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. 2022 Jul;63(7):1761-1777.
doi: 10.1111/epi.17274. Epub 2022 May 12.

International consensus on diagnosis and management of Dravet syndrome

Elaine C Wirrell  1 , Veronica Hood  2 , Kelly G Knupp  3 , Mary Anne Meskis  2 , Rima Nabbout  4 , Ingrid E Scheffer  5 , Jo Wilmshurst  6 , Joseph Sullivan  7
Affiliations

International consensus on diagnosis and management of Dravet syndrome

Elaine C Wirrell et al. Epilepsia. 2022 Jul.

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.

Keywords: SCN1A; cannabidiol; developmental and epileptic encephalopathy; disease-modifying treatment; fenfluramine; stiripentol.

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Conflict of interest statement

E.C.W. has served as a paid consultant for Encoded Therapeutics, Eisai, Epygenix, and BioMarin. She is Editor‐in‐Chief of Epilepsy.com. K.G.K. has received research funding from Zogenix, Encoded, Eisai, and West Pharmaceuticals. She has participated on data and safety monitoring boards for GW Pharmaceuticals and Epygenix, and has received consulting funds from BioMarin, Zogenix, Encoded, Eisai, Stoke, and Biocodex. R.N. has served as principal investigator in clinical trials for Novartis, Nutricia, Eisai, UCB, GW Pharma, and LivaNova. She has received consulting and lecturer honoraria from Biogene, BioMarin, Praxis, GW Pharma, Zogenix, Novartis, Nutricia, Stoke, Ionis, Targeon, Neuraxpharma, Takeda, Nutricia, Biocodex, Advicennes, and Eisai. She has received unrestricted research grants from Eisai, UCB, LivaNova, and GW Pharma and academic research grants from EJP‐RD (Horizons 2020). I.S. has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon, Chiesi, Encoded Therapeutics, Knopp Biosciences, and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, Chiesi, LivaNova, and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, BioMarin, and Eisai; has served as an investigator for Zogenix, Zynerba, Ultragenyx, GW Pharma, UCB, Eisai, Xenon Pharmaceuticals, Anavex Life Sciences, Ovid Therapeutics, Epygenix, Encoded Therapeutics, and Marinus; has consulted for Zynerba Pharmaceuticals, Atheneum Partners, Ovid Therapeutics, Care Beyond Diagnosis, Epilepsy Consortium, and UCB; and is a Non‐Executive Director of Bellberry. She may accrue future revenue on pending patent WO61/010176 (filed 2008): Therapeutic Compound; has a patent for SCN1A testing held by Bionomics and licensed to various diagnostic companies; has a Patent Molecular Diagnostic/Theranostic Target for Benign Familial Infantile Epilepsy (BFIE) (PRRT2) 2011904493 & 2012900190 and PCT/AU2012/001321 (TECH ID: 2012‐009). J.W. has received an honorarium for activities as Associate Editor for Epilepsia. J.S. has served as a paid consultant for the Epilepsy Study Consortium, Encoded Therapeutics, Greenwich Biosciences, Epygenix Therapeutics, Invitae, and Longboard, and has stock options in Epygenix. Neither of the other authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Figures

FIGURE 1
FIGURE 1
Expertise of the physician and caregiver panel. Shown are the percentage of physicians who have ever cared for or are currently caring for <10, 11–50, or >50 persons with Dravet syndrome (DS) and the percentage of caregivers who are familiar with <10, 11–50, or >50 persons with DS
FIGURE 2
FIGURE 2
Therapeutic algorithm for maintenance therapies for management of seizures in Dravet syndrome. There was consensus for use of valproic acid as first‐line therapy, and for use of clobazam, fenfluramine, or stiripentol as first‐ or second‐line therapy. There was also consensus for contraindicated medications. **Phenytoin may be helpful for status epilepticus. "Other" includes vagal nerve stimulation, levetiracetam, zonisamide, bromides, clonazepam, and ethosuximide (for absences)
See this image and copyright information in PMC

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Supplementary concepts