Nienke E Verbeek1, Nicoline A T van der Maas2, Anja C M Sonsma2, Elly Ippel2, Patricia E Vermeer-de Bondt2, Eveline Hagebeuk2, Floor E Jansen2, Huibert H Geesink2, Kees P Braun2, Anton de Louw2, Paul B Augustijn2, Rinze F Neuteboom2, Jolanda H Schieving2, Hans Stroink2, R Jeroen Vermeulen2, Joost Nicolai2, Oebele F Brouwer2, Marjan van Kempen2, Carolien G F de Kovel2, Jeanet M Kemmeren2, Bobby P C Koeleman2, Nine V Knoers2, Dick Lindhout2, W Boudewijn Gunning2, Eva H Brilstra2. 1. From the Department of Medical Genetics (N.E.V., A.C.M.S., E.I., M.v.K., C.G.F.d.K., B.P.C.K., N.V.K., D.L., E.H.B.) and Department of Child Neurology, Brain Center Rudolf Magnus (F.E.J., K.P.B.), University Medical Center Utrecht; Centre for Infectious Disease Control (N.A.T.v.d.M., P.E.V.-d.B., J.M.K.), National Institute for Public Health and Environment-RIVM, Bilthoven; Stichting Epilepsie Instellingen Nederland (E.H., W.B.G.), Zwolle; Stichting Epilepsie Instellingen Nederland (H.H.G., P.B.A.), Heemstede; Epilepsy Center Kempenhaeghe (A.d.L.), Heeze; Department of Child Neurology (R.F.N.), Erasmus Medical Centre, Rotterdam; Department of Child Neurology (J.H.S.), Radboud Medical Centre, Nijmegen; Department of Neurology (H.S.), Canisius-Wilhelmina Hospital, Nijmegen; Department of Child Neurology (R.J.V.), VU Medical Centre, Amsterdam; Department of Child Neurology (J.N.), Maastricht University Medical Centre; and Department of Neurology (O.F.B.), University of Groningen, University Medical Centre of Groningen, the Netherlands. n.verbeek@umcutrecht.nl. 2. From the Department of Medical Genetics (N.E.V., A.C.M.S., E.I., M.v.K., C.G.F.d.K., B.P.C.K., N.V.K., D.L., E.H.B.) and Department of Child Neurology, Brain Center Rudolf Magnus (F.E.J., K.P.B.), University Medical Center Utrecht; Centre for Infectious Disease Control (N.A.T.v.d.M., P.E.V.-d.B., J.M.K.), National Institute for Public Health and Environment-RIVM, Bilthoven; Stichting Epilepsie Instellingen Nederland (E.H., W.B.G.), Zwolle; Stichting Epilepsie Instellingen Nederland (H.H.G., P.B.A.), Heemstede; Epilepsy Center Kempenhaeghe (A.d.L.), Heeze; Department of Child Neurology (R.F.N.), Erasmus Medical Centre, Rotterdam; Department of Child Neurology (J.H.S.), Radboud Medical Centre, Nijmegen; Department of Neurology (H.S.), Canisius-Wilhelmina Hospital, Nijmegen; Department of Child Neurology (R.J.V.), VU Medical Centre, Amsterdam; Department of Child Neurology (J.N.), Maastricht University Medical Centre; and Department of Neurology (O.F.B.), University of Groningen, University Medical Centre of Groningen, the Netherlands.
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.
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.