Dravet Syndrome

Dravet syndrome is a complex genetic epileptic syndrome first described by Dr. Charlotte Dravet in 1978. It is a rare disorder, but a cause for significant morbidity in those children who have it. But luckily, new means of diagnosis and treatment are now available so these children can spend near-normal lives.

What Causes Dravet Syndrome?

The underlying defect causing Dravet Syndrome lies in the SCNA1 sodium channel in the brain which is determined genetically. But later, with the discovery of SCNA1 mutation-negative individuals, scientists realized that there were other causes as well. 

How Do Dravet Syndrome Children Present?

Children with Dravet Syndrome will be completely normal at birth with normal EEGs. Then subtle behavioral disturbances and a plateau in the development will appear closely followed by seizures which generally tend to occur before the child is 18 months of age. The initial seizures will be following fever, but later they will occur spontaneously. The seizures will get worse, and the frequency will also increase as the child gets older to reach a stable phase by 6-8 years. From that point onwards the seizure frequency gradually decreases, and the nature of the seizures turn more towards myoclonic, generalized tonic-clonic, atypical absent seizures, and drop attacks.
Seizures in Dravet Syndrome are usually focal hemiclonic or myoclonic which means usually only one half of the body is involved. They occur more on the right side and the affected side can change with time. The main feature of these seizures is that they last for a long time, up to 10 minutes in some cases. This condition is known as status epilepticus and ED admissions and emergency drug treatment is required to terminate the seizure.
One important trigger for seizures in Dravet Syndrome is raised body temperature. This may be due to a fever, taking a hot bath, going out on a hot summer day or even moving out from a hot environment. However, vaccines do not cause seizures unless fever follows, on contrary to the common misconception.

What Other Problems Do Children with Dravet Syndrome Have?

Behavioral disturbances can be the initial presentation of Dravet Syndrome. Children can have ADHD with hyperactivity and inattentiveness or have repetitive behaviors like in autism. Their development can plateau or regress as the seizures develop, and the deficiencies may be more prominent in speech and cognitive domains.
These children can also have feeding problems. They have a poor appetite and can be very picky eaters. This leads to long feeding times where the parents have to struggle with the child but still come off as unsuccessful. These children anyway have low height and weight due to their genetics and poor feeding can worsen it. Some children need feeding tubes to meet the required calorie intake.
They also have sleep disturbances. They go to sleep very late and wake up early in the morning. The parents can get frustrated as they themselves will get very little sleep. Some children need sleeping pills as habit-forming can be difficult for them. However, medications must be used cautiously as some drugs can aggravate the seizures like Diphenhydramine (Benadryl).
Due to muscle stiffness, Dravet children will adopt a crouching gait making them slow and easily tired. With all of these comorbidities, caregiver burnout and depression are extremely common. On top of all that, Dravet Syndrome children have an increased risk of SUDEP (Sudden Unexplained Death in Epilepsy).

How Is Dravet Syndrome Diagnosed?

Diagnosis of Dravet syndrome is based on clinical features and genetic testing. It is important to make a correct diagnosis as some medications used in other seizure disorders can actually worsen seizures in Dravet Syndrome. Brain MRI will be normal initially, but scarring in the hippocampus area can be recognized in patients later in life due to repeated and prolonged seizures causing brain damage.

How Do You Treat Dravet Syndrome?

Many new advancements have been made in Dravet Syndrome treatment in the recent past. The most important thing is knowing what medications to avoid. This includes a list of drugs that exert their action by sodium channel blockade which itself is the primary reason for the pathogenesis of this disease. Drugs to avoid include antiepileptics like lamotrigine, carbamazepine, oxcarbazepine, and other drugs with a similar mode of action. Phenytoin may be used, but only in the management of status epilepticus.
Now, there is a new consensus on what antiepileptics to use. The recommended first-line medication is valproate. It is a well-established antiepileptic that is effective in Dravet Syndrome as well. 
If valproate fails to achieve good control of seizures, second-line medications like fenfluramine, Stiripentol, and clobazam may be considered. Clobazam is a benzodiazepine while the former two are relatively novel drugs. Both fenfluramine and Stiripentol can cause weight loss. Fenfluramine is suspected to cause heart problems though nothing has been reported so far. However, regular Echocardiograms are done just in case. Stiripentol on the other hand inhibits liver enzymes which can lead to toxicity of concomitantly administered medications.
Pharmaceutical-grade cannabidiol and topiramate are the recommended third-line and fourth-line drugs respectively. Levetiracetam is used as a last resort if everything else fails, but we should be wary of its psychiatric side effects.
Non-pharmacological management includes ketogenic diets which are effective in some patients. Resistant cases are referred for surgical interventions like placement of vagus nerve stimulation devices. Surgical resection is not recommended even in the presence of temporal sclerosis as the ion channel defect is present throughout the brain and another location could act as a seizure focus following resection.
All parents should be given a seizure action plan with rescue medications like nasal midazolam and oral diazepam. Routine vaccination as per the national program is recommended for Dravet children, but prophylactic antipyretics may be needed to prevent vaccine-induced fever triggering seizures.