People with myasthenia gravis (MG) have autoantibodies — immune system proteins that mistakenly attack the neuromuscular junction (the connection between nerves and muscles), causing muscle weakness. If your doctor suspects you have MG, they’ll likely order blood tests to look for these autoantibodies. Finding certain autoantibodies in your blood helps confirm an MG diagnosis and provides details about the specific type you have.

However, some people have MG symptoms but don’t test positive for the usual autoantibodies. After ruling out other conditions, your doctor may diagnose you with seronegative MG. “Seronegative” means that the autoantibodies typically seen in people with MG weren’t found in your blood.

How does seronegative MG differ from other types? Does it affect symptoms, treatment, or long-term outlook? This article explores key facts about seronegative MG.

1. Seronegative Myasthenia Gravis Is the Rarest Type

Typically, when a person is being examined for MG, healthcare providers look for autoantibodies that attack acetylcholine receptor (AChR) or muscle-specific receptor tyrosine kinase (MuSK) proteins in their blood. If these autoantibodies are found, the person is said to have seropositive MG, the more common form of the disease.

MG is already a rare autoimmune disease (a condition in which the immune system mistakenly attacks healthy tissue). In around 1 in 10 people with MG, neither AChR nor MuSK antibodies are found, even though other symptoms match an MG diagnosis. In these cases, doctors diagnose seronegative MG.

Sometimes, people with seronegative MG may go undiagnosed or be misdiagnosed. Unfortunately, this form is still poorly understood. Research is ongoing to learn more about seronegative MG.

2. Seronegative MG Tends To Affect Younger People

According to current research, seronegative MG appears to be more common in younger people, including young adults and children.

Younger individuals may experience a milder disease course. They’re more likely to experience ocular myasthenia gravis (MG that mainly affects the eyes) rather than generalized MG, which can cause muscle weakness throughout the body. Younger people with seronegative MG also have a lower risk of thymoma — a tumor of the thymus gland, which helps regulate the immune system.

3. Diagnosing Seronegative MG Requires Extra Testing

Without the typical MG autoantibodies, diagnosing seronegative MG can be more challenging. The symptoms also occur with many other conditions, including:

• Stroke, which happens when blood flow to the brain is stopped
• Multiple sclerosis, a disease that affects the brain and spinal cord
• Amyotrophic lateral sclerosis (ALS), which affects nerve cells controlling muscles
• Lambert-Eaton myasthenic syndrome (LEMS), a rare disorder that causes muscle weakness
• Thyroid eye disease, which affects eye muscles and vision

Because of these overlapping symptoms, a thorough evaluation by a neurologist (a doctor specializing in brain and nerve disorders) is crucial for an accurate diagnosis. In addition to testing for MG, which may include repetitive nerve stimulation or single fiber electromyography (tests that measure how well nerves and muscles work), healthcare providers must rule out conditions that can mimic MG. Your doctor may order tests such as:

• Imaging studies, such as MRI or CT scans, to look at the brain, spinal cord, or thymus gland
• A muscle biopsy, which involves taking a small sample of muscle tissue to check for disease
• A lumbar puncture (sometimes called a spinal tap) to examine fluid around the brain and spinal cord

4. Delays in Diagnosis May Stall Treatment

The extensive diagnostic process for seronegative MG diagnosis may take months or even years. This can delay treatment and cause stress for people waiting to find out the cause of their symptoms.

According to a study published in the Journal of Neurology, Neurosurgery and Psychiatry, people who received appropriate treatment for MG within six months of the start of their first symptoms fared better than those whose treatment was delayed. Unfortunately, this means that undiagnosed and untreated seronegative MG may lead to worse outcomes. Although waiting for a diagnosis can be difficult, it’s important to remember that research is ongoing, and doctors are working to improve the diagnostic process for seronegative MG.

5. Tests Can’t Yet Find All the Autoantibodies

In people with seropositive MG, the main autoantibodies are anti-AChR and anti-MuSK. However, researchers continue discovering new autoantibodies that can cause MG. These include an antibody that attacks low-density lipoprotein receptor-related protein 4 (LRP4).

If someone was previously diagnosed with seronegative MG, new cutting-edge testing might show that they’re LRP4-positive. Other autoantibodies, such as those that target agrin (a protein involved in nerve-muscle communication), may play a role. Some cases of seronegative MG may be caused by antibodies that scientists have not yet identified.

It’s also possible that older, less sensitive testing may fail to show low levels of AChR or MuSK autoantibodies and lead to a false diagnosis of seronegative MG. A newer, more precise method called a cell-based assay, which uses living cells to detect antibodies, is becoming more widely available. Studies show that almost one-fifth of people who were originally thought to be seronegative turned out to have AChR antibodies when this newer test was used.

Some researchers have also suggested that certain medications, illnesses, or other factors may affect blood test results and lead to a seronegative diagnosis.

6. Seronegative MG Symptoms Are Similar to Those of Other Types

Most often, people with seronegative MG experience symptoms similar to those of people with seropositive MG. These symptoms may include:

• Ptosis (droopy eyelid)
• Blurry or double vision
• Changes in facial expressions
• Muscle weakness
• Dypnea (difficulty breathing)
• Dysphonia (difficulty talking)
• Trouble swallowing or chewing

In both autoantibody-positive and autoantibody-negative MG, symptoms can vary widely. Symptoms may range from mild to severe, affect one group of muscles or a few, and change throughout the day or over time. MG symptoms can even differ among people with the same type of MG, which is why MG is known as the “snowflake disease.”

7. Treatment Options Tend To Include Approaches for AChR-Positive MG

MG is usually a lifelong condition that can’t be cured, but it can be managed. Generally, treatment options for seronegative MG are similar to those recommended to people with AChR-positive MG.

However, MG treatment is tailored to each person’s needs and symptoms, and a neurologist will help develop the most effective plan. Options may include:

• The acetylcholinesterase inhibitor pyridostigmine (Mestinon), which may help improve muscle-nerve communication
• Immunosuppressants, including corticosteroids like prednisone or other medications such as azathioprine, cyclosporine, and tacrolimus, which help reduce the immune system’s attack on muscles
• Intravenous immunoglobulin (IVIG), a treatment that temporarily alters the immune system to relieve MG symptoms
• Plasma exchange, also called plasmapheresis, a procedure that removes abnormal antibodies from the blood and replaces them with healthy ones from a donor
• Thymectomy (surgical removal of the thymus gland) for people with a thymoma

Access to Treatments

Some newer treatments for MG may be U.S. Food and Drug Administration (FDA)-approved only for people with confirmed AChR or MuSK antibodies, which can make it more difficult for those with seronegative MG to access them. In some cases, these medications may be prescribed off-label — meaning they’re used to treat a condition or group of people not specifically included in the original approval. Your doctor can help you understand all your treatment options and develop a treatment plan that will work for you.

If newer treatments aren’t covered by insurance, talk to your doctor about appealing the decision or exploring off-label use when appropriate. Advocacy groups can also be valuable resources in navigating these challenges.

Talk With Others Who Understand

On MGteam, the social network for people with myasthenia gravis and their loved ones, more than 2,800 members come together to ask questions, give advice, and share their stories with others who understand life with MG.

Have you been diagnosed with seronegative MG? Were you misdiagnosed before receiving your MG diagnosis? Share your experience in the comments below, or start a conversation by posting on your Activities page.