DUCTION ¡ª When any problem related to muscle function occurs, the result is weakness. But weakness has many causes, only some of which are related to actual disease of the muscles. When a doctor sees a patient complaining of weakness, a first step is to determine if the patient's muscles are actually weak, or if there is some other reason (such as heart disease or depression) that makes it hard for the patient to function normally. Usually, a careful physical examination will establish if there is actual weakness in the muscles.

Once it has been established that there is true muscle weakness, it is important to look at the series of events that leads to a strong muscle contraction and determine which portion has gone wrong. Normally, electrical signals travel from the brain through the spinal cord and into the nerves that lead to the muscles. From there, they are transmitted into the muscles themselves where they stimulate muscle tissue to contract. Along the way, the nerves must be in good working order, and the muscles in a proper state to accept the impulses and generate a response.

Problems can occur anywhere along this route. If the brain, spinal cord, or nerves are damaged or diseased, the electrical signal may not be generated or get through. If muscles are inflamed or abnormal, they may not be able to respond properly to a nerve impulse.

Some of the diseases of muscles, or "myopathies", that can cause weakness to occur are discussed in this patient information review. In these diseases, nerve impulses reach the muscles without any problem, but the muscles themselves, usually, some muscles more than others, are diseased and unable to respond in a normal way.

Many things can cause muscle disease, or myopathy, to occur. They include:

• Inflammation of the muscles
• Inherited conditions, especially muscular dystrophies
• Problems with certain hormones that affect muscle function
• Chemical imbalances in the body
• Drugs and toxic substances
• Infections

Some of the causes of myopathy are discussed here. Your doctor can provide additional information as needed on these and other causes of muscle disease.

DERMATOMYOSITIS AND POLYMYOSITIS ¡ª These are two conditions that cause inflammation of the muscles. They are rare disorders, with incidence rates estimated at about one per 100,000 in the general population per year. More women than men are affected. Although the peak age of onset is in the 50s, the disorders can occur at any age. The two diseases have similar symptoms, though careful analysis of the muscles of affected individuals shows two different mechanisms causing the muscle inflammation.

Signs and symptoms ¡ª Patients complain of muscle weakness that usually worsens over several months, though in some cases symptoms come on suddenly. The affected muscles are close to the trunk (as opposed to in the wrists or feet), involving for example the hip, shoulder, or neck muscles. Muscles on both sides of the body are equally affected. In some cases, muscles are sore or tender. There may be muscle atrophy (wasting of the muscles) in more advanced disease.

Some patients have involvement of the muscles of the pharynx (throat) or the esophagus (the tube leading from the throat to the stomach), causing problems with swallowing. In some cases, this leads to food being misdirected from the esophagus to the lungs, causing severe pneumonia.

In dermatomyositis, there is a rash, though sometimes the rash resolves before muscle problems occur. A number of different types of rash can occur, including rashes on the fingers, the chest and shoulders, or on the upper eyelids. In rare cases, the rash of dermatomyositis appears but myopathy never develops.

Other problems sometimes associated with these diseases include fever, weight loss, arthritis, cold-induced color changes in the fingers or toes (Raynaud phenomenon), and heart or lung problems.

Diagnosis ¡ª In addition to a careful history and physical exam, a number of tests are useful in diagnosing these conditions. Blood tests typically show evidence of muscle damage. An electromyogram (EMG) shows abnormal muscle function. Muscle biopsy is the definitive test in establishing the diagnosis, as careful analysis of the cells will reveal the typical inflammation seen in each disorder. Recently, magnetic resonance imaging (MRI) has proven useful in evaluating patients with these disorders. In time, MRI may replace EMG and muscle biopsy in the evaluation of these conditions.

INCLUSION BODY MYOSITIS ¡ª Inclusion body myositis is another type of inflammatory muscle disease. It differs in a number of ways from polymyositis and dermatomyositis. It affects more men than women, and the age of onset is almost always after age 50.

