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MYASTHENIA GRAVIS

Myasthenia gravis is characterized by abnormal fatigability of striated muscles after repetitive contraction which improves after rest and often is first manifested by weakness of the extraocular muscles. Unilateral fatiguing ptosis is a frequent first sign, with subsequent bilateral involvement of extraocular muscles, so that diplopia is often an early symptom. Unusual ocular presentations may simulate gaze palsies, internuclear ophthalmoplegias, vertical nystagmus, and progressive external ophthalmoplegia. Generalized weakness of the arms and legs, difficulty in swallowing, weakness of jaw muscles, and difficulty in breathing may follow rapidly in untreated cases. This weakness shows diurnal variations and often worsens as the day progresses but can be improved by a nap. There are no sensory changes.

The incidence of the disease is in the range of 1:30,000 to 1:20,000. Myasthenia gravis usually affects young adults aged 20-40 (70% are under 40 years of age), though it may occur at any age and is often misdiagnosed as hysteria, especially because the weakness can be greater in exciting or embarrassing situations. Older patients are more commonly male and are more likely to have a thymoma.

The onset may follow an upper respiratory infection, stress, pregnancy, or any injury, and the disease has been noted as a transitory condition in newborn infants of myasthenic mothers. Myasthenia gravis has been associated with hyperthyroidism (5%), thyroid abnormalities (15%), autoimmune diseases (5%), and diffuse metastatic carcinoma (7%).

In about one-third of cases, the disease is confined to the extraocular muscles at onset. In about two-thirds of these cases, the disease will become generalized with time, usually within the first year.

The differential diagnosis includes progressive external ophthalmoplegia, brainstem lesions, epidemic encephalitis, bulbar and pseudobulbar palsy, postdiphtheritic paralysis, botulism, multiple sclerosis, and toxic reactions to the beta-blockers (eg propranolol) or penicillamine. Many other drugs may unmask or exacerbate myasthenia gravis; they include lithium, aminoglycoside antibiotics, chloroquine, and phenytoin.

The disease has its origin at the neuromuscular junction, especially at the postsynaptic site, probably due to antibodies against it and the presynaptic site. A commercial test of anti-acetylcholine receptor antibodies can diagnose the disease in 80-90% of patients with systemic myasthenia and 40-60% of patients with pure ocular myasthenia; the titers do not correlate with severity of disease, however.

Most patients have merely histologic thymic hyperplasia, often apparent on lateral oblique chest x-rays or CT scans of the mediastinum or noted at surgical removal of the thymus. Thymomas occur in 15% of patients.

Cholinesterase destroys acetylcholine at the myo-neural junction, and cholinesterase-inhibiting drugs improve the condition by increasing the amount of acetylcholine available to the damaged postsynaptic site. The edrophonium chloride test is used in addition to the neostigmine diagnostic test. Edrophonium, 2 mg (0.2 mL), is given intravenously over 15 seconds. Relief of ptosis constitutes a positive response and confirms the diagnosis of myasthenia gravis. If no response occurs in 30 seconds, an additional 5-7 mg (0.5-0.7 mL) is given. The test is most helpful when marked ptosis is present, but myasthenia can affect any muscle or combination of muscles, and significant improvement in function is also helpful. Slightly positive edrophonium tests can occur in neurogenic palsies, however, and there may be false-negative results when myasthenia is complicated by muscle wasting.

Repetitive nerve stimulation, especially of the facial or proximal muscles, can also demonstrate abnormal muscle fatigability (a more than 10% decrease in the response is diagnostic of myasthenia). Variation in size and shape of motor unit potentials is noted on needle electromyography of affected muscles, and single-fiber studies show increased variability (jitter) in the temporal pattern of action potentials from muscle fibers of the same motor unit.

Myasthenia can be treated with pyridostigmine, systemic steroids, azathioprine, cyclosporine, immunoglobulins, and plasmapharesis according to the severity of disease. During severe exacerbations, artificial ventilation may be necessary. Thymectomy may be indicated in patients with thymoma (though it may not influence the severity of the myasthenia) and in patients with early-onset generalized disease without evidence of thymoma-in one third of whom it may produce complete remission without the need for immunosuppressants. Ocular myasthenia tends to respond less well to anticholinesterase agents than generalized disease, but the response to systemic steroids is usually good. Extraocular muscle surgery can be undertaken but should be delayed until the ocular motility deficit has been stable for a long time.

Myasthenia is generally a chronic disease with a tendency to pursue a relapsing and remitting course. The prognosis depends upon the extent of the disease, the response to medication and thymectomy, and the careful management of severe exacerbations.

10.1036/1535-8860.ch14

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