International consensus on diagnosis and management of Dravet syndrome

Abstract

Objective: This study was undertaken 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.Methods: A core working group was convened consisting of six physicians with recognized expertise in DS and two representatives of the Dravet Syndrome Foundation. This core group summarized the current literature (focused on clinical presentation, comorbidities, maintenance and rescue therapies, and evolving disease-modifying therapies) and nominated the 31-member expert panel (ensuring international representation), which 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 old, presenting with either a first prolonged hemiclonic seizure 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 first-to third-line maintenance therapies, which included the newly approved agents. Whereas there was agreement for recommendation of disease-modifying therapies, if they are proven safe and efficacious for seizures and/or reduction of comorbidities, 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 disease-modifying therapies. K E Y W O R D Scannabidiol, developmental and epileptic encephalopathy, disease-modifying treatment, fenfluramine, SCN1A, stiripentol Note: Bold and all-capital text indicates Strong consensus; bold and italic text indicates Moderate consensus; nonbold and italic text indicates no consensus.

Utility of genetic testing in pediatric epilepsy: Experience from a low to middle-income country

“…The ketogenic diet is moderately effective for seizure control and could also be considered as second line management in patients with suboptimal response to clobazam and valproic acid. Recent studies also show that newer medications like cannabinoids and fenfluramine would be beneficial in conditions where first-line medications do not help [18] , [19] , [20] .…”

The Charlotte Project: Recommendations for patient-reported outcomes and clinical parameters in Dravet syndrome through a qualitative and Delphi consensus study

“…In addition, further studies involving professionals from a wider range of disciplines involved in the care and management of patients with DS, such as social workers or therapists, may provide a more accurate view on the management of PROs in the daily life of DS patients and their families. Another limitation of the study associated to the Delphi technique is related to the consensus definition, which is not standard, and therefore, different criteria can be found in the literature (23,29). For this reason, we deemed appropriate to define two categories of consensus, moderate and strong (29).…”

“…Another limitation of the study associated to the Delphi technique is related to the consensus definition, which is not standard, and therefore, different criteria can be found in the literature (23,29). For this reason, we deemed appropriate to define two categories of consensus, moderate and strong (29). We considered that although agreement was reached on most of the items consulted, those that fell into the moderate consensus category may have raised more controversy among the experts.…”

“…A strong consensus was defined if 80% or more of panelists providing an opinion rated the statement with 7 or higher. A moderate consensus was considered if 67-79% of panelists rated the statement with 7 or higher (29). Statements that did not reach this level of agreement were interpreted as "undetermined".…”

Fenfluramine: A Review of Pharmacology, Clinical Efficacy, and Safety in Epilepsy

“…Multiple rigorous RCTs have shown that FFA is highly efficacious against Dravet syndrome-associated convulsive seizures and, to a lesser degree, against LGS-associated drop seizures. An international consensus on the management of Dravet syndrome noted FFA as a possible first-line therapy with moderate to strong consensus among physicians and caregivers [ 93 ]. Both physicians and caregivers rated it as an agent with excellent tolerability.…”