Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junction (NMJ) at the postsynaptic level. Its name is derived from both Greek and Latin words meaning “grave muscular weakness.” Although the cause of the disorder is unknown, the role of immune responses in its disease process is well established. The person’s own immune system abnormally creates antibodies that circulate in the body and attack the nicotinic acetylcholine receptor. In normal voluntary muscle function, impulses from the brain are sent down the nerves to where the axon terminal meets the muscle fibers. A nerve action potential is created and acetylcholine (ACh) is released into the synapse. This eventually leads to muscle contraction when ACh has activated enough receptors. In myasthenia gravis, there is up to an 80 percent decrease in ACh receptors, which leads to dysfunction at the NMJ as well as produces sensory dysfunction (MGFA, 2010). Thus, the nerves cannot communicate with the muscles the way that they should.
MG is not rare, with a prevalence of 50 to 125 cases per million persons (MGFA, 2010). However, this number may be much higher as MG is thought to be underdiagnosed. The incidence is age- and sex-related, generally affecting women less than 40 years old and men greater than 60 years old. The cardinal features are weakness and fatigue of skeletal muscles. The weakness tends to increase with repeated activity and improve with rest. Ptosis (drooping eyelid) and diplopia (double vision) occur early in the majority of patients. Weakness remains localized to the extraocular and eyelid muscles in about 15 percent of patients (MGFA, 2010). When the facial muscles are affected, there may be a characteristic flattened smile, “mushy” or nasal speech, and difficulty in chewing and swallowing. Generalized weakness develops in most patients. If weakness of respiration becomes severe enough to require mechanical ventilation, the patient is said to be in crisis. Some patients may have symptoms only late in the day or after physical exertion. This disorder is highly treatable so prompt recognition is crucial.
Patients experiencing muscle pain that does not affect all skeletal muscles, such as arm and leg weakness with no eye muscle symptoms, are not likely to have MG. A variety of neurological conditions can mimic MG, such as botulism and amyotrophic lateral sclerosis. In addition, a large number of medications that can cause a patient to experience muscle weakness must be addressed before diagnosing the disease as MG. The list includes but is not limited to antibiotics, cardiovascular agents, and other various drugs.
The most sensitive test for MG is an ACh receptor antibody (AChR-Ab); however, not all patients with MG will present with positive antibodies. Another test to determine MG is to give the patient in question a medication—edrophonium (an acetylcholinesterase inhibitor)—and evaluate the response. This medication prevents the breakdown of ACh and therefore allows more receptors to interact with the muscle fibers. After a patient receives the drug, health care providers look for an unequivocal increase in strength. A subjective feeling of strength increase will not be enough to diagnose MG. Thus, an objective finding by the provider can be used, such as if the person’s drooping eyelids improve. Clinicians can also use electrodiagnostic studies that look at nerve conduction, repetitive nerve stimulation, exercise testing, and sometimes an electromyelogram.
Prior to 1958, the mortality rate for MG patients was very high, most had deteriorating symptoms, and very few patients improved. Since then, the mortality rate is essentially zero, and many patients lead normal functioning lives. There are four ways of treating MG: (1) acetylcholinesterase inhibitors (ACh-i), (2) thymectomy, (3) immunosuppression, and (4) plasma-exchange or immune globulin.
As discussed previously, an ACh-i will improve muscle strength in MG patients and these are popular methods of treatment. The drugs will be tailored to the patients’ needs and the doses can range as well. Higher doses, however, can exacerbate muscle weakness. Since the thymus has been implicated in MG, those between puberty and age 60 should have their thymus surgically removed. The goal for any patient undergoing this procedure is remission of the disease, or at least great improvement of MG that limits the need for other medications.
Immunosuppressive therapy is indicated when the patient experiences progressive weakness despite treatment with anticholinergic drugs. Because suppressing the body’s immune system puts patients at higher risk for infection and many other side effects, the decision to step up therapy is made after weighing the costs and benefits. Patients on these drugs should do their best to take care of their health like hand washing, eating well, and being vaccinated, because they will not be able to fight simple infections.
Plasmaphoresis is a technique that takes the plasma out of the patient, cleans it by taking out the ACh antibodies, and puts it back into the patient. This procedure is typically performed when an MG patient is having a crisis or if a patient is undergoing a surgical thymectomy. The effect of this treatment is seen very rapidly, but then it goes away after a few weeks, which is why this is used in emergency situations and not for long-term treatment options.
Jeremy E. Brothers
See also: Diplopia; Ptosis
Myasthenia Gravis Foundation of America (MGFA). (2010). What is myasthenia gravis? Retrieved from http://www.myasthenia.org/WhatisMG.aspx