Update on Muscle Disease
By Robert G. Miller M.D., director, Forbes Norris MDA/ALS Research and Treatment Center
There have been many advances in the understanding and treatment of muscle disease in recent years. One of the most important is the muscle complications of statins, or cholesterol –lowering drugs. Now that 30 million people are taking statins in the United States, we are beginning to see many of the complications affecting muscle (1). The earliest sign is aching pain in the muscles, especially thighs and calves, often made worse by exercise. When the drug is considered essential for cholesterol-lowering, many people can tolerate the symptoms, but when it becomes severe or impairs function, intervention is usually needed (2). The muscle enzyme creatine kinase is often elevated, and when this gets more severe, muscle weakness may become debilitating. Muscle testing,including electromyography (EMG), can give clear indications about the extent of the severity. Occasionally a muscle biopsy is needed to confirm the diagnosis. Generally speaking, early intervention is generally best to avoid severe complications. We recently published, along with our collaborators at Harvard, a study of 25 patients with a statin-induced myositis, often severe, and sometimes relapsing even long after statins were stopped. We proposed the hypothesis that statins may trigger an immune-mediated myositis requiring immune suppressive therapy (3).
Diagnosing Neuromuscular Diseases
Often we see patients with muscle pain, myalgia, or debilitating fatigue.
Generally these patients require a full diagnostic evaluation to arrive at a clear conclusion. When all other neuromuscular diseases, such as myasthenia or ALS, have been excluded, and the patient fits criteria for fibromyalgia and/or chronic fatigue syndrome, we explain to the patient what is known about these conditions (4). Although there is still some controversy about whether these conditions truly represent disorders that are distinct, controlled trials have recently demonstrated effective therapies that included exercise, duloxetine, pregabalin, cognitive behavioral therapy, as well as other therapies (5,6,7). An individualized treatment program is helpful for most patients. The treatment has included improved sleep hygiene, reconditioning exercise, cognitive behavioral therapy, medication for depression, or medication for pain.
Inclusion Body Myositis
Another important muscle condition, the most common cause of chronic, progressive weakness in the age group over 40, is inclusion body myositis (IBM). This condition may be mistaken for polymyositis and many patients are given corticosteroid or other immunesuppressive therapy, sometimes for years, before the diagnosis is clarified (8). Important clinical clues are the selective weakening of the long-finger flexors and the quadriceps muscles—nearly pathognomonic for the disease. Diagnosis is important to spare the patient ineffective immunosuppressive treatment and also to recognize and treat the respiratory insufficiency and dysphagia and immobility that develop with advanced disease.
A newly recognized condition that may be mistaken for IBM is hereditary inclusion body myopathy. These patients may have onset in the second or third decade, and develop striking leg weakness, but unlike IBM patients, this is a quadriceps-sparing disorder.Two gene mutations have been identified; gene testing is free for patients and there is a clinical trial under way testing the efficacy of sialic acid, which appears to hold promise as treatment (9).
Recently, important progress has been made in understanding the pathobiology of genetically determined myopathies and dystrophies. This is especially true of the Duchenne and Becker dystrophinopathies. A number of promising therapeutics are already in clinical trials, as is gene therapy. Corticosteroid treatment is now the standard of care to slow the disease in the young ambulatory patient: 0.75 mg/kg/day of prednisone. Although the mechanism of action is still unclear, important benefits on function are quite significant for many patients (10). Advances in our understanding of myotonic muscular dystrophy and fascioscapulohumeral muscular dystrophy may provide new targets for therapy.
A multidisciplinary clinic for patients with debilitating neuromuscular diseases provides leading-edge care. Patients often need assistive devices to remain mobile, and breathing assistive devices to help with respiratory insufficiency. Cardiomyopathy often develops, many times requiring medication or a pacemaker insertion. Additionally, feeding tubes or spine surgery may be indicated for dysphagia or scoliosis, respectively.
- Stagnitti MN. Trends in statins utilization and expenditures for the U.S. civilian noninstitutionalized population, 2000 and 2005. Rockville, MD: Quality AfHRa; 2008.
- Mammen AL, Amato AA. Statin myopathy: a review of recent progress. Curr Opin Rheumatol 2010; 22:644–650.
- Grable-Esposito P, Katzberg HD, Greenberg SA, Srinivasan J, Katz J, Amato AA. Immune-mediated necrotizing myopathy associated with statins. Muscle Nerve 2010;41:185–190.
- Abeles M, Solitar BM, Pillinger MH, Abeles AM. Update on fibromyalgia therapy. Am J Med. 2008; 121:555-561.
- Häuser W, Bernardy K, Üceyler N, Sommer C. Treatment of fibromyalgia syndrome with antidepressants. JAMA. 2009; 3 01: 198-209.
- Wolfe F, Rasker JJ. Fibromyalgia. In: Firestein GS,Budd RC, Harris ED Jr., et al., eds. Kelley’s Textbook of Rheumatology. 8th ed. Philadelphia, Pa: Saunders Elsevier; 2008: chap 38.
- Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010; 62(5):600-610
- Griggs RC. The current status of treatment for inclusion-body myositis. Neurology 2006; 66:S30.
- Boyden SE, Anna R Duncan AR, Estrella EA, Lidov HGW, Mahoney LJ, Katz JS, Kunkel LM, Kang PB. Molecular diagnosis of hereditary inclusion body myopathy by linkage analysis and identification of a novel splice site mutation in GNE BMC Medical Genetics 2011, 12:87
- Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, Kronberg AJ, Bertorini TE, et al. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology 2011; 77:444-452
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