In the JournalsPerspective

Genetic, structural defects triggered epileptic seizures after vaccination

Recent data show that genetic or structural defects were the common underlying cause of epilepsy onset after routine vaccination.

Nienke E. Verbeek, MD, MSc, of the University Medical Centre Utrecht in the Netherlands, and colleagues reviewed data from the National Institute for Public Health and Environment in the Netherlands for 990 children who experienced seizures after vaccination during the first 2 years of life. Of these, 26 children were subsequently diagnosed with epilepsy and had seizure onset within 24 hours after inactivated vaccine administration or 5 to 12 days after receiving the measles-mumps-rubella vaccine. Study data was reported from 1997 to 2006.

During the study period, the vaccination schedule included four doses of DTaP, Haemophilus influenzae type B vaccine by age 1 year and one dose of MMR vaccine at age 14 months.

Of the 1,022 possible epileptic seizures among 990 children, 68% occurred after receipt of an inactivated vaccine and 32% after receipt of live-attenuated vaccine in the first 2 years of life. These children had a median age of 11.6 months at first vaccination and 14.2 months at first reported seizure.

Forty-five children were diagnosed with epilepsy. Of these, 26 had vaccination-related seizure onset and 19 had seizure onset before vaccination-related seizure occurred. Children with epilepsy and vaccination-related seizure onset had a median age of 11.5 months at epilepsy diagnosis.

Genetic testing was performed for 14 of 23 children with epilepsy and vaccination-related onset during follow-up. Median age at follow-up was 10.6 years.

Of the 23 children with epilepsy and vaccination-related onset available for follow-up, three had developmental delay before seizure onset and developed mild to severe intellectual disability. Thus, they were considered to have pre-existing encephalopathy. Twelve children were considered to have epileptic encephalopathy. Eight children were diagnosed with Dravet syndrome. One child had epilepsy and mental retardation due to a de novo protocadherin 19 mutation. One child had fever-sensitive epilepsy, which was well controlled after infancy, and another child was diagnosed with West syndrome.

Eight of the 23 children with vaccination-related epilepsy onset were considered to have benign epilepsy. Of these, seven were seizure-free without use of medication at follow-up.

Seizures occurred more often after inactivated vaccines among children pre-existing or epileptic encephalopathy and began at a younger age compared with children with benign epilepsy.

“Underlying genetic or structural causes were identified in 65% of children with epilepsy with vaccination-related onset. These underlying causes were not limited to SCN1A-related Dravet syndrome but extended to other genetically determined fever-sensitive epilepsies,” the researchers wrote. “These results imply that early genetic testing should be considered in children with vaccination-related onset of epilepsy and might help to support public faith in vaccination programs.”

Disclosure: The researchers report no relevant financial disclosures.

Recent data show that genetic or structural defects were the common underlying cause of epilepsy onset after routine vaccination.

Nienke E. Verbeek, MD, MSc, of the University Medical Centre Utrecht in the Netherlands, and colleagues reviewed data from the National Institute for Public Health and Environment in the Netherlands for 990 children who experienced seizures after vaccination during the first 2 years of life. Of these, 26 children were subsequently diagnosed with epilepsy and had seizure onset within 24 hours after inactivated vaccine administration or 5 to 12 days after receiving the measles-mumps-rubella vaccine. Study data was reported from 1997 to 2006.

During the study period, the vaccination schedule included four doses of DTaP, Haemophilus influenzae type B vaccine by age 1 year and one dose of MMR vaccine at age 14 months.

Of the 1,022 possible epileptic seizures among 990 children, 68% occurred after receipt of an inactivated vaccine and 32% after receipt of live-attenuated vaccine in the first 2 years of life. These children had a median age of 11.6 months at first vaccination and 14.2 months at first reported seizure.

Forty-five children were diagnosed with epilepsy. Of these, 26 had vaccination-related seizure onset and 19 had seizure onset before vaccination-related seizure occurred. Children with epilepsy and vaccination-related seizure onset had a median age of 11.5 months at epilepsy diagnosis.

