In Simpson’s opinion, and this coincides with our observations, the danger of death from generalized myasthenia gravis is greatest in the first year after onset of the disease. A second period of danger in progressive cases is from 4 to 7 years after onset. After this time, the disease tends to stabilize and the risk of severe relapse diminishes. Fatalities relate mainly to the respiratory complications of pneumonia and aspiration. The mortality rate in the first years of illness, formerly in excess of 30 percent, is now less than 5 percent and with appropriate therapy virtually all patients lead normal lives.
An aspect of interest is the timing and frequency of conversion from ocular and restricted oropharyngeal patterns of weakness to more widespread involvement including the diaphragm. Bever and coworkers have confirmed the general impression that an increasing duration of purely ocular myasthenia is associated with a decreasing risk of late generalization of weakness. In a retrospective study of 108 patients, these authors found that only 15 percent of the observed instances of generalization occurred more than 2 years after isolated ocular manifestations.
A later age at onset was also associated with a higher incidence of fatal respiratory crises. In general, patients whose disease begins at a younger age run a more benign course. Grob and colleagues, who recorded the course of an astonishing 1,036 patients for a mean duration of 12 years, found that the clinical manifestations remained confined to the extraocular muscles and orbicularis oculi in 16 percent. Their data further indicated that localized ocular myasthenia present for only a month was associated with a 60 percent likelihood that the disease would generalize, but in those cases that remained restricted for more than a year, only 16 percent became generalized. In contrast, of 37 consecutive cases carefully studied by Weinberg et al with only ocular signs, 17 had more widespread weakness within a period of 6 years. Also informative in Grob’s series was that in 67 percent the disease attained its maximum severity within a year of onset, and in 83 percent, within 3 years. It has been stated that the progression of symptoms is more rapid in male than in female patients.
It is not widely recognized that isolated muscle groups may occasionally remain permanently weak even when the ocular and generalized weakness has resolved. The muscles most often affected in this way are the anterior tibialis, triceps, and portions of the face.
The long-term outlook for children with myasthenia is better than it is for adults, and their life expectancy is only slightly reduced. Rodriguez and colleagues followed a group of 149 children for an average of 17 years; 85 of them had thymectomies, one of the main treatments for myasthenia as discussed further on. Approximately 30 percent of the nonthymectomized and 40 percent of the thymectomized patients underwent remission and were free of symptoms, usually in the first 3 years of illness. Those children with bulbar symptoms and no ocular or generalized weakness had the most favorable outcome.
A nonneoplastic lymphofollicular hyperplasia of the thymic medulla occurs in 65 percent or more of cases of myasthenia and thymic tumors occur in 10 to 15 percent. Thymomas with malignant characteristics may spread locally in the mediastinum and to regional lymph nodes but they rarely metastasize beyond these structures; when they do, the lungs and liver are usually affected. It should be emphasized that thymic enlargement and tumors may be missed in plain films of the chest and should be sought by CT with contrast.