Research Article| Volume 358, ISSUE 1-2, P178-182, November 15, 2015

Quantitative muscle ultrasound measures rapid declines over time in children with SMA type 1

  • Kay W. Ng
    Washington University School of Medicine, Department of Neurology, St. Louis, MO 63110, United States
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  • Anne M. Connolly
    Washington University School of Medicine, Department of Neurology, St. Louis, MO 63110, United States

    Washington University School of Medicine, Department of Pediatrics, St. Louis, MO 63110, United States
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  • Craig M. Zaidman
    Corresponding author at: Washington University School of Medicine, Department of Neurology, 660 S. Euclid Ave, Box 8111, St. Louis, MO 63110, United States.
    Washington University School of Medicine, Department of Neurology, St. Louis, MO 63110, United States

    Washington University School of Medicine, Department of Pediatrics, St. Louis, MO 63110, United States
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Published:August 26, 2015DOI:


      • Muscle ultrasound in three children with SMA type 1 showed progressive atrophy and increased echogenicity over time.
      • Proximal muscles atrophied more than distal muscles.
      • Muscle ultrasound can appear normal in very young children with SMA type 1.
      • Quantitative muscle ultrasound may be a useful biomarker in SMA type 1.


      Muscles are small in spinal muscular atrophy (SMA). It is not known if muscle size changes over time in SMA type 1. We quantified changes over time in muscle size and echointensity during two repeated ultrasound examinations of unilateral proximal (biceps brachii/brachialis and quadriceps) and distal (anterior forearm flexors and tibialis anterior) muscles in three children with SMA type 1. We compared muscle thickness (MT) to body weight-dependent normal reference values. Children were 1, 6, and 11 months old at baseline and had 2, 2 and 4 months between ultrasound examinations, respectively. At baseline, MT was normal for weight in all muscles except an atrophic quadriceps in the oldest child. MT decreased and echointensity increased (worsened) over time. At follow up, MT was below normal for weight in the quadriceps in all three children, in the biceps/brachioradialis in two, and in the anterior forearm in one. Tibialis anterior MT remained normal for weight in all three children. Muscle echointensity increased over time in all muscles and, on average, more than doubled in two children. In children with SMA type 1, muscle atrophies and becomes hyperechoic over time. Quantitative muscle ultrasound measures disease progression in SMA type 1 that warrants additional study in more children.


