International Consensus On Diagnosis and Management of Dravet Syndrome

Objectives: To gain consensus from experienced physicians and caregivers regarding optimal diagnosis and management of Dravet syndrome (DS), in the context of recently-approved, DS-specific therapies and emerging disease-modifying treatments (DMTs) Methods: A core working group was convened consisting of 6 physicians with recognized expertise in DS and 2 representatives of the Dravet Syndrome Foundation. This core group summarized the current literature (focused on clinical presentation, co-morbidities, maintenance and rescue therapies and evolving DMTs) and nominated the 31-member expert panel (ensuring international representation) who participated in two rounds of a Delphi process to gain consensus on diagnosis and management of DS. Results: There was strong consensus that infants 2-15 months, presenting with either a first prolonged hemiclonic seizures or first convulsive status epilepticus with fever or following vaccination, in the absence of another cause should undergo genetic testing for DS. Panelists agreed on evolution of specific comorbidities with time, but less agreement was achieved on optimal management. There was also agreement on appropriate 1st-3rd line maintenance therapies, which included the newly approved agents. While there was agreement for recommendation of DMTs, if they are proven safe and efficacious for seizures and/or reduction of co-morbidities, there was less consensus for when these should be started, with caregivers being more conservative than physicians. Significance: This International DS Consensus, informed by both experienced global caregiver and physician voices, provides a strong overview of the impact of DS, therapeutic goals and optimal management strategies incorporating the recent therapeutic advances in DS and evolving DMTs.