Natural History of Adult-Onset Myotonic Dystrophy Type 1: Longitudinal Changes in Radiologic, Clinical, and...

Area of Science:

• Neurology
• Medical Imaging
• Clinical Trials

Background:

• Adult-onset myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disorder.
• Emerging disease-modifying therapies necessitate sensitive outcome measures for clinical trials.

Purpose of the Study:

• Characterize the 2-year natural history of adult-onset DM1.
• Evaluate quantitative MRI (qMRI) and clinical outcomes for trial suitability.

Main Methods:

• Prospective study of 30 DM1 patients and 30 controls over 24 months.
• qMRI measured proton density fat fraction (PDFF) and T2H2O in leg muscles.
• Assessed clinical outcomes including MFM32, 6MWD, and patient-reported measures (DM1-ActivC, INQoL).

Main Results:

• Baseline PDFF was significantly higher in DM1 patients' leg muscles.
• PDFF increased significantly over 24 months, particularly in distal leg muscles, with detectable changes in 6-month intervals.
• MFM32, MRC sum score, and DM1-ActivC declined significantly; INQoL showed deterioration at 12 and 18 months.

Conclusions:

• PDFF is a sensitive, objective outcome measure for adult-onset DM1, detecting change within 6-month intervals.
• MFM32, MRC sum score, DM1-ActivC, and INQoL are valuable clinical outcomes for trials.
• Combined use of qMRI and clinical measures is supported for future DM1 trials.