5. Weakness of a shoulder or one leg with increasing atrophy. This is usually a result of a radiculopathy or mononeuritis, the beginning of motor system disease (progressive spinal muscular atrophy), but rarely may be the early stage of a muscular dystrophy. The first two diseases may develop silently, in mild form, and attract notice only when wasting begins (denervation atrophy takes 3 to 4 months to reach its peak). Points in favor of these acquired diseases are (1) acute or subacute onset and pain; (2) confinement of the disease to muscles originally affected and sparing of other muscles; and (3) an EMG showing denervation effects. Facioscapulohumeral dystrophy may begin with asymmetrical shoulder weakness. Biopsy is seldom performed under such circumstances, because, by temporizing, the problem eventually settles itself. Invariably muscle dystrophy becomes bilateral and symmetrical; mononeuritis stabilizes or recovers; motor neuron disease declares itself by the presence of fasciculations and relatively rapid progression of weakness.
6. The distinctions, in the child or adolescent, between dystrophy and one of the congenital or metabolic myopathies are considered later in this chapter.
Treatment of the Muscular Dystrophies
There has, until recently, been no specific treatment for any of the muscular dystrophies. The physician is forced to stand by and witness the unrelenting progression of weakness and wasting. The various vitamins, amino acids, testosterone, and drugs, such as penicillamine, recommended in the past, have all proved to be ineffective. The administration of prednisone appears to slightly retard the tempo of progression of Duchenne dystrophy for a period of up to 3 years (Fenichel et al). The optimal dose is 0.75 mg/kg given daily, but it must often be reduced because of intolerable side effects (weight gain, behavioral and gastrointestinal disorders).
In recent years, there has been interest in three novel approaches to treatment of Duchenne dystrophy in particular. One is the injection of human myoblasts, stem cells, or satellite cells that contain a full complement of dystrophin and other structural elements into the muscles of patients with muscular dystrophy. The preclinical aspects of this strategy have been summarized by Blau and are being slowly implemented in patients. There is an analogous effort to use the technology of viral-mediated gene delivery to allow gene and protein replacement in the recessively inherited dystrophies. The difficulties of injecting every dystrophic muscle are obvious.
With another remarkable approach, it has been possible to cause the skipping of selected exons during splicing of pre-mRNA and to correct the open reading frame in mutated dystrophin. For example, van Deutekom and colleagues have been able to elicit expression of normal dystrophin in the anterior tibialis at the site of injection of an antisense oligonucleotide that promotes the exon skipping. The same oligonucleotide administered subcutaneously for 5 weeks was shown by Goermans and coworkers to produce dystrophin expression and modestly improve the ability of patients to accomplish a standardized 6-min walk test.