Motor unit number estimation in adult patients with spinal muscular atrophy treated with nusinersen

Abstract

Background and purpose: The aim was to assess the organization and short-term changes of motor units in adult patients with spinal muscular atrophy (SMA) treated with nusinersen. Methods: In this single-centre cross-sectional and longitudinal study 15 adult patients with SMA type 3 were assessed and compared to 15 age-matched healthy controls and nine patients with amyotrophic lateral sclerosis. Moreover, 10 patients with SMA were followed up after 4–8 months. All patients were investigated clinically and by the motor unit number estimation method MScanFit of the abductor pollicis brevis muscle. Results: The number of motor units (p < 0.001) was significantly lower in patients with SMA compared to healthy controls at study entry. Mean unit amplitude, median amplitude and largest unit (p < 0.001) were significantly increased in patients with SMA. Patients with amyotrophic lateral sclerosis showed a significant reduction of compound muscle action potential (p = 0.005) and number of motor units (p = 0.03) compared to patients with SMA, accompanied by a larger median amplitude (p = 0.03). A prospective analysis identified patients with the ability to walk to improve the number of motor units (p = 0.046) accompanied by a decreased median amplitude (p = 0.03). Electrophysiological measures showed a moderate to strong correlation with clinical scores. Conclusion: Patients with SMA show loss of motor units in distal muscles. MScanFit variables indicate that compound muscle action potential amplitudes are maintained by collateral sprouting. Prospective analyses suggest that milder affected adult patients with SMA preferentially benefit from nusinersen treatment through recovery of smaller motor units. Correlations with clinical scores underline the potential of MScanFit as a surrogate marker.