Central fatigue during isometric exercise in amyotrophic lateral sclerosis

While both upper and lower motor neuron dysfunction may contribute to impaired muscle function in amyotrophic lateral sclerosis (ALS), the precise mechanisms of muscle fatigue have not been clarified in this disease. Therefore, the central and peripheral factors in muscle fatigue were investigated during intermittent submaximal isometric ankle dorsiflexion in 7 patients with ALS and 6 healthy control subjects. Voluntary and electrically stimulated force, central and peripheral indices of muscle activation, and intramuscular energy metabolism were measured before and during exercise. At the end of exercise, only the ALS group had an increase in the "added force" in response to a stimulus train imposed during maximal voluntary contraction, indicating significant central fatigue in ALS. In support of this conclusion, patients with ALS had less intramuscular phosphocreatine depletion and less fatigue of stimulated tetanic force during exercise compared to control. Thus, due to the central failure, there was decreased muscle activation resulting in a smaller metabolic demand and less fatigue within the muscle itself. These data demonstrate a major contribution of central factors to muscle fatigue in ALS.