Abstracts

Rationale:
Diphtheria-tetanus-pertussis vaccination is an inactivated vaccine that triggers onset of seizures in one-third of patients with Dravet Syndrome. We aimed to determine whether live-attenuated vaccines, measles-mumps-rubella and measles-mumps-rubella-varicella (MMR and MMRV), also trigger seizures in patients with Dravet syndrome.
Method:
We performed a retrospective review of patients with a diagnosis of SCN1A-positive Dravet syndrome recruited to the Epilepsy Research Centre, Australia. Source data, including vaccination records, seizure diaries and hospital medical records, were obtained to examine seizure occurrence around the time of MMR and MMRV vaccination at age 12 and 18 months respectively, taking into account changes in vaccination schedules over time. A self-controlled case series analysis compared the incidence of seizures occurring in the risk period, from 5-12 days post-vaccination, to seizures in the control period, defined as 13-30 days post-vaccination. Results68/147 (46%) families participated in the study, 35 of which were eligible (51%), having accurate seizure records for a month following their MMR and MMRV vaccinations. 20/35 (57%) were female; mean age of seizure onset was 6 months (range 6 weeks – 19 months). Of the 33 ineligible patients, 22 (67%) did not have vaccination records and seizure diaries for the required periods, and 11 (33%) did not receive the MMR and MMRV vaccine within 12 months of the scheduled age. 33/35 (94%) patients had data for their first dose of MMR vaccine; 17/33 (52%) patients had a seizure in the 5-12 day risk period, with a peak seizure day on day 8, whilst 14/33 (42%) had a seizure in the control period. Self-controlled case series analysis showed an increased incidence rate ratio (IRR) of 1.54 for seizures occurring 5-12 days following live-attenuated vaccine (95% CI, 0.93-2.53). Of the 26 seizures in the risk period; 2/26 were focal impaired awareness seizures whilst 24/26 were tonic-clonic seizures; 6/24 comprised convulsive status epilepticus and 6/24 were febrile. The IRR for convulsive status epilepticus was increased in the risk period compared with the control period (13.5), despite a small sample size (95% CI 1.63 – 112.13). 18/35 (51%) patients had data for their second dose of MMR vaccine; 5/18 (28%) experienced a seizure in the risk period, compared with 9/18 (50%) in the control period. Analysis showed an increased IRR of 1.19 for seizures occurring 5-12 days following live-attenuated vaccine (95% CI, 0.53-2.67). Of the 9 seizures in the risk period; 3/9 were tonic-clonic seizures, 1/9 was a focal impaired awareness seizure and the remaining 5/9 lacked seizure descriptions.
Conclusion:
The live-attenuated vaccines, measles-mumps-rubella (MMR) and the combined measles-mumps-rubella-varicella (MMRV), did not significantly increase risk of seizures in patients with Dravet syndrome. Understanding the likelihood of which vaccines trigger seizures in Dravet syndrome informs vaccination planning and clinical care.
Funding:
:National Health and Medical Research Council of Australia