Electrical and mechanical properties of skeletal muscle underlying increased fatigue in patients with amyotrophic lateral sclerosis

To investigate the mechanical efficiency of surviving motor units of anterior tibial muscle in patients with amyotrophic lateral sclerosis (ALS), we studied motor unit action potentials, muscle force, and muscle fatigability in patients with ALS and controls using 25 min of low to moderate intensity voluntary isometric exercise. During exercise, tetanic force (TF) and maximum voluntary contraction declined more in patients than in controls. The mean motor unit action potential duration, amplitude, and polyphasia were increased in patients compared to controls but did not change during 9 months of disease progression. The enlarged motor units in patients were negatively correlated to the muscle force and positively correlated to muscle fatigability. Furthermore, after a mean follow-up period of 9 months, the decline in force-generating capacity of the anterior tibial muscle in patients (twitch tension by 37.5 ± 11.2%, TF by 30.6 ± 7.4%) was greater than the decline in the amplitude of the compound muscle action potential (21.1 ± 8.8%, P < 0.05), suggesting a relative dissociation between electrical and mechanical properties. In conclusion, the enlarged motor units in patients with ALS are mechanically less efficient and fatigue relatively more than in healthy muscles, possibly due to an abnormality that is primarily distal to the muscle membrane.