Clinical Presentation

The hallmark of myasthenia gravis is chronic muscle fatigue. The muscles become progressively weaker during periods of activity and improve after periods of rest. Signs and symptoms include facial muscle weakness; ptosis (drooping of one or both eyelids); diplopia (double vision); difficulty in breathing, speaking, chewing, and swallowing; unstable gait; and weakness in arms, hands, fingers, legs, and neck brought on by repetitive motions. The muscles that control the eyes, eyelids, face, and throat are especially susceptible and are usually affected first. The respiratory muscles of the diaphragm and chest wall can become weak and impair the patient’s ventilation. Impairment in deep breathing and coughing predispose the patient to excessive bronchial secretions, atelectasis, and pneumonia.

The signs and symptoms of myasthenia gravis during the early stages are often elusive. The onset can be subtle, intermittent, or sudden and rapid. The patient may (1) demonstrate normal health for weeks or months at a time, (2) show signs of weakness only late in the day or evening, or (3) develop a sudden and transient generalized weakness that includes the diaphragm. Because of this last characteristic, ventilatory failure is always a sinister possibility. In most cases, the first noticeable symptom is weakness of the eye muscles (droopy eyelids) and a change in the patient’s facial expressions. As the disorder becomes more generalized, weakness develops in the arms and legs. The muscle weakness is usually more pronounced in the proximal parts of the extremities. The patient has difficulty in climbing stairs, lifting objects, maintaining balance, and walking. In severe cases the weakness of the upper limbs may be such that the hand cannot be lifted to the mouth. Muscle atrophy or pain is rare. Tendon reflexes almost always remain intact.

Neurologic Examination

Neurologic tests may include the evaluation of reflexes, muscle strength, muscle tone, senses of touch and sight, gait, posture, coordination, balance, and mental abilities.

Electromyography

Electromyography usually is performed to confirm the diagnosis of myasthenia gravis, identify the specific muscles involved, and determine the degree of fatigability. Electromyography entails the repetitive stimulation of a nerve, such as the ulnar nerve, with the simultaneous recording of the muscle response. Clinically, the degree of fatigability often is evaluated by having the patient use certain muscles for a sustained period. For example, the patient may be instructed to gaze upward for an extended period, blink continuously, hold both arms outstretched as long as possible, or count aloud as long as possible in one breath (normal is about 50). A dynamometer sometimes is used to measure the force of repetitive muscle contractions.

Blood Analysis

A blood test may reveal the presence of ACh receptor antibodies. About 85% to 90% of patients with myasthenia gravis have an elevated level of these antibodies.

Edrophonium Test

The diagnosis of myasthenia gravis is usually is confirmed with the injection of edrophonium (Enlon). Edrophonium, a short-acting drug, blocks cholinesterase from breaking down ACh after it has been released from the terminal axon. This action increases the myoneural concentration of ACh, which in turn offsets the influx of antibodies at the neuromuscular junction. When muscular weakness is caused by myasthenia gravis, a dramatic transitory improvement in muscle function (lasting about 10 minutes) is seen after the administration of edrophonium. A disadvantage of the edrophonium test is that it can be complicated by cholinergic side effects that include cardiopulmonary arrest.

Ice Pack Test

The ice pack test (Figure 29-2) is a very simple, safe, and reliable procedure for diagnosing myasthenia gravis in patients who have ptosis (droopy eye). In addition, the ice pack test does not require special medications or expensive equipment and is free of adverse effects. The test consists of the application of an ice pack to the patient’s symptomatic eye for 3 to 5 minutes. The test is considered positive for myasthenia gravis when there is improvement of the ptosis (an increase of at least 2 mm in the palpebral fissure from before to after the test).

A major disadvantage of the ice pack test is that it is useful only when ptosis is present. Even though the symptoms associated with diplopia (double vision) may also improve with the ice pack test, the reliability of the ice pack test in patients with diplopia without ptosis is usually questionable because the patient’s personal impression of the diplopia is subjective. Therefore caution should be exercised in patients with isolated diplopia without ptosis. The ice pack test may be especially useful in patients in whom the edrophonium test is contraindicated by either cardiac status or age.

Sleep Test

Because the signs and symptoms associated with myasthenia gravis increase with fatigue and improve after a period of rest, the sleep test is safe, moderately sensitive, and specific. Myasthenia gravis is indicated when ptosis improves after a 20- to 30-minute period of sleep. The reappearance of ptosis over the next 5 minutes further supports the diagnosis of myasthenia gravis. The sleep test is often not practical for the busy physician because it entails a dark room and quiet area to enhance sleep and is time-consuming.

Computed Tomography or Magnetic Resonance Imaging

A CT or MRI scan may be used to identify an abnormal thymus gland or the presence of a thymoma (a usually benign tumor of the thymus gland that may be associated with myasthenia gravis). A thymectomy has been shown to reduce symptoms in more than 70% of patients with myasthenia gravis. In fact, a thymectomy may be recommended even when there is no tumor. The removal of the thymus seems to improve the condition in many patients.