Friday, August 7, 2015

Vaccination-associated seizures and outcome in Dravet syndrome

Vaccination-associated seizures generally do not affect cognitive outcome or the course of disease in children with Dravet syndrome (DS), a rare and severe form of epilepsy, a new retrospective cohort study suggests.

The study also showed that the risk for seizures after the acellular pertussis combination vaccine is significantly lower than that following the whole-cell pertussis combination vaccine in children with DS.

The results support earlier research but provide "more direct evidence," said author Nienke Verbeek, MD, clinical geneticist, Department of Medical Genetics, University Medical Center, Utrecht, the Netherlands. "Parents might be reassured by the results of our and previous studies showing that vaccination-associated seizures probably do not affect disease course in children with DS."

Verbeek NE, van der Maas NA, Sonsma AC, Ippel E, Vermeer-de Bondt PE, Hagebeuk
E, Jansen FE, Geesink HH, Braun KP, de Louw A, Augustijn PB, Neuteboom RF,
Schieving JH, Stroink H, Vermeulen RJ, Nicolai J, Brouwer OF, van Kempen M, de
Kovel CG, Kemmeren JM, Koel



To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS).


We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared.


Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination.


Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific.

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