A registry for Dravet syndrome: The Italian experience.

Margherita Nosadini, Elisabetta Cesaroni, Lucio Giordano, Patrizia Accorsi, Vittorio Sciruicchio, Paolo Tinuper, Tullio Messana, Angelo Russo, Dario Pruna, Sara Matricardi, Valentina De Giorgis, Davide Caputo, Serena Pellegrin, Tommaso Lo Barco, Francesca Darra, Bernardo Dalla Bernardina, Renzo Guerrini, Simona Balestrini, Carla Marini, Annarita Ferrari, Simona Pellacani, Tiziana Granata, Francesca Ragona, Nicola Specchio, Domenica Battaglia, Marco Perulli, Federica Pieroni, Isabella Brambilla, Elisa Giarola, Salvatore De Masi, Ersilia Lucenteforte, Sabrina Giometto, Viola Doccini

Journal: Epilepsia open 2023;8(2):517-534

PMID: 36938796

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Abstract

OBJECTIVES

We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality.

METHODS

Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included.

RESULTS

At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0-9) while at last follow-up was 11 years (IQR 5-18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001).

SIGNIFICANCE

The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes.

Address: Neuroscience Department, Meyer Children's Hospital IRCSS, University of Florence, Florence, Italy.; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Chalfont Centre for Epilepsy, Buckinghamshire, UK.; Unit of Medical Statistics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.; Clinical Trial Center, University Hospital Careggi, Florence, Italy.; Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Research Center for Pediatric Epilepsies, Verona, Italy.; Dravet Italia Onlus, Verona, Italy.; Rare Epilepsies Alliance, Verona, Italy.; ERN EpiCare (Epag), Verona, Italy.; Fondazione Toscana "G. Monasterio", Pisa, Italy.; Pediatric Neuropsychiatry, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Gemelli, IRCCS - Università Cattolica del Sacro Cuore, Rome, Italy.; Department of Neuroscience, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy.; Department of Pediatric Neuroscience, Fondazione IRCSS Istituto Neurologico Carlo Besta, Milan, Italy.; Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, Pisa, Italy.; Department of Child Neuropsychiatry, Children's Hospital, Ancona, Italy.; Paediatric Neurology and Psychiatry Unit, Spedali Civili Children's Hospital, University of Brescia, Brescia, Italy.; Children Epilepsy and EEG Center, Bari, Italy.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'età pediatrica, Bologna, Italy.; Child Neurology and Epileptology Unit, Paediatric Department, ARNAS Brotzu, Cagliari, Italy.; Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy.; Department of Child Neurology and Psychiatry, IRCSS Mondino Foundation, Pavia, Italy.; Epilepsy Center, ASST Santi Paolo Carlo, Health Sciences Department, University of Milan, Milan, Italy.; Department of Pediatric Neurology, Bolzano Hospital, Bolzano, Italy.; Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.

DOI: 10.1002/epi4.12730

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MeSH Terms: Humans, NAV1.1 Voltage-Gated Sodium Channel, Retrospective Studies, Epilepsies, Myoclonic, Epilepsy, Epileptic Syndromes