Myasthenia Gravis Update

Posted by Elaine Moore Oct 11, 2006

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder that primarily causes muscle weakness in the voluntary muscle groups. In MG, peripheral nerves are unable to send basic commands to muscles, predominantly bulbar muscles. In patients with myasthenia gravis, muscle weakness increases with continued activity and improves after periods of rest. MG ranges from a mild disorder with variable periods of weakness to a severe condition affecting breathing and movement. Myasthenia is derived from the Latin and Greek words for "grave muscle weakness."

WHO IS AFFECTED?

In younger patients, females are affected more often than males although after age 50, MG tends to affect men more than women. In children with MG who have coexisting autoimmune conditions girls are affected 5 times more often than boys. Transient conditions of neonatal MG may occur in newborns from passive transfer of maternal antibodies. The peak ages for MG are young adulthood (20-30 yrs) and people older than 50. Before the introduction of effective treatments for MG, mortality ranged from 30-70 percent. Today, with proper diagnosis and treatment, life expectancy is not affected.

CAUSES OF MG

MG is caused by a reduction in the number of available acetylcholine nicotinic postsynaptic receptor sites. Voluntary muscles are normally controlled by impulses sent from the brain to these receptor sites. When we intend to move an arm, for instance, a signal is sent from the brain through nerves. The space where the nerves meet the muscle fibers is called the neuromuscular junction. When the nerve impulse from the brain meets the muscle fiber it releases a chemical neurotransmitter called acetylcholine. Acetylcholine normally crosses the neuromuscular junction and attaches to numerous receptor sites on muscle fibers. Here, acetylcholine activates muscle fibers. This signal from the nerves via acetylcholine causes the muscle to respond the way we intend it to.

ACETYLCHOLINE RECEPTOR ANTIBODIES

Patients with MG have autoantibodies to the acetylcholine receptor. In MG, acetylcholine receptor antibodies block acetylcholine from reacting with muscle cell receptors. The intended impulse isn't received and the muscle doesn't get the intended command. This prevents muscles from contracting. In addition to blocking the receptor sites, acetylcholine receptor antibodies destroy the muscle's acetylcholine receptor sites. Most people with MG experience an 80 percent reduction in acetylcholine receptor sites.

SYMPTOMS IN MG

Symptoms in MG typically occur when the reduction in available acetylcholine receptor sites reaches 30 percent. Most symptoms are related to weakness of skeletal muscle groups, for instance, the muscles involved in climbing stairs. Cardiac and smooth muscle are not affected. In about 20 percent of patients, vision alone is affected. Typical visual disturbances in MG include diploplia (double vision), ptosis (eyelid drooping or sagging) and blurred vision. Other symptoms include weakness of neck muscles and proximal muscles such as the biceps or thighs, slack facial muscles, slurred speech, uncontrolled facial expressions, unstable or wobbly gait, shortness of breath, weakness in arms, hands, fingers and legs, vocal (nasal tone) changes, difficulty swallowing, chewing or talking, generalized weakness and limpness, absent gag reflex, and respiratory weakness.

About 75 percent of patients with MG have thymus gland abnormalities, usually thymus enlargement, although thymus gland tumors (thymomas) may occur in about 15 percent of cases. About 10 percent of patients have thyroid gland disorders.

A myasthenic crisis occurs when the muscles that control breathing weaken and interfere with ventilation. Myasthenic crises can be triggered by infection, fever, interfering medications or emotional stress.

DIAGNOSIS

Patients with symptoms of MG are tested for acetylcholine receptor antibodies. Imaging tests are used to detect thymomas. The tensilon (edrophonium) challenge test is also used to diagnose MG and to differentiate MG crises from crises caused by excessive cholinergic medications. In this test edrophinium is administered and the effects observed. People with MG show dramatic improvement in muscle strength within 1 minute of administration. Electromyography (EMG) is used to evaluate the electrical potential of muscles cells. In MG, muscle cells don't respond well to electrical stimulation. An ice pack test is used to differentiate eye symptoms in MG from eye symptoms with other causes. In patients with MG applying ice over the eyelid improves conditions of ptosis.

TREATMENT

Patients with MG show a good response to cholinesterase-inhibiting medications such as physostigmine to improve and reduce muscle weakness. Immunosuppressant drugs such as azathioprine or cyclosporine also offer benefits. Prednisone is used to reduce autoantibody production. Other medications may be used as needed to reduce specific symptoms, for instance albuterol is used in patients with respiratory problems and intravenous immunoglobulins are used in patients unable to use other medications. Surgical removal of the thymus gland (thymectomy) reduces symptoms in up to 70 percent of patients without thymoma and has the ability to rebalance the immune system.

Certain medications can exacerbate or worsen symptoms in patients with MG and cause symptoms of MG in patients without MG. These include certain antibiotics, particularly macrolides, fluoroquinolones, gentamicin, and tetracycline; cardiac agents such as beta blockers, calcium channel blockers, quinidine and lidocaine; miscellaneous drugs including diphenytoin, lithium, chlorpromazine, levothyroxine, muscle relaxants, and in some cases corticosteroids.

Resources:

Edward Newton, Myasthenia Gravis, eMedicine, Sept 19, 2005

Facts about Autoimmune Myasthenia Gravis for Patients and Families.

Myasthenia Gravis Fact Sheet, National Institute of Neurological Disorders and Stroke, National Institutes of Health.