The motor neuron response to SMN1 deficiency in spinal muscular atrophy

Muscle Nerve. 2014 May;49(5):636-44. doi: 10.1002/mus.23967.


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.

Keywords: compound motor action potential; electrophysiology; motor neuron disease; motor unit number estimation; spinal muscular atrophy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Adaptation, Physiological / physiology*
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Disease Progression
  • Electromyography
  • Exons
  • Female
  • Gene Deletion
  • Homozygote
  • Humans
  • Infant
  • Linear Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Motor Neurons / physiology*
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiopathology*
  • Prospective Studies
  • Spinal Muscular Atrophies of Childhood / genetics*
  • Spinal Muscular Atrophies of Childhood / physiopathology
  • Survival of Motor Neuron 1 Protein / genetics*
  • Young Adult


  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein