Measles Vaccine The first published case of encephalopathy (acute cerebellar ataxia) attributed to measles vaccine was discussed above (Trump and White, 1967). Retrospective analyses of populations who have received measles vaccine have been reported from many countries, including the United States. These uncontrolled observational studies provide no information on the concurrent background rates of encephalopathy. Table 6-2 summarizes case series and uncontrolled observational studies in which the incidence rates of encephalopathy or encephalitis following administration of measles vaccine were calculated by the authors.

Two case series addressed early concerns in the United States that measles vaccine might cause encephalitis. The first was a report of 23 cases of neurologic disease following measles vaccination in the United States from January 1965 to February 1967 (Nader and Warren, 1968). The authors characterized 18 of the 23 cases as "encephalitis" (described as including disturbances of sensorium, seizure, major loss of motor function, and cerebral edema; no data are provided regarding pleocytosis in the CSF). The interval from vaccination to the onset of symptoms ranged between 3 and 24 days. Postmortem findings in one case revealed herpes simplex virus in brain tissue. There were two cases of aseptic meningitis, two cases of cerebellar ataxia, and one case of extraocular muscle paralysis. The authors estimated a rate of 1.5 reported cases of "encephalitis" within a 4-week period of vaccination per 1 million doses of vaccine distributed. They compared this with a background rate of 2.8 cases of encephalitis (unrelated to vaccination or known parainfectious causes) per 1 million children for any 4-week period. The authors concluded, ''No single clinical or epidemiologic characteristic appears consistently in the reports of cases of possible neurologic sequelae of measles vaccination" (p. 998).

A review of 84 patients with neurologic disorders occurring within 30 days of vaccination against measles virus reported to the Centers for Disease Control from 1963 to 1971 revealed 59 patients with extensive neurologic disorders, which included encephalomyelitis (Landrigan and Witte, 1973). The cases reported by Nader and Warren (1968) and discussed above are a subset of the data of Landrigan and Witte (1973). Although in all 59 patients the onset of symptoms occurred between 1 and 25 days after vaccination, in 45 it coincided with the period of maximal viral replication (6 to 15 days after vaccination). Of 50 patients for whom follow-up information was available (follow-up presumably from 1963 to sometime before 1973), 26 recovered fully, 5 died (2 of the 5 had pathologic features of Reye syndrome), and 19 were left with permanent neurologic damage. Thirteen of the 59 patients were classified as having encephalomyelitis. Long-term follow-up of 12 of the patients showed residual neurologic signs in 3 patients. Long-term follow-up was available for 31 of 36 patients considered to have encephalopathy. Ten of those 31 patients recovered fully, 5 died,



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