Myasthenia Gravis

Myasthenia gravis produces sporadic but progressive weakness and abnormal fatigability of striated (skeletal) muscles, which are exacerbated by exercise and repeated movement but improved by anticholinesterase drugs. Usually, this disorder affects muscles innervated by the cranial nerves (face, lips, tongue, neck, and throat), but it can affect any muscle group.

Myasthenia gravis follows an unpredictable course of periodic exacerbations and remissions. There is no known cure. Drug treatment has improved the prognosis and allows patients to lead relatively normal lives, except during exacerbations. When the disease involves the respiratory system, it may be life-threatening.

Myasthenia gravis (MG) is a rare condition affecting the nerves that supply the muscles around the body. Affected muscles suffer varying degrees of weakness. In the UK every year up to 1 in 20,000 people will be newly diagnosed with MG.

Despite having treatments available to keep the symptoms under control the precise reason why myasthenia gravis starts is still a mystery.

Causes

Myasthenia gravis causes a failure in transmission of nerve impulses at the neuromuscular junction. Theoretically, such impairment may result from an autoimmune response, ineffective acetylcholine release, or inadequate muscle fiber response to acetylcholine. Myasthenia gravis affects 1 in 25,000 people at any age, but incidence peaks between the ages of 20 and 40. It's three times more common in women than in men in this age-group, but after age 40, the incidence is similar.

About 20% of infants born to myasthenic mothers have transient (or occasionally persistent) myasthenia. This disease may coexist with immune and thyroid disorders; about 15% of myasthenic patients have thymomas. Remissions occur in about 25% of patients.

Signs and symptoms

The most common and earliest symptoms of myasthenia gravis are double vision, caused by weakness of the eye muscle, and drooping eyelids, caused by weakness of the eyelid muscle. Weakness in the muscles of the mouth and throat can make swallowing, chewing, and speech difficult. Weakness in the muscles of the arms and legs may restrict everyday activities, such as lifting a child or climbing stairs. If the respiratory muscles become too weak for the patient to breathe properly, symptoms include rapid heartbeat, shallow breathing, and pale or blue-tinged skin. This condition is called myasthenic crisis and requires emergency medical treatment. Physical exertion makes the symptoms of myasthenia gravis worse, but they improve with rest. Symptoms are also affected by heat, stress, and illness caused by any type of infection. Muscle weakness can vary from day to day, and many patients experience periods in which they are symptom free (remissions). Infants with neonatal myasthenia may have muscle weakness, lack of muscle tone, a weak cry, and feeding difficulties. This condition may also affect the child's ability to breathe. Symptoms usually resolve within one month after birth.

Diagnosis

Muscle fatigability that improves with rest strongly suggests a diagnosis of myasthenia gravis. Tests for this neurologic condition record the effect of exercise and subsequent rest on muscle weakness. Electromyography, with repeated neural stimulation, may help confirm this diagnosis.

The classic proof of myasthenia gravis is improved muscle function after an I.V. injection of edrophonium or neostigmine. In myasthenic patients, muscle function improves within 30 to 60 seconds and lasts up to 30 minutes. Long-standing ocular muscle dysfunction may fail to respond to such testing. This test can differentiate a myasthenic crisis from a cholinergic crisis (caused by acetylcholine overactivity at the neuromuscular junction). The acetylcholine receptor antibody titer may be elevated in generalized myasthenia. Evaluation should rule out thyroid disease and thymoma. Rheumatoid arthritis, lupus erythematosus, and polymyositis are often associated with myasthenia gravis.

Treatment

In myasthenia gravis, treatment is aimed at relieving symptoms. Anticholinesterase drugs, such as neostigmine and pyridostigmine, counteract fatigue and muscle weakness and allow about 80% of normal muscle function. However, these drugs become less effective as the disease worsens. Decreasing the immune response toward acetylcholine receptors at the neuromuscular junction is the goal of immunosuppressant therapy. Corticosteroids, azathioprine, cyclosporine, and cyclophosphamide are used in a progressive fashion (when the previous drug response is poor, the next one is used). To suppress the immune system during acute relapses, gamma globulin (IgG) may also be used. Plasmapheresis is used in severe exacerbations.

Patients with thymomas require a thymectomy, which may cause remission in some cases of adult-onset myasthenia. Acute exacerbations that cause severe respiratory distress necessitate emergency treatment. Tracheotomy, positive-pressure ventilation, and vigorous suctioning to remove secretions usually produce improvement in a few days.

Because anticholinesterase drugs aren't effective in myasthenic crisis, they're stopped until respiratory function improves. Myasthenic crisis requires immediate hospitalization and vigorous respiratory support.

Self-care tips

If you have been diagnosed with myasthenia gravis, avoid conditions that make your symptoms worse, such as heat, stress, and intense exercise. Because some drugs can also make your symptoms worse, make sure your doctors and pharmacist are aware of your condition. Take all medications as prescribed by your doctor, at the same time each day.