Relationship between muscle inflammation and fat replacement assessed by MRI in facioscapulohumeral muscular dystrophy

Dahlqvist, Julia R.; Andersen, Grete; Khawajazada, Tahmina; Vissing, Christoffer Rasmus; Thomsen, Carsten; Vissing, John

doi:10.1007/s00415-019-09242-y

Cited by 33 publications

(36 citation statements)

References 18 publications

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“…We also found that the hamstring (semimembranosus) was the most fatty-infiltrated and the medial gastrocnemius to be the second most fatty infiltrated, similar to a large set of prior reports [7,[12][13][14]. Our finding that muscles with a baseline fat fraction less than 0.10 or greater than 0.80 are less likely to progress significantly in fat fraction over a 12-month interval is similar to findings in Andersen et al and Dahlqvist et al [1,5]. In our cohort, the highest percentage of measurable change peaked in those muscles having intermediate fat fraction of0 .40-0.50 at baseline; with large changes in fat fraction (≥ 0.20) only seen in less affected muscles.…”

Section: T1 Fat Fraction At Baseline and 12-month Follow-upsupporting

confidence: 91%

“…Several studies have demonstrated that magnetic resonance imaging (MRI) measures can effectively follow FSHD disease progression over relatively short time scale. The primary finding is an approximately 2-5% fatty increase per year if a muscle progresses [1][2][3][4], with the suggestion that muscles showing moderate fatty infiltration and short tau inversion recovery (STIR) elevation at baseline are more likely to have a greater increase in fat fraction [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal study of MRI and functional outcome measures in facioscapulohumeral muscular dystrophy

Wang

Shaw

Faino

et al. 2021

BMC Musculoskelet Disord

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Background Facioscapulohumeral muscular dystrophy (FSHD) is a patchy and slowly progressive disease of skeletal muscle. For MRI to be a useful biomarker in an FSHD clinical trial, it should reliably detect changes over relatively short time-intervals (~ 1 year). We hypothesized that fatty change over the study course would be most likely in muscles already demonstrating disease progression, and that the degree of MRI burden would be correlated with function. Methods We studied 36 patients with FSHD and lower-extremity weakness at baseline. Thirty-two patients returned in our 12-month longitudinal observational study. We analyzed DIXON MRI images of 16 lower-extremity muscles in each patient and compared them to quantitative strength measurement and ambulatory functional outcome measures. Results There was a small shift to higher fat fractions in the summed muscle data for each patient, however individual muscles demonstrated much larger magnitudes of change. The greatest increase in fat fraction was observed in muscles having an intermediate fat replacement at baseline, with minimally (baseline fat fraction < 0.10) or severely (> 0.70) affected muscles less likely to progress. Functional outcome measures did not demonstrate marked change over the interval; however, overall MRI disease burden was correlated with functional outcome measures. Direct comparison of the tibialis anterior (TA) fat fraction and quantitative strength measurement showed a sigmoidal relationship, with steepest drop being when the muscle gets more than ~ 20% fatty replaced. Conclusions Assessing MRI changes in 16 lower-extremity muscles across 1 year demonstrated that those muscles having an intermediate baseline fat fraction were more likely to progress. Ambulatory functional outcome measures are generally related to overall muscle MRI burden but remain unchanged in the short term. Quantitative strength measurement of the TA showed a steep loss of strength when more fatty infiltration is present suggesting that MRI may be preferable for following incremental change or modulation with drug therapy.

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Section: T1 Fat Fraction At Baseline and 12-month Follow-upsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Longitudinal study of MRI and functional outcome measures in facioscapulohumeral muscular dystrophy

Wang

Shaw

Faino

et al. 2021

BMC Musculoskelet Disord

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“…Counter‐intuitively, specific force was higher in FSHD patients with more severe fatty infiltration. In FSHD, quadriceps involvement starts with distal atrophy and fatty infiltration 4,25 . Given that the absolute amount of force generated by a muscle is determined by its largest cross‐sectional area, reflecting the number of sarcomeres in parallel, distal atrophy and fatty infiltration in patients with severe FSHD may result in overestimation of specific force.…”

Section: Discussionmentioning

confidence: 99%

Reduced specific force in patients with mild and severe facioscapulohumeral muscular dystrophy

et al. 2020

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Background: Specific force, that is the amount of force generated per unit of muscle tissue, is reduced in patients with facioscapulohumeral muscular dystrophy (FSHD). The causes of reduced specific force and its relation with FSHD disease severity are unknown. Methods: Quantitative muscle magnetic resonance imaging (MRI), measurement of voluntary maximum force generation and quadriceps force-frequency relationship, and vastus lateralis muscle biopsies were performed in 12 genetically confirmed patients with FSHD and 12 controls. Results: Specific force was reduced by~33% in all FSHD patients independent of disease severity. Quadriceps force-frequency relationship shifted to the right in severe FSHD compared to controls. Fiber type distribution in vastus lateralis muscle biopsies did not differ between groups. Conclusions: Reduced quadriceps specific force is present in all FSHD patients regardless of disease severity or fatty infiltration. Early myopathic changes, including fibrosis, and non-muscle factors, such as physical fatigue and musculoskeletal pain, may contribute to reduced specific force.

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“…Multiple studies have assessed muscle MRI in patients with FSHD focusing on determining muscles to follow in a clinical trial either by imaging or muscle biopsy (looking for DUX4-downstream signature markers) [5][6][7][8][9][10]. MRI STIR sequences null the fat signal and highlight elevated free water signal.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Johnstone

Bindschadler

et al. 2021

BMC Musculoskelet Disord

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Background Facioscapulohumeral muscular dystrophy (FSHD) is a patchy and slowly progressive disease of skeletal muscle. MRI short tau inversion recovery (STIR) sequences of patient muscles often show increased hyperintensity that is hypothesized to be associated with inflammation. This is supported by the presence of inflammatory changes on biopsies of STIR-positive muscles. We hypothesized that the STIR positivity would normalize with targeted immunosuppressive therapy. Case presentation 45-year-old male with FSHD type 1 was treated with 12 weeks of immunosuppressive therapy, tacrolimus and prednisone. Tacrolimus was treated to a goal serum trough of > 5 ng/mL and prednisone was tapered every month. Quantitative strength exam, functional outcome measures, and muscle MRI were performed at baseline, week 6, and week 12. The patient reported subjective worsening as reflected in quantitative strength exam. The MRI STIR signal was slightly increased from 0.02 to 0.03 of total muscle; while the T1 fat fraction was stable. Functional outcome measures also were stable. Conclusions Immunosuppressive therapy in refractive autoimmune myopathy in other contexts has been shown to reverse STIR signal hyperintensity, however this treatment did not reverse STIR signal in this patient with FSHD. In fact, STIR signal slightly increased throughout the treatment period. This is the first study of using MRI STIR and T1 fat fraction to follow treatment effect in FSHD. We find that STIR might not be a dynamic marker for suppressing inflammation in FSHD.

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Relationship between muscle inflammation and fat replacement assessed by MRI in facioscapulohumeral muscular dystrophy

Cited by 33 publications

References 18 publications

Longitudinal study of MRI and functional outcome measures in facioscapulohumeral muscular dystrophy

Longitudinal study of MRI and functional outcome measures in facioscapulohumeral muscular dystrophy

Reduced specific force in patients with mild and severe facioscapulohumeral muscular dystrophy

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

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