Magnetic resonance imaging in facioscapulohumeral muscular dystrophy

Leung, Doris G.

doi:10.1002/mus.26064

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…7 In the last years, the increasingly widespread use of standard and quantitative muscle magnetic resonance imaging (MRI) in FSHD patients suggested a non-linear model of disease progression that proceeds with a muscle-by-muscle type of involvement, 8 in which an early phase of muscle damage, identifiable by increased signal on short-tau inversion recovery (STIR) sequences accounting for oedema/inflammation, precedes fatty replacement of single muscles. [9][10][11][12] This would be consistent with the proposed model of disease pathophysiology, according to which bursts of inappropriate expression of the DUX4 retrogene, normally repressed in adult striated skeletal muscle, lead to a cascade of downstream events, not yet fully understood but potentially inclusive of an inflammatory-immune response, [13][14][15][16] that in the end generate skeletal muscle wasting. 17 In this context, STIR positive (STIR+) muscle lesions have been proposed as biomarkers of disease activity.…”

Section: Introductionsupporting

confidence: 83%

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

Monforte

Laschena

Ottaviani

et al. 2019

J cachexia sarcopenia muscle

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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.

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Section: Introductionsupporting

confidence: 83%

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

Monforte

Laschena

Ottaviani

et al. 2019

J cachexia sarcopenia muscle

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“…It is important to mention that muscle inflammation in FSHD is described as an intermittent process, affecting specific muscles at any given time [ 40 ]. The presence of active disease in FSHD patients can be radiologically characterized with MRI studies as STIR hyperintensity [ 41 ]. STIR is an MRI dedicated sequence that enables the detection of tissue edema or inflammation [ 42 ] and STIR hyperintensity is a well-known marker of active disease in FSHD patients [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies

Greco

Straasheijm

Mul

et al. 2021

JND

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Background: FSHD is caused by specific genetic mutations resulting in activation of the Double Homeobox 4 gene (DUX4). DUX4 targets hundreds of downstream genes eventually leading to muscle atrophy, oxidative stress, abnormal myogenesis, and muscle inflammation. We hypothesized that DUX4-induced aberrant expression of genes triggers a sustained autoimmune response against skeletal muscle cells. Objective: This study aimed at the identification of autoantibodies directed against muscle antigens in FSHD. Moreover, a possible relationship between serum antibody reactivity and DUX4 expression was also investigated. Methods: FSHD sera (N = 138, 48±16 years, 48%male) and healthy control sera (N = 20, 47±14 years, 50%male) were analyzed by immunoblotting for antibodies against several skeletal muscle protein extracts: healthy muscle, FSHD muscle, healthy and FSHD myotubes, and inducible DUX4 expressing myoblasts. In addition, DUX4 expressing myoblasts were analyzed by immunofluorescence with FSHD and healthy control sera. Results: The results showed that the reactivity of FSHD sera did not significantly differ from that of healthy controls, with all the tested muscle antigen extracts. Besides, the immunofluorescent staining of DUX4-expressing myoblasts was not different when incubated with either FSHD or healthy control sera. Conclusion: Since the methodology used did not lead to the identification of disease-specific autoantibodies in the FSHD cohort, we suggest that autoantibody-mediated pathology may not be an important disease mechanism in FSHD. Nevertheless, it is crucial to further unravel if and which role the immune system plays in FSHD pathogenesis. Other innate as well as adaptive immune players could be involved in the complex DUX4 cascade of events and could become appealing druggable targets.

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“…[119] Recently, muscle MRI has also shown its utility in corroborating the diagnosis of FSHD; MRI is more sensitive than physical examination in identifying muscles involved in the disease process and it is able to detect muscle pathology before clinical involvement of muscles. [101,120,121] MRI provides an objective measure of disease progression and can be a helpful endpoint in follow-up and trials in patients with FSHD. [101,122,123] Nevertheless, the current diagnostic approach rests on modalities other than radiological evidence, as shown in Figure 2, and finding a compatible pattern on MRI may serve as corroborative evidence for the diagnosis of FSHD2 in cases of diagnostic uncertainty or an atypical phenotype despite results from investigations highlighted in the algorithm.…”

Section: Diagnosismentioning

confidence: 99%

Facioscapulohumeral muscular dystrophy type 2: an update on the clinical, genetic, and molecular findings

Jia

Drew

Nicholson

et al. 2021

Neuromuscular Disorders

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Magnetic resonance imaging in facioscapulohumeral muscular dystrophy

Cited by 6 publications

References 24 publications

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

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

Profiling Serum Antibodies Against Muscle Antigens in Facioscapulohumeral Muscular Dystrophy Finds No Disease-Specific Autoantibodies

Facioscapulohumeral muscular dystrophy type 2: an update on the clinical, genetic, and molecular findings

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