Managing Dravet syndrome requires a multidisciplinary approach open to both pharmacological and non-pharmacological treatments, because of the severe nature of this disease and its poor prognosis, a review study reports.
Dravet syndrome is a severe type of drug-resistant epilepsy whose symptoms usually emerge in infancy and is characterized by seizures, cognitive deficits, and a risk of early death. Most patients carry genetic mutations in the SCN1A gene, which encodes for a sub-unit of a sodium channel essential for the generation and transmission of electrical signals in the brain.
There is no cure for Dravet syndrome, and treatments largely focus on reducing the frequency and duration of seizures, and particularly on helping to prevent and manage long epileptic episodes known as status epilepticus, one of the major causes of death in people with Dravet.
This review study focused on summarizing the main features of Dravet syndrome, and current treatment options to manage the disorder.
Because Dravet is characterized by seizures that usually do not respond to conventional anti-epileptic medications (called refractory seizures), developmental, cognitive and motor delays are usually evident in children early (before one year of age).
A diagnosis is mostly based on the clinical presentation of symptoms and a patient’s medical history, and can be confirmed by genetic analyses and/or electroencephalogram (EEG) — a technique used to analyze the brain’s electrical activity and to study seizures.
Depacon (valproate) and Onfi (clobazam), two types of anti-seizure medications, are usually the first-line treatment recommended for Dravet. If these fail, patients may be started on Diacomit (stiripentol), topiramate (sold as Topamax, among other names) or a ketogenic diet (high-fat, low-carb) in addition to their routine anti-seizure medications.
“Surgical options for DS [Dravet syndrome] are limited. However, deep brain stimulation (DBS) and vagal nerve stimulators (VNS) are shown to be effective in decreasing the incidence of breakthrough seizures,” the researchers wrote.
DBS is a type of surgery that involves implanting a device that sends electrical signals (produced by a battery) to stimulate specific regions of the patient’s brain. The U.S. Food and Drug Administration (FDA) approved the use of DBS as an add-on therapy for patients whose seizures failed to respond to at least three different anti-epileptic medications in 2018.
Unlike DBS, VNS uses a device that detects brain electrical activity, implanted in the patient’s neck. When brain’s electrical activity increases above a given threshold, the device sends signals to the vagus nerve to block the excessive electrical activity associated with seizures. This approach is recommended for patients with refractory seizures who are not suitable for surgery.
Epidiolex is a plant-derived cannabidiol, a non-psychoactive marijuana extract, meaning it does not have the mind-altering effects that are characteristic of delta (9)-tetrahydrocannabinol (THC), the main psychoactive component of marijuana that gets people “high.”
Although its exact mechanism of action is only partially understood, oral Epidiolex has shown promising efficacy in several clinical trials and “has created a new hope in the DS community to better control seizure frequency and help them to manage their condition effectively,” the researchers wrote.
According to recommendations given by the North American consensus panel — which included 14 expert epileptologists and five parents of children with Dravet — “[t]he family must be educated at first visit about risk and management of prolonged seizure, rescue medications, and emergency treatment plan. Risk of death and developmental outcomes should be discussed within four weeks of diagnosis.”
“Overall, DS has a poor prognosis and needs multidisciplinary healthcare management,” the researchers concluded.