Myopathies
Overview
Myopathies are diseases that affect muscles connected to bones (called skeletal muscles), such as the biceps in the upper arm and the quadriceps in the thigh. Myopathies can be caused by inherited genetic defects (e.g., muscular dystrophies), and endocrine, inflammatory (e.g., polymyositis), and metabolic disorders.
Nearly all of the myopathies produce weakening and atrophy of skeletal muscles, especially those closest to the center of the body (called the proximal muscles), such as the thigh and shoulder muscles. Muscles furthest from the center of the body (called the distal muscles), such as those in the hands and feet, are generally less affected.
Some myopathies, such as the muscular dystrophies, develop at an early age; others develop later in life. Some worsen over time and do not respond well to treatment; others are treatable and remain stable. Many times a myopathy is simply labeled "nonspecific muscle myopathy" because there are few treatments available that address the root cause of disease.
Skeletal Muscle
Every time the body moves, a skeletal muscle contracts. Skeletal muscles are attached to parts of the skeleton and make voluntary movements (e.g., walking, reaching, talking) possible.
Depending on where they are and how they function, skeletal muscles vary considerably in size and shape, but they are all made up of bundles of fibers. Each fiber is made up of a sophisticated system of sliding filaments that, when "told" what do by the brain via the nervous system, cause contraction and movement. The nerves that command the muscle are called motorneurons, and the place where a motorneuron meets the muscle is called the neuromuscular junction.
Motorneurons communicate to muscles by secreting biochemical substances. The skeletal muscles receive that biochemical energy and transform it into the mechanical energy that causes muscles to contract and move the human body.
When muscles are affected by disease, many changes occur that may lead to weakness, pain, and atrophy. The muscle fibers can be destroyed or can show significant shrinkage (atrophy). In the inflammatory myopathies, white blood cells and other blood elements may attack parts of the muscle and surrounding blood vessels. Scar tissue may take the place of normal muscle. In some of the metabolic myopathies, abnormal amounts of biochemical substances may accumulate in the muscles.
Incidence and Prevalence
Worldwide incidence of all inheritable myopathies is about 14%. Central core disease accounts for 16% of cases; nemaline rod myopathy for 20%; centronuclear myopathy for 14%; and multicore myopathy for 10%.
Prevalence of muscular dystrophy is higher in males. In the United States, Duchenne and Becker MD occur in approximately 1 in 3300 boys. Overall incidence of muscular dystrophy is about 63 per 1 million.
Worldwide incidence of inflammatory myopathies (e.g., dermatomyositis, polymyositis) is about 5-10 per 100,000 people. These disorders are more common in women.
Incidence and prevalence of endocrine and metabolic myopathies are unknown. Corticosteroid myopathy is the most common endocrine myopathy and endocrine disorders are more common in women. Metabolic myopathies are rare but diagnosis of these conditions is increasing in the United States.
Treatment
Treatment depends on the cause and goals are to slow progression of the disease and relieve symptoms. Treatments range from drug therapy for the muscular dystrophies and inflammatory myopathies to simply avoiding situations that work the muscles too hard for the metabolic myopathies. Some physicians recommend that patients keep their weight down (a lighter body demands less work from the muscles) and avoid overexerting their muscles.
An incentive spirometer might improve breathing function when breathing problems develop. It is not clear that this works for many patients. Unfortunately, there is no way to strengthen the breathing muscles.
Muscular Dystrophies
The goals of treatment are to slow progression of disease and relieve symptoms. Duchenne MD and Becker MD are the subjects of current medical research and clinical trials may be available for patients with either disease.
The corticosteroids deflazacort and prednisone seem to be the most effective medications. Both improve strength and walking ability for about 6 months in boys with Duchenne dystrophy. Following initial improvement, further progression of the disease may be delayed for 3 to 5 years.
Prolonged use of corticosteroids can cause severe side effects including the following:
- Bone loss (osteoporosis)
- Depression
- High blood pressure (hypertension)
- Thinning of the skin
- Weight gain
Calcium supplements and antidepressants may be prescribed to counteract the side effects.
Preventive treatment for permanent contraction of a muscle (contractures) includes physical therapy and bracing. There are currently no drugs available to prevent or treat contractures.
