 24011701
Handb Clin Neurol. 2018;148:541-548
pubmed: 29478599
Neuromuscul Disord. 2009 May;19(5):357-62
pubmed: 19329315
Eur Radiol. 2016 Mar;26(3):693-705
pubmed: 26115655
Hum Mol Genet. 2019 Feb 1;28(3):476-486
pubmed: 30312408
PLoS One. 2014 Jun 16;9(6):e100292
pubmed: 24932477
Muscle Nerve. 2014 Feb;49(2):257-60
pubmed: 23720194
Neuromuscul Disord. 2018 Jun;28(6):508-511
pubmed: 29655530
Neurology. 2008 Sep 2;71(10):758-65
pubmed: 18765652
Muscle Nerve. 2014 Apr;49(4):520-7
pubmed: 23873337
J Neurol. 2018 Nov;265(11):2646-2655
pubmed: 30191320
Neurology. 2017 Nov 14;89(20):2057-2065
pubmed: 29030457
Ann Neurol. 2016 May;79(5):854-864
pubmed: 26994363
Muscle Nerve. 2018 Jun;57(6):872-874
pubmed: 29328515
J Neurol. 2017 Oct;264(10):2053-2067
pubmed: 28669118
Ann Neurol. 1999 Jun;45(6):751-7
pubmed: 10360767
PLoS One. 2017 Aug 25;12(8):e0183825
pubmed: 28841698
PLoS One. 2012;7(6):e38779
pubmed: 22719944
J Neurol. 2017 Mar;264(3):438-447
pubmed: 28000006