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

NE Verbeek, Nicoline Maas, ACM Sonsma, E Ippel, PEVD Bondt, E Hagebeuk, FE Jansen, HH Geesink, KP Braun, A Louw, PB Augustijn, Rinze Neuteboom, JH Schieving, H (Hans) Stroink, RJ Vermeulen, J Nicolai, OF Brouwer, M van Kempen, CGF de Kovel, JM KemmerenBPC Koeleman, NV Knoers, D (Dick) Lindhout, WB (Boudewijn) Gunning, EH Brilstra

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Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)596-603
Number of pages8
JournalNeurology
Volume85
Issue number7
DOIs
Publication statusPublished - 2015

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