Tracking muscle wasting and disease activity in facioscapulohumeral muscular dystrophy by qualitative longitudinal imaging

Mauro Monforte, Francesco Laschena, Pierfrancesco Ottaviani, Maria Rosaria Bagnato, Anna Pichiecchio, Giorgio Tasca, Enzo Ricci

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJournal of Cachexia, Sarcopenia and Muscle
DOIs
Publication statusE-pub ahead of print - Oct 30 2019

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Facioscapulohumeral Muscular Dystrophy
Wasting Syndrome
Muscles
Natural History
Disease Progression
Magnetic Resonance Imaging
Clinical Trials
Muscular Dystrophies
Longitudinal Studies
Lower Extremity
Edema

Cite this

@article{f8f9bc7cd51245dba1a45cd8cb343e01,
title = "Tracking muscle wasting and disease activity in facioscapulohumeral muscular dystrophy by qualitative longitudinal imaging",
abstract = "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.",
author = "Mauro Monforte and Francesco Laschena and Pierfrancesco Ottaviani and Bagnato, {Maria Rosaria} and Anna Pichiecchio and Giorgio Tasca and Enzo Ricci",
note = "{\circledC} 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.",
year = "2019",
month = "10",
day = "30",
doi = "10.1002/jcsm.12473",
language = "English",
journal = "Journal of Cachexia, Sarcopenia and Muscle",
issn = "2190-5991",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Tracking muscle wasting and disease activity in facioscapulohumeral muscular dystrophy by qualitative longitudinal imaging

AU - Monforte, Mauro

AU - Laschena, Francesco

AU - Ottaviani, Pierfrancesco

AU - Bagnato, Maria Rosaria

AU - Pichiecchio, Anna

AU - Tasca, Giorgio

AU - Ricci, Enzo

N1 - © 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.

PY - 2019/10/30

Y1 - 2019/10/30

N2 - 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.

AB - 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.

U2 - 10.1002/jcsm.12473

DO - 10.1002/jcsm.12473

M3 - Article

C2 - 31668022

JO - Journal of Cachexia, Sarcopenia and Muscle

JF - Journal of Cachexia, Sarcopenia and Muscle

SN - 2190-5991

ER -