The motor neuron response to SMN1 deficiency in spinal muscular atrophy

Authors

  • Peter B. Kang MD,

    Corresponding author
    1. Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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  • Clifton L. Gooch MD,

    1. Department of Neurology, Columbia University, New York, New York, USA
    2. Department of Neurology, University of South Florida College of Medicine, Tampa, Florida, USA
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  • Michael P. McDermott PhD,

    1. Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA
    2. Department of Neurology, University of Rochester, Rochester, New York, USA
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  • Basil T. Darras MD,

    1. Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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  • Richard S. Finkel MD,

    1. Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    2. Division of Neurology, Nemours Children's Hospital, Orlando, Florida, USA
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  • Michele L. Yang MD,

    1. Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    2. Division of Neurology, Children's Hospital Colorado, Aurora, Colorado, USA
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  • Douglas M. Sproule MD, MSc,

    1. Department of Neurology, Columbia University, New York, New York, USA
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  • Wendy K. Chung MD, PhD,

    1. Department of Pediatrics, Columbia University, New York, New York, USA
    2. Department of Medicine, Columbia University, New York, New York, USA
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  • Petra Kaufmann MD, MSc,

    1. Department of Neurology, Columbia University, New York, New York, USA
    2. National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA
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  • Darryl C. de Vivo MD,

    1. Department of Neurology, Columbia University, New York, New York, USA
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  • for the Muscle Study Group and the Pediatric Neuromuscular Clinical Research Network for Spinal Muscular Atrophy


  • Disclosure: The content of this report is solely the responsibility of the authors and should not be considered as the opinion or position of the NIH or its affiliates.

  • This study was funded by the Spinal Muscular Atrophy Foundation. Additional clinical research support was provided to Columbia University through the CTSA (UL1 RR024156) from NCRR/NIH and the NSADA K12 program (NINDS training grant); to The Children's Hospital of Philadelphia through the CTSA (UL1-RR-024134) from NCRR/NIH; and to Harvard University (UL1 RR025755-01), Harvard Catalyst Clinical and Translational Science Center, from NCRR/NIH.

ABSTRACT

Introduction: The purpose of this study was to measure and analyze motor unit number estimation (MUNE) values longitudinally in spinal muscular atrophy (SMA). Methods: Sixty-two children with SMA types 2 and 3 were observed prospectively for up to 42 months. Longitudinal electrophysiological data were collected, including compound motor action potential (CMAP), single motor unit action potential (SMUP), and MUNE. Results: Significant motor neuron loss and compensatory collateral reinnervation were noted at baseline. Over time, there was a significant mean increase in MUNE (4.92 units/year, P = 0.009), a mean decrease in SMUP amplitude (−6.32 μV/year, P = 0.10), and stable CMAP amplitude. Conclusions: The unexpected longitudinal results differ from findings in amyotrophic lateral sclerosis studies, perhaps indicating that compensatory processes in SMA involve new motor unit development. A better understanding of the mechanisms of motor unit decline and compensation in SMA is important for assessing novel therapeutic strategies and for providing key insights into disease pathophysiology. Muscle Nerve 49: 636–644, 2014

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