Heel cord surgery (also called tendon release) and spine-straightening surgery (i.e., rod insertion) may be necessary in cases of severe contractures. Heel cord surgery is performed when the patient is still able to walk. Braces are usually required following surgery.
Endocrine Myopathies
Often, treating the underlying condition helps relieve muscle weakness and pain associated with the endocrine myopathies.
Inflammatory Myopathies
The inflammatory myopathies, such as polymyositis and dermatomyositis, are usually treated with drugs that suppress the action of the immune system. Prednisone is most commonly used to treat inflammatory myopathies. It is used initially in high doses (up to 100mg/day) and then slowly tapered to the lowest possible dose that relieves symptoms. Long-term use of prednisone can cause severe side effects .
Metabolic Myopathies
The primary goal in treating metabolic myopathies is simply to avoid situations, like strenuous exercise, that tax the muscles and promote muscle pain and weakness.
Follow-Up
People with myopathies generally visit their physician once a year, though they may be asked to make more frequent visits, depending on how the disease progresses.
Physical, Occupational, & Respiratory Therapy-The Muscular Dystrophy Association (MDA) helps patients find health practitioners certified in these therapies. Although physical therapy cannot restore already weakened muscles, it can prevent healthy muscles from weakening. Occupational and respiratory therapy help patients learn to use special equipment that can improve a person's quality of life.
MDA Social Services-The MDA provides resources that help patients and their families with financial concerns.
Genetic Counseling -Genetic counselors can provide information on the risk of passing the disease to your children.
Support Groups-Support groups help patients learn how to cope with the stress and complex range of emotions that result from chronic illness.
Flu Shot -People with neuromuscular diseases are susceptible to complications from influenza and should ask their physicians about receiving yearly flu shots.
Prognosis
If the underlying cause of the disorder can be treated successfully, as in the case of endocrine myopathies, the prognosis is usually good. Progressive myopathies that develop later in life usually have a better prognosis than conditions that develop during childhood.
Patients with Duchenne MD rarely live beyond their middle to late 20s. Patients with Becker MD may live until middle age.
Other Types
Endocrine Myopathies
Endocrine myopathies are caused by underlying conditions caused by the over- or underproduction of hormones. These conditions can develop in children and adults and usually respond well to treatment.
- Steroid myopathy is the most common endocrine muscle disease. Steroid excess, whether caused by an adrenal gland disorder (e.g., Addison disease) or chronic administration of glucocorticoid drugs, causes muscle weakness and wasting.
- Hyperthyroid myopathy is caused by the thyroid gland producing too much thyroxine. Its symptoms include weakening and wasting of the muscles, especially in the shoulders and hips, and sometimes the eyes.
- Hypothyroid myopathy is caused by the underproduction of thyroxine and results in muscle weakening in the legs and arms. The muscles may become enlarged.
- Cushing's disease, characterized by overproduction of hormones produced by the pituitary and adrenal glands, cause myopathy.
- Excess parathyroid hormone results in hypercalcemia, which causes proximal muscle pain and weakness.
- Hormone-secreting tumors (e.g., growth-hormone secreting pituitary adenoma) can cause endocrine disorders that produce myopathy.
Inflammatory Myopathies
Inflammatory myopathies are autoimmune disorders. An autoimmune disorder is caused by the body's immune system mistakenly attacking healthy tissue. In this case, it attacks healthy muscle fibers and causes inflammation, which in turn damages the muscle. It is not known what triggers this autoimmune response.
The severity and progression of these myopathies vary considerably. Some people develop other disorders, such as abnormal heart rhythms, lung disease, gastrointestinal problems, arthritis, or cancer.
- Polymyositis (PM) can occur at any age in either sex, but is more common in children and in women between 40 and 60 years old. Most people with PM suffer muscle aches, cramping, and tenderness. The muscle weakness is, however, quite intense and may fluctuate over weeks to months. It is often worse in the neck, arms, and thighs, making it difficult to stand up from a sitting position. Many patients also experience fever, general discomfort (malaise), and loss of appetite.
- Dermatomyositis (DM) is characterized by a skin rash and all of the muscle symptoms of PM. The rash is a purple discoloration around the eyes and on the cheeks but may also appear on other parts of the body. Eventually the skin becomes thin and fragile. DM most commonly develops in children between the ages of 5 and 14 years. People who have DM have an increased risk for developing cancer.
