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Clinical Description
A residual seizure disorder (RSD) caused by vaccination can be defined as a
seizure that occurs within 72 hours of vaccination and that is followed by
two or more afebrile seizures during the next 12 months (U.S. Department of
Health and Human Services, 1992). Subsequent seizures would be anticipated
in succeeding years. Approximately 0.5 to 2 percent of the population
experience epilepsy. It can occur at any age. Chapter 3 contains a more
lengthy discussion of RSD. The cases of RSD reported in this section would
not necessarily fit the criteria for RSD presented above. The committee
accepted an author's statement that a case was RSD. In addition, the
committee considered all cases in which a person experienced repeated (more
than one) afebrile seizures to be RSD to not exclude incorrectly any true
cases of RSD.

Evidence for Association
Biologic Plausibility
Naturally acquired measles infection is associated with encephalitis, and
patients with encephalitis can present with seizures. There are no specific
data bearing on the biologic plausibility of an association between measles
or mumps vaccine and RSD.

Case Reports, Case Series, and Uncontrolled Observational Studies
The National Collaborative Perinatal Project followed about 54,000 pregnant
women, living in 13 cities in the United States, between 1959 and 1966
(Hirtz et al., 1983). Among the children born to those women, 2,766
children experienced at least one seizure within the first 7 years of life.
Thirty-nine of those children experienced a convulsion within 2 weeks
following an immunization. One child had convulsions following two separate
immunizations (against measles and smallpox), so there were a total of 40
seizures. Ten seizures occurred following measles vaccination, generally
with a latency of 7 to 10 days. All but one of the seizures were associated
with fever; however, the vaccine administered to the child with the febrile
seizures was not specified. The children were followed for up to 7 years,
and all 10 children who had received measles vaccination ''did well'' with
no long-term neuralgic sequel.

Nader and Warren (1968) described 23 cases of neuralgic disease that
followed administration of measles vaccine and that were reported to the
U.S. National Communicable Disease Center between 1965 and 1967. During
that time, 15 million doses of measles vaccine were distributed throughout
the United States. Eleven of the 23 patients were reported to have seizures
or convulsions (three of which were noted to be accompanied by fever), and
there was one case of persistent spastic quadriplegia. One of the cases of
seizures persisted after the acute phase of the illness.

Beale (1974) reported on the measles vaccine experience in the United
Kingdom. From 1968 to 1974, more than 3 million children were immunized
with Schwarz or Beckenham 31 measles vaccines. Adverse reactions were
reported to the governmental Committee on Safety of Medicines. There were
57 febrile convulsions associated with the Schwarz vaccine and 65
associated with the Beckenham 31 vaccine. No other data describing the
nature of the seizures or long-term follow-up of the patients were available.

In a study of voluntary reporting of reactions to vaccination in the North
West Thames region of England between 1975 and 1981, when approximately
170,000 children received live measles vaccine (as well as other childhood
vaccines), there were 26 reports of convulsions without evidence of
neuralgic damage following measles vaccination (Pollock and Morris, 1983).
No further details were provided, except that at follow-up the children
were normal.

Maspero and colleagues (1991) reported a case series of 1,148 children
immunized in 1990 in Lombardy, Italy, with the Edmonston-Zagreb vaccine
strain and compared them with a case series of children in a nearby
district immunized from 1980 to 1987 with the Schwarz vaccine strain. The
authors reported that they saw no neuralgic events following administration
of the Edmonston-Zagreb vaccine. There was no comparable statement
regarding the incidence of neuralgic outcomes in the population immunized
with the Schwarz strain.

A 19-month-old Japanese boy was immunized with measles vaccine (Schwarz
strain) and 11 days later developed a fever and prolonged (30 minutes)
convulsions with loss of consciousness (Abe, 1985). He had four more brief
convulsions over the next 6 months, all with fever, and his
electroencephalogram exhibited transient abnormalities 14 months later. The
report indicated that 2.5 years following the first seizure, the boy's
development appeared to be normal.

