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Effect of vaccinations on seizure risk and disease course in Dravet syndrome

Verbeek, N. E., van der Maas, N. A. T., Sonsma, A. C. M., Ippel, E., Bondt, P., Hagebeuk, E., Jansen, F. E., Geesink, H. H., Braun, K. P., de Louw, A., Augustijn, P. B., Neuteboom, R. F., Schieving, J. H., Stroink, H., Vermeulen, R. J., Nicolai, J., Brouwer, O. F., Van Kempen, M., De Kovel, C. G. F., Kemmeren, J. M., Koeleman, B. P. C., Knoers, N. V., Lindhout, D., Gunning, W. B., & Brilstra, E. H. (2015). Effect of vaccinations on seizure risk and disease course in Dravet syndrome. Neurology, 85(7), 596-603. doi:10.1212/wnl.0000000000001855.
Objective: 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). Methods: 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. Results: 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. Conclusions: 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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