Toxic Myopathies
Exposure to certain medications, chemicals, and excessive alcohol intake can damage skeletal muscle. Drugs and types of chemicals that can cause myopathy include the following:
- Anesthetics (e.g., lidocaine, mepivacaine, ethyl chloride)
- Cholesterol-lowering agents (e.g., clofibrate, genfibrozil, lovastatin, simivastatin, niacin)
- Glucocorticoids (e.g., triamcinolone, dexamethasone, betamethasone)
- Narcotics (e.g., cocaine, heroin, meperidine)
- Other drugs (e.g., zidovudine, D-penicillamine, procainamide, chloroquine, gallamine)
- Herbicides, insecticides, flame retardants
Causes and Risk Factors
Inheritable myopathies are caused by a genetic defect. The most common muscular dystrophies, Duchenne and Becker MD, result from a genetic defect on the X chromosome.
Risk factors for other myopathies include the following:
- Autoimmune disorders (e.g., myasthenia gravis, scleroderma, thyroiditis)
- Endocrine disorders (e.g., Cushing syndrome, hypothyroidism, hyperthyroidism, Addison disease)
- Exposure to toxins (e.g., herbicides, insecticides, flame retardant chemicals)
- Infection (e.g., HIV, Lyme disease, trichinosis)
- Vitamin D deficiency, vitamin E or A toxicity
- Medication (e.g., some antihistamines, long-term corticosteroid use)
- Metabolic disorder (e.g., glycogen and lipid storage diseases)
Signs and Symptoms
Although symptoms depend on the type of myopathy, some generalizations can be made. Skeletal muscle weakness is the hallmark of most myopathies, with some noticeable exceptions, such as myotonia and paramyotonia congenita. In these two inheritable muscular disorders the muscles become enlarged, rather than weakened and atrophied, and do not relax after contracting.
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 the advanced stage of disease.
Other typical symptoms of muscle disease include the following:
- Aching
- Cramping
- Pain
- Stiffness
- Tenderness
- Tightness
Initially, individuals may feel fatigued doing 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.
Complications
If heart (cardiac) muscle is affected in later stages of disease, abnormal heart rhythms or weakness of the heart muscle (cardiomyopathy) may develop. A patient with cardiomyopathy is at risk for congestive heart failure.
When the 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 machine that assists breathing (respirator). When swallowing muscles are affected, patients are at increased risk for choking and malnutrition.
Diagnosis
There is a national network of Muscular Dystrophy Association (MDA) clinics that specialize in diagnosing and treating myopathies. Anyone who suspects that they or their child may have a myopathy should visit one of these centers or find a neuromuscular specialist who is familiar with current diagnostic tests and treatments.
Often a specific diagnosis is unnecessary, unless a patient wants to know for their own peace of mind. They may want to know if the myopathy is inheritable and if their children are or would be at risk for the disease.
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.
Medical History
A complete family history will help determine whether the disease is an inheritable myopathy.
Clinical and Neurological Evaluation
Some of the early symptoms associated with myopathies include muscle weakness, muscle pain or tenderness, muscle pain during exercise, and muscle fatigue. Some may fall a lot, have trouble walking, or may experience difficulty getting out of a chair.
Various signs and symptoms the physician looks for include the following:
- Endocrine abnormalities
- Heart problems
- Mental dysfunction
- Muscle weakness that occurs in any particular pattern
- Muscular shrinkage (atrophy)
- Skin rash
The neurological exam involves testing the following:
- Ability to rise from sitting
- Ability to walk
- Coordination
- Deep tendon reflexes (the knee jerk reaction)
In some cases the neurologist tests for the inability of a muscle to relax after it contracts (myotonia) by having a patient squeeze their hand muscles very hard and watching for signs of failure to relax.
Blood Tests
A serum enzyme test measures how much muscle protein is circulating in the blood. Usually, a serum enzyme test is helpful only at the early stages of the disease, when the sudden increase of protein level in the blood is conspicuous.
These proteins include
- creatine kinase (CK),
- lactic dehydrogenase (LDH),
- and pyruvate kinase (PK).
Later, as muscle tissue wastes away, there is less and less protein to circulate and the amount in the blood drops to a normal level. The CK level is especially important in diagnosing Duchenne MD and the metabolic myopathies.
