Introduction: The motor unit size index (MUSIX) may provide insight into reinnervation in amyotrophic lateral sclerosis (ALS). Presently unknown is whether MUSIX detects clinically relevant changes in reinnervation.
Methods: 57 patients with ALS were assessed at 3-monthly intervals for 12 months in 4 centres: Sheffield, St. Gallen, and Milwaukee and Lisbon. Muscles tested were abductor pollicis brevis, abductor digiti minimi, biceps brachii and tibialis anterior. Two groups were formed: muscles with increases in MUSIX and those with no increases in MUSIX. Longitudinal changes in MUSIX, motor unit number index (MUNIX), compound muscle action potential (CMAP) amplitude and medical research council (MRC) strength score between these two groups were calculated.
Results: 133 muscles were examined. 59% of muscles exhibited an increase in MUSIX during the study. Muscles with MUSIX increases lost more motor units (MUNIX decline at 12 months -58%, p <0.001) than muscles that did not increase MUSIX (MUNIX decline at 12 months -34.6%, p <0.001). Despite this, longitudinal changes in muscle strength were similar (p = 0.816). When motor unit loss (i.e. MUNIX decline) was similar, patients with no MUSIX increase became weaker than those in whom MUSIX did increase.
Discussion: MUSIX increases are associated with greater motor unit loss but preservation of muscle strength. This suggests MUSIX is quantifying a clinically important response that could be used to monitor reinnervation in clinical trials Reinnervation may play an important role in determining the progression of weakness in ALS.