Symptoms ¡ª Typically, symptoms come on very slowly, over a period of years. There is usually weakness of the hips and upper legs. Some patients with inclusion body myositis may have weakness in the hands or feet, and, in 10 to 15 percent of cases, one side of the body is affected more than the other. Facial muscles may be involved.

There is muscle atrophy that progresses with the duration and severity of weakness. Some patients may have profound atrophy of the upper arms or upper legs. There may be difficulty swallowing.

Diagnosis ¡ª Blood tests done to look for signs of muscle damage may be mildly elevated or normal. Electromyogram shows abnormal muscle function, and MRI may reveal abnormalities in some cases. Muscle biopsy shows the definitive diagnostic feature of this disorder, characteristic abnormal structures in the muscle cells (filamentous inclusions and vacuoles), which are seen in over 90 percent of affected patients.

MUSCULAR DYSTROPHIES ¡ª There are a number of different types of muscular dystrophy. They are all inherited disorders that cause progressive muscle disease due to defects in one or more genes that are required for normal muscle function. In some types of muscular dystrophy, other problems occur, such as heart disease or mental retardation.

The diseases are distinguished from one another both by the type of symptoms seen and by the nature of the genetic abnormality causing the disorder. A number of tools can be used to diagnose the disorders, including genetic testing, blood tests that search for signs of muscle damage, EMG, muscle biopsy, and electrocardiogram (EKG). The selection of appropriate diagnostic tests depends in part on the type of disease that is suspected. This is particularly true of genetic tests, which must be tailored to search for specific abnormalities.

Typical features of the various types of muscular dystrophy are presented here.

Duchenne muscular dystrophy (DMD) ¡ª The genetic abnormality is passed on by the mother, but the disease is seen primarily in boys. (However, in a minority of cases, female carriers of the abnormal gene can develop symptoms.) The genetic problem is related to abnormalities in a gene called the dystrophin gene. Symptoms usually appear between two and three years of age. Weakness starts near the trunk, and spreads to the extremities, affecting the legs before the arms. Those affected are usually wheelchair bound by age 12.

DMD may also cause heart problems, with enlargement of the heart tissue and problems with regulation of the heartbeat. Abnormal curvature of the spine (scoliosis) along with muscle weakness can lead to lung problems. In many cases, there is mental retardation, though an occasional child may have average or above-average intelligence.

Becker muscular dystrophy (BMD) ¡ª The pattern of inheritance is the same, with the abnormality passed on by the mother and the disease occurring mainly in boys. BMD is also caused by problems with the dystrophin gene which normally produces a large muscle protein. Compared with DMD, the age of onset is usually later and the degree of symptoms is milder. Patients typically can walk until about age 15, and commonly into adult life. Mental retardation is less common. Heart problems are not common; however, when they occur, they can be more severe in patients with BMD than in those with DMD.

BMD/DMD outliers ¡ª Some patients are found to have the genetic abnormalities of the dystrophin gene, but, clinically, have symptoms somewhere in between those typical of DMD or BMD. These so-called "outliers" may be thought of as having mild DMD or severe BMD. They usually become confined to a wheelchair between the ages of 12 and 16 years.

Emery-Dreifuss dystrophy ¡ª A number of inheritance patterns are possible with this type of muscular dystrophy. It can affect both boys and girls. Symptoms of muscle weakness and wasting begin in the first or second decade of life, and typically begin in the arms. Leg and peroneal muscle weakness follows, and, in some cases, mild facial weakness is also seen. The disease tends to be slowly progressive. Contractures of the elbows are common and are sometimes the first sign of disease. Involvement of the heart is also common and leads to serious problems with the regulation of heartbeat.

Myotonic dystrophy ¡ª Myotonic dystrophy is the most common form of muscular dystrophy among Caucasians. It can affect both boys and girls. Symptoms typically occur in adolescence or adulthood, although a neonatal form does occur. It is a disorder that affects multiple body systems, causing weakness and wasting affecting facial muscles, arms, and legs. Myotonia, or delayed muscle relaxation after contraction, is also seen, as are heart problems, cataracts, problems with glands, and abnormal intellectual functioning. In some cases, there are joint problems or difficulty swallowing.

