Validation of Motor Outcome Measures in Myotonic Dystrophy Type 2.

Federica Montagnese,Emanuele Rastelli,Nina Khizanishvili,Benedikt Schoser,Kristina Stahl,Roberto Massa

doi:10.3389/fneur.2020.00306

Abstract

Introduction: Myotonic dystrophy type 2 (DM2) lacks disease-specific, validated, motor outcome measures (OMs), and patients' reported outcomes (PROs). This represents a limit for the monitoring of disease progression and treatment response. Our aim was to identify the most appropriate OMs to be translated in clinical practice and clinical trials on DM2. This study has been registered on clinicaltrials.gov NCT03603171 (https://clinicaltrials.gov/ct2/show/NCT03603171).Methods: Sixty-six patients with genetically confirmed DM2 underwent a baseline and a follow-up visit after 1 year. The tested OMs included: hand opening time, pressure pain threshold (PPT), manual muscle testing (MMT), hand held dynamometry (HHD), scale for the assessment and rating of ataxia (SARA), quantitative motor function test (QMFT), gait stairs Gowers chair (GSGC), 30-s sit to stand test, functional index 2 (FI-2) and 6MWT. The PROs included DM1-Active-C, Rasch-built Pompe-specific activity scale (R-Pact), fatigue and daytime sleepiness (FDSS), brief pain inventory short form (BPI-sf), myotonia behavior scale (MBS), and the McGill pain questionnaire.Results: All patients completed the MBS and the results correlated well with the hand-opening time. The PPT showed a low reliability, no correlation with pain questionnaires, and did not differentiate patients with or without myalgia. Both muscle strength assessments, MMT and HHD, showed good construct validity. The QMFT showed an acceptable ceiling effect (14.5%), good convergent and differential validity and performed overall better than GSGC. The SARA score showed high flooring effect and is not useful in DM2. 6MWT proved a valid outcome measure in DM2. The 30-s sit to stand is a feasible test with good convergent validity, showing a flooring effect of 20% as it cannot be used in more severely affected patients. The FI-2 is time-consuming and has a high ceiling effect. At the 1-year visit the only assessments able to detect a worsening of DM2 were HHD, QMFT, and 6MWT, which are the most sensitive to change, and therefore clinically meaningful OMs in DM2.Conclusion: The clinical meaningful motor outcome measures that best depict the multifaceted phenotype of DM2 and its slow progression are MBS, MMT, or HHD (depending on the clinical setting), QMFT, and the 6MWT.

Highlights

Myotonic dystrophy type 2 (DM2) lacks disease-specific, validated, motor outcome measures (OMs), and patients’ reported outcomes (PROs)
The first symptoms usually occur after the 3rd to 4th decade of life, when patients complain of myalgia, mostly exerciseinduced, and proximal as well as axial weakness; a smaller proportion of patients show signs and symptoms of a usually mild myotonia
As in myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2) patients present a multisystemic involvement with higher risk for developing heart diseases, cataract and endocrine dysfunction in comparison to the general population [3, 4]

Summary

Introduction

Myotonic dystrophy type 2 (DM2) lacks disease-specific, validated, motor outcome measures (OMs), and patients’ reported outcomes (PROs). In order to evaluate the efficacy of any future therapies, reliable and disease-specific outcome measures are necessary to detect any clinically relevant changes of patients under treatment. In this regard, several functioning and disability scales have already been tested and validated in DM1 patients (6-min walk test, muscle impairment rating scale, DM1-Active-C, scale for assessment and rating of ataxia) [5,6,7,8]. The aim of our study is to test how the most widely used motor outcome measures would perform in the DM2 population, in order to identify a feasible test battery to be adopted in clinical trials and patients’ follow-up

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Results

Conclusion