Seronegative Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disease that affects your muscles. Those living with MG have antibodies in their blood that attack the areas where nerves communicate with the muscles they control. This area where muscles and nerves communicate is called the neuromuscular junction. There are many receptors in this area for molecules that tell the muscle to move. These antibodies bind to different receptors and disrupt their signal.1

Because the muscles do not receive signals correctly, those living with MG experience muscle weakness. This weakness often worsens throughout the day the more those muscles are used.1

MG comes in 2 main types, generalized and ocular. There are also subtypes of MG, including seronegative MG.1

What is seronegative MG?

In people with MG, the body creates chemicals called antibodies. These chemicals attack healthy parts of the muscle that communicate with nerves. This keeps the muscles from working correctly and leads to weakness. MG antibodies include:2,3

  • Acetylcholine receptor (AChR)
  • Muscle-specific tyrosine kinase (MuSK)
  • Low-density lipoprotein receptor-related protein 4 (LRP4)

Blood tests show whether the body is making these antibodies. About 80 percent of people with MG have AChR in their blood. About 10 percent have MuSK antibodies, and ever fewer have LRP4.4

However, between 6 and 12 percent of people with MG have no antibodies found in their blood. This is defined as seronegative mysasthenia gravis. Seronegative MG is more common in people with ocular MG.4

What are the symptoms?

The symptoms of seronegative myasthenia gravis are similar to other forms of MG. The defining symptom is muscle weakness that worsens during the day and improves after waking in the morning. The weakness affects specific muscles, not the whole body. The most common muscles affected are in the eyes and throat, though a small set of people may have arm or leg weakness.5,6

The muscle weakness may make it difficult to keep your eyes open, cause double vision, and make it hard to swallow.5,6

How is it diagnosed?

If your doctor thinks you have MG, they will use a combination of a health history, physical exam, and a variety of tests to make a diagnosis. Tests to check breathing and lung function, blood work, and muscle strength tests are commonly used.4

Your doctor may also try the ice pack test. With this test, your eye will be covered with an ice pack for 2 minutes to see if your eyelid strength improves. Improvement means your symptoms may be related to MG.4

Blood work is often used to make a definitive diagnosis of MG. However, since people with seronegative MG do not have detectable antibodies in their blood, diagnosis may be difficult. In fact, some studies have found that many people with seronegative fail to receive a correct diagnosis.7

Nerve conduction studies may be a better tool to diagnose seronegative MG. These tests measure the speed and strength of the electrical activity in the nerves and neuromuscular junction. Electromyography (EMG) and repetitive nerve stimulation (RNS) are the most common tests. A more sensitive test, called a single-fiber electromyography (SFEMG), may be needed in some cases.4

How is it treated?

Those living with seronegative MG have very similar symptoms to those living with seropositive MG. However, seronegative MG often only affects the eye muscles and usually responds better to treatment.4

Some treatments focus on the symptoms of MG by improving nerve signals to the muscles. These drugs are known as acetylcholine inhibitors. They are effective for some people but may not help everyone. Those living with seronegative MG may not have antibodies against acetylcholine or those antibodies may be hard to find. However, these drugs may still be effective.8

Another treatment is to suppress the immune system. If the immune system is less active, it will create fewer antibodies to attack the receptors where nerves communicate with certain muscles. These drugs include steroids and immunosuppressants.5

Some people with MG have a tumor on the thymus gland. The gland is located in the middle of the chest and is an important part of the body’s immune system. Surgery to remove the thymus gland (thymectomy) may improve symptoms in some people.8

Both seronegative and seropositive MG are chronic disorders, but they can be successfully treated. Many people even go into remission. If you have more questions about seronegative MG or believe you may be experiencing symptoms, talk to your doctor.8

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Written by: Leah Steinberg | Last reviewed: March 2021