TY - JOUR
T1 - Motor Unit Patterns Correlate With Severity in Symptomatic Patients With Spinal Muscular Atrophy
AU - Ros, Leandra A A
AU - van der Pol, W Ludo
AU - García, Diederik J L Stikvoort
AU - Goedee, H Stephan
AU - Franssen, Hessel
AU - Asselman, Fay-Lynn
AU - Bartels, Bart
AU - van der Woude, Danny R
AU - van Eijk, Ruben P A
AU - Sleutjes, Boudewijn T H M
AU - Wadman, Renske I
N1 - Publisher Copyright:
© 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
PY - 2025/12
Y1 - 2025/12
N2 - BACKGROUND: We systematically evaluated the different components of the motor unit using an integrated set of noninvasive electrophysiological techniques across a broad spectrum of disease severity in symptomatic adolescents and adults with spinal muscular atrophy types 1-4.METHODS: We performed detailed electrophysiological mapping of the median nerve, including the compound muscle action potential scan, and repetitive nerve stimulation, in 104 genetically confirmed patients with SMA (aged ≥ 12 years, types 1c-4) before the start of DMT. We compared data to a reference group of 65 healthy controls.RESULTS: Motor unit patterns were significantly altered in patients with SMA, showing severe motor unit loss and enlarged motor units. Distinct patterns reflected disease severity, independent of age or disease duration. Patterns were characterized by varying proportions of enlarged motor units relative to motor unit number, with significantly reduced motor unit number and high contributions of enlarged units in advanced disease stages. Neuromuscular junction (NMJ) dysfunction (≥ 10% decrement) was present in 13%-38% of patients, irrespective of SMA severity. In line with these findings, clinical motor function scores correlated with greater motor unit loss and higher contributions of enlarged motor units.CONCLUSIONS: We identified altered motor unit patterns and NMJ function in patients with SMA, with distinct patterns across SMA severity independent of age or disease duration. These measures may serve as complementary biomarkers for disease severity in patients with SMA.TRIAL REGISTRATION: Dutch registry for clinical studies and trials (www.toetsingonline.nl): NL72562.041.20 (March 26, 2020).
AB - BACKGROUND: We systematically evaluated the different components of the motor unit using an integrated set of noninvasive electrophysiological techniques across a broad spectrum of disease severity in symptomatic adolescents and adults with spinal muscular atrophy types 1-4.METHODS: We performed detailed electrophysiological mapping of the median nerve, including the compound muscle action potential scan, and repetitive nerve stimulation, in 104 genetically confirmed patients with SMA (aged ≥ 12 years, types 1c-4) before the start of DMT. We compared data to a reference group of 65 healthy controls.RESULTS: Motor unit patterns were significantly altered in patients with SMA, showing severe motor unit loss and enlarged motor units. Distinct patterns reflected disease severity, independent of age or disease duration. Patterns were characterized by varying proportions of enlarged motor units relative to motor unit number, with significantly reduced motor unit number and high contributions of enlarged units in advanced disease stages. Neuromuscular junction (NMJ) dysfunction (≥ 10% decrement) was present in 13%-38% of patients, irrespective of SMA severity. In line with these findings, clinical motor function scores correlated with greater motor unit loss and higher contributions of enlarged motor units.CONCLUSIONS: We identified altered motor unit patterns and NMJ function in patients with SMA, with distinct patterns across SMA severity independent of age or disease duration. These measures may serve as complementary biomarkers for disease severity in patients with SMA.TRIAL REGISTRATION: Dutch registry for clinical studies and trials (www.toetsingonline.nl): NL72562.041.20 (March 26, 2020).
KW - compound muscle action potential
KW - motor unit
KW - neuromuscular junction
KW - repetitive nerve stimulation
KW - spinal muscular atrophy
UR - https://www.scopus.com/pages/publications/105024385626
U2 - 10.1111/ene.70416
DO - 10.1111/ene.70416
M3 - Article
C2 - 41369146
SN - 1351-5101
VL - 32
JO - European Journal of Neurology
JF - European Journal of Neurology
IS - 12
M1 - e70416
ER -