Quantitative MRI reveals decelerated fatty infiltration in muscles of active FSHD patients.

To investigate the effects of aerobic exercise training (AET) and cognitive-behavioral therapy (CBT), directed towards an increase in daily physical activity, on the progression of fatty infiltration and edema in skeletal muscles of patients with facioscapulohumeral muscular dystrophy (FSHD) type 1 by T2 MRI. Quantitative T2 MRI (qT2 MRI) and fat-suppressed T2 MRI of the thigh were performed at 3T on 31 patients, 13 of whom received usual care (UC), 9 AET, and 9 CBT. Muscle-specific fat fractions (%), derived from qT2 MRI, were recorded pretreatment and posttreatment. Intervention effects were analyzed by comparing fat fraction progression rates of the UC with the treated groups using Mann-Whitney tests, and intermuscle differences by a linear mixed model. Edematous hyperintense lesions were identified on the fat-suppressed T2 MRI. The intraclass correlation coefficient for reproducibility of qT2 MRI fat assessment was 0.99. In the UC group, the fat fraction increased by 6.7/year (95% confidence interval [CI] 4.3 to 9.1). This rate decreased to 2.9/year (95% CI 0.7 to 5.2) in the AET (p = 0.03) and 1.7/year (95% CI -0.2 to 3.6) in the CBT group (p = 0.00015). The treatment effect differed among individual muscles. Fewer new edematous lesions occurred after therapy. Fat fraction derived from qT2 MRI is a reproducible and sensitive biomarker to monitor the effects of increased physical activity in individual muscles. This biomarker reports a favorable effect of AET and CBT on the rate of muscular deterioration in FSHD as reflected in decelerated fat replacement. This study provides Class II evidence that for patients with FSHD type 1, both AET and CBT decrease the rate of fatty infiltration in muscles.

Janssen B ，Voet N ，Geurts A ，van Engelen B ，Heerschap A ... -  《-》

Both aerobic exercise and cognitive-behavioral therapy reduce chronic fatigue in FSHD: an RCT.

To investigate the effect of aerobic exercise training (AET) and cognitive-behavioral therapy (CBT) on chronic fatigue in patients with facioscapulohumeral muscular dystrophy (FSHD). We performed a multicenter, assessor-blinded, randomized clinical trial (RCT). Fifty-seven patients with FSHD type 1 with severe chronic fatigue were randomly allocated to AET, CBT, or usual care (UC). Outcomes were assessed before treatment, following 16 weeks of intervention, and after a 12-week follow-up. A linear mixed model for repeated measurements was used to study the estimated group differences. Following treatment, both the AET (28 participants) and CBT (25 participants) intervention groups had less fatigue relative to the UC group (24 participants), with a difference of -9.1 for AET (95% confidence interval [CI] -12.4 to -5.8) and -13.3 for CBT (95% CI -16.5 to -10.2). These beneficial effects lasted through follow-up, with a difference of -8.2 for AET (95% CI -12.4 to -5.8) and -10.2 for CBT (95% CI -14.0 to -6.3). The patients who received CBT had an increase in registered and experienced physical activity, sleep quality, and social participation. The patients who received AET had an increase in registered physical activity only. The increase in registered physical activity in both groups and the improvement in social participation following CBT were still present at follow-up. This RCT shows that AET and CBT can ameliorate chronic fatigue in patients with FSHD. This study provides Class III evidence that, in patients with FSHD type 1 and severe chronic fatigue, AET or CBT reduces the severity of chronic fatigue.

Voet N ，Bleijenberg G ，Hendriks J ，de Groot I ，Padberg G ，van Engelen B ，Geurts A ... -  《-》

MRI as outcome measure in facioscapulohumeral muscular dystrophy: 1-year follow-up of 45 patients.

Andersen G ，Dahlqvist JR ，Vissing CR ，Heje K ，Thomsen C ，Vissing J ... -  《-》

Distinct disease phases in muscles of facioscapulohumeral dystrophy patients identified by MR detected fat infiltration.

Janssen BH ，Voet NB ，Nabuurs CI ，Kan HE ，de Rooy JW ，Geurts AC ，Padberg GW ，van Engelen BG ，Heerschap A ... -  《PLoS One》

Evaluation of inflammatory lesions over 2 years in facioscapulohumeral muscular dystrophy.

We followed up 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. 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 a magnetic resonance scan once for determination of normal values of T2 relaxation time. We identified 68 ROIs with T2 elevation in the patients with FSHD. New ROIs with T2 elevation arising during the study had muscle fat content of 6.4% to 33.0% (n = 8) and 47.0% to 78.0% lesions that resolved (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 < 0.0001). Severe T2 elevations were always followed by an accelerated replacement of muscle by fat. Our results suggest that muscle inflammation starts in mildly affected muscles in FSHD, is related to a faster muscle degradation, and continues until the muscles are completely fat replaced. NCT02159612.

Dahlqvist JR ，Poulsen NS ，Østergaard ST ，Fornander F ，de Stricker Borch J ，Danielsen ER ，Thomsen C ，Vissing J ... -  《-》