Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune condition that manifests as weakness in the muscles and formation of anti-acetylcholine receptor (AchR) antibodies.¹ Myasthenia gravis can be exacerbated by infection, immunization, surgery, and certain drugs.² 

Age of Onset

The disease has a female predominance in patients under 40 years of age and a male predominance in those over 50 years of age. Childhood MG is uncommon in Western nations, but it is common in Asian countries where roughly half of MG patients are under the age of 15 years; extraocular muscle weakness is usually the presenting sign in these patients.² Myasthenia gravis can be classed as either a temporary neonatal disease or an adult autoimmune disease.³ 

Genetics 

Most people with MG have no family history of the disease, and it is sporadic with no known cause in these patients. However, up to 5% of patients have relatives with MG or other autoimmune diseases. Some genetically determined human leukocyte antigens (HLAs) are more common in people with MG, suggesting that genetic susceptibility may contribute to the development of MG.⁴ Early-onset MG is linked to the HLA-DR3, HLA-B8, and non-HLA genes, all of which affect the immune system and, hence, autoimmune disease risk; late-onset disease is linked to the HLA-DR2, HLA-B7, and HLA-DRB1 15.01 genes.⁵ 

Immune Dysregulation

Myasthenia gravis occurs due to an abnormal immunological reaction in the form of an antibody-mediated autoimmune response, in which antibodies inappropriately target particular proteins in muscles that receive nerve impulses. Neuromuscular junctions (NMJs) are the points where nerve terminals and skeletal muscle fibers meet.⁴ Autoantibodies are most commonly formed against nicotinic AChRs, muscle-specific kinase (MuSK), and lipoprotein-related protein 4 (LPR4) in the NMJs. The Agrin–LRP4–MuSK protein complex is required for NMJ formation and maintenance, as well as for AChR distribution and clustering. Thymomas occur in about 10% of MG cases and are linked to the generation of autoantibodies.² 

Drug-Induced Myasthenia Gravis and Other Factors

D-penicillamine has been reported to cause MG. Clinical symptoms of drug-induced MG may resemble those of typical acquired autoimmune MG, and antibodies to AChR may be detected. After discontinuing the drug, the disease usually clears. Curare, aminoglycosides, quinine, procainamide, and calcium channel blockers are other drugs that might cause myasthenia-like weakness or aggravate weakness in patients with MG. Fatigue, illness, infection, surgery, stress, pregnancy, and menstruation are other factors that might exacerbate MG.^3,6

Transient Neonatal Myasthenia Gravis

Few children born to mothers with MG may have transitory muscular weakness and other symptoms referred to as transient neonatal MG. Anti-AchR antibodies pass through the placenta to the unborn child during pregnancy, causing this disease.⁴ In most cases, the illness is temporary and symptoms resolve within 2 to 3 months after birth.⁷

Risk Factors for Myasthenic Crisis

Myasthenic crisis is a potentially fatal condition that affects 10% to 20% of patients with MG. Precipitating factors include aspiration pneumonitis; physical, environmental and emotional stressors; infection; surgery; pregnancy; perimenstrual state; sleep deprivation; extremes of temperature; pain; tapering of immune-modulating drugs; and some medications, including beta blockers, quinidine gluconate, quinidine sulfate, quinine (Qualaquin^®), phenytoin, specific anesthetics, and some antibiotics. The most common precipitating factor is believed to be infection.^8,9 

Another type of myasthenic crisis is postoperative myasthenic crisis (PMC). Progressively worsening function of the NMJs after thymectomy can lead to PMC, which is caused by respiratory muscle paralysis and manifests as prolonged mechanical ventilation or reventilation after extubation. It is a fatal complication and a significant condition following thymectomy. PMC can affect anywhere from 6.2% to 30.3% of patients.¹ 

References

1. Geng Y, Zhang H, Wang Y. Risk factors of myasthenia crisis after thymectomy among myasthenia gravis patients: a meta-analysis. Medicine (Baltimore). 2020;99(1):e18622. doi:10.1097/MD.0000000000018622
2. Beloor Suresh A, Asuncion RMD. Myasthenia gravis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed February 9, 2022.
3. Thanvi BR, Lo TCN. Update on myasthenia gravis. Postgrad Med J. 2004;80(950):690-700. doi:10.1136/pgmj.2004.018903
4. Myasthenia gravis. National Organization for Rare Disorders (NORD). Accessed February 9, 2022.
5. Gilhus NE. Myasthenia gravis. N Engl J Med. 2016;375(26):2570-2581. doi:10.1056/NEJMra1602678
6. Myasthenia gravis: symptoms & causes. Mayo Clinic. June 22, 2021. Accessed February 9, 2022.
7. Myasthenia gravis. Saint John’s Cancer Institute. Accessed February 9, 2022.
8. Wendell LC, Levine JM. Myasthenic crisis. Neurohospitalist. 2011;1(1):16-22. doi:10.1177/1941875210382918
9. Huang Y, Tan Y, Shi J, Li K, Yan J, Guan Y. Patients with myasthenia gravis with acute onset of dyspnea: predictors of progression to myasthenic crisis and prognosis. Front Neurol. 2021;12:767961. doi:10.3389/fneur.2021.767961

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.