ABSTRACT
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 membrane. 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.
Subject(s)
Energy Metabolism , Multiple Sclerosis/physiopathology , Muscle Fatigue , Adult , Electric Stimulation , Evoked Potentials , Exercise , Female , Humans , Isometric Contraction , Male , Middle Aged , Time FactorsABSTRACT
We used a 4-minute sustained maximum voluntary contraction to investigate fatigability of the anterior tibial muscle in eight healthy boys and 11 boys with Duchenne muscular dystrophy (DMD) (ages 5 to 10 years). Before exercise, the force generation of dystrophic muscle and the compound muscle action potential amplitude were lower and half-relaxation time of the tetanus was longer in patients than in controls. During exercise, the decline in tetanic force and potentiation in twitch tension were similar in both groups. However, during exercise, there was less decline in maximum voluntary contraction and less added force in DMD patients, suggesting that there was less central fatigue in patients than in controls. Thus, patients with DMD and controls have similar intramuscular fatigability and excitation-contraction coupling, and central activation in patients is functioning as well as or better than in healthy controls.
Subject(s)
Muscle Fatigue , Muscle, Skeletal/physiopathology , Muscular Dystrophies/physiopathology , Adolescent , Analysis of Variance , Child , Electric Stimulation , Exercise Test , Humans , Isometric Contraction , Male , Muscle Contraction , Muscle Relaxation , Muscle, Skeletal/physiology , Reference ValuesABSTRACT
To investigate anterior tibial muscle fatigability and metabolism in postpoliomyelitis syndrome patients and controls, we performed measurements of force and relaxation time, as well as 31P magnetic resonance spectroscopy, during intermittent, low-intensity, isometric, voluntary exercise. Both maximum voluntary contraction and tetanic force declined significantly more during exercise and subsequently recovered less in patients compared with controls, indicating greater fatigue in patients. However, intracellular pH and phosphocreatine were not different in the two groups at rest or during exercise or recovery, suggesting that the greater fatigue of the patients was not due to an excessive change of metabolites. Moreover, the pre-exercise half-relaxation time of the tetanus was significantly prolonged in patients compared with controls, and the decline in tetanic force during exercise was linearly related to the half-relaxation time of tetanus, suggesting impaired calcium kinetics. Taken together, the findings of increased fatigability, delayed recovery, and prolonged half-relaxation time, without differences in metabolites, suggest that the fatigue in postpoliomyelitis syndrome may be due to impaired activation beyond the muscle membrane.
Subject(s)
Muscular Diseases/complications , Postpoliomyelitis Syndrome/complications , Action Potentials , Aged , Female , Humans , Isometric Contraction , Male , Middle Aged , Muscle Contraction , Muscles/metabolism , Muscles/physiopathology , Muscular Diseases/physiopathology , Phosphocreatine/metabolism , Physical ExertionABSTRACT
We investigated the effect of cyclosporine (CsA) on force generation in 15 boys with Duchenne muscular dystrophy (DMD) by obtaining monthly measures of tetanic force and maximum voluntary contraction (MVC) of both anterior tibial muscles. During 4 months of a natural history phase, both tetanic force and MVC declined significantly. During 8 weeks of CsA treatment (5 mg/kg/day), significantly increased tetanic force (25.8 +/- 6.6%) and MVC (13.6 +/- 4.0%) occurred within 2 weeks. The maximum mean increase during treatment was 35.2 +/- 5.9% (tetanic force) and 19.0 +/- 4.6% (MVC). Side effects from CsA, gastrointestinal and flu-like symptoms, were transient and self-limiting. Thus, as previously reported with prednisone, CsA increases muscular force generation in the anterior tibial muscles of DMD patients.