Limb-girdle muscular dystrophy ¡ª This is actually a group of disorders that have a number of inheritance patterns. It refers to dystrophies that affect the shoulder girdle (or area surrounding the shoulder), the pelvic girdle (the area surrounding the hips), or both. Low back pain may be a prominent symptom. Age of onset varies from early childhood to adulthood. The course is usually slowly progressive. Intellect is usually normal and cardiac involvement is rare. (See "Limb-girdle, facioscapulohumeral, oculopharyngeal, distal, and congenital muscular dystrophies").

Facioscapulohumeral muscular dystrophy ¡ª This disorder can also affect both boys and girls. It is usually slowly progressive, but is extremely variable in its severity and age of onset.

In the infant form, symptoms appear within the first few years of life, with wheelchair confinement by the age of 9 or 10 years in most cases. There is profound facial weakness, with an inability to close the eyes in sleep, to smile, or to show other facial expressions. The weakness rapidly involves the shoulder and hip girdles. There may be marked weakness of the wrist.

In the classical form, the onset is usually in the second or third decade. Progression is slow, and the life span is almost normal. The facial muscles are involved initially, with inability to close the eyes tightly, smile, or whistle. There may be a pouting appearance to the face. The facial weakness, however, can be mild and may remain mild for many years. The muscles of the shoulders and upper arms are also involved. In a number of cases, the disease progresses rapidly in middle age, leading to significant disability. There may be problems with vision or hearing.

Congenital muscular dystrophies ¡ª This term does not refer to a single disorder. Rather, it is used to describe cases of muscular dystrophy that are apparent at birth. There are several types, including Fukuyama type (seen primarily in Japan), Caucasian form, Walker-Warburg syndrome, and muscle-eye-brain disease.

TREATMENT OF MUSCLE DISEASES ¡ª Treatment varies widely depending on the exact diagnosis. Physical therapy is important to maintain optimum functioning and to prevent contractures. Braces can sometimes be used to help preserve function. Prednisone may be useful in some muscle diseases that are due to inflammation, and may also be of some benefit in Duchenne muscular dystrophy, but they are not indicated or frankly unhelpful in other cases. Gene therapy, which involves introducing a normal gene to the affected muscles in a patient's body, is being actively investigated as an option for the treatment of muscular dystrophy.

If there is cardiac involvement, the patient may receive a cardiac pacemaker or other treatment aimed at decreasing the chance of life-threatening problems with heart rhythm. In still other cases, surgery may be done to help stabilize and/or improve function in a particular muscle group.

Ask your doctor for detailed information about treatment of a particular muscle disorder.

WHERE TO GET MORE INFORMATION ¡ª Your doctor is the best resource for finding out important information related to your particular case. Not all patients with muscle disease are alike, and it is important that your situation is evaluated by someone who knows you as a whole person.

This discussion will be updated as needed every four months on our web site

Additional topics as well as selected discussions written for health care professionals are also available for those who would like more detailed information. for physicians are also available for those who would like more detailed information.

A number of other sites on the internet have information about diseases of the muscle. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (http://www.nlm.nih.gov/medlineplus/)

• American Academy of Family Physicians

      11400 Tomahawk Creek Parkway
      Leawood, KS 66211-2672
      (913) 906-6000
      (http://www.aafp.org)

• National Institute of Arthritis and Musculoskeletal and Skin Diseases

      (http://www.niams.nih.gov)
      National Institutes of Health
      1 AMS Circle
      Bethesda, MD 20892-3675
      phone: 301-495-4484

• American College of Rheumatology

      (www.rheumatology.org)
      1800 Century Place, Suite 250
      Atlanta, GA 30345
      phone: 404-633-3777
      fax: 404-633-1870

• Muscular Dystrophy Association

      (www.mdausa.org)
      3300 East Sunrise Drive
      Tuscon AZ 85718
      phone: 520-529-2000
      fax: 520-529-5300