Epilepsy and immunisation

Background

Epilepsy is a disorder of the brain that leads to a person having seizures (disruptions to the electrical activity in the brain). Epilepsy can result from genetic conditions, brain injury or infection, hypoxic insult at birth, brain tumours or neurodegenerative diseases. However, the cause of epilepsy in most people is unknown. It can develop at any stage of life but is most commonly diagnosed in childhood, adolescence and in adults over 60 years of age. Approximately 250,000 Australians (or 1% of) are currently living with epilepsy.

Seizures of epilepsy can be controlled with anti-epileptic medication/s and by recognising and managing triggers. Common triggers include lack of sleep, stress, illness, hormonal fluctuations, drug and alcohol use, and photosensitivity. 

In general, vaccination is recommended for individuals with epilepsy. 

While, in rare instances, vaccines can trigger seizures, it is important to note that infections, including vaccine-preventable diseases (e.g., measles, influenza or COVID-19), can trigger seizures in individuals with epilepsy. Therefore, a risk/benefit assessment is important when planning vaccination. 

Any seizure that occurs within 14 days of receiving a vaccine are defined as vaccine-proximate seizures (VPS). Most types of epilepsy do not have a high risk of VPS. However, there are some genetic epilepsies with a strong association with VPS. These include Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+). 

Dravet syndrome

Dravet syndrome is a rare and severe form of infantile onset epilepsy with a prevalence of 1 in 15,500 – 40,000 children. It is caused by a genetic mutation, usually a new/non inherited (de novo) change in the sodium channel gene (SCN1A). Children with Dravet syndrome classically present with prolonged febrile seizures in the first year of life. Seizures can be hemiclonic (one-sided) or generalised tonic-clonic. They can be sustained (lasting an extended period of time) such as in status epilepticus (SE). Following the first seizure, children with Dravet syndrome can develop refractory (uncontrolled) afebrile seizures, particularly myoclonic seizures, and a plateau or regression in their development. In approximately 30% of children with Dravet syndrome, the first seizure is vaccine-proximate (often occurring following the 4 or 6 month vaccines).  VPS occurring in infants, particularly if they are prolonged or classed as SE, should raise suspicion of Dravet syndrome.  

Immunisation can cause an earlier age of seizure onset in children with Dravet syndrome. However, there is no difference in developmental or seizure outcomes in children who had a first seizure proximate to immunisation compared to children whose first seizure was unrelated to immunisation. 

Genetic epilepsy with febrile seizures plus (GEFS+)

Genetic epilepsy with febrile seizures plus (GEFS+) describes a spectrum of seizure disorders of varying severity. A diagnosis of GEFS+ is usually made in individuals who are experiencing febrile seizures beyond the usual age range of up to 6 years and who have family members across different generations with a history of different types of epilepsy involving febrile seizures and/or recurrent afebrile seizures. 

Individuals with GEFS+ may experience VPS. 

Immunisation

Whilst vaccination is generally recommended in individuals with Dravet syndrome and other genetic epilepsies, there is a well-reported association with febrile seizures/SE following vaccination. Seizures most commonly occur within the first 48 hours following inactivated vaccines (e.g., influenza vaccines, COVID-19 vaccines, Infanrix hexa) and 5-10 days following live-attenuated vaccines (such as the measles-mumps-rubella, MMR, vaccine given at 12 months of age). 

Recommendations and management

Children with Dravet syndrome or GEFS+ and other children at risk of vaccine-proximate seizures should be referred to a specialist immunisation clinic for assessment prior to vaccination. 

Vaccination requires a comprehensive discussion between the patient’s family and the treating medical teams. Usually, expert advice from both immunisation specialists and neurologists is required and a clear plan is devised to ensure that vaccines can be administered under careful medical supervision (refer to protocol in resources). Vaccine administration for these groups includes admission for immunisation under observation and sometimes the prophylactic administration of paracetamol and benzodiazepines. Whilst there is no published data evaluating prophylactic measures to prevent seizures in children with Dravet syndrome undergoing immunisations, there is anecdotal evidence that this can reduce the rate of immunisation-related seizures and SE. 

Individuals with stable epilepsy, who have not had a previous VPS and whose type of epilepsy is not strongly associated with VPS, can generally be vaccinated safely in the community. However, where there are questions or concerns about the safety of vaccination in an individual, a referral to a specialist immunisation clinic could be considered. 

Resources

• RCH Kids health information: Epilepsy
• RCH Kids health information: Febrile seizures
• Epilepsy Action Australia: Seizure Types and Classification
• Symonds, J. et al Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort Brain: A journal of neurology 2019 August 142(8)2303-2318
• Protocol for immunisation in children with Dravet Syndrome and other children with vaccine-proximate seizures (RCH intranet access only)
• Protocol for immunisation of children with Dravet syndrome or other vaccine-proximate seizures
• Epilepsy Foundation: what causes epilepsy?