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What is myasthenia gravis?
Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. The name myasthenia gravis, which is Latin and Greek in origin, literally means "grave muscle weakness." With current therapies, however, most cases of myasthenia gravis are not as "grave" as the name implies. In fact, for the majority of individuals with myasthenia gravis, life expectancy is not lessened by the disorder.
The hallmark of myasthenia gravis is muscle weakness that increases with activity of the affected muscle and improves with resting of the muscle. Certain muscles such as those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are involved in about 2/3 of patients. The muscles that control breathing and neck and limb movements may also be affected to a variable extent.
What causes myasthenia gravis?
Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction - the place (the motor endplate) where nerve cells connect with the muscles they control. Normally when impulses travel down the nerve, releasing a neurotransmitter substance called acetylcholine from the nerve ending. The acetylcholine travels across the neuromuscular junction and binds to acetylcholine receptors situated in the surface of the muscle membrane. The receptors are activated by the acetylcholine, generating a muscle contraction.
In myasthenia gravis, specific antibodies (acetylcholine receptor antibodies, AChR-Abs) block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction which prevents the muscle contraction from occurring. The AChR-Abs are produced by the body's own immune system. Thus, myasthenia gravis is an autoimmune disease because the immune system, which normally protects the body from foreign organisms, mistakenly attacks a part of the body itself.
What is the role of the thymus gland in myasthenia gravis?
The thymus gland, which lies in the midline in the chest between the breastbone and the heart, plays an important role in the development of the immune system in early life. Its cells form a part of the body's normal immune system. The gland is somewhat large in infants, grows gradually until puberty, and then gets smaller and is replaced by fat with age. In most adults with myasthenia gravis, the thymus gland is abnormal. It contains certain clusters of immune cells indicative of lymphoid hyperplasia - a condition usually found only in the spleen and lymph nodes during an active immune response. In about 10% of patients, the myasthenia is due to a tumour of the thymus, a thymoma.
The relationship between the thymus gland and myasthenia gravis is not yet fully understood. Scientists believe the thymus gland may give incorrect instructions to developing immune cells, ultimately resulting in autoimmunity and the production of the acetylcholine receptor antibodies, thereby setting the stage for the attack on neuromuscular transmission.
What are the symptoms of myasthenia gravis?
Although myasthenia gravis may affect any voluntary muscle, muscles that control eye and eyelid movement, facial expression, and swallowing are most frequently affected. The onset of the disorder may be sudden. Symptoms often are not immediately recognized as myasthenia gravis.
In many cases, the first symptom is double vision or drooping of an eyelid. In others, difficulty in swallowing and slurred speech may be the first signs. The extent of muscle weakness involved in myasthenia gravis varies greatly among patients, ranging from a localized form, limited to eye muscles (ocular myasthenia), to a generalized form in which many muscles - sometimes including those that control breathing - are affected. Characteristically, the weakness becomes worse as the day goes on, and with continuing activity of the muscle group affected, so that chewing becomes progressively more difficult, speech becomes slurred with prolonged conversation and walking becomes gradually more difficult. The other characteristic is the recovery of muscle strength on resting.
Who gets myasthenia gravis?
Myasthenia gravis occurs in all ethnic groups and both genders. It most commonly affects young adult women (under 40) and older men (over 60), but it can occur at any age. It can be associated with other autoimmune disorders such as rheumatoid arthritis and thyroid disease.
Myasthenia gravis is not directly inherited nor is it contagious. Occasionally, the disease may occur in more than one member of the same family as the tendency to autoimmune disorders has a genetic basis.
Rarely, children may show signs of congenital myasthenia or congenital myasthenic syndrome. These are not autoimmune disorders, but are caused by defective genes that produce proteins in the acetylcholine receptor or in acetylcholinesterase.
How is myasthenia gravis diagnosed?
Unfortunately, a delay in diagnosis of one or two years is not unusual in cases of myasthenia gravis. Because weakness is a common symptom of many other disorders, the diagnosis is often missed in people who experience mild weakness or in those individuals whose weakness is restricted to only a few muscles. Nevertheless, the diagnosis is usually made on the basis of the symptoms together with a detailed clinical examination.
