The National Childhood Vaccine Injury Act of 1986 requires physicians and others who administer vaccines to report occurrences of certain adverse events to the U.S. Department of Health and Human Services. The National Vaccine Injury Compensation Program (VCIP) receives claims and medical records of children with epileptic disorders following vaccination, documenting initial presentation, clinical course, vaccination history, developmental status, and clinical and laboratory evaluations.
Deidentified records were retrospectively reviewed of young children diagnosed with epilepsy, encephalopathy, or both after immunization and whose caretakers had petitioned the VCIP for compensation during the decade 1995 through 2005. Among a total of 222 claims submitted with “seizures” and/or “encephalopathy” as the alleged injury among children 2 years of age and younger, 165 had records with sufficient information to permit a comprehensive, independent review. The implicated vaccines included one or more administrations of whole-cell diphtheria-tetanus-pertussis (61%), acellular diphtheria-tetanus-pertussis (19%), mumps-measles-rubella (18%), Haemophilus influenzae type B (9%), and others (17%). Approximately 16% of children received more than one vaccine around the time of the alleged injury. The majority (59%) of claims listed seizures, 5% listed encephalopathy, and 36% listed seizures and encephalopathy as the alleged injury resulting from vaccination. More than half of cases were reported before six months of age, with three-quarters before 1 year of age; 45% had onset of seizures within 72 hours after vaccination; and 45% had documented fever.
Clinical cases were assessed independently by a single pediatric neurologist who developed a final study diagnosis on the basis of history, laboratory studies, imaging studies, EEG, and course of illness. The diagnoses included: 55% with epilepsy, including 18% of children having myoclonic epilepsy, almost all of whom were diagnosed with severe myoclonic epilepsy of infancy (SMEI), or Dravet syndrome; 7% with infantile spasms; 8% with febrile seizures; 18% with a specific diagnosis such as tuberous sclerosis; and 2% normal. Among the cases, before vaccination, 15% had pre-existing seizures, 10% had abnormal findings on neurological examination, and 4% were considered developmentally suspect.
Assessment of a causal relationship between vaccines and neurologic abnormalities in infancy is highly problematic because numerous rare neurologic disorders present during this age. Previous studies of the possible association between pertussis vaccination and neurologic disorders were performed prior to the recognition of SMEI, or Dravet syndrome, and before genetic testing was generally available. Many children previously diagnosed as having “pertussis encephalopathy” have been diagnosed as having SMEI, which is characterized clinically by febrile and afebrile, generalized and focal, clonic or tonic-clonic seizures presenting in the first year of life in an otherwise healthy infant. Many of these children have been shown to have a de novo mutation in the sodium channel gene SCN1A. In this retrospective analysis, although most cases occurred in infants and therefore were not easy to assess, approximately one-quarter of cases had evidence of a pre-existing abnormality of neurologic status.
Association does not prove causality. Because many genetic and underlying developmental abnormalities emerge during childhood, temporal association with vaccinations, most of which are administered during childhood, is likely. It has been difficult to demonstrate causality, or the lack of causality. The Institute of Medicine in 1994 stated that the evidence supporting a causal link of whole-cell pertussis vaccine and brain injury was “weak but not consistent.” There are no epidemiologic studies to date that support a causal relationship of acellular pertussis vaccine and permanent neurological injury.
The results of this new analysis do not support concerns about vaccine safety, including use of the term “pertussis encephalopathy,” which has been a diagnostic wastebasket for seizures of unknown etiology that begin in childhood. Physicians need to be circumspect about using this term as a clinical diagnosis and also careful suggesting to families that vaccinations are a cause of seizures and encephalopathy.