Dataset Information

Associations between lower extremity muscle fat fraction and motor performance in myotonic dystrophy type 2: A pilot study.

ABSTRACT:

Introduction/aims

Although muscle structure measures from magnetic resonance imaging (MRI) have been used to assess disease severity in muscular dystrophies, little is known about how these measures are affected in myotonic dystrophy type 2 (DM2). We aim to characterize lower extremity muscle fat fraction (MFF) as a potential biomarker of disease severity, and evaluate its relationship with motor performance in DM2.

Methods

3-Tesla MRIs were obtained from nine patients with DM2 and six controls using a T1W-Dixon protocol. To calculate MFF, muscle volumes were segmented from proximal, middle, and distal regions of the thigh and calf. Associations between MFF and motor performance were calculated using Spearman's correlations (ρ).

Results

Mean age of DM2 participants was 62 ± 11 y (89% female), and mean symptom duration was 20 ± 12 y. Compared to controls, the DM2 group had significantly higher MFF in the thigh and the calf segments (p-value = .002). The highest MFF at the thigh in DM2 was located in the posterior compartment (39.7 ± 12.9%) and at the calf was the lateral compartment (31.5 ± 8.7%). In the DM2 group, we found a strong correlation between the posterior thigh MFF and the 6-min walk test (ρ = -.90, p-value = .001). The lateral calf MFF was also strongly correlated with the step test (ρ = -0.82, p-value = .006).

Discussion

Our pilot data suggest a potential correlation between lower extremity MFF and some motor performance tests in DM2. Longitudinal studies with larger sample sizes are required to validate MFF as a marker of disease severity in DM2.

SUBMITTER: Madrid DA

PROVIDER: S-EPMC10898809 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Associations between lower extremity muscle fat fraction and motor performance in myotonic dystrophy type 2: A pilot study.

Madrid Diana A DA Knapp Rebecca A RA Lynch Delanie D Clemens Paula P Weaver Ashley A AA Puwanant Araya A

Muscle & nerve 20230403 6

<h4>Introduction/aims</h4>Although muscle structure measures from magnetic resonance imaging (MRI) have been used to assess disease severity in muscular dystrophies, little is known about how these measures are affected in myotonic dystrophy type 2 (DM2). We aim to characterize lower extremity muscle fat fraction (MFF) as a potential biomarker of disease severity, and evaluate its relationship with motor performance in DM2.<h4>Methods</h4>3-Tesla MRIs were obtained from nine patients with DM2 an ...[more]

PMID: 36938823

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Project description:Cardiac involvement is one of the most important manifestations of the multisystemic phenotype of patients affected by myotonic dystrophy (DM) and represents the second cause of premature death. Molecular mechanisms responsible for DM cardiac defects are still unclear; however, missplicing of the cardiac isoform of troponin T (TNNT2) and of the cardiac sodium channel (SCN5A) genes might contribute to the reduced myocardial function and conduction abnormalities seen in DM patients. Since, in DM skeletal muscle, the TNNT2 gene shows the same aberrant splicing pattern observed in cardiac muscle, the principal aim of this work was to verify if the TNNT2 aberrant fetal isoform expression could be secondary to myopathic changes or could reflect the DM cardiac phenotype. Analysis of alternative splicing of TNNT2 and of several genes involved in DM pathology has been performed on muscle biopsies from patients affected by DM type 1 (DM1) or type 2 (DM2) with or without cardiac involvement. Our analysis shows that missplicing of muscle-specific genes is higher in DM1 and DM2 than in regenerating control muscles, indicating that these missplicing could be effectively important in DM skeletal muscle pathology. When considering the TNNT2 gene, missplicing appears to be more evident in DM1 than in DM2 muscles since, in DM2, the TNNT2 fetal isoform appears to be less expressed than the adult isoform. This evidence does not seem to be related to less severe muscle histopathological alterations that appear to be similar in DM1 and DM2 muscles. These results seem to indicate that the more severe TNNT2 missplicing observed in DM1 could not be related only to myopathic changes but could reflect the more severe general phenotype compared to DM2, including cardiac problems that appear to be more severe and frequent in DM1 than in DM2 patients. Moreover, TNNT2 missplicing significantly correlates with the QRS cardiac parameter in DM1 but not in DM2 patients, indicating that this splicing event has good potential to function as a biomarker of DM1 severity and it should be considered in pharmacological clinical trials to monitor the possible effects of different therapeutic approaches on skeletal muscle tissues.

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Dataset Information

Associations between lower extremity muscle fat fraction and motor performance in myotonic dystrophy type 2: A pilot study.

Introduction/aims

Methods

Results

Discussion

Publications

Associations between lower extremity muscle fat fraction and motor performance in myotonic dystrophy type 2: A pilot study.

Similar Datasets

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