Myasthenia gravis (MG) is an autoimmune disease that affects the neuromuscular junction, causing weakness and fatigue in voluntary muscles. Because these symptoms can be caused by many other disorders, diagnosing MG can be difficult and is often delayed.

To diagnose the condition, a physician will review the patient’s symptoms, take a medical history, and conduct a physical and neurological examination. Tests to confirm the diagnosis include blood, nerve, muscle, and imaging.

Physical and neurological examination

With these tests, the physician will determine the extent of muscle weakness by checking reflexes, muscle strength and tone, coordination, sense of touch, and impairment in eye movements.

MG may be suspected based on a characteristic distribution of muscle weakness and fatigue, without impairment of other neurologic function.

Tests to confirm MG diagnosis

The key sign that points to the possibility of MG is muscle weakness that improves with rest. If the physical exam is consistent with MG, the doctor will conduct tests to help confirm the diagnosis. These include:

  • Edrophonium test
  • Ice pack test
  • Blood test
  • Repetitive nerve stimulation
  • Single-fiber electromyography (EMG)
  • Imaging scans

Edrophonium test

This test, typically used to test eye muscle weakness, uses injections of edrophonium chloride to improve muscle strength. Edrophonium chloride blocks an enzyme that breaks down acetylcholine, the chemical that transmits signals from the nerve endings to the muscle receptor sites, activating the muscle and causing it to contract. Patients with MG have a reduced number of acetylcholine receptors, so increasing levels of acetylcholine may improve their symptoms. If patients have a sudden but temporary improvement in muscle strength after the injection of edrophonium chloride, their condition is likely to be MG.

Ice pack test

During this test, the doctor places a bag filled with ice on the patient’s eyelid. After two minutes, the ice is removed and the droopy eyelid analyzed for signs of improvement. A temporary improvement in eyelid droopiness indicates the presence of MG. This is because cold decreases the activity of the acetylcholinesterase enzyme, which breaks down acetylcholine, meaning that more acetylcholine can bind to the receptors on the surface of muscle cells allowing the passage of nerve signals, therefore increasing muscle contraction.

Doctors may conduct this test instead of the edrophonium test.

Blood test

This is the main test to diagnose MG. It can reveal the presence of high levels of abnormal antibodies that disrupt the acetylcholine receptors on the surface of muscle cells.

Acetylcholine receptor antibodies may be detected in the blood of up to 90 percent of patients with the generalized MG and up to 50 percent of those with the ocular MG.

A blood test also can detect another type of antibody, called MuSK (muscle-specific kinase) antibodies, that have been associated with some forms of MG. How MuSK antibodies alter or damage nerve-muscle transmission has not been clearly defined. But patients who test positive for MuSK antibodies often have symptoms involving face muscles, swallowing, speech, and breathing.

In a small proportion of MG patients, the so-called seronegative MG, abnormal antibodies may not be detected with a blood test.

Repetitive nerve stimulation test

In repetitive nerve stimulation test, doctors attach electrodes to the patient’s skin over the muscles to be tested and send small pulses of electricity to measure the nerve’s ability to transmit a signal to the muscle.

MG is diagnosed when the capacity to send signals worsens with fatigue.

Single-fiber electromyography (EMG)

A single fiber electromyography considered the most sensitive test for MG, measures the electrical activity traveling between the brain and the muscle. During this test, single muscle fibers are electrically stimulated by the insertion of a fine wire electrode through the skin and into a muscle.

Muscle fibers of people with MG do not respond to repeated electrical stimulation as well as muscles that function normally.

EMG can be very helpful in diagnosing mild cases of MG when other tests fail to demonstrate abnormalities.

Imaging scans

A computerized tomography (CT) scan or a magnetic resonance imaging (MRI) scan can be used to assess the presence of a tumor or other abnormality in the thymus gland. The thymus gland is a small gland in the chest that forms part of the immune system and seems to play a role in MG, but its function is not fully understood. Some patients with MG have an abnormally large thymus or have a tumor in the thymus (thymoma).

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