Katarzyna Kotulska1, David J Kwiatkowski2, Paolo Curatolo3, Bernhard Weschke4, Kate Riney5,6, Floor Jansen7, Martha Feucht8, Pavel Krsek9, Rima Nabbout10, Anna C Jansen11,12, Konrad Wojdan13,14, Kamil Sijko1,13, Jagoda Głowacka-Walas1,15, Julita Borkowska1, Krzysztof Sadowski1, Dorota Domańska-Pakieła1, Romina Moavero16, Christoph Hertzberg4, Hanna Hulshof7, Theresa Scholl8, Barbora Benova9, Eleonora Aronica17, Jessie de Ridder18, Lieven Lagae18, Sergiusz Jóźwiak1,19. 1. Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland. 2. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 3. Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Rome, Italy. 4. Department of Child Neurology, Charité University Medicine Berlin, Berlin, Germany. 5. Neurosciences Unit, Queensland Children's Hospital, South Brisbane, QLD, Australia. 6. School of Medicine, University of Queensland, St Lucia, QLD, Australia. 7. Department of Child Neurology, Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands. 8. Department of Pediatrics, University Hospital Vienna, Vienna, Austria. 9. Motol University Hospital, Charles University, Prague 5, Czech Republic. 10. Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Necker- Enfants Malades Hospital, University Paris Descartes, Imagine Institute, Paris, France. 11. Pediatric Neurology Unit-UZ Brussel, Brussels, Belgium. 12. Neurogenetics Research Group, Vrije Universiteit Brussel, Brussels, Belgium. 13. Transition Technologies, Warsaw, Poland. 14. Warsaw University of Technology, Institute of Heat Engineering, Warsaw, Poland. 15. Warsaw University of Technology, The Faculty of Electronics and Information Technology, Warsaw, Poland. 16. Child Neurology Unit, Neuroscience and Neurorehabilitation Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 17. Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 18. Department of Development and Regeneration-Section Pediatric Neurology, University Hospitals KU Leuven, Leuven, Belgium. 19. Department of Child Neurology, Medical University of Warsaw, Warsaw, Poland.
Abstract
OBJECTIVE: Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants. METHODS: In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open-label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure. RESULTS: In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty-seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment [RCT: 364 days (95% confidence interval [CI] = 223-535) vs 124 days (95% CI = 33-149); OLT: 426 days (95% CI = 258-628) vs 106 days (95% CI = 11-149)]. At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21, p = 0.032), drug-resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted. INTERPRETATION: Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2020.
RCT Entities:
OBJECTIVE:Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSCinfants. METHODS: In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open-label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure. RESULTS: In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty-seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment [RCT: 364 days (95% confidence interval [CI] = 223-535) vs 124 days (95% CI = 33-149); OLT: 426 days (95% CI = 258-628) vs 106 days (95% CI = 11-149)]. At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21, p = 0.032), drug-resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted. INTERPRETATION: Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2020.
Authors: Eleni Zarakoviti; Roz Shafran; David Skuse; Amy McTague; Neha Batura; Tom Palmer; Emma Dalrymple; Sophie D Bennett; Colin Reilly Journal: J Autism Dev Disord Date: 2022-07-29
Authors: Aristea S Galanopoulou; Wolfgang Löscher; Laura Lubbers; Terence J O'Brien; Kevin Staley; Annamaria Vezzani; Raimondo D'Ambrosio; H Steve White; Harald Sontheimer; John A Wolf; Roy Twyman; Vicky Whittemore; Karen S Wilcox; Brian Klein Journal: Epilepsia Open Date: 2021-05-06
Authors: S Katie Z Ihnen; Jamie K Capal; Paul S Horn; Molly Griffith; Mustafa Sahin; E Martina Bebin; Joyce Y Wu; Hope Northrup; Darcy A Krueger Journal: Pediatr Neurol Date: 2021-07-06 Impact factor: 4.210