Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.
Myasthenia gravis (MG) is a rare condition characterized by the production of pathogenic antibodies that affect communication between nerves and muscles at the neuromuscular junction.1 Patients with MG experience weakness and fatigue in specific groups of muscles, such as those of the eyes, as well as generalized fatigue.2
It is important that patients with MG stay active through regular exercise. Patients should also maintain a healthy diet adapted to their condition that will help them achieve an adequate nutritional status while reducing difficulties in chewing and swallowing.3 There are several treatments available to either address and alleviate symptoms or tackle the underlying cause of the disease.
The main focus of MG treatment is to induce remission or minimize symptoms.4 The treatment prescribed will depend on the age and sex of the patient, as well as on the disease severity and degree of functional impairment.5,6
Acetylcholinesterase inhibitors such as pyridostigmine bromide (Mestinon®) and neostigmine bromide (Prostigmin®) can help reduce the hydrolysis of acetylcholine in the synaptic cleft.1,6 The accumulation of this neurotransmitter at the neuromuscular junction improves neurotransmission and consequently muscle contraction and strength.5 The onset of clinical effects after the administration of a cholinesterase inhibitor is about 3 to 4 hours; however, patients with MG show different responses to these drugs and their responses may vary from day to day.1,6 These drugs are not recommended for treating myasthenic crisis, as they can increase secretions and compromise the airways.1
Side effects associated with cholinesterase inhibitors include abdominal cramping, diarrhea, nausea, sweating, and flatulence.1,5 The side effects following high doses of cholinesterase inhibitors can lead to a cholinergic crisis with a worsening of weakness and respiratory crisis.4
Corticosteroids are used to inhibit the immune system, and they are commonly recommended as a first-line therapy for MG.1 Their mechanism of action is not completely understood, however, it is reported that corticosteroids reduce the endothelial adhesion of leukocytes and decrease the production of inflammatory cytokines.1 Prednisolone or prednisone are the immunomodulatory drugs typically used in the long-term treatment of MG.4 Most patients experience treatment benefits during the first 2 weeks of administration and a maximal improvement after 6 months.7
The use of corticosteroids can result in several severe side effects that require patients to have bone and gastric protection. Other side effects include ocular issues such as increased intraocular pressure, mood and sleep changes, and increased susceptibility to infections. Patients should also be monitored for the development of other medical conditions such as diabetes mellitus or hypertension.1,4
Other Immunosuppressant Drugs
Other drugs that can inhibit the immune system are available for MG treatment. These include azathioprine (Imuran®), mycophenolate mofetil (CellCept®), cyclosporine (Sandimmune®), tacrolimus (Astagraf XL® and Prograf®), methotrexate (Trexall®), cyclophosphamide, and rituximab.1,5
These drugs are associated with a higher risk of infection and damage to the liver and/or kidneys.5 The administration of drugs such as mycophenolate mofetil and cyclosporine may be also associated with an increased risk of malignancy.1
Plasmapheresis, also known as plasma exchange, is a widely accepted procedure for MG treatment. In this procedure, the level of harmful autoantibodies is temporarily reduced by removing the antibodies from the patient’s blood through a filtration process.1 A recent study reported a 96% complete response rate to the treatment, regardless of antibody status.8 This treatment is used in patients who present with a worsening of symptoms and in those who do not respond to other therapies.6 It is also used in patients before surgery to improve their overall condition and in patients with myasthenic crisis.2,6 The effects associated with plasmapheresis can last for several weeks.2,5
The complications linked to this procedure are minor and include bleeding, heart rhythm issues, and muscle cramps.1,5
Intravenous Immunoglobulin Infusion
The infusion of intravenous immunoglobulins (IVIG) collected from blood donors is performed to induce changes in the patient’s immune system.5 The immunomodulatory mechanism of action of these immunoglobulins involves the suppression of antibody production and blockage of complement activation.1 The benefits of this procedure can be expected within 1 week after infusion and may last for up to 6 weeks.5 Like plasmapheresis, this procedure can temporarily relieve symptoms, and it can be used before surgery or in patients with severe weakness or myasthenic crisis.1 Complications, typically mild to moderate in severity, have been shown with the use of IVIG in neuromuscular diseases.1 Side effects include dizziness and headaches.5 Rare reactions include anaphylaxis, stroke, and pulmonary emboli.1
The development of MG can be related to abnormal changes in the thymus gland, including hyperplasia and tumor formation (thymoma). The removal of the thymus is indicated not only in MG patients presenting with a thymoma, but also in some patients with generalized disease who do not show tumor formation.9 The benefits of this approach have been evaluated in a phase 3 clinical trial involving 126 participants. Thymectomy was effective in reducing symptoms and the doses of immunosuppressants required by patients to manage the disease.10
1. Farmakidis C, Pasnoor M, Dimachkie MM, Barohn RJ. Treatment of myasthenia gravis. Neurol Clin. 2018;36(2):311-337. doi:10.1016/j.ncl.2018.01.011
2. Myasthenia gravis. National Organization for Rare Disorders (NORD). Accessed February 11, 2022.
3. Wellness strategies. Myasthenia Gravis Foundation of America. Accessed February 11, 2022.
4. Farrugia ME, Goodfellow JA. A practical approach to managing patients with myasthenia gravis-opinions and a review of the literature. Front Neurol. 2020;11:604. doi:10.3389/fneur.2020.00604
5. Myasthenia gravis: diagnosis & treatment. Mayo Clinic. June 22, 2021. Accessed February 11, 2022.
6. Howard JF Jr. Clinical overview of MG. Myasthenia Gravis Foundation of America. Accessed February 11, 2022.
7. Pascuzzi RM, Coslett HB, Johns TR. Long-term corticosteroid treatment of myasthenia gravis: report of 116 patients. Ann Neurol. 1984;15(3):291-298. doi:10.1002/ana.410150316
8. Usmani A, Kwan L, Wahib-Khalil D, Trivedi J, Nations S, Sarode R. Excellent response to therapeutic plasma exchange in myasthenia gravis patients irrespective of antibody status. J Clin Apher. 2019;34(4):416-422. doi:10.1002/jca.21694
9. Beloor Suresh A, Asuncion RMD. Myasthenia gravis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed February 11, 2022.
10. Wolfe GI, Kaminski HJ, Aban IB, et al; MGTX Study Group. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511-522. doi:10.1056/NEJMoa1602489
Reviewed by Kyle Habet, MD, on 2/11/2022.