title: Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study.
abstract: BACKGROUND
  Pertussis vaccination has been alleged to cause an encephalopathy that involves seizures and subsequent intellectual disability. In a previous retrospective study, 11 of 14 patients with so-called vaccine encephalopathy had Dravet syndrome that was associated with de-novo mutations of the sodium channel gene SCN1A. In this study, we aimed to establish whether the apparent association of Dravet syndrome with vaccination was caused by recall bias and, if not, whether vaccination affected the onset or outcome of the disorder.
  
  
  METHODS
  We retrospectively studied patients with Dravet syndrome who had mutations in SCN1A, whose first seizure was a convulsion, and for whom validated source data were available. We analysed medical and vaccination records to investigate whether there was an association between vaccination and onset of seizures in these patients. Patients were separated into two groups according to whether seizure onset occurred shortly after vaccination (vaccination-proximate group) or not (vaccination-distant group). We compared clinical features, intellectual outcome, and type of SCN1A mutation between the groups.
  
  
  RESULTS
  Dates of vaccination and seizure onset were available from source records for 40 patients. We identified a peak in the number of patients who had seizure onset within 2 days after vaccination. Thus, patients who had seizure onset on the day of or the day after vaccination (n=12) were included in the vaccination-proximate group and those who had seizure onset 2 days or more after vaccination (n=25) or before vaccination (n=3) were included in the vaccination-distant group. Mean age at seizure onset was 18.4 weeks (SD 5.9) in the vaccination-proximate group and 26.2 weeks (8.1) in the vaccination-distant group (difference 7.8 weeks, 95% CI 2.6-13.1; p=0.004). There were no differences in intellectual outcome, subsequent seizure type, or mutation type between the two groups (all p values >0.3). Furthermore, in a post-hoc analysis, intellectual outcome did not differ between patients who received vaccinations after seizure onset and those who did not.
  
  
  CONCLUSIONS
  Vaccination might trigger earlier onset of Dravet syndrome in children who, because of an SCN1A mutation, are destined to develop the disease. However, vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome.
authors.affiliation: Epilepsy Research Centre and Department of Medicine (Neurology), University of Melbourne, Victoria, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: Jacinta
authors.initials: J
authors.lastname: McMahon
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Xenia
authors.initials: X
authors.lastname: Iona
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000009:adverse effects*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000009:adverse effects*; D018450:Disease Progression; D004831:Epilepsies, Myoclonic / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007360:Intelligence; D009154:Mutation; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010567:Pertussis Vaccine / Q000009:adverse effects*; D012189:Retrospective Studies; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects; D055815:Young Adult
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D010567:Pertussis Vaccine; C568242:SCN1A protein, human; D015222:Sodium Channels