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The Seronegative MG Resource Center

You may have questions about what seronegative MG is, how to diagnose it, and how treatment might differ from antibody-positive MG. This resource center is a helpful overview for patients and caregivers and provides diagnostic and treatment resources for medical providers.

 

What is seronegative myasthenia gravis?

The majority of people diagnosed with MG have AcHR or MuSK antibodies in their blood. If your blood does not contain these antibodies, you can still have MG if you meet certain diagnostic criteria. This is called seronegative myasthenia gravis. Between 10 - 20% of people diagnosed with MG are seronegative. Anti-musk information is scarce but more is being done to research and develop better treatments for this “Rare-of-the Rare” disease.

 

What Causes Seronegative Myasthenia Gravis? (read more)

We don't fully understand what causes MG. Patients generally have an acquired immunological abnormality, but some cases result from genetic abnormalities at the neuromuscular junction.

In terms of seronegative MG, clinical research is underway to determine whether seronegative MG symptoms could be caused by antibodies for other proteins such as agrin or LRP4 antibodies, or an as-yet determined antibody. If so, a blood test could be developed to help with diagnosis. Genetic testing may also help determine the causes of seronegative MG. If you’re interested in participating in a clinical trial, visit our research page.

 

In rare cases, babies or children will present with MG symptoms and will not have AcHR or MuSK antibodies in their blood. These symptoms are caused by a range of genetic mutations in components of the neuromuscular junction and are referred to as congenital myasthenic syndromes, or CMS. CMS is extremely rare.

How is Seronegative Myasthenia Gravis Diagnosed? (read more)

Seronegative MG is a diagnosis of exclusion. Your doctor may think you have MG, but without AcHR or MuSk antibodies in your blood, they will want to rule out other possible diagnoses. MG can look like stroke, muscular dystrophy, ASL, and even anemia or thyroid disorders.

There are a few different ways that a doctor can confirm a seronegative MG diagnosis:

  • Your symptoms. MG patients generally present with variable weakness and fatigue that improves with rest. Seronegative MG patients are more likely to have muscle weakness in the face, head, and neck versus other areas of the body. Repetitive testing of motor strength is used to determine how quickly your muscles fatigue and which muscles are affected.
  • Repetitive nerve stimulation. Your doctor will stimulate some of your nerves with an electrode. The response should be the same with each stimulation, but with MG each successive stimulation gets a smaller nerve response. This response happens in about 65% of diagnosed MG patients, even if you don’t have antibodies.
  • Test an acetylcholinesterase inhibitor. This class of drugs has been very successful in improving muscle strength in patients with neuromuscular junction disorders. Mestinon is commonly used to treat MG. Your doctor may ask you to take this medication when experiencing your symptoms and track how well it resolves them.  A few specialized tests are also available — these tend to be an option at academic research hospitals, so they are harder to obtain. A neurologist with a neuromuscular specialty can typically perform these tests.
  • Single-fiber EMG. Practitioners put a very thin needle into muscle tissue, and a branch of the motor nerve is stimulated with an electrical current. Targeting that nerve should lead to a cascade of muscle activation. For patients with neuromuscular junction disorders, the muscle response will be delayed. This is the case for more than 95% of MG patients, including seronegative patients.
  • Muscle Biopsy. A muscle biopsy can show researchers what’s happening in your body at the cellular level.

 Learn more detail about how MG is diagnosed HERE.

What Treatments are Available for Seronegative MG? (read more)

A "wellness strategy" is a plan of action you can develop to live as full a life as possible with your myasthenia gravis (MG). As you make a plan to live your best life with MG, you may need some tips and tools to help you along the way. We’ve pulled together some advice from leading experts in MG; ranging from doctors, to community leaders to people living with MG.

We’ve pulled together some advice from leading experts in MG; ranging from doctors, to community leaders to people living with MG. MG is treated as an autoimmune disease, and patients are given treatments and medication to stop the production and distribution of antibodies that the immune cascade creates at the neuromuscular junction.

Many treatments on the market today are only approved for patients who are AcHR-antibody positive. Options for a seronegative patient may include:

  • Rituximab
  • Mestinon
  • Prednisone
  • Plasmapheresis
  • IvIG

In addition, lifestyle changes can be very helpful in resolving your symptoms. A pulmonary specialist or respiratory therapist can teach you ways to improve your breathing. Getting enough rest every night will help your muscles activate properly during the day. Find foods that are nutritious yet won't tax your jaw muscles, eg. swap steak for lentils to get your protein and steam your carrots versus eating them raw.

 

Obstructive sleep apnea is common among seronegative patients because they are more likely to have weakness of the muscles in the tongue and soft pallet. Having a sleep evaluation can prevent you from having trouble breathing while you sleep, as well as ensure you get the rest you need to support your muscle function during the day.

 

Learn more about treatment strategies HERE.

MGFA Seronegative Support Group (read more)

Join the MGFA Seronegative Support Group.

 

Our support groups offer virtual and in-person support opportunities to our MG Community. Search the MGFA support groups here.

Finding a Care Provider Near You (read more)

Specialists can help ensure you get a treatment plan that’s right for you.

 

Our medical advisors recommend you seek out a neurologist with a neuromuscular specialty. If you have access to medical care at an academic research center, you are more likely to have access to specialized diagnostic tests to confirm a seronegative MG diagnosis.

SEARCH OUR LIST of Partners in MG Care.

Additional Seronegative Resources

Learn more about seronegative MG with the additional external resources below.

Clinical Overview of MG

International Consensus Guidance for Management of Myasthenia Gravis

Resources for Professionals

Cortés-Vicente, Elena, MD; et al. “Clinical Characteristics of Patients With Double-Seronegative Myasthenia Gravis and Antibodies to Cortactin,” JAMA Neurology. 2016;73(9):1099-1104. 

Selvan, V. Arul. “Single fiber EMG: A review.” Annuals of Indian Academy of Neurology. 2011 Jan-Mar; 14(1): 64–67.

Singh, Shivangi; et al. “Eculizumab in the Treatment of Seronegative Refractory Generalized Myasthenia Gravis.” Neurology. April 15, 2020. 

Susman, Ed. “Triple Seronegative Myasthenia Gravis Patients Have Milder Disease With Ocular Manifestations,” Neurology Today. Oct. 18, 2021.

A World Without MG