Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies

  • Objective: The term ‘precision medicine’ describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy. Methods: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management. Results: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%). Significance: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.

Download full text files

Export metadata

Author:Simona Balestrini, Daniela Chiarello, Maria Gogou, Katri Silvennoinen, Clinda Puvirajasinghe, Wendy D. Jones, Philipp Sebastian ReifGND, Karl Martin KleinORCiD, Felix RosenowORCiDGND, Yvonne G. Weber, Holger LercheORCiDGND, Susanne Schubert-BastORCiDGND, Ingo Borggräfe, Antonietta CoppolaORCiD, Serena Troisi, Rikke S. MøllerORCiDGND, Antonella Riva, Pasquale StrianoORCiDGND, Federico ZaraORCiD, Cheryl Hemingway, Carla Marini, Anna Rosati, Davide Mei, Martino Montomoli, Renzo GuerriniORCiDGND, J. Helen Cross, Sanjay M. SisodiyaORCiD
Parent Title (English):Journal of neurology, neurosurgery, and psychiatry
Publisher:BMJ Publishing Group
Place of publication:London
Document Type:Article
Date of Publication (online):2021/09/15
Date of first Publication:2021/09/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/01/21
Page Number:9
First Page:1044
Last Page:1052
This work was supported by Epilepsy Society, UK. Part of this work was undertaken at University College London Hospitals, which received a proportion of funding from the NIHR Biomedical Research Centres funding scheme. SB was supported by the Muir Maxwell Trust and the Epilepsy Society. KS was supported by a Wellcome Trust Strategic Award (WT104033AIA). AR, PS and FZ developed this work within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (legge 232 del 2016).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0