Evaluation of inflammatory lesions over 2 years in facioscapulohumeral muscular dystrophy

Abstract

<jats:sec><jats:title>Objective:</jats:title><jats:p>We followed patients with facioscapulohumeral muscular dystrophy (FSHD) with sequential examinations over 2 years to investigate whether inflammatory lesions always precede fat replacement, if inflammation can be resolved without muscle degeneration, and if inflammatory lesions in muscle are always followed by fat replacement.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>In this longitudinal study of 10 sequential MRI assessments over 2.5 years, we included 10 patients with FSHD. We used MRI with short TI inversion recovery to identify regions of interest (ROIs) with hyperintensities indicating muscle inflammation. Muscle T2 relaxation time mapping was used as a quantitative marker of muscle inflammation. Dixon sequences quantified muscle fat replacement. Ten healthy controls were examined with an MR scan once for determination of normal values of T2 relaxation time.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>We identified 68 ROIs with T2-elevation in the FSHD patients. New ROIs with T2-elevation arising during the study had muscle fat content of 6.4–33.0% (N=8) and lesions that resolved, 47.0–78.0% (N=6). ROIs with T2-elevation had a higher increase in muscle fat content from visits 1 to 10 (7.9±7.9%) compared to ROIs with normal muscle T2 relaxation times (1.7±2.6%; p&lt;0.0001). Severe T2-elevations were always followed by an accelerated replacement of muscle by fat.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>Our results suggest that muscle inflammation starts in mildly affected muscles in FSHD, is related to a faster muscle degradation, and continue until the muscles are completely fat replaced.</jats:p></jats:sec>

Adapting MRI as a clinical outcome measure for a facioscapulohumeral muscular dystrophy trial of prednisone and tacrolimus: case report

“…Despite literature data (Tasca, Frisullo, Dahlqvist, our prior work [10,[12][13][14]) suggesting that STIR+ features may be primarily related to inflammation, we saw no , and STIR images are shown from the same anatomical locations. Note the overlap between T2-weighted water measures and STIR+ signal.…”

“…In the Seattle Wellstone FSHD study of 36 patients with MRI-guided biopsies, we found that MRI STIR positivity was associated with inflammation or active myopathy iñ 70% of the muscle biopsies versus 25% of the STIR negative muscles [10]. A most recent paper by Dahlqvist et al found that STIR-positive muscles indicating muscle inflammation were associated with faster muscle degradation [14]. Therefore, our hypothesis was that if STIR hyperintensities represent active inflammation, these abnormalities would normalize with targeted therapy.…”

Muscle biopsy and MRI findings in ANO5‐related myopathy

“…As seen in the other muscular dystrophies, muscle tissue in anoctaminopathy is progressively replaced by fat during the course of the disease. The presence of and possible relation to preceding inflammation are unknown, and longitudinal MR studies of inflammatory lesions are warranted to find a possible link to fatty degeneration of the musculature, similar to what has been done for FSHD 14 . The present findings of inflammatory changes in muscle biopsies and STIR+ lesions on MRI in our study suggest that muscle inflammation could possibly contribute to the pathophysiology of LGMDR12.…”

Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: roles of DUX4 and PAX7

“…MRI measures of macroscopic inflammation are indicators of muscles at greater risk of fatty replacement as detected using T1‐weighted imaging (Fig 3 ), a feature correlated to clinical severity. However, these inflammatory markers are transient and fluctuating and, as a static measure, do not correlate to clinical severity (Monforte et al , 2019 ; Dahlqvist et al , 2020a ). A small proportion of inflamed FSHD muscles also resolve without progression of fatty replacement, and fatty replacement can also occur in absence of inflammation, albeit at a slower rate.…”