Abstracts

Rationale: Dravet Syndrome represents a severe genetic epilepsy of childhood and mutations in the SCN1A gene have been identified in the majority of cases. Dravet Syndrome usually starts in the first year of life with subsequent refractory seizures and intellectual disability. Children with Dravet Syndrome may have their first seizure after a vaccination as fever in the setting of vaccinations is a common feature and prolonged febrile seizures are a clinical hallmark of Dravet Syndrome. Several cases of alleged vaccine encephalopathy have been shown to present with the clinical picture of Dravet syndrome and pathogenic SCN1A mutations were identified in these patients. It is unknown, however, what percentage of patients with severe epilepsies starting in the setting of vaccination are in fact patients with Dravet Syndrome. The VACENC study aims to describe the clinical and genetic features of children presenting with seizures after vaccination using a register-based cohort. Methods: In cooperation with the Paul-Ehrlich-Institute (national surveillance authority for biomedical drugs in Germany) the national database of vaccination-related events was surveyed for reported seizures in association with vaccinations. All cases reported in 2006 and 2007 were analysed. Clinical information was re-evaluated and follow-up of cases suggestive of severe childhood epilepsies was attempted. Results: In total, 317 cases reported in 2006 and 2007 were characterized clinically. In 164/317 patients (51.7%), clinical information supported the occurrence of epilepsy or seizures, while 122/317 (38.5%) presented with syncope, hypotonic-hyporesponsive episodes (HHE) or other non-epileptic events. For 31/317 cases (9.8%) clinical characterization was difficult due to incomplete information. Clinical history was strongly suggestive of Dravet Syndrome in 6/317 (1.9%; 3.7% of 164 cases with confirmed seizures). Furthermore, 9/317 (2.8%; 5.5% of cases with confirmed seizures) presented with West Syndrome and 20/317 (6.3%; 12.2% of cases with confirmed seizures) with other types of epilepsy. Febrile seizures were present in 85/317 (26.8%) cases. Status epilepticus was described for 17/317 (5.4%) patients, two thirds of which were febrile. Febrile seizures and status epilepticus were preceded relatively more often by immunisation with attenuated live vaccines (measles, mumps, rubella, chicken pox, rotavirus) compared to the whole group (33.1% vs. 19.2%). Conclusions: Using a national register, we aimed to characterize the clinical and genetic features of seizures associated with vaccination. Cases with a strong clinical suspicion of Dravet Syndrome represent 3.7% of all reported events with confirmed seizures. We hypothesize that a significant proportion of these cases are associated with a SCN1A mutation causing Dravet syndrome and related syndromes. Early diagnosis of these syndromes by clinical recognition and confirmation by DNA analysis is important for treatment decisions, genetic counselling and public health evaluation of vaccine safety.