Genetic testing was performed for 14 of 23 children with epilepsy and vaccination-related onset during follow-up. Median age at follow-up was 10.6 years.

Of the 23 children with epilepsy and vaccination-related onset available for follow-up, three had developmental delay before seizure onset and developed mild to severe intellectual disability. Thus, they were considered to have pre-existing encephalopathy. Twelve children were considered to have epileptic encephalopathy. Eight children were diagnosed with Dravet syndrome. One child had epilepsy and mental retardation due to a de novo protocadherin 19 mutation. One child had fever-sensitive epilepsy, which was well controlled after infancy, and another child was diagnosed with West syndrome.

Eight of the 23 children with vaccination-related epilepsy onset were considered to have benign epilepsy. Of these, seven were seizure-free without use of medication at follow-up.

Seizures occurred more often after inactivated vaccines among children pre-existing or epileptic encephalopathy and began at a younger age compared with children with benign epilepsy.

“Underlying genetic or structural causes were identified in 65% of children with epilepsy with vaccination-related onset. These underlying causes were not limited to SCN1A-related Dravet syndrome but extended to other genetically determined fever-sensitive epilepsies,” the researchers wrote. “These results imply that early genetic testing should be considered in children with vaccination-related onset of epilepsy and might help to support public faith in vaccination programs.”

Disclosure: The researchers report no relevant financial disclosures.

    Perspective
    Paul A. Offit

    Paul A. Offit

    The modern American anti-vaccine movement was born in the early 1980s with the belief that the whole-cell pertussis vaccine (DTP) caused permanent brain damage. Specifically, parents were concerned that the vaccine caused epilepsy and developmental delays. To these parents, the issue was clear: Our children were fine, then they got a vaccine, then they weren’t fine anymore. Surely, the vaccine must be at fault.

    It took almost 25 years for genetic tools to become available to answer these parents’ question. In 2006, Sam Berkovic and colleagues at the University of Melbourne in Australia were the first to show that most of these children had an SCN1A mutation. This mutation, which causes a defect in sodium transport across the cell membrane, causes epilepsy and developmental delay in all affected, independent of whether children received a vaccine or not. The study by Verbeek and colleagues provides further evidence that Dr. Berkovic’s original finding was correct.

    Sadly, despite abundant evidence to the contrary, the notion that vaccines cause permanent neurological damage still has an active life on the Internet, refusing to die among those who oppose vaccines.

    • Paul A. Offit, MD
    • Infectious Diseases in Children Editorial Board member

    Disclosures: Offit reports no relevant financial disclosures.

    Perspective

    Febrile seizures are a known adverse event that can follow vaccination due to the fever induced by some vaccinations in children susceptible to such seizures. Febrile seizures alone are associated with benign outcomes.

    Of more concern have been reports of children developing epilepsy or other chronic neurologic disorders with onset temporally related to vaccination. Some have attributed that epilepsy to vaccinations. Recently, several studies have found that a substantial proportion of those children have underlying disorders associated with epilepsy and that the long-term neurologic disorder is more likely due to the underlying abnormality, such as Dravet Syndrome, rather than to induction by vaccination.

    The new study by Verbeek et al, adds support to the hypothesis that most cases of epileptic disorders with onset temporally related to vaccination are likely due to other underlying causes, including genetic disorders. In this comprehensive study of children from the Netherlands, 65% of cases with epilepsy onset after vaccination had genetic disorders predisposing to epilepsy including Dravet syndrome, genetic epilepsy with febrile seizures, a protocadherin 19 mutation, a 1qter microdeletion neuronal migration disorders and monogenic familial epilepsy. Less than 3% of children who had a seizure temporally related to vaccination went on to develop epilepsy, but as the authors note, it is important to consider genetic testing in those children who do develop epilepsy. Further, when counseling families raising questions about the relationship of vaccines to chronic seizure disorders, physicians should make such families aware of the information pointing to underlying conditions that likely would have resulted in epilepsy even in the absence of vaccination.

    • Walter A. Orenstein, MD
    • Infectious Diseases in Children Editorial Board member

    Disclosures: Orenstein reports no relevant financial disclosures.

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