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The motor neuron response to SMN1 deficiency in spinal muscular atrophy
Peter B Kang1, Clifton L Gooch, Michael P McDermott
1Department of Neurology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA.
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.
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