The level of potassium in the blood helps diagnose periodic paralysis.
When an endocrine myopathy is suspected, appropriate blood tests are performed to detect hormone excesses or deficiencies. For example, thyroid function testing would reveal hyper- or hypothyroidism.
Antibodies found in the blood might indicate an inflammatory myopathy.
DNA may be collected from the blood to evaluate whether one of the known genetic defects is present.
Electromyogram
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 TV monitor (oscilloscope). This helps identify which muscles are weakened. It is especially helpful for diagnosing myotonia and paramyotonia congenita.
Muscle Tissue Biopsy
A muscle biopsy involves surgically removing a very small amount of tissue to be examined under the microscope and analyzed for cellular and protein abnormalities. Biopsy is especially helpful for diagnosing central core disease, nemaline myopathy, and myotubular myopathy.
Treatment
Treatment depends on the cause and goals are to slow progression of the disease and relieve symptoms. Treatments range from drug therapy for the muscular dystrophies and inflammatory myopathies to simply avoiding situations that work the muscles too hard for the metabolic myopathies. Some physicians recommend that patients keep their weight down (a lighter body demands less work from the muscles) and avoid overexerting their muscles.
An incentive spirometer might improve breathing function when breathing problems develop. It is not clear that this works for many patients. Unfortunately, there is no way to strengthen the breathing muscles.
Muscular Dystrophies
The goals of treatment are to slow progression of disease and relieve symptoms. Duchenne MD and Becker MD are the subjects of current medical research and clinical trials may be available for patients with either disease.
The corticosteroids deflazacort and prednisone seem to be the most effective medications. Both improve strength and walking ability for about 6 months in boys with Duchenne dystrophy. Following initial improvement, further progression of the disease may be delayed for 3 to 5 years.
Prolonged use of corticosteroids can cause severe side effects including the following:
- Bone loss (osteoporosis)
- Depression
- High blood pressure (hypertension)
- Thinning of the skin
- Weight gain
Calcium supplements and antidepressants may be prescribed to counteract the side effects.
Preventive treatment for permanent contraction of a muscle (contractures) includes physical therapy and bracing. There are currently no drugs available to prevent or treat contractures.
Heel cord surgery (also called tendon release) and spine-straightening surgery (i.e., rod insertion) may be necessary in cases of severe contractures. Heel cord surgery is performed when the patient is still able to walk. Braces are usually required following surgery.
Endocrine Myopathies
Often, treating the underlying condition helps relieve muscle weakness and pain associated with the endocrine myopathies.
Inflammatory Myopathies
The inflammatory myopathies, such as polymyositis and dermatomyositis, are usually treated with drugs that suppress the action of the immune system. Prednisone is most commonly used to treat inflammatory myopathies. It is used initially in high doses (up to 100mg/day) and then slowly tapered to the lowest possible dose that relieves symptoms. Long-term use of prednisone can cause severe side effects .
Metabolic Myopathies
The primary goal in treating metabolic myopathies is simply to avoid situations, like strenuous exercise, that tax the muscles and promote muscle pain and weakness.
Follow-Up
People with myopathies generally visit their physician once a year, though they may be asked to make more frequent visits, depending on how the disease progresses.
Physical, Occupational, & Respiratory Therapy-The Muscular Dystrophy Association (MDA) helps patients find health practitioners certified in these therapies. Although physical therapy cannot restore already weakened muscles, it can prevent healthy muscles from weakening. Occupational and respiratory therapy help patients learn to use special equipment that can improve a person's quality of life.
MDA Social Services-The MDA provides resources that help patients and their families with financial concerns.
Genetic Counseling -Genetic counselors can provide information on the risk of passing the disease to your children.
Support Groups-Support groups help patients learn how to cope with the stress and complex range of emotions that result from chronic illness.
Flu Shot -People with neuromuscular diseases are susceptible to complications from influenza and should ask their physicians about receiving yearly flu shots.
Prognosis
If the underlying cause of the disorder can be treated successfully, as in the case of endocrine myopathies, the prognosis is usually good. Progressive myopathies that develop later in life usually have a better prognosis than conditions that develop during childhood.
Patients with Duchenne MD rarely live beyond their middle to late 20s. Patients with Becker MD may live until middle age.