According to the Myasthenia Gravis Foundation of America, around 36,000 to 70,000 people have been diagnosed with myasthenia gravis (MG) in the United States alone.
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Myasthenia gravis is an autoimmune neurological disorder that causes severe muscle weakness, which can later lead to respiratory failure as the muscles that function to keep the airway open are compromised.
Though the exact cause that triggers this neurological condition remains unclear, it is believed that a combination of genetic, immunological, environmental, and physiological factors is involved in the onset of myasthenia gravis.
Below, we have listed some myasthenia gravis causes that are believed to contribute to the onset of this condition.
Myasthenia Gravis Causes
Several common factors, like age, thymus gland irregularities, immune attack, infection (viral or bacterial), immunization, or rarely surgery, can trigger the onset of myasthenia gravis. However, among all factors, immune dysfunction plays a significant role in the onset and progression of myasthenia gravis.
Let’s discuss the mechanism through which the immune system and other factors trigger this neurological condition.
Immune System Dysfunction
Under normal conditions, the immune system works to protect your body from harmful pathogens by producing antibodies that detect and kill them. However, when the immune system becomes dysfunctional, it starts attacking your healthy cells, mistaking them for these foreign pathogens.
In myasthenia gravis, the neuromuscular junction (an area where the nerve and muscle connect and communicate) is attacked by the immune system. In a healthy person, acetylcholine binds to the acetylcholine receptor (AChR) at this junction of muscle cells which subsequently causes muscle contraction. However, in MG, the immune system produces autoantibodies that block the acetylcholine receptor protein.
When the autoantibodies bind to the acetylcholine receptors (AChR), the ability of the receptor to receive the chemical signal, acetylcholine, is reduced. As a result, due to insufficient or low chemical signals, muscles do not contract. Hence, people with MG experience extreme fatigue and profound muscle weakness.
Thymus Gland Abnormalities
Abnormalities in the thymus gland have also been associated with MG. Normally, the thymus gland regulates the development of T-cells (a type of immune cell) and trains them to distinguish the healthy body’s cells from harmful pathogens. This gland grows gradually until puberty, then shrinks and is replaced by fats.
Sometimes, thymus glands remain large even after puberty and transform into cancerous cells. Researchers believe that it is possible that when the thymus gland does not work properly, the developing T-cells lose their ability to distinguish between healthy and harmful cells. As a result, they attack the body’s healthy cells and tissue.
For example, in 15% of cases, people with MG have a thymic tumor (or thymoma), and in 75% of cases, MG people have thymic abnormalities (thymic hyperplasia).
Age
Age is a risk factor for MG. Young women in their 30s and older men in their 60s and 70s are most likely to develop MG. It is more common in adults; however, MG can be diagnosed in children.
Viral or Bacterial Infection
Viral or bacterial infection may also trigger or contribute to the onset of myasthenia gravis symptoms. Sometimes, bacterial or viral proteins mimic the structure of acetylcholine receptor protein (AChR), which stimulates the immune system to attack the healthy AChR protein.
For instance, in a case report, three patients with no previous record of neurological condition showed symptoms of myasthenia gravis within 5 – 7 days after the onset of COVID-19 infection. Researchers suspected that antibodies produced against COVID-19 proteins may cross-react with acetylcholine receptor subunits, which results in the onset of MG.
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Genetics
Though MG is not a hereditary disease, it is possible that if an individual has any autoimmune conditions like rheumatoid arthritis or hyperthyroidism, they may also be susceptible to developing MG. However, the research on the association of autoimmune conditions with MG is still ongoing.
Conclusion
Myasthenia gravis or MG is a complex neurological condition that can be caused by multiple factors, including immune system dysfunction, thymus gland abnormality, age, infection, or genetics. However, further research is needed to understand how each factor can cause myasthenia gravis in order to develop effective treatment strategies.
REFERENCES:
- Myasthenia Gravis Clinical Overview | MGFA. https://myasthenia.org/Professionals/Clinical-Overview-of-MG#:~:text=other%20autoimmune%20disorders.-,Epidemiology,cases%20in%20the%20United%20States.
- Myasthenia gravis. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/myasthenia-gravis
- Suresh, A. B., & Asuncion, R. M. D. (2023, August 8). Myasthenia gravis. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK559331/#:~:text=Myasthenia%20gravis%2C%20similar%20to%20other,immunization%2C%20surgeries%2C%20and%20drugs
- Farmakidis, C., Pasnoor, M., Dimachkie, M. M., & Barohn, R. J. (2018). Treatment of myasthenia gravis. Neurologic clinics, 36(2), 311-337. https://doi.org/10.1016/j.ncl.2018.01.011
- Jayam Trouth, A., Dabi, A., Solieman, N., Kurukumbi, M., & Kalyanam, J. (2012). Myasthenia gravis: a review. Autoimmune diseases, 2012. https://doi.org/10.1155/2012/874680
- Dresser, L., Wlodarski, R., Rezania, K., & Soliven, B. (2020). Myasthenia Gravis: Epidemiology, Pathophysiology, and Clinical Manifestations. Journal of Clinical Medicine, 10(11), 2235. https://doi.org/10.3390/jcm10112235
- Restivo, D. A., Centonze, D., Alesina, A., & Marchese-Ragona, R. (2020). Myasthenia gravis associated with SARS-CoV-2 infection. Annals of Internal Medicine, 173(12), 1027-1028. https://doi.org/10.7326/L20-0845