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Abstract
Background and Objectives Limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12) is a rare hereditary muscular dystrophy for which outcome measures are currently lacking. We evaluated quantitative MRI and clinical outcome measures to track disease progression to determine which tests could be useful in future clinical trials to evaluate potential therapies.
Methods We prospectively measured the following outcome measures in all participants at baseline and after 1 and 2 years: 6-minute walk distance (6MWD), 10-meter walk test (10MWT), the Medical Research Council (MRC) sum scores, Biodex isometric dynamometry, serum creatine kinase, and 6-point Dixon MRI of the thighs.
Results We included 24 genetically confirmed, adult patients with LGMDR12 and 24 age-matched and sex-matched healthy controls. Patients with intermediate-stage thigh muscle fat replacement at baseline (proton density fat fraction [PDFF] 20%–70%) already showed an increase in PDFF in 8 of the 14 evaluated thigh muscles after 1 year. The standardized response mean demonstrated a high responsiveness to change in PDFF for 6 individual muscles over 2 years in this group. However, in patients with early-stage (<20%) or end-stage (>70%) muscle fat replacement, PDFF did not increase significantly over 2 years of follow-up. Biodex isometric dynamometry showed a significant decrease in muscle strength in all patients in the right and left hamstrings (−6.2 Nm, p < 0.002 and −4.6 Nm, p < 0.009, respectively) and right quadriceps muscles (−9 Nm, p = 0.044) after 1 year of follow-up, whereas the 6MWD, 10MWT, and MRC sum scores were not able to detect a significant decrease in muscle function/strength even after 2 years. There was a moderately strong correlation between total thigh PDFF and clinical outcome measures at baseline.
Discussion Thigh muscle PDFF imaging is a sensitive outcome measure to track progressive muscle fat replacement in selected patients with LGMDR12 even after 1 year of follow-up and correlates with clinical outcome measures. Biodex isometric dynamometry can reliably capture the loss of muscle strength over the course of 1 year in patients with LGMDR12 and should be included as an outcome measure in future clinical trials as well.
Glossary
- 10MWT=
- 10-meter walk test;
- 6MWD=
- 6-minute walk distance;
- ANO5=
- anoctamin-5;
- ASIS=
- anterior superior iliac spine;
- CK=
- creatine kinase;
- CNN=
- convolutional neural network;
- FOV=
- field of view;
- ICC=
- intraclass correlation coefficient;
- LGMDR12=
- Limb-girdle muscular dystrophy autosomal recessive type 12;
- MCID=
- minimal clinically important difference;
- MRC=
- Medical Research Council;
- PDFF=
- Proton density fat fraction;
- SRM=
- standardized response mean;
- TE=
- echo time;
- TR=
- repetition time
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Anthony Amato, MD, FAAN.
- Received December 19, 2021.
- Accepted in final form March 24, 2022.
- © 2022 American Academy of Neurology
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- Author Response: Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years of Follow-up
- Reader Response: Prospective Natural History Study in 24 Adult Patients With LGMDR12 Over 2 Years of Follow-up: Quantitative MRI and Clinical Outcome Measures
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