MG is a disorder of the neuromuscular junction and therefore of great significance to the anesthesiologist. It is a chronic disorder characterized by fluctuating painless weakness and fatigability of voluntary muscles made worse on exertion with improvement following rest. The onset is usually slow and insidious; any skeletal muscle or muscle group may be affected. The most common onset is ocular, presenting with ptosis and diplopia. If the symptoms remains localized to the eyes for 2 years, the likelihood of progression to generalized disease is low. In many cases, however, MG is generalized and may involve the bulbar musculature, causing problems with breathing, speaking, mastication, and swallowing. Proximal muscles are more commonly involved than distal. Peripheral muscle weakness may manifest as clumsiness, difficulty holding up the head, or in ambulating. Respiratory muscle weakness may cause dyspnea, a decrease in the ability to cough and therefore to remove secretions.

The incidence of MG appears to be increasing. The most accurate estimate of incidence of MG was around 30 per 1,000,000 per year. The incidence in children and adolescents aged 0 to 19 years was found to be between 1.0 and 5.0 per 1,000,000 per year. These rates may well be an underestimate of the true incidence rates because mild cases may have been missed and cases in the elderly may have been misdiagnosed. People of any age may be affected, but peaks of incidence occur in the third decade for women and the fifth decade for men.

In normal neuromuscular transmission, the acetylcholine released from the motor nerve terminal stimulates postsynaptic nicotinic receptors at the motor end plate to generate an action potential leading to depolarization of the membrane and contraction of the motor unit. The normal neuromuscular junction has a very large number of postsynaptic acetylcholine receptors (AChRs) such that muscle weakness only becomes apparent when 70% or more of the receptors have been blocked. This excess of receptors has been termed the “margin of safety of neuromuscular transmission.” MG patients have a significant decrease in the number of postsynaptic AChRs at the end plates of affected muscles resulting in a decreased margin of safety of neuromuscular transmission.

MG is an autoimmune disorder, and about 80% of affected patients have detectable circulating antibodies to the nicotinic AChR. These anti-AChR antibodies may cause complementmediated lysis of the postsynaptic membrane, directly block the receptors, or may modulate the receptor turnover such that the rate of degradation exceeds the rate of resynthesis. Studies of the motor end plate area show loss of synaptic folds and a widening of the synaptic cleft. Some MG patients who do not have anti-AChR antibodies, have antibodies to muscle-specific tyrosine kinase (MuSK). These MuSK-antibody-positive MG patients often develop prominent oculobulbar muscle weakness.

The cause of MG is unknown but appears to be related in some way to the thymus gland. It has been suggested that thymic T cells are stimulated to produce antibodies following
sensitization by a protein similar to the AChR. MG patients also have a higher incidence of other autoimmune diseases including thyroid, lupus, and rheumatoid.

Since the original clinical classification by Osserman and Genkins who described four classes and two subclasses, several others have been published. The Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America Clinical Classification describes five main classes and several subclasses as follows:

The diagnosis of MG is suspected from the patient’s history and confirmed by clinical, electrophysiologic, pharmacologic, or immunologic testing. Typically, the patient cannot sustain or repeat muscular contraction. Clinical tests of fatigability include maintaining an upward gaze, holding out an affected limb, and respiratory function testing (vital capacity, maximum breathing capacity).

The electrical counterpart of fatigability is a decrement in the compound muscle action potentials evoked by repetitive stimulation of a motor nerve. Supramaximal stimulation of a peripheral nerve at 2 Hz is applied; a decrement in the size of the fourth or fifth response compared to the first is diagnostic. This is the most specific of the nerve tests for MG, but it can be performed only on certain muscles, which may not be the ones affected in an individual patient. A more sensitive electrophysiologic test is single-fiber electromyography (EMG) where an increase in jitter is found.

Pharmacologic testing is based on administration of an anticholinesterase and observing a rapid improvement in function. Mechanical and electrical (e.g., EMG), decrements
improve with 2 to 10 mg of intravenous edrophonium (Tensilon test). MG patients characteristically are sensitive to nondepolarizing muscle relaxants. When the routine EMG results are equivocal, a regional nondepolarizing muscle relaxant test may be performed using a tourniquet to isolate the limb and limit the action of the drug. In the regional nondepolarizer muscle relaxant test, EMGs are performed before and after the administration of 0.2 mg of curare. In MG, there is an exaggerated response to this small dose of curare.

Antibodies to the AChR are detectable in 80% of patients with MG. In equivocal cases, a positive result of a test for anti-AChR antibodies is considered diagnostic. Interestingly, the anti-AChR antibody titer is unrelated to the severity of the disease or the patient’s prognosis.

A number of disorders can mimic MG and should be included in the initial differential diagnosis.

Thyrotoxicosis can present with generalized weakness and abnormal thyroid function. Patients with neurasthenia characteristically have weakness, which disappears when individual muscle groups are tested. Progressive external ophthalmoplegia; restrictive cardiomyopathies; muscular dystrophies; brain tumors; amyotrophic lateral sclerosis; myasthenic polymyopathy with hypersensitivity to neostigmine; and drugs such as D-penicillamine, aminoglycosides, quinine, procainamide, and calcium channel blockers can also cause myasthenia-like symptoms.

Myasthenic syndrome is a very rare immune-mediated disorder of neuromuscular transmission, associated with antibodies to the presynaptic voltage-gated calcium channel. The prevalence is estimated to be about 1 per 100,000. It is associated with small cell carcinoma of the lung in 50% to 60% of cases. Complaints of weakness may be mistaken for MG, but in Lambert-Eaton syndrome, symptoms do not respond to administration of anticholinesterases or steroids, and activity improves strength. The defect in this condition is prejunctional, is associated with diminished release of acetylcholine from nerve terminals, and is improved by facilitating agents such as 4-aminopyridine that increase repetitive firing. Affected patients are particularly sensitive to the effects of all muscle relaxants, which should be used with great caution or avoided entirely. The possibility of Lambert-Eaton syndrome should be considered in all patients with known malignant disease and those patients undergoing diagnostic procedures for suspected carcinoma of the lung. Anesthesia considerations in these patients are essentially the same as in those with MG.