Fatigue in muscular dystrophies

Abstract

Fatigue is a frequent complaint in muscular dystrophies but it is yet not well defined or studied. We have examined the issue of muscle fatigue in a series of molecularly defined muscular dystrophies. A greater fatigability is seen in muscular dystrophy patients and can be an acute or chronic status. In Duchenne Muscular Dystrophy and beta-sarcoglycanopathy besides the alteration of dystrophin and/or sarcoglycan complex, a neuronal nitric oxide synthase depletion is frequently found and might correlate with post-exercise fatigability as well as with cardiac involvement. Therefore, it might be an important modulating factor of the severity of myopathy. In myotonic dystrophy, fatigue is a common complaint: muscle is involved and type 1 atrophy is a frequent feature; brain involvement and depressed mood might likely explain the extent of fatigue and daytime sleepiness commonly observed in these patients. Furthermore, in our observation in a series of 24 cases, muscle and brain can be independently involved in DM1 patients. These observations have profound impact on the type of physical therapy to be prescribed in such patients.

Fig. 1

Cascade of events consequent to muscle exercise when normal or defective nNOS is present.

Fig. 2

Muscle pathology in DM1. Cross sections of muscle fibers showing with hematoxylin-eosin stain (A) several internal nuclei and size variability, with NADH-TR (B) central nuclei, type 1 fiber hypotrophy and some moth eaten fibers, with Gomori trichrome (C) sarcoplasmic masses, central nuclei and atrophic fibers, with acid ATP-ase (D), type 1 fiber atrophy and type 2 fiber hypertrophy.

Fig. 3

Brain MRI images in DM1 showing cranial hyperostosis (A), enlargement of paranasal cavities (B) and ventriculomegaly (C).