Post-Vaccination Seizures in Children With Dravet Syndrome: Can They Be Prevented?

Background: One third of children with Dravet syndrome have seizures triggered by vaccination. In children with Dravet syndrome and previous vaccine proximate seizures (VPS), we aimed to establish whether prophylactic benzodiazepine use prevented further seizures following vaccination. Methods: In this retrospective multicentre cohort study, we analysed the course of children with Dravet syndrome and previous VPS who presented to a Specialist Immunisation Clinic at one of four Australian tertiary paediatric hospitals between 2013-2017 for management of further vaccination. Clinical history, vaccination management and outcomes were obtained from medical records. We compared the clinical management of patients who did and did not experience further VPS within 14 days of vaccination. Findings: We identified 18 children with Dravet syndrome who had a previous VPS; for 11/18 (58%) children, the VPS was their first seizure. Of the 18 children, 16 had further vaccination encounter(s) (46 encounters, median 3 encounters/child). There were 12 recurrent VPS in 11/16 (69%) children, with one child having two further VPS;  all 12 were afebrile seizures of which 7 (58%) were afebrile status epilepticus. VPS recurrence did not differ by age at revaccination (range: 6-62 months) or revaccination setting (outpatient, day stay or inpatient). Prophylactic benzodiazepine (clobazam/clonazepam) use occurred in 26/46 (57%) of vaccination encounters and was associated with lower VPS recurrence (odds ratio OR 0.033 (95%CI 0.004-0.291), P <0.01). Interpretation: Two-thirds of children with Dravet syndrome who have an initial VPS experienced recurrent VPS, most frequently comprising life-threatening episodes of afebrile status epilepticus. As prophylactic post-vaccination use of a benzodiazepine lowered the likelihood of VPS recurrence by 30 fold, benzodiazepine administration in the at-risk post-vaccination period should be routinely implemented into vaccination management in children with confirmed or even suspected Dravet syndrome. Funding Information: None. Declaration of Interests: Prof Scheffer has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon, Chiesi, Encoded Therapeutics, Xenon Pharmaceuticals, and Knopp Biosciences; has re-ceived speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin, and Eisai; has served as an investigator for Zogenix, Zynerba, Ultragenyx, GW Pharma, UCB, Eisai, Anavex Life Sciences, Ovid Therapeutics, Epigenyx, Encoded Therapeutics and Marinus; and has consulted for Zynerba Pharmaceuticals, Atheneum Partners, Ovid Therapeutics, Care Beyond Diagnosis, Epilepsy Consortium, and UCB. She may accrue future revenue on a pending patent WO2009/086591 (filed: 2008); has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies (WO/2006/133508), and has a patent for a molecular diagnostic/therapeutic target for benign familial infantile epilepsy (BFIE) [PRRT2] O/2013/059884. All other authors have nothing to declare. Ethics Approval Statement: This study was approved by Sydney Children’s Hospital Network Human Research Ethics Committee (2019/ETH05430).