.A special blood test can detect the presence of acetylcholine receptor antibodies. Most patients with myasthenia gravis have abnormally elevated levels of these antibodies. However, antibodies are detected in only bout 50% of patients with myasthenia restricted to the eye muscles (ocular myasthenia).
Other methods to confirm the diagnosis include a version of nerve conduction study which tests for specific muscle "fatigue" by repetitive nerve stimulation. This test records weakening muscle responses when the nerves are repetitively stimulated. Repetitive stimulation of a nerve during a nerve conduction study may demonstrate decrements of the muscle action potential due to impaired nerve-to-muscle transmission.
A different test called single fibre electromyography (EMG), in which single muscle fibres are stimulated by electrical impulses, can also detect impaired nerve-to-muscle transmission. EMG measures the electrical potential of muscle cells. Muscle fibres in myasthenia gravis, as well as other neuromuscular disorders, do not respond as well to repeated electrical stimulation compared to muscles from normal individuals. Computed tomography (CT) of the chest is used to identify an abnormal thymus gland or the presence of a thymoma.
How is myasthenia gravis treated?
Today, myasthenia gravis can be controlled. There are several therapies available to help reduce and improve muscle weakness. Medications used to treat the disorder include anticholinesterase agents such as neostigmine and pyridostigmine, which reduce the breakdown of acetylcholine, improving neuromuscular transmission and thereby increasing muscle strength. These medications do not alter the underlying immune disorder. Immunosuppressive drugs such as prednisone and azathioprine may also be used. These medications improve muscle strength by suppressing the production of abnormal antibodies.
Thymectomy, the surgical removal of the thymus gland (which often is abnormal in myasthenia gravis patients), reduces symptoms in more than 70 percent of patients without thymoma and may cure some individuals, possibly by rebalancing the immune system. Other therapies used to treat myasthenia gravis include plasmapheresis, a procedure in which abnormal antibodies are removed from the blood, and high-dose intravenous immune globulin, which temporarily modifies the immune system and provides the body with normal antibodies from donated blood. These therapies may be used to help individuals during especially difficult periods of weakness. A neurologist will determine which treatment option is best for each individual depending on the severity of the weakness, which muscles are affected, and the individual's age and other associated medical problems.
What is the prognosis?
With treatment, the outlook for most patients with myasthenia gravis is bright: they will have significant improvement of their muscle weakness and they can expect to lead normal or nearly normal lives. Some cases of myasthenia gravis may go into remission temporarily and muscle weakness may disappear completely so that medications can be discontinued. Stable, long-lasting complete remissions are the goal of thymectomy. In a few cases, the severe weakness of myasthenia gravis may cause a crisis (respiratory failure), which requires immediate emergency medical care.
What progress is being made in diagnosis and treatment?
Much has been learned about myasthenia gravis in recent years. Technological advances have led to more timely and accurate diagnosis, and new and enhanced therapies have improved management of the disorder. Much knowledge has been gained about the structure and function of the neuromuscular junction, the fundamental aspects of the thymus gland and of autoimmunity, and the disorder itself. Despite these advances, however, there is still much to learn. The ultimate goal of myasthenia gravis research is to increase scientific understanding of the disorder. Researchers are seeking to learn what causes the autoimmune response in myasthenia gravis, and to better define the relationship between the thymus gland and myasthenia gravis.
Today's myasthenia gravis research includes a broad spectrum of studies throughout the world. In America, the US Government agency NINDS has scientists evaluating new and improving current treatments for the disorder. One study is testing the efficacy of intravenous immune globulin in patients with myasthenia gravis. The goal of the study is to determine whether this treatment safely improves muscle strength. Another study seeks further understanding of the molecular basis of synaptic transmission in the nervous system. The objective of this study is to expand current knowledge of the function of receptors and to apply this knowledge to the treatment of myasthenia gravis.
This article is based on information supplied by the
National Institute of Neurological Disorders and Stroke (NINDS)
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