The goals of this study were to investigate muscle fatigue in patients with multiple sclerosis (MS), and to determine the relationships between muscle fatigue, clinical status, and perceived fatigue. The fatigability of the anterior tibial muscle was quantitated in patients and controls during 9 min of intermittent stimulation (used to eliminate central sources of muscle fatigue). During exercise, the decline in tetanic force, phosphocreatine, and intracellular pH was greater in patients than in controls. The compound muscle action potential amplitude did not decrease during exercise, indicating that there was no failure of neuromuscular transmission during fatigue. Thus, the excessive fatigue in MS developed from sources beyond the muscle memberane. Following exercise, the recovery of tetanic force was delayed in patients (a pattern that suggests abnormal excitation-contraction coupling), whereas the recovery of metabolites was complete in both groups. Muscular fatigue was correlated with clinical disability but not with perceived fatigue. These results suggests that fatigue in MS has both central (perception, upper motor neuron dysfunction) and peripheral (impaired metabolism and excitation-contraction coupling) components. Keywordsexercise; excitation-contraction coupling; metabolism; magnetic resonance spectroscopy Fatigue is a common and frequently disabling symptom in patients with multiple sclerosis (MS). 11 However, the mechanisms of fatigue in MS remain unclear. 5,28 Central sources of fatigue might well be a factor for MS patients, and could involve at least two different mechanisms. First, recruitment of alpha motor neurons is impaired because of lesions in corticospinal pathways. 33 Second, reaction times are delayed and cognitive activity is abnormal in many patients with MS, suggesting that the processes involved in preparing for and initiating motor responses are also affected. 34,35 Previous studies have shown that peripheral sources of fatigue are also important in spastic muscles. 24,29 Lenman et al. suggested secondary changes in spastic muscles are similar to those of immobilization and disuse. 24 In another study of a small number of patients with various types of spastic paraparesis, greater changes in energy metabolites accompanied the excessive muscle fatigue observed in patients compared to controls, which suggested that intramuscular factors may contribute to fatigue in spastic paraparesis. 29 Recently, in patients with MS, we have observed both reduced muscular oxidative capacity, 19 Therefore, the main objective of this study was to investigate muscle fatigue in MS patients, and to determine the extent to which muscle fatigue was related to clinical status and perceived fatigue. We examined fatigue in a group of MS patients and in healthy control subjects by measuring muscle force, activation, and energy metabolism during electrical stimulation of the anterior tibial muscle. By using stimulated contractions to induce muscle fatigue, central factors were eliminated and the per...

Magnetic resonance imaging and maps of T1 and T2 values were used to study muscle composition in Duchenne muscular dystrophy (DMD). The mean T2 of anterior tibial muscle was 27 msec in healthy control subjects and 43 msec with increased fatty infiltration in DMD patients. In stronger DMD patients, the distribution of muscle T2 values was narrow, centered at 27 msec as in the controls, with a nonoverlapping fat peak centered at 49 msec. In weaker DMD patients, the width of the muscle T2 peak increased and the peak shifted toward the fat peak. Mean muscle T1 decreased from 1.7 to 0.6 second with increasing fatty infiltration. These results show that quantitative T1 and T2 maps may be used to assess muscle status and monitor DMD progression.

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We evaluated myoblast implantation in 10 boys with Duchenne muscular dystrophy (DMD) and absent dystrophin (age 5-10 years) who were implanted with 100 million myoblasts in the anterior tibial muscle of one leg and placebo in the other. Cyclosporine (5 mg/kg/day) was administered for 7 months. Pre-and postimplantation (after 1 and 6 months) muscle biopsies were analyzed. Force generation (tetanic tension and maximum voluntary contraction) was measured monthly in a double-blind design. There was increased force generation in both legs of all boys, probably due to cyclosporine. Using the polymerase chain reaction, evidence of myoblast survival and dystrophin mRNA expression was obtained in 3 patients after 1 month and in 1 patient after 6 months. These studies suggest a salutary effect of cyclosporine upon muscular force generation in Duchenne muscular dystrophy; however, myoblast implantation was not effective in replacing clinically significant amounts of dystrophin in DMD muscle.