From the Guidelines
Dravet syndrome is a genetic epileptic encephalopathy characterized by severe and recurrent seizures, typically starting in the first year of life. According to a recent study published in 2023 1, Dravet syndrome is associated with lower urinary oxalate excretion than healthy individuals. The condition is often caused by genetic mutations, most commonly in the SCN1A gene, which affects sodium channels in the brain.
Key Characteristics of Dravet Syndrome
- Seizures triggered by fever, typically starting in the first year of life
- Multiple types of seizures, including myoclonic, tonic-clonic, absence, and focal seizures
- Developmental delays, movement and balance issues, sleep disturbances, and cognitive impairment
Treatment Options
- Anti-seizure medications such as clobazam, valproate, stiripentol, fenfluramine, and cannabidiol (Epidiolex)
- Medications to avoid: sodium channel blockers like carbamazepine and lamotrigine
- Preventing seizure triggers like high temperatures, bright lights, and emotional stress
- A ketogenic diet may be beneficial for some patients Stiripentol, an LDHA-targeted oral commercial medication, has been shown to be effective in reducing urinary oxalate levels in patients with primary hyperoxaluria, and is also used to treat Dravet syndrome 1. Management of Dravet syndrome requires a multidisciplinary approach involving neurologists, developmental specialists, physical therapists, and other healthcare providers to address both seizure control and developmental support.
From the FDA Drug Label
To be enrolled in either study, patients were required to be 3 years to less than 18 years of age, to have Dravet syndrome (ILAE classification of epilepsy, 1989), Dravet syndrome is a type of epilepsy, as classified by the International League Against Epilepsy (ILAE) in 1989.
- It is characterized by multiple types of seizures, including generalized clonic or tonic-clonic seizures.
- Patients with Dravet syndrome often experience seizures that are difficult to control with optimized antiepileptic therapy 2.
From the Research
Definition and Characteristics of Dravet Syndrome
- Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies 3.
- It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments 3, 4, 5.
- The syndrome typically arises during the first year of life, with seizures often triggered by fever, infections, or vaccinations 3, 4, 6.
Genetic Involvement
- Most cases of Dravet syndrome result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability 3, 6.
- The SCN1A gene is located on chromosome 2q24, and the loss-of-function mutations lead to decreased function of Nav1.1 sodium channels in GABAergic inhibitory interneurons 6.
Treatment and Management
- The goals of treatment are to balance reduction of seizure burden with adverse effects of therapies, as complete seizure control is generally not achievable with current therapies 4.
- Accepted first-line agents include clobazam and valproic acid, although these rarely provide adequate seizure control 4, 7.
- Other effective treatments include stiripentol, topiramate, levetiracetam, the ketogenic diet, and vagal nerve stimulation 4, 6, 7.
- Novel antiepileptic drugs, such as fenfluramine and cannabidiol, have shown efficacy in clinical trials 4, 6, 7.