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. 2023 Dec;10(12):2208-2222.
doi: 10.1002/acn3.51906. Epub 2023 Sep 21.

Differential impact on motor unit characteristics across severities of adult spinal muscular atrophy

Kristina Marie Kelly  1   2 , Jordan Mizell  3 , Ladan Bigdeli  3 , Samuel Paul  3 , Marco Antonio Tellez  4 , Amy Bartlett  5 , Sarah Heintzman  4 , Jerold Everett Reynolds  4 , Gary Brent Sterling  4 , Kiran Francis Rajneesh  4 , Stephen James Kolb  4 , Bakri Elsheikh  4 , William David Arnold  1   2
Affiliations

Differential impact on motor unit characteristics across severities of adult spinal muscular atrophy

Kristina Marie Kelly et al. Ann Clin Transl Neurol. 2023 Dec.

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.

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Conflict of interest statement

KMK: Advisory board for Biogen, member of Neuromuscular Study Group Planning Committee, travel support from Neuromuscular Study Group; SH: salary support from Muscular Dystrophy Association; SJK: consulting for Novartis; BE: research funding from Biogen, Genentech, Alexion, Pharnext, Viela Bio, advisory board for Biogen, Genentech, Argenx, Honoraria from Muscular Dystrophy Association, Stanford University, Travel Support from Cure SMA, Muscular Dystrophy Association, Committee Member for Cure SMA, receipt of drug for clinical trial from Celgene; WDA: research funding from NMD Pharma, Avidity Biosciences, Consulting for NMD Pharma, Avidity Biosciences, Dyne Therapeutics, Novartis, La Hoffman Roche, Genentech, Design Therapeutics, Cadent Therapeutics, Catalyst Pharmaceuticals, Honoraria from University of Rochester, Travel Support from NMD Pharma, Chair/Member of Novartis Data Safety and Monitoring Board, Chair of Neuromuscular Study Group Planning Committee, Patent for “Methods and compositions for treating disorders and diseases using Survival Motor Neuron (SMN) protein.”

Figures

Figure 1
Figure 1
Ordinary one‐way ANOVA was used to analyze comparisons of average motor unit action potential (MUAP) amplitude (A), peak motor unit firing rate (B), and average motor unit firing rate (C) in individual motor units among ambulatory (blue) and non‐ambulatory (brown) adults with SMA and controls (black).
Figure 2
Figure 2
Correlations of average motor unit action potential (MUAP) amplitude compared to measures of strength and function in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 28).
Figure 3
Figure 3
Correlations of peak motor unit firing rate compared to measures of strength and function in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 28).
Figure 4
Figure 4
Correlations of average motor unit firing rate compared to measures of function in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 28).
Figure 5
Figure 5
Correlations of average single motor unit potential (SMUP) compared to measures of strength and function in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 11).
Figure 6
Figure 6
Correlations of compound muscle action potential (CMAP) and motor unit number estimation (MUNE) compared to elbow flexion and elbow extension strength in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 11). Please note that there are two completely superimposed data points in the figure on the right (MUNE = 86, elbow extension = 1.0 kg); one was non‐ambulatory and one was ambulatory.
Figure 7
Figure 7
Correlations of compound muscle action potential (CMAP) and motor unit number estimation (MUNE) compared to Revised Upper Limb Module (RULM) and SMA Functional Rating Scale (SMAFRS) in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 11).
Figure 8
Figure 8
Correlations of average motor unit action potential (MUAP) amplitude compared to traditional electrophysiology measures in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 11). CMAP, compound muscle action potential; SMUP, single motor unit potential.
Figure 9
Figure 9
Correlations of peak motor unit firing rate compared to traditional electrophysiology measures in ambulatory (blue) and non‐ambulatory (brown) adults with SMA (n = 11). CMAP, compound muscle action potential; SMUP, single motor unit potential.
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