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        • Sproule D.M.
        • Kaufmann P.
        Therapeutic developments in spinal muscular atrophy.
        Ther. Adv. Neurol. Disord. 2010; 3: 173-185
        • Mercuri E.
        • Bertini E.
        • Iannaccone S.T.
        Childhood spinal muscular atrophy: controversies and challenges.
        Lancet Neurol. 2012; 11: 443-452
        • Hirtz D.
        • Iannaccone S.
        • Heemskerk J.
        • Gwinn-Hardy K.
        • Moxley 3rd, R.
        • Rowland L.P.
        Challenges and opportunities in clinical trials for spinal muscular atrophy.
        Neurology. 2005; 65: 1352-1357
        • Zanetta C.
        • Nizzardo M.
        • Simone C.
        • Monguzzi E.
        • Bresolin N.
        • Comi G.P.
        • et al.
        Molecular therapeutic strategies for spinal muscular atrophies: current and future clinical trials.
        Clin. Ther. 2014; 36: 128-140
        • Sproule D.M.
        • Montgomery M.J.
        • Punyanitya M.
        • Shen W.
        • Dashnaw S.
        • Montes J.
        • et al.
        Thigh muscle volume measured by magnetic resonance imaging is stable over a 6-month interval in spinal muscular atrophy.
        J. Child Neurol. 2011; 26: 1252-1259
        • Sproule D.M.
        • Montes J.
        • Montgomery M.
        • Battista V.
        • Koenigsberger D.
        • Shen W.
        • et al.
        Increased fat mass and high incidence of overweight despite low body mass index in patients with spinal muscular atrophy.
        Neuromuscul. Disord. 2009; 19: 391-396
        • Sproule D.M.
        • Punyanitya M.
        • Shen W.
        • Dashnaw S.
        • Martens B.
        • Montgomery M.
        • et al.
        Muscle volume estimation by magnetic resonance imaging in spinal muscular atrophy.
        J. Child Neurol. 2011; 26: 309-317
        • Juul-Kristensen B.
        • Bojsen-Moller F.
        • Holst E.
        • Ekdahl C.
        Comparison of muscle sizes and moment arms of two rotator cuff muscles measured by ultrasonography and magnetic resonance imaging.
        Eur. J. Ultrasound. 2000; 11: 161-173
        • Worsley P.R.
        • Kitsell F.
        • Samuel D.
        • Stokes M.
        Validity of measuring distal vastus medialis muscle using rehabilitative ultrasound imaging versus magnetic resonance imaging.
        Man. Ther. 2014; 19: 259-263
        • Reeves N.D.
        • Maganaris C.N.
        • Narici M.V.
        Ultrasonographic assessment of human skeletal muscle size.
        Eur. J. Appl. Physiol. 2004; 91: 116-118
        • Zaidman C.M.
        • Wu J.S.
        • Wilder S.
        • Darras B.T.
        • Rutkove S.B.
        Minimal training is required to reliably perform quantitative ultrasound of muscle.
        Muscle Nerve. 2014; 50: 124-128
        • Pillen S.
        • van Keimpema M.
        • Nievelstein R.A.
        • Verrips A.
        • van Kruijsbergen-Raijmann W.
        • Zwarts M.J.
        Skeletal muscle ultrasonography: visual versus quantitative evaluation.
        Ultrasound Med. Biol. 2006; 32: 1315-1321
        • Jacobs J.
        • Jansen M.
        • Janssen H.
        • Raijmann W.
        • Van Alfen N.
        • Pillen S.
        Quantitative muscle ultrasound and muscle force in healthy children: a 4-year follow-up study.
        Muscle Nerve. 2013; 47: 856-863
        • Zaidman C.M.
        • Holland M.R.
        • Anderson C.C.
        • Pestronk A.
        Calibrated quantitative ultrasound imaging of skeletal muscle using backscatter analysis.
        Muscle Nerve. 2008; 38: 893-898
        • Zaidman C.M.
        • Holland M.R.
        • Hughes M.S.
        Quantitative ultrasound of skeletal muscle: reliable measurements of calibrated muscle backscatter from different ultrasound systems.
        Ultrasound Med. Biol. 2012; 38: 1618-1625
        • Shklyar I.
        • Geisbush T.R.
        • Mijialovic A.S.
        • Pasternak A.
        • Darras B.T.
        • Wu J.S.
        • et al.
        Quantitative muscle ultrasound in Duchenne muscular dystrophy: a comparison of techniques.
        Muscle Nerve. 2015; 51: 207-213
        • Zaidman C.M.
        • Malkus E.C.
        • Connolly A.M.
        Muscle ultrasound quantifies disease progression over time in infants and young boys with Duchenne muscular dystrophy.
        Muscle Nerve. 2015; 52: 334-348
        • Schmidt R.
        • Voit T.
        Ultrasound measurement of quadriceps muscle in the first year of life. Normal values and application to spinal muscular atrophy.
        Neuropediatrics. 1993; 24: 36-42
        • Wu J.S.
        • Darras B.T.
        • Rutkove S.B.
        Assessing spinal muscular atrophy with quantitative ultrasound.
        Neurology. 2010; 75: 526-531
        • Pillen S.
        • Arts I.M.
        • Zwarts M.J.
        Muscle ultrasound in neuromuscular disorders.
        Muscle Nerve. 2008; 37: 679-693
        • Srivastava T.
        • Darras B.T.
        • Wu J.S.
        • Rutkove S.B.
        Machine learning algorithms to classify spinal muscular atrophy subtypes.
        Neurology. 2012; 79: 358-364
        • Scholten R.R.
        • Pillen S.
        • Verrips A.
        • Zwarts M.J.
        Quantitative ultrasonography of skeletal muscles in children: normal values.
        Muscle Nerve. 2003; 27: 693-698
        • WHO
        Child growth standards based on length/height, weight and age.
        Acta Paediatr. 2006; 450: 76-85
        • Mentis G.Z.
        • Blivis D.
        • Liu W.
        • Drobac E.
        • Crowder M.E.
        • Kong L.
        • et al.
        Early functional impairment of sensory–motor connectivity in a mouse model of spinal muscular atrophy.
        Neuron. 2011; 69: 453-467
        • Swoboda K.J.
        • Prior T.W.
        • Scott C.B.
        • McNaught T.P.
        • Wride M.C.
        • Reyna S.P.
        • et al.
        Natural history of denervation in SMA: relation to age, SMN2 copy number, and function.
        Ann. Neurol. 2005; 57: 704-712
        • Abe T.
        • Kawakami Y.
        • Suzuki Y.
        • Gunji A.
        • Fukunaga T.
        Effects of 20 days bed rest on muscle morphology.
        J. Gravit. Physiol. 1997; 4: S10-S14
        • Finkel R.S.
        • McDermott M.P.
        • Kaufmann P.
        • Darras B.T.
        • Chung W.K.
        • Sproule D.M.
        • et al.
        Observational study of spinal muscular atrophy type I and implications for clinical trials.
        Neurology. 2014; 83: 810-817
        • Kaufmann P.
        • McDermott M.P.
        • Darras B.T.
        • Finkel R.
        • Kang P.
        • Oskoui M.
        • et al.
        Observational study of spinal muscular atrophy type 2 and 3: functional outcomes over 1 year.
        Arch. Neurol. 2011; 68: 779-786
        • Fivez T.
        • Hendrickx A.
        • Van Herpe T.
        • Vlasselaers D.
        • Desmet L.
        • Van den Berghe G.
        • et al.
        An analysis of reliability and accuracy of muscle thickness ultrasonography in critically ill children and adults.
        JPEN J. Parenter. Enteral Nutr. 2015;