Responsiveness and Minimal Clinically Important Difference of the Motor Function Measure in Collagen VI-Related Dystrophies and Laminin Alpha2-Related Muscular Dystrophy

Published:November 05, 2020DOI:



      To investigate the responsiveness of the motor function measure (MFM) and determine the minimal clinically important difference (MCID) in individuals with 2 common types of congenital muscular dystrophy (CMD).


      Observational, prospective, single center, cohort study.


      National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH).


      Individuals (N=44) with collagen VI-related dystrophies (COL6-RD, n=23) and 21 individuals laminin alpha2-related muscular dystrophy (LAMA2-RD, n=21) enrolled in a 4-year longitudinal natural history study.


      Not applicable.

      Main Outcome Measures

      Responsiveness of the MFM-32 and the Rasch-scaled MFM-25 and the MCID of the MFM-32 determined from a patient-reported anchor with 2 different methods, within-patient and between-patient.


      The original MFM-32 and Rasch-scaled MFM-25 performed similarly overall in both the COL6-RD and LAMA2-RD populations, with all subscores (D1, standing and transfers; D2, axial and proximal; D3, distal) showing a significant decrease over time, except MFM D1 and D3 for LAMA2-RD. The MFM D1 subscore was the most sensitive to change for ambulant individuals, whereas the MFM D2 subscore was the most sensitive to change for nonambulant individuals. The MCID for the MFM-32 total score was calculated as 2.5 and 3.9 percentage points according to 2 different methods.


      The MFM showed strong responsiveness in individuals with LAMA2-RD and COL6-RD. Because a floor effect was identified more prominently with the Rasch-Scaled MFM-25, the use of the original MFM-32 as a quantitative variable with the assumption of scale linearity appears to be a good compromise. When designing clinical trials in congenital muscular dystrophies, the use of MCID for MFM should be considered to determine if a given intervention effects show not only a statistically significant change but also a clinically meaningful change.


      List of abbreviations:

