Myasthenia gravis (MG) is an autoimmune disorder in which autoantibodies are produced that interfere with the transmission of nerve impulses at the neuromuscular junction.1 MG causes weakness and fatigue in several muscles, including those of the eyes, limbs, jaw, face, and neck. The disease also causes weakness of the respiratory muscles, which may result in a potentially life-threatining myasthenic crisis.1,2

MG may be difficult to diagnose because muscle weakness is a symptom of many other diseases. The patient may experience weakness only in specific muscles, rather than generalized fatigue, and the symptoms may fluctuate, so that a diagnosis of MG can be delayed for months and sometimes for as long as 2 years.3,4 

Neurological Evaluation

A physical examination is required to diagnose MG. The medical team will ask about the patient’s medical history and symptoms and will evaluate his or her neurological status. Reflexes, muscle strength, muscle tone, coordination, balance, mental skills, and the senses of touch and sight will be tested.3,5,6 A diagnosis of MG is suspected when muscle weakness and fatigue are not associated with any changes in neurological function.1 Additional tests like edrophonium or Tensilon test involving intravenous injection of a drug that inhibits the action of an enzyme involved in the breakdown of acetylcholine help to confirm the diagnosis.

Ice Pack Test

The ice pack test, commonly used by ophthalmologists, can help to confirm a diagnosis of MG. While the patient’s eyes are closed, an ice pack is applied to an eyelid for 2 minutes. Cooling the ocular muscles may mitigate the weakness associated with MG because acetylcholinesterase activity is inhibited.3,7 After removal of the ice pack, a full or partial resolution of ptosis (drooping of eyelid) indicates a diagnosis of MG.2

Edrophonium Chloride Test (Tensilon® Test)

Edrophonium chloride is a reversible acetylcholinesterase inhibitor.7 When it is administered intravenously, neuromuscular transmission temporarily improves, indicating the presence of MG.3 Edrophonium chloride has several side effects, including a slow heart rate and dizziness; therefore, this test is performed only if absolutely necessary and in a hospital setting.6,7 

Alternatives to edrophonium chloride are intramuscular neostigmine, which has a longer duration of action, and oral pyridostigmine bromide (Mestinon).3,4 These tests should not be conducted if the patient is medically unstable. Instead, the ice pack test should be used.7 

Blood Tests

Antibodies to various proteins, such as acetylcholine receptor (AChR), muscle-specific receptor tyrosine kinase (MuSK), and lipoprotein receptor protein 4 (LRP-4), may be found in the serum of patients with MG. These antibodies disrupt neuromuscular transmission.1 Not all patients with MG have high levels of autoantibodies, particularly those with ocular MG.6,7 Levels of AChR antibodies are elevated in 85% of patients with generalized MG and approximately 50% of those with ocular MG. However, the antibody titers correlate poorly with the patient’s clinical condition.7 Other disorders, including systemic lupus erythematosus and amyotrophic lateral sclerosis, may also be associated with high levels of antibodies.4 

Anti-MuSK antibodies are found in approximately 40% of patients with MG who are seronegative for AChR antibodies, and anti-LRP-4 antibodies are detected in a small percentage of seronegative patients.4,7 Other antibodies, again proteins such as myosin and actin, are also found in patients with MG. The myosin and actin antibodies are present in approximately 84% of patients with MG who also have a thymoma, and their presence may be a reliable indicator of the existence of a tumor.7 Anti-striational muscle antibodies are detected in patients with MG who have a thymoma, patients with a thymoma who do not have MG, patients with MG who do not have a thymoma, and patients with autoimmune liver disease.4


In this test, electrodes are attached to the skin over the muscles to be evaluated. Small pulses of electricity are sent through the electrodes to evaluate the communication between nerves and muscles and to determine the .amplitude of the compound muscle action potential (CMAP).4,5 Electromyography is a repetitive nerve stimulation (RNS) test, conducted to determine if the communication between nerves and muscles decreases with fatigue.5 A positive RNS test result can be expected in the hand or shoulder muscles of nearly 60% of patients with MG.4

Single-Fiber Electromyography

In single-fiber electromyography (SFEMG), a sterile needle electrode or a concentric needle EMG electrode with a small recording surface is inserted into a muscle, which the patient then contracts and activates.3,4 The sensitivity of SFEMG is higher than that of RNS testing. The test result is abnormal in approximately 94% of patients with generalized MG and approximately 80% of patients with ocular MG.7 However, SFEMG is a demanding and lengthy study during which patient cooperation is essential.7

Imaging Tests

Computed tomography or magnetic resonance imaging (MRI) may be required to evaluate the thymus gland and check for a thymoma. These imaging tests can also be performed to exclude brain disorders.3,6 


1. Myasthenia gravis. National Organization for Rare Disorders (NORD). Accessed February 8, 2022.

2. Rubin M. Myasthenia gravis. MSD Manual. Updated December 2020. Accessed February 8, 2022.

3. How to diagnose myasthenia gravis. Conquer Myasthenia Gravis. Accessed February 8, 2022.

4. Howard JF Jr. Clinical overview of MG. Myasthenia Gravis Foundation of America. Accessed February 8, 2022.

5. Myasthenia gravis diagnosis. Mayo Clinic. Accessed February 8, 2022.

6. Diagnosis myasthenia. NHS. Accessed February 8, 2022.

7. Pasnoor M, Dimachkie MM, Farmakidis C, Barohn RJ. Diagnosis of myasthenia gravis. Neurol Clin. 2018;36(2):261-274. doi: 0.1016/j.ncl.2018.01.010

Reviewed by Debjyoti Talukdar, MD, on 2/9/2022.