Definition
Myopathy is a general term referring to any skeletal muscle disease or neuromuscular disorder. Myopathy can be acquired or inherited, and can occur at birth or later in life. Myopathies can result from endocrine disorders, metabolic disorders, muscle infection or inflammation, drugs, and mutations in genes.
Description
Skeletal muscle diseases, or myopathies, are disorders with structural changes or functional impairment of the muscle. These conditions can be differentiated from other diseases of the motor unit by characteristic clinical and laboratory findings. The main symptom is muscle weakness that can be either intermittent or persistent. Different myopathy types exist with different associated causes. The main types include congenital myopathy, muscular dystrophy, inflammatory myopathy, and drug-induced myopathy.
Congenital myopathy (CM) is a term used for muscle disorders present at birth. According to this definition, the CMs could include hundreds of distinct neuromuscular syndromes and disorders. In general, this disease causes loss of muscle tone and muscle weakness in infancy and delayed motor skills, such as walking, later in childhood. Four distinct disorders are classified as CMs: central core disease, nemaline rod myopathy, centronuclear (myotubular) myopathy, and multicore myopathy.
Muscular dystrophy (MD) refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles that control movement. The muscles of the heart and some other involuntary muscles are also affected in some forms of MD, and a few forms involve other organs as well. The major forms of MD include myotonic, Duchenne, Becker, limbgirdle, facioscapulohumeral, congenital, oculopharyngeal, distal, and Emery-Dreifuss.
Inflammatory myopathies (IM) are a group of muscle diseases involving the inflammation and degeneration of skeletal muscle tissues. They are thought to be autoimmune disorders. In IMs, inflammatory cells surround, invade, and destroy normal muscle fibers as though they were defective or foreign to the body. This eventually results in discernible muscle weakness. This muscle weakness is usually symmetrical and develops slowly over weeks to months or even years. The IMs include dermatomyositis, polymyositis, and inclusion body myositis.
Drug induced myopathy (DIM) is a muscle disease caused by toxic substances that produce muscle damage. The toxic substances may act directly on muscle cells, but muscle damage can also be secondary to electrolyte disturbances, excessive energy requirements, or the inadequate delivery of oxygen and nutrients due to muscle compression. Drug use may also result in development of an immunologic reaction directed against the muscle. Muscle damage can be generalized or local, as occurs when a drug is injected into a muscle.
Demographics
Worldwide, CMs account for about 14% of all myopathies. Central core disease accounts for 16% of cases; nemaline rod myopathy for 20%; centronuclear myopathy for 14%; and multicore myopathy for 10%. Prevalence of MD is higher in males. In the United States, Duchenne and Becker MD occur in approximately one in 3,300 boys. Overall incidence of MD is about 63 per one million people.
Worldwide incidence of IM is about five to 10 per 100,000 people. These disorders are more common in women. Incidence and prevalence of DIM are unknown. Myopathy caused by corticosteroids is the most common disorder, and it is more common in women.
Causes and symptoms
CMs and MDs are caused by a genetic defect. In both conditions, mutations have been identified in genes that encode for muscle proteins. The loss or dysfunction of these proteins presumably leads to the specific morphological feature in the muscle and to clinically noticeable muscle disease. For example, in Becker dystrophy, there is a less-active form of dystrophin (a protein involved in the complex interactions of the muscle membrane and extracellular environment) that may not be effective as a gateway regulator, allowing some leakage of intracellular substances, resulting in the myopathy.
The causes of IM are not known. An autoimmune process is likely, as these conditions are often associated with other autoimmune diseases and because they respond to immunosuppressive medication. Muscle biopsy typically shows changes attributed to destruction by infiltrating lymphocytes (white blood cells).
In DIMs, there are a number of causative agents. Drugs such as lipid-lowering agents (statins, clofibrate and gemfibrizol), agents that cause hypokalemia (diuretics, theophylline, amphotericin B), lithium, succinylcholine, antibiotics (trimethoprim, isoniazid), anticonvulsants (valproic acid, lamotrigine, prolonged propofol infusion), vasopressin, colchicine, episilon, aminocaproic acid, high dose alfa-interferon, and illicit drugs (cocaine, heroin, phencyclidine, amphetamines) are possible myopathy inducers.
Although symptoms depend on the type of myopathy, some generalizations can be made. Skeletal muscle weakness is the hallmark of most myopathies. In most myopathies, weakness occurs primarily in the muscles of the shoulders, upper arms, thighs, and pelvis (proximal muscles). In some cases, the distal muscles of the hands and feet may be involved during advanced stages of the disease. Other typical symptoms of muscle disease include the following:
- muscle aching
- muscle cramping
- muscle pain
- muscle stiffness
- muscle tenderness
- muscle tightness
Initially, individuals may feel fatigued during very light physical activity. Walking and climbing stairs may be difficult because of weakness in the pelvic and leg muscles that stabilize the trunk. Patients often find it difficult to rise from a chair. As the myopathy progresses, there may be muscle wasting.
