Dataset Information

Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy.

ABSTRACT: BACKGROUND:Pathogenic variants in the FKRP gene cause impaired glycosylation of ?-dystroglycan in muscle, producing a limb-girdle muscular dystrophy with cardiomyopathy. Despite advances in understanding the pathophysiology of FKRP-associated myopathies, clinical research in the limb-girdle muscular dystrophies has been limited by the lack of normative biomarker data to gauge disease progression. METHODS:Participants in a phase 2 clinical trial were evaluated over a 4-month, untreated lead-in period to evaluate repeatability and to obtain normative data for timed function tests, strength tests, pulmonary function, and body composition using DEXA and whole-body MRI. Novel deep learning algorithms were used to analyze MRI scans and quantify muscle, fat, and intramuscular fat infiltration in the thighs. T-tests and signed rank tests were used to assess changes in these outcome measures. RESULTS:Nineteen participants were observed during the lead-in period for this trial. No significant changes were noted in the strength, pulmonary function, or body composition outcome measures over the 4-month observation period. One timed function measure, the 4-stair climb, showed a statistically significant difference over the observation period. Quantitative estimates of muscle, fat, and intramuscular fat infiltration from whole-body MRI corresponded significantly with DEXA estimates of body composition, strength, and timed function measures. CONCLUSIONS:We describe normative data and repeatability performance for multiple physical function measures in an adult FKRP muscular dystrophy population. Our analysis indicates that deep learning algorithms can be used to quantify healthy and dystrophic muscle seen on whole-body imaging. TRIAL REGISTRATION:This study was retrospectively registered in clinicaltrials.gov (NCT02841267) on July 22, 2016 and data supporting this study has been submitted to this registry.

SUBMITTER: Leung DG

PROVIDER: S-EPMC7236878 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy.

Leung Doris G DG Bocchieri Alex E AE Ahlawat Shivani S Jacobs Michael A MA Parekh Vishwa S VS Braverman Vladimir V Summerton Katherine K Mansour Jennifer J Bibat Genila G Morris Carl C Marraffino Shannon S Wagner Kathryn R KR

BMC neurology 20200519 1

<h4>Background</h4>Pathogenic variants in the FKRP gene cause impaired glycosylation of α-dystroglycan in muscle, producing a limb-girdle muscular dystrophy with cardiomyopathy. Despite advances in understanding the pathophysiology of FKRP-associated myopathies, clinical research in the limb-girdle muscular dystrophies has been limited by the lack of normative biomarker data to gauge disease progression.<h4>Methods</h4>Participants in a phase 2 clinical trial were evaluated over a 4-month, untre ...[more]

PMID: 32429923

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Project description:BackgroundFacioscapulohumeral 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.MethodsWe 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.ResultsThere 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.ConclusionsAssessing 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.

Dataset Information

Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy.

Publications

Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy.

Similar Datasets

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