WHAT IS MYASTHENIA GRAVIS?
Myasthenia gravis is a chronic autoimmune disorder affecting the neuromuscular system. It is caused by an immunological reaction in which antibodies interfere with the communication between the nerves and the muscles. This prevents muscles from contracting correctly and causes weakness.

In normal neuromuscular communication, the nerves release a chemical called acetylcholine (Ach) which binds to an acetylcholine receptor (AChR) on the muscle. This chemical signal instructs the muscle to contract. In people with myasthenia gravis, there are fewer receptors or the receptors become blocked by antibodies, inhibiting proper signal transmission.

WHAT ARE THE SYMPTOMS?
Muscle weakness, especially of the muscles controlling the eyes, eyelids, facial expressions and swallowing, is the primary symptom of myasthenia gravis. Difficulty chewing, swallowing or talking is the initial symptom in some patients, while weakness is the first symptom in others.   Initial weakness is rarely limited to single muscle groups such as neck or finger extensors or hip flexors. The severity of weakness fluctuates during the day, usually being least severe in the morning and worse as the day progresses, especially after prolonged use of affected muscles.

HOW IS IT DIAGNOSED?
Myasthenia gravis is diagnosed by considering physical symptoms in conjunction with various lab tests. Some of the lab tests that may be ordered to help confirm a diagnosis are:

Laboratory Tests

Edrophonium Chloride (Tensilon) test
Weakness caused by abnormal neuromuscular transmission improves after intravenous administration of edrophonium chloride. Some patients who don't respond to intravenous edrophonium chloride may respond to intramuscular neostigmine, because of the longer duration of action. Intramuscular neostigmine is particularly useful in infants and children whose response to intravenous edrophonium chloride may be too brief for adequate observation. In other patients, a therapeutic trial of daily oral pyridostigmine may produce improvement that can't be appreciated after a single dose of edrophonium chloride or neostigmine.

Antibodies Against Acetylcholine Receptor (AChR)
A majority of patients with myasthenia gravis have an AChR antibody present. Tests may return false positive results when blood is drawn within 48 hours of a surgical procedure involving the use of general anesthesia and muscle relaxants. An elevated concentration of AChR binding antibodies in a patient with compatible clinical features confirms the diagnosis of myasthenia gravis, but normal antibody concentrations do not exclude the diagnosis.

Electromyography

Repetitive Nerve Stimulation (RNS)
Repetitive nerve stimulation performed on the arms may result in a decrement response. This decrementing response to RNS is observed more often in proximal muscles, such as the facial muscles, biceps, deltoid, and trapezius than in hand muscles. A significant decrement to RNS in either a hand or shoulder muscle is found in about 60% of patients with myasthenia gravis.

Single Fiber EMG (SFEMG)
SFEMG is the most sensitive test of neuromuscular transmission and shows increased jitter in some muscles in almost all patients with myasthenia gravis. Jitter is greatest in weak muscles but may be abnormal even in muscles with normal strength. Normal jitter in a weak muscle excludes abnormal neuromuscular transmission as the cause of weakness.

HOW IS IT TREATED?
Treatment decisions should be based on knowledge of the natural history of disease in each patient and the predicted response to a specific form of therapy. Treatment goals must be individualized according to the severity of disease, the patient's age and sex, and the degree of functional impairment. The response to any form of treatment is difficult to assess because the severity of symptoms fluctuates. Spontaneous improvement and even remission may occur without specific therapy, especially during the early stages of the disease.

Cholinesterase (ChE) Inhibitors
ChE inhibitors slow the breakdown of acetylcholine (ACh) at cholinergic synapses, so that ACh accumulates at the neuromuscular junction and its effect is prolonged. Pyridostigmine bromide (Mestinon) and neostigmine bromide (Prostigmin) are the most commonly used ChE inhibitors.

Thymectomy
Thymectomy is recommended for most patients with myasthenia gravis. The best responses to thymectomy are in young people early in the course of their disease, but improvement can occur even after 30 years of symptoms. Patients with disease onset after the age of 60 rarely show substantial improvement from thymectomy. Patients with thymomas do not respond as well to thymectomy as do patients without thymoma.

Corticosteroids
Marked improvement with complete relief of symptoms occurs in 70% of patients treated with prednisone. Patients with thymoma have an excellent response to prednisone before or after removal of the tumor. The major disadvantages of chronic corticosteroid therapy are the side effects, including glaucoma, ulcers, obesity and hypertension.

Azathioprine
Azathioprine is an immunosuppressant that reverses symptoms in most patients, though it may take 4 to 8 months for the effects of the drug to be felt. Improvement is typically maintained for as long as the drug is given though symptoms may recur 2 to 3 months after discontinuing therapy.

Cyclosporine
Cyclosporine is another immunosuppressant that may alleviate the symptoms of myasthenia gravis. It may take patients up to 6 months of cyclosporine therapy to experience the maximum therapeutic benefit. Two of the major side effects of this drug are renal toxicity and hypertension.

Cyclophosphamide
Cyclophosphamide is also an immunosuppressant that is used intravenously and orally for the treatment of myasthenia gravis.   Many patients respond well to this therapy, though side effects are common.   Side effects include hair loss, vomiting, diarrhea, kidney failure and anemia.

Plasma Exchange
Plasma exchange is used as a short-term intervention for patients with sudden worsening of myasthenic symptoms. It is also used to rapidly improve strength before surgery and as a chronic intermittent treatment for patients who are refractory to all other treatments.

Intravenous Immune Globulin (IVIG)
Several groups have reported a favorable response to high-dose (2 grams/kg infused over 2 to 5 days) IVIG. Possible mechanisms of action include down-regulation of antibodies directed against AChR. Improvement occurs in 50 to 100% of patients and can be seen as quickly as within 1 week of treatment. Relief of symptoms may last for several weeks or months. The common side effects of IVIG are related to the rate of infusion and include headache and flu-like symptoms.

WHAT IS THE PROGNOSIS?
There is no cure for myasthenia gravis, but it is possible to achieve long-term remission. Some patients that only have eye symptoms (ocular myasthenia gravis), may progress to have generalized myasthenia over time. Some patients experience a sudden decline into myasthenic crisis with breathing difficulty, which can be life threatening. However, many people are able to lead normal lives with only minimal restrictions on activity.

SUPPORT GROUPS
The Myasthenia Gravis Foundation of America has 33 chapters nationwide and is an excellent resource for information and support.