Diagnosis
Generally, diagnosis involves several outpatient tests to determine the type of myopathy. Sometimes it is necessary to wait until the disease progresses to a point at which the syndrome can be identified.
A blood serum enzyme test measures how much muscle protein is circulating in the blood. Usually, this is helpful only at the early stages of the disease, when the sudden increase of muscle protein in the blood is conspicuous. Antibodies found in the blood might indicate an IM. DNA may be collected to evaluate whether one of the known genetic defects is present.
An electromyogram (EMG) measures the electrical activity of the muscle. It involves placing a tiny needle into the muscle and recording the muscular activity on a monitor (oscilloscope). This helps identify which muscles are weakened.
A muscle tissue biopsy involves surgically removing a very small amount of tissue to be examined under the microscope and analyzed for abnormalities.
Treatment team
A multidisciplinary team is involved in the treatment of myopathy patients. This team may include a neurologist, a rheumatologist, an orthopedic surgeon, a pulmonologist, a cardiologist, an orthopedist, a dermatologist, and a genetic counselor. It can also include physical and occupational therapists.
Treatment
Treatment depends on the cause, and goals are to slow progression of the disease and relieve symptoms. Treatments range from drug therapy for MD and IM to simply avoiding situations that work the muscles too hard. Some physicians recommend that patients keep their weight down (a lighter body demands less work from the muscles) and avoid overexerting their muscles. For MD, the corticosteroids deflazacort and prednisone seem to be the most effective medications. Calcium supplements and antidepressants may be prescribed to counteract the side effects. The IMs are usually treated with drugs that suppress the action of the immune system such as methotrexate, cyclosporine, and azathioprine, all of which have potentially serious side effects. For CM, treatment involves supportive measures to help patients cope with the symptoms.
Recovery and rehabilitation
Physical therapy can prevent weakening in a patient's healthy muscles, however, it cannot restore already weakened muscles. Occupational and respiratory therapy help patients learn how to use special equipment that can improve their quality of life.
Clinical trials
There are numerous open clinical trials for myopathies, including:
- Study and Treatment of Inflammatory Muscle Diseases and Infliximab to Treat Dermatomyositis and Polymyositis, sponsored by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Diagnostic Evaluation of Patients with Neuromuscular Disease and Screening Protocol for Patients with Neurological Disorders with Muscle Stiffness, sponsored by National Institute of Neurological Disorders and Stroke (NINDS)
- Physiologic Effects of PRMS & Testosterone in the Debilitated Elderly, sponsored by Department of Veterans Affairs Medical Research Service
- Myositis in Children, sponsored by National Institute of Environmental Health Sciences (NIEHS)
More updated information on clinical trials can be found on the National Institutes of Health clinical trials website at .
Prognosis
The prognosis for persons with myopathy varies. Some individuals have a normal life span and little or no disability. In others, however, the disorder may be progressive, severely disabling, life threatening, or fatal. If the underlying cause of the disorder can be treated successfully, the prognosis is usually good. Progressive myopathies that develop later in life usually have a better prognosis than conditions that develop during childhood. Persons with Duchenne MD rarely live beyond their middle to late 20s, and persons with Becker MD may live until middle age.
Special concerns
If the cardiac muscle is affected in later disease stages, abnormal heart rhythms or heart muscle insufficiency (cardiomyopathy) may develop. Cardiomyopathy patients are at risk for congestive heart failure.
When muscles involved in breathing weaken, there may be significant breathing difficulties and increased risk for pneumonia, flu, and other respiratory infections. In severe cases, patients may require a respirator. When swallowing muscles are affected, persons are at increased risk for choking and malnutrition.
Resources
BOOKS
Vinken, Pierre J., et al. Myopathies. New York: Elsevier Health Sciences, 1992.
Askanas, Valerie, et al. Inclusion-Body Myositis and Myopathies. New York: Cambridge University Press, 1998.
PERIODICALS
Mastaglia, F. L., M. Garlepp, B. Phillips, and P. Zilko. "Inflammatory myopathies: clinical, diagnostic and therapeutic aspects." Muscle & Nerve 27 (April 2003): 407–425.
OTHER
"NINDS Myopathy Information Page." National Institute of Neurological Disorders and Stroke.http://www.ninds.nih.gov/health_and_medical/disorders/myopathy.htm (March 15, 2004).
"Facts about Duchenne and Becker Muscular Dystrophies (DMD and BMD)." Muscular Dystrophy Association.http://www.mdausa.org/publications/fa-dmdbmd.html (March 15, 2004).
ORGANIZATIONS
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): National Institutes of Health. Bldg. 31, Rm. 4C05, Bethesda, MD 20892-2350. (301) 496-8188 or (877) 22-NIAMS (226-4267). NIAMSInfo@ mail.nih.gov. http://www.nih.gov/niams.
Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718-3208. (520) 529-2000 or (800) 572-1717; Fax: (520) 529-5300. mda@mdausa.org. http://www.mdausa.org.
Greiciane Gaburro Paneto
Iuri Drumond Louro, MD, PhD
