Dravet Syndrome

Dravet Syndrome (DS) is a severe type of epilepsy characterised by often prolonged (5+ minute) seizures that usually begin in the first year of life. It affects one in 20,000 – 40,000 people worldwide. Early diagnosis is critical to proper treatment and achieving the best outcome. Up to 8% of children who have their first seizure by 12 months old may have Dravet Syndrome. It was formerly known as Severe Myoclonic Epilepsy of Childhood (SMEI).

Causes of DS

It is a genetic condition, often caused by SCN1A gene mutations in around 80% of children with Dravet Syndrome. Often these are completely new mutations, unique to the child and not inherited, but genetic testing can confirm if this is the case or not and parents will be advised accordingly

Characteristics

Seizures are tonic-clonic (convulsive) or clonic (jerking) type and may occur with high temperature.  These febrile seizures can last 15 minutes or longer in Dravet Syndrome and can lead to febrile status epilepticus. They are more prolonged than in typical febrile convulsions. With age, the seizures may increase in frequency and may present as focal or myoclonic seizures, which may occur without fever also. Some children may develop photosensitive epilepsy triggered by flicker or geometric patterns, grids and stripes. Seizures may also be triggered by exposure to heat in some children.

Most children have normal development when seizures begin but as seizures continue, they typically develop developmental disability and miss developmental milestones. Language skills may be affected - as well as sleep disorders, behavioural problems, sensitivity to infections and ataxia (difficulty with walking).

Prognosis

In Dravet Syndrome, seizures remain difficult to control and may be associated with varying degrees of learning disability. With age, children with Dravet Syndrome may develop other conditions such as autism and have issues with gait or unsteadiness in walking. Seizures may become less frequent with age but the children typically require care and support long-term. Due to the nature of their seizures earlier in life the risk pf SUDEP (Sudden Unexplained Death in Epilepsy) is slightly raised in younger children with Dravet Syndrome and your child’s neurology team can advise on measures to help monitor seizures and reduce risk.

Diagnosis

Diagnosis is made by a paediatric neurologist. Having a detailed history of the seizures as well as videos where these are available is very important. Early in the child’s life an EEG may not show any abnormalities but usually these are seen in the second year. These episodes of abnormal activity may affect both sides of the brain or just one part. The EEG will also detect photosensitivity in children with this epilepsy.

Treatment

Achieving the best seizure control possible is the main treatment goal and so treatment of DS typically begins with anti-seizure medications (ASMs). Seizures are difficult to control with ASM’s or other treatments.

Anti- Seizure Medications

  • Sodium Valproate (Epilim) is typically used as a first line drug in Dravet Syndrome. It is a broad spectrum drug. Sodium valproate is often the first ASM tried and then other ASM’s may be introduced such as stiripentol (Diacomit) and clobazam (Frisium). Stiripentol is not reimbursed in Ireland.
  • Clobazam is a benzodiazepine which can be effective in Dravet Syndrome but there can be a range of cognitive and behavioural issues associated with it. When combined with valproate, it can be more effective. Clobazam’s concentrations are increased by stiripentol and so they are frequently prescribed in combination with one another and sodium valproate. Stiripentol has been used for over a decade in Dravet Syndrome and has been shown to be effective as an add-on medication.
  • If control is not achieved, other ASM’s such as topiramate (Topamax), levetiracetam (Keppra), ethosuximide (Zarontin), clonazepam (Rivotril) or zonisamide (Zonegran) may be introduced. ASM’s which can cause problems in DS include carbamazepine and lamotrigine. Bromides can be used in some instances of resistance where other drugs have failed but these are difficult to obtain.
  • Since being licenced for use with Dravet Syndrome and approved for reimbursement in Ireland Cannabidiol (Epidyolex) is now a potential treatment option also when combined with clobazam and has been shown to be effective in reducing seizures in some children and adults with Dravet Syndrome.
  • With regard to ASM side effects, drowsiness and sleepiness have difficult implications in children whose cognition is impaired and could have effects on communication and interaction skills.
  • Emergency medication such as Buccal Midazolam is also typically prescribed.

Surgery

Surgery is not typically indicated in Dravet Syndrome, although vagus nerve stimulation (VNS) may be useful in some cases.

Ketogenic Diet

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet. There are several variations such as the classical MCT oil diet, low glycaemic index diet and the modified Atkins diet. It is a non-pharmacological treatment and is used in combination with ASM’s. The diet has been effective at reducing seizures and is regarded as safe with side effects being transient and less likely to lead to cognition difficulties and drowsiness.

The use of the KD in Dravet Syndrome has been shown to reduce seizures, but complete seizure control is achieved by only a minority. It is therefore used in conjunction with ASM’s. In one study of Dravet patients 75% had a significant reduction in seizures when used in conjunction with ASM’s.

Another study showed KD improvement in behaviour issues including hyperactivity.

Among children with Dravet Syndrome, there can be compliance problems with the older age groups compared to young children on the liquid form of the diet. In addition, access to the diet is limited in Ireland to a small number of hospitals providing the service.

Further Information