History of Suspected Association

The occurrence of encephalitis following a natural measles virus infection is well described. The condition is quite severe, often leading to permanent brain damage or even death. There may be no detectable pathologic lesion, but in most cases some edema and demyelination are noted. Early studies of the adverse events associated with measles vaccine concentrated on "encephalitis." These are described below (Landrigan and Witte, 1973; Nader and Warren, 1968).

The first report of encephalopathy following vaccination with the live attenuated Edmonston B (Rubeovax) measles vaccine appeared in 1967 (Trump and White, 1967). A 2-year-old girl developed unsteadiness 7 days following vaccination. This was followed by pronounced generalized ataxia (diagnosed as cerebellar ataxia), fever, vomiting, and an exanthem. There was pleocytosis in the CSF 1 month after vaccination. The ataxia persisted for at least 8 months. Because of the child's history and physical and laboratory findings, the investigators attributed the condition to measles vaccination. Two early case series investigations of neuralgic disorders following measles vaccination included reports of "encephalitis." These are discussed below.

Mumps affects the central nervous system as well, but it is more likely to cause meningitis than encephalitis (Azimi et al., 1969). This condition tends to be self-limited and has a good prognosis. Cases of pure encephalitis following mumps are rare, but they can be quite severe.

Evidence for Association

Biologic Plausibility

Chapter 3 contains a discussion of the biologic plausibility for certain types of encephalopathies and vaccination. As described above, natural (wild-type) measles virus infection is associated with a well-described, frequently very severe encephalitis.

Case Reports, Case Series, and Uncontrolled Observational Studies

Many uncontrolled observational studies in the literature describe the occurrence of encephalopathy after administration of measles vaccine. These are reviewed first. Data from similar studies regarding multivalent preparations are described next. Individual case reports and unpublished case reports from U.S. Public Health Service passive surveillance systems are discussed last. There are no data regarding monovalent mumps vaccine and encephalopathy.

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