The motor neuron response to SMN1 deficiency in spinal muscular atrophy

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