Responsiveness of outcome measures in myotonic dystrophy type 1

Abstract

Objective As myotonic dystrophy type 1(DM1) evolves slowly and interventional trials often have a short duration, responsive outcomes in DM1 are needed. The objective of this study was to determine the responsiveness of muscle strength, balance, and functional mobility measurements after a 1‐year follow‐up period in individuals with DM1. Methods Sixty‐three adults with noncongenital DM1 completed the following assessments at baseline and at 1‐year follow‐up: Handheld dynamometry (lower limbs), stationary dynamometry (lower limbs), step test, timed‐up‐and‐go test (TUG), modified clinical test of sensory integration and balance (mCTSIB), feet‐together stance, tandem stance, one‐leg stance, 10‐meter walk test, and sit‐to‐stand test. Results Change was captured by stationary dynamometry (proximal flexor and extensor muscles), handheld dynamometry (proximal flexor and distal extensor muscles), TUG, and mCTSIB (P ≤ 0.04). Ceiling or floor effects were shown for most static balance tests. Interpretation Overall, adequate responsiveness was shown for both muscle strength dynamometers, TUG and mCTSIB. These outcomes are therefore likely candidate endpoints for clinical trials lasting 1 year. Most static balance tests are not responsive and not recommended in a heterogeneous DM1 population.

Outcome measures frequently used to assess muscle strength in patients with myotonic dystrophy type 1: a systematic review

“…From the 39 studies that used quantitative muscle test, 17 studies did not report the method used [57,[68][69][70]73,[75][76][77][78][79]81,82,85,86,107,108,110], ten studies assessed maximum isometric torque [53,59,62,63,65,[70][71][72]79,108], seven studies assessed maximal voluntary isometric contraction [54,55,58,66,67,73,87] Maximal voluntary isometric contraction was used to assess the strength of Abductor digiti minimi [54], ankle dorsiflexors [58,87], ankle plantar flexors [87], grip strength [56,66,67], elbow flexors [73], elbow extensors [73], hip abductors [87], hip extensors [87], knee extensors [58, 73,87], knee flexors [73,87] and pinch strength [56]. Maximal voluntary isometric contraction results were between...…”

“…Maximum isometric torque was used to assess the strength of ankle dorsiflexors [53,59,62,63,65,70,71,72,108], ankle evertors [62,63], ankle plantar flexors [53,71,72], elbow extensors [53,59,70,71,72,108] in controls (table 2 and Figure 2C).…”

“…Only 17 studies reported on longitudinal data: a cardiac study [105], 14 skeletal muscle strength studies [55,59,61,62,68,70,71,72,76,79,80,81,86,105], and two respiratory muscle strength studies [88,93].…”

“…7 Nm [59,72] and a median change of -25.2 Nm [70] over two week to 9 years. A negative mean of -17.0±13.1 Nm [59] and median between -2.2 Nm to -16.5 Nm change over one year to 9 years was also observed for knee flexors [70,71].…”

Corrigendum

“…In Knak et al, 2020, 1 the error bars (AUC 95% CI) in Figure 3 were incorrect. The corrected error bars appear in the revised figure below.…”