Haun and Ehrhardt (1973) described an 11-month-old child who developed
clonic seizures and CSF pleocytosis within 12 days of receiving the
Leningrad-16 SSW measles vaccine strain and died soon thereafter. (This
case is discussed again in Chapter 10.)

Griffin and colleagues (1991) examined the records of a cohort of children
in Tennessee enrolled in the Medicaid program who had received MMR or
measles-rubella vaccine (MR) in their first 3 years of life to estimate the
incidence of neuralgic outcomes. As determined from computerized records,
children who were enrolled in the Medicaid program within 90 days of birth
in one of four counties, who had a Tennessee birth certificate indicating a
birth date within the study period (approximately 1974 to 1984), and who
received during those years at least one diphtheria and tetanus toxoid and
pertussis vaccine (DPT) immunization at ages 29-365 days and at least one
MMR or MR immunization between 12 and 36 months of age were included in the
study. Follow-up began at the time of the first MMR or MR immunization and
was restricted to the first 36 months of life. Of the population of 18,364
children enrolled in the Medicaid program who received immunizations, 100
were confirmed to have had a seizure. Of these, 77 had febrile seizures (4
children had seizures between days 7 and 14 postimmunization and none were
recurrent), 15 had febrile seizures (1 child had two seizures at 1 and 3
days postimmunization, and another child had a seizure at 29 days
postimmunization), and 8 had seizures associated with other acute neuralgic
illnesses. Most seizures occurred more than 30 days following the
immunization. It is possible that there was underascertainment of seizure
cases in this cohort, because only those patients for whom a medical claim
was filed were counted. Thus, children who moved, went off the Medicaid
program, or whose parents did not file a claim were not counted as seizure
cases. The authors made no attempts to follow seizure cases for long-term

Fescharek et al. (1990) described convulsions that occurred in 41 patients
following administration of vaccine containing measles antigen, mumps
antigen, or both. Seven of the 41 patients had convulsions that were not
accompanied by fever. More detailed information was not supplied. It is not
clear whether any of the convulsions represented the early signs of an RSD.

A report from the passive surveillance system used to detect adverse events
following immunization in Canada provided the rates of occurrence of
adverse events but not long-term outcomes (Koch et al., 1989). Included in
that report were all adverse events reported prior to the end of 1988 for
individuals who had received immunizations at any time in 1987. For the
purposes of classification, convulsions/seizures were defined as those
involving muscle contractions and a decreased level of consciousness, with
or without a fever, and had to have been diagnosed by a physician.
Forty-four cases were classified as convulsions/seizures following the
administration of MMR; the associated rate was 9.3 cases per 100,000 doses.
Although some follow-up beyond 1 year was done to identify residual
disorders, the authors did not provide data regarding seizures.

Controlled Observational Studies
The committee was not able to identify any controlled observational studies
that reported on the possible association between measles or mumps vaccine
and RSD.

Controlled Clinical Trials
As noted above, the Medical Research Council of the United Kingdom reported
follow-up data (up to 4 years and 9 months) from a randomized trial of
36,000 patients who received either live attenuated measles vaccine or
killed vaccine followed by live attenuated vaccine or no vaccine (Medical
Research Council, 1971). Although follow-up was designed to examine the
incidence and complications of wild-type measles infection, had an RSD
occurred, it might have been noted in such a long-term study. There was no
mention of RSD.

Causality Argument
There is evidence that acute seizures are possible sequel of immunization
with measles and mumps vaccines. Therefore, it is biologically plausible
that there is a connection between immunization and RSD. However, it would
be essential to rule out the possibility that the acute cases described in
the literature are not febrile seizures, which are common in children and
which would not be expected to lead to an RSD. The available data are from
case reports and case series; there are no data from observational studies
that would allow the calculation of a risk of RSD for vaccinated as opposed
to unvaccinated individuals. Perhaps most important, none of the available
cases can be confirmed as RSD on the basis of the report alone.

The evidence is inadequate to accept or reject a causal relation between
measles vaccine and residual seizure disorder.

There is no evidence bearing on a causal relation between mumps vaccine and
residual seizure disorder.

The evidence is inadequate to accept or reject a causal relation between
multivalent measles or mumps vaccines and residual seizure disorder.