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Statins (3-hydroxy-3-methylglutaryl-coezyme A [HMG-CoA] reductase inhibitors) are a highly effective group of cholesterol-lowering drugs. Although generally well tolerated, they may exert a toxic effect on skeletal muscle. In considering the myotoxicity of the statins, it is helpful to make a distinction between minimally or asymptomatic elevations in serum creatine kinase (CK) concentrations on the one hand, and the presentation with myositis or rhabdomyolysis on the other. In the relevant literature, significant elevations of serum CK concentration are taken to be those that are at least 9–10 times the upper limit of normal. Asymptomatic or minimally symptomatic patients with such elevations of CK have been distinguished from those with myositis (muscle pain and/or weakness) that is accompanied by a marked (greater than 10 times the upper limit of normal) elevation of serum CK concentration. The term “rhabdomyolysis” has variably been used to describe this latter syndrome, especially when accompanied by renal failure. In some studies, the term rhabdomyolysis is reserved for those in whom the CK concentration is at least 40 times the upper limit of normal. The potential for such severe statininduced myotoxicity achieved particular prominence following the voluntary withdrawal of cerivastatin from the US market in 2001 because of the apparently high risk of rhabdomyolysis. Notwithstanding this adverse publicity, the statins remain a frequently prescribed class of dugs given their efficacy in reducing the risk of coronary heart disease.

The metabolic myopathies are a group of disorders characterized by impaired energy production in muscle that results from inherited defects in glycogen, lipid, or mitochondrial metabolism. Although onset in the neonatal period and during infancy is typical of many of these disorders, others may present for the first time during adolescence of adulthood. The typical presentation in adolescence or adulthood is with either (1) dynamic (i.e., fluctuating) symptoms like myoglobinuria and muscle weakness related to exercise that resolve completely, or (2) static (present all the time) symptoms such as slowly progressive muscle weakness. The gold standard for the diagnosis of these disorders usually relies on biochemical analysis of a muscle biopsy specimen with demonstration of the specific enzymatic defect. Such testing, however, is not part of the routine evaluation of every muscle biopsy, and because biochemical evaluation of muscle requires special preparation of the tissue sample at the time of biopsy, it cannot be requested post hoc. The diagnosis of a metabolic myopathy, therefore, requires a high index of clinical suspicion so that the appropriate testing can be arranged at the time of muscle biopsy. What are the typical presentations of the adult-onset metabolic myopathies? And what is the utility of more readily available investigations such as serum creatine kinase (CK), electromyography (EMG), and the forearm exercise test in ranking the likelihood of the presence or absence of a metabolic myopathy? Questions such as these, relating to the diagnosis of metabolic myopathy, form the bulk of this chapter, although some attention is also paid to the role of therapeutic interventions such as dietary modifications (e.g., lowcarbohydrate or low-fat diets) as well as supplements like creatine and coenzyme Q10.

Weakness may complicate the course of a significant number of intensive care unit (ICU) patients. This weakness may affect the respiratory musculature, in which case it is usually recognized as a failure to wean from the ventilator. It may also commonly affect limb muscles, and more rarely, both facial and extra-ocular muscles. Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are two of the better recognized causes of such weakness that arise during the course of the ICU stay.

Myotonic dystrophy (MD) is the most common adult-onset muscular dystrophy with a prevalence reported as approximately 2.5 to 5.5 per 100,000. Inheritance is autosomaldominant. Early linkage studies assigned the MD gene to chromosome 19, and the mutation underlying the most common form of MD, dystrophia myotonica type 1 (DM1) was subsequently identified as a CTG triplet repeat expansion in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Subsequent studies have revealed a second genetic locus on chromosome 3, with the responsible mutation being an expansion of a CCTG tetranucleotide repeat in an apparently unrelated gene, the zinc finger transcription factor 9 gene; this genotype is referred to as dystrophia myotonica type 2 (DM2). MD is characterized by tremendous variability in the phenotypic expression and severity of the disease. In the congenital form of the disease, infants are born with severe generalized weakness and hypotonia and death ensues from respiratory failure. In the noncongenital forms of the disease, age of onset may vary from the teenage years to the sixth decade of life. The phenotype may be sufficiently mild that the affected individual is entirely asymptomatic.

Facioscapulohumeral (FSH) muscular dystrophy is the third most common dystrophy, after myotonic dystrophy and the dystrophinopathies (Duchenne and Becker), with a prevalence of approximately 1 in 20,000. It is inherited in an autosomal-dominant fashion and has been linked to microsatellite markers on chromosome 4q35. A deletion of a variable number of repetitive elements (known as D4Z4 repeats) leads to the generation of a small EcoRI restriction fragment that is recognized by the p13E-11 probe. The precise mechanism whereby this genetic abnormality results in disease is unclear, but it is thought that the deletion alters chromosomal structure and influences the expression of more centromerically located genes. Because of its slow progression and relatively benign course, FSH is the second most common dystrophy (after myotonic dystrophy) in adults.