      6WMT (6-minute walk test), CMD (congenital muscular dystrophy), COL6-RD (collagen VI-related dystrophy), D1 (motor function measure D1 subscore), D2 (motor function measure D2 subscore), D3 (motor function measure D3 subscore), DMD (Duchenne muscular dystrophy), LAMA2-RD (laminin, alpha2-related muscular dystrophy), MCID (minimal clinically important difference), MFM (motor function measure), NIH (National Institutes of Health), NMD (neuromuscular disease), SMA (spinal muscular atrophy), TS (motor function measure total score)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Archives of Physical Medicine and Rehabilitation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Muntoni F.
        • Voit T.
        The congenital muscular dystrophies in 2004: a century of exciting progress.
        Neuromuscul Disord. 2004; 14: 635-649
        • Bönnemann C.G.
        • Rutkowski A.
        • Mercuri E.
        • Muntoni F.
        CMD Outcomes Consortium. 173rd ENMC International Workshop: congenital muscular dystrophy outcome measures 5-7 March 2010, Naarden, The Netherlands.
        Neuromuscul Disord. 2011; 21: 513-522
        • Bérard C.
        • Payan C.
        • Hodgkinson I.
        • Fermanian J.
        • MFM Collaborative Study Group
        A motor function measure for neuromuscular diseases. Construction and validation study.
        Neuromuscul Disord. 2005; 15: 463-470
        • Vuillerot C.
        • Rippert P.
        • Kinet V.
        • et al.
        Rasch analysis of the motor function measure in patients with congenital muscle dystrophy and congenital myopathy.
        Arch Phys Med Rehabil. 2014; 95: 2086-2095
        • Jain M.S.
        • Meilleur K.
        • Kim E.
        • et al.
        Longitudinal changes in clinical outcome measures in COL6-related dystrophies and LAMA2-related dystrophies.
        Neurology. 2019; 93: e1932-e1943
        • Norman G.R.
        • Stratford P.
        • Regehr G.
        Methodological problems in the retrospective computation of responsiveness to change: the lesson of Cronbach.
        J Clin Epidemiol. 1997; 50: 869-879
        • Guyatt G.H.
        • Deyo R.A.
        • Charlson M.
        • Levine M.N.
        • Mitchell A.
        Responsiveness and validity in health status measurement: a clarification.
        J Clin Epidemiol. 1989; 42: 403-408
        • Sloan J.
        • Symonds T.
        • Vargas-Chanes D.
        • Fridley B.
        Practical guidelines for assessing the clinical significance of health-related quality of life changes within clinical trials.
        Ther Innov Regul Sci. 2003; 37: 23-31
        • de Vet H.C.
        • Terwee C.B.
        • Ostelo R.W.
        • Beckerman H.
        • Knol D.L.
        • Bouter L.M.
        Minimal changes in health status questionnaires: distinction between minimally detectable change and minimally important change.
        Health Qual Life Outcomes. 2006; 4: 54
        • Rai S.K.
        • Yazdany J.
        • Fortin P.R.
        • Aviña-Zubieta J.A.
        Approaches for estimating minimal clinically important differences in systemic lupus erythematosus.
        Arthritis Res Ther. 2015; 17: 143
        • Wright B.D.
        • Linacre J.M.
        Observations are always ordinal; measurements, however, must be interval.
        Arch Phys Med Rehabil. 1989; 70: 857-860
        • Brentani E.
        • Golia S.
        Unidimensionality in the Rasch model: how to detect and interpret.
        Statistica. 2007; 67: 253-261
        • Meilleur K.G.
        • Jain M.S.
        • Hynan L.S.
        • et al.
        Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies.
        Neuromuscul Disord. 2015; 25: 43-54
        • McHorney C.A.
        • Tarlov A.R.
        Individual-patient monitoring in clinical practice: are available health status surveys adequate?.
        Qual Life Res. 1995; 4: 293-307
        • Terwee C.B.
        • Bot S.D.M.
        • de Boer M.R.
        • et al.
        Quality criteria were proposed for measurement properties of health status questionnaires.
        J Clin Epidemiol. 2007; 60: 34-42
        • Kirshner B.
        • Guyatt G.
        A methodological framework for assessing health indices.
        J Chronic Dis. 1985; 38: 27-36
        • Oeffinger D.
        • Bagley A.
        • Rogers S.
        • et al.
        Outcome tools used for ambulatory children with cerebral palsy: responsiveness and minimum clinically important differences.
        Dev Med Child Neurol. 2008; 50: 918-925
        • Vuillerot C.
        • Payan C.
        • Iwaz J.
        • Ecochard R.
        • Bérard C.
        • MFM Spinal Muscular Atrophy Study Group
        Responsiveness of the motor function measure in patients with spinal muscular atrophy.
        Arch Phys Med Rehabil. 2013; 94: 1555-1561
        • Bartels B.
        • Pangalila R.F.
        • Bergen M.P.
        • Cobben N.A.M.
        • Stam H.J.
        • Roebroeck M.E.
        Upper limb function in adults with Duchenne muscular dystrophy.
        J Rehabil Med. 2011; 43: 770-775
        • Middel B.
        • van Sonderen E.
        Statistical significant change versus relevant or important change in (quasi) experimental design: some conceptual and methodological problems in estimating magnitude of intervention-related change in health services research.
        Int J Integr Care. 2002; 2: e15
        • Terwee C.B.
        • Roorda L.D.
        • Dekker J.
        • et al.
        Mind the MIC: large variation among populations and methods.
        J Clin Epidemiol. 2010; 63: 524-534
        • Revicki D.
        • Hays R.D.
        • Cella D.
        • Sloan J.
        Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes.
        J Clin Epidemiol. 2008; 61: 102-109
        • King M.T.
        A point of minimal important difference (MID): a critique of terminology and methods.
        Expert Rev Pharmacoecon Outcomes Res. 2011; 11: 171-184
        • Vuillerot C.
        • Payan C.
        • Girardot F C.
        • et al.
        Responsiveness of the motor function measure in neuromuscular diseases.
        Arch Phys Med Rehabil. 2012; 93 (2251-6.e1)
        • Mayhew A.G.
        • Cano S.J.
        • Scott E.
        • et al.
        Detecting meaningful change using the North Star Ambulatory Assessment in Duchenne muscular dystrophy.
        Dev Med Child Neurol. 2013; 55: 1046-1052
        • McDonald C.M.
        • Henricson E.K.
        • Abresch R.T.
        • et al.
        The 6-minute walk test and other clinical endpoints in Duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study.
        Muscle Nerve. 2013; 48: 357-368
        • Finkel R.S.
        • Mercuri E.
        • Darras B.T.
        • et al.
        Nusinersen versus sham control in infantile-onset spinal muscular atrophy.
        N Engl J Med. 2017; 377: 1723-1732
        • Swoboda K.J.
        • Scott C.B.
        • Crawford T.O.
        • et al.
        SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of l-carnitine and valproic acid in spinal muscular atrophy.
        PLoS One. 2010; 5e12140
        • Henricson E.
        • Abresch R.
        • Han J.J.
        • et al.
        The 6-minute walk test and person-reported outcomes in boys with Duchenne muscular dystrophy and typically developing controls: longitudinal comparisons and clinically-meaningful changes over one year.
        PLoS Curr. 2013; 5
        • Maydeu-Olivares A.
        • Fairchild A.J.
        • Hall A.G.
        Goodness of fit in item factor analysis: effect of the number of response alternatives.
        Struct Equ Modeling. 2017; 24: 495-505