Abstracts

Rationale: We previously found that most cases of so-called “vaccine encephalopathy” had unrecognised Dravet syndrome, with de novo mutations in the sodium channel subunit gene SCN1A, thus exonerating vaccination as the primary cause. In Dravet syndrome, vaccination has been often reported to precede disease onset. In order to clarify this relationship we asked two questions. How often is vaccination proximate to disease onset? Do cases with vaccine-related onset differ from other cases? Methods: We retrospectively analyzed our database of 100 children with Dravet syndrome and SCN1A mutations for the dates of first convulsive seizure and triple antigen vaccination in the first year of life. Because of the problem of recall bias and possible false attribution of cause, we selected cases where source data (hospital and treating doctors’ original notes, child immunization booklets) documented both the dates of vaccination and first convulsive seizure. We analyzed the clinical and molecular features of these cases. Results: We obtained precise source data in 38 cases. Seizure onset occurred within 48 hours of vaccination in 13 (vaccination-proximate) and 25 had onset either before (n=3) or apparently randomly distributed 4-98 days after (n = 22) their most recent vaccination (vaccination-distant). Of the 35 cases with onset after vaccination, 8 had onset after the first, 15 after the second and 12 after the third immunization. Of the 13 vaccine-proximate cases, 3,8 and 2 cases occurred after the three serial immunizations. The vaccination-proximate group had an earlier age of onset (4.1±1.3 vs 6.0±1.9 months; p=0.003) but did not differ from the vaccination-distant group in terms of occurrence of status epilepticus at onset, subsequent seizure patterns, presence of regression or outcome. The vaccination-proximate group had mutations predicted to truncate the protein in 10/13 cases versus 16/25 cases in the vaccine-distant group (not significant). Conclusions: Clinical onset of Dravet syndrome occurs proximate to vaccination in a third of cases. Those with onset proximate to vaccination have a slightly earlier onset. These data suggest that vaccination may trigger onset during a critical developmental period, when onset is destined to occur, but without effect on clinical features or outcome. We presume this reflects a developmental stage when the function of SCN1A becomes particularly crucial. Avoiding vaccination for fear of causing this disorder has no rational basis.