Differential Impact on Motor Unit Characteristics Across Severities of Adult Spinal Muscular Atrophy

Overview

Journal Ann Clin Transl Neurol

Specialty Neurology

Date 2023 Sep 22

PMID 37735861

Authors

Kristina Marie Kelly

Jordan Mizell

Ladan Bigdeli

Samuel Paul

Marco Antonio Tellez

Amy Bartlett

Sarah Heintzman

Jerold Everett Reynolds

Gary Brent Sterling

Kiran Francis Rajneesh

Stephen James Kolb

Bakri Elsheikh

William David Arnold

Affiliations

Soon will be listed here.

Abstract

Objective: To test the hypotheses that decomposition electromyography (dEMG) motor unit action potential (MUAP) amplitude and firing rate are altered in SMA; dEMG parameters are associated with strength and function; dEMG parameters are correlated with traditional electrophysiological assessments.

Methods: Ambulatory and non-ambulatory adults with SMA on nusinersen and healthy controls were enrolled. MUAPs were decomposed from multielectrode surface recordings during 30-s maximum contraction of the abductor digiti minimi (ADM). Isometric strength, upper limb function, patient-reported function, and standard electrophysiologic measures of the ADM (compound muscle action potential [CMAP], single motor unit potential [SMUP], motor unit number estimation [MUNE]) were collected.

Results: dEMG MUAP amplitudes were higher in ambulatory versus control and non-ambulatory groups and were higher in controls versus non-ambulatory SMA. In contrast, dEMG firing rates were higher in ambulatory versus non-ambulatory and control groups but similar between non-ambulatory and control. dEMG parameters showed moderate to strong positive correlation with strength and function whereas CMAP and MUNE better correlated with function than strength. SMUP did not correlate with strength, function, or dEMG MUAP amplitude. dEMG parameters show overall good test-retest reliability.

Interpretation: dEMG provided reliable, noninvasive measure of MUAP amplitude size and firing rate and revealed divergent patterns across disease severity in adults with SMA. Firing rate enhancement, as seen in milder SMA, may provide a therapeutic avenue for improving function in more severe SMA, where firing rates appear preserved. MUAP amplitude size and firing rate, quantified with dEMG, may be promising monitoring biomarker candidates for noninvasive assessment of SMA.

Citing Articles

Long-term impact of nusinersen on motor and electrophysiological outcomes in adolescent and adult spinal muscular atrophy: insights from a multicenter retrospective study.

Wang N, Hu Y, Jiao K, Cheng N, Sun J, Tang J J Neurol. 2024; 271(9):6004-6014.

PMID: 39030456 DOI: 10.1007/s00415-024-12567-y.

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