Diagnosis of Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disease that affects the neuromuscular junction — the region where nerves and muscles come into contact and communicate — causing muscle weakness and fatigue. Because these symptoms can be caused by many other disorders, diagnosing MG can be challenging and is often delayed.

To diagnose the condition, a physician will typically review a patient’s symptoms, take a detailed medical history, and conduct a thorough physical and neurological examination. To confirm the diagnosis, blood, nerve, muscle, and imaging tests may also be performed.

Physical and neurological examination

With these tests, a physician will determine the extent of muscle weakness by checking a patient’s reflexes, muscle strength and tone, coordination, sense of touch, and problems with eye movement. MG may be suspected based on a typical distribution of muscle weakness and fatigue, without neurological dysfunction.

Ice pack test

During this test, a doctor places a bag filled with ice on a patient’s eyelid. After a few minutes, the ice is removed and a patient’s droopy eyelid is analyzed for signs of improvement. Temporary improvement in eyelid droopiness indicates the presence of MG. This is thought to occur because cold decreases the activity of the acetylcholinesterase enzyme, which breaks down acetylcholine — the signaling molecule that triggers muscle contraction. This means that more acetylcholine can now bind to receptors found on the surface of muscle cells, increasing muscle contraction and easing the eyelid droopiness caused by MG.

Blood test

A blood test is the main test to diagnose MG. It can reveal high levels of self-reactive antibodies that disrupt the function of acetylcholine receptors found on the surface of muscle cells.

These antibodies, which are considered the main cause of MG, may be found in the blood of up to 90% of all patients with generalized MG and up to 50% of those with ocular MG.

A blood test can also detect another type of self-reactive antibodies, which target a protein called muscle-specific kinase (MuSK), and found in some MG patients. How MuSK antibodies alter or impair nerve-muscle communication has not been clearly defined. But patients who test positive for MuSK antibodies often have weakness in facial, neck, and respiratory muscles.

In a small subset of patients with seronegative MG, neither acetylcholine receptor antibodies nor MuSK antibodies are detected in blood tests.

Repetitive nerve stimulation test

In a repetitive nerve stimulation test, doctors attach electrodes to a patient’s skin above the muscles they wish to examine. Small pulses of electricity are sent through these electrodes, allowing a doctor to assess a nerve’s ability to transmit a signal to muscle. MG is diagnosed when a nerve’s capacity to send signals worsens with fatigue, which usually occurs over the course of multiple rounds of electrical stimulation.

Single fiber electromyography

Single fiber electromyography is considered the most sensitive diagnostic test for MG. It measures the electrical activity traveling between the brain and a muscle. During this test, a fine wire electrode is inserted through the skin into a muscle to electrically stimulate a single muscle fiber.

In MG patients, muscle fibers do not respond well to repeat electrical stimulation, while they do in people without such a disease.

Single fiber electromyography can also be helpful in diagnosing mild cases of MG, when all other tests have failed to detect abnormalities.

Imaging scans

Computerized tomography (CT) or magnetic resonance imaging (MRI) scans of the chest can help to assess the presence of a tumor or other abnormalities in the thymus gland.

The thymus, a small gland found in the chest that is part of the body’s immune system, is thought to contribute to the production of the harmful self-reactive antibodies that cause MG. Some MG patients have an unusually large thymus or a tumor in the gland (thymoma). Doctors may recommend surgery to remove the entire gland, a procedure known as a thymectomy.

An MRI scan may also be requested to rule out brain disorders.

Pulmonary function tests

MG often affects the respiratory system. Respiratory muscle weakness can lead to difficulties with breathing for patients. Assessing breathing strength can help to predict a patient’s risk of respiratory failure and a myasthenic crisis.

Pulmonary function tests using spirometry are routinely used to monitor a patient’s respiratory health. Spirometry uses a small device, called a spirometer, to measure how much air a person can breathe in and out, and how fast a person breathes.

Edrophonium test

In some cases, an edrophonium test may also be performed to confirm an MG diagnosis. This test, typically used to assess eye muscle weakness, uses injections of edrophonium chloride to briefly improve muscle strength.

Edrophonium chloride prevents the breakdown of acetylcholine by blocking the activity of the acetylcholinesterase enzyme. Because MG patients typically have fewer functional acetylcholine receptors, increasing acetylcholine levels may briefly ease disease symptoms.

If patients have a sudden, but temporary, improvement in muscle strength after receiving an injection of edrophonium chloride, they likely have MG.

In some cases, doctors may replace the edrophonium test by the ice pack test, which is based on the same principle but often considered to be safer.


Last updated: Aug. 3, 2021


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