Jan Lotte1, Thomas Bast2, Peter Borusiak3, Antonietta Coppola4, J Helen Cross4, Petia Dimova5, Andras Fogarasi6, Irene Graneß7, Renzo Guerrini8, Helle Hjalgrim9, Reinhard Keimer10, Christian M Korff11, Gerhard Kurlemann12, Steffen Leiz13, Michaela Linder-Lucht14, Tobias Loddenkemper15, Christine Makowski16, Christian Mühe17, Joost Nicolai18, Marina Nikanorova9, Simona Pellacani8, Sunny Philip19, Susanne Ruf20, Iván Sánchez Fernández15, Kurt Schlachter21, Pasquale Striano22, Biayna Sukhudyan23, Deyana Valcheva24, R Jeroen Vermeulen18, Tanja Weisbrod10, Bernd Wilken25, Philipp Wolf26, Gerhard Kluger27. 1. Neuropädiatrie, Schön Klinik Vogtareuth, Germany. Electronic address: jan.lotte@web.de. 2. Epilepsy Center Kork, Kehl-Korg, Germany. 3. Department of Pediatrics, HELIOS Hospital Wuppertal, Witten/Herdecke University, Germany. 4. Department of Clinical & Experimental Epilepsy, Great Ormond Street Hospital, University College London, England. 5. Epilepsy Center, St. Ivan Rilski University Hospital, Sofia, Bulgaria. 6. Neurology Department, Bethesda Children's Hospital, Budapest, Hungary. 7. Neuropädiatrie, Waldklinikum Gera, Germany. 8. Child Neurology Unit, A. Meyer Children's Hospital, University of Florence, Italy. 9. Epilepsihospitalet Filadelfia, Danish Epilepsie Center, Dianalund, Denmark. 10. Kinderklinik, Stauferklinik, Schwäbisch Gmünd, Germany. 11. Pediatric Neurology, Geneva University Hospitals, Geneva, Switzerland. 12. Neuropädiatrie, Universitätskinderklinik Münster, Germany. 13. Neuropädiatrie, Kinderklinik Dritter Orden, München, Germany. 14. Servicio de Pediatría y Unidad de Epilepsia, Hospital del Mar, Barcelona, Spain. 15. Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Boston, USA. 16. Kinderklinik der Technischen Universität München, Klinikum Schwabing, Germany. 17. Neuropädiatrische Schwerpunktpraxis, München, Germany. 18. Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands. 19. Children's Hospital Birmingham, England. 20. Neuropädiatrie, Universitätskinderklinik Tübingen, Germany. 21. Department of Pediatrics, Landeskrankenhaus Bregenz, Austria. 22. Pediatric Neurology, Institute Gaslini, University of Genova, Italy. 23. "Arabkir" Medical Complex, Pediatric Neurology, Yerevan, Armenia. 24. Neuropädiatrie, Wedau Kliniken, Duisburg, Germany. 25. Department of Pediatric Neurology, Kassel Hospital, Germany. 26. Department of Neuropediatrics, DRK-Children's Hospital, Siegen, Germany. 27. Neuropädiatrie, Schön Klinik Vogtareuth, Germany; Paracelsus Medical University, Salzburg, Austria.
Abstract
PURPOSE: PCDH19 mutations cause epilepsy and mental retardation limited to females (EFMR) or Dravet-like syndromes. Especially in the first years of life, epilepsy is known to be highly pharmacoresistant. The aim of our study was to evaluate the effectiveness of antiepileptic therapy in patients with PCDH19 mutations. METHODS: We report a retrospective multicenter study of antiepileptic therapy in 58 female patients with PCDH19 mutations and epilepsy aged 2-27 years (mean age 10.6 years). RESULTS: The most effective drugs after 3 months were clobazam and bromide, with a responder rate of 68% and 67%, respectively, where response was defined as seizure reduction of at least 50%. Defining long-term response as the proportion of responders after 12 months of treatment with a given drug in relation to the number of patients treated for at least 3 months, the most effective drugs after 12 months were again bromide and clobazam, with a long-term response of 50% and 43%, respectively. Seventy-four percent of the patients became seizure-free for at least 3 months, 47% for at least one year. SIGNIFICANCE: The most effective drugs in patients with PCDH19 mutations were bromide and clobazam. Although epilepsy in PCDH19 mutations is often pharmacoresistant, three quarters of the patients became seizure-free for at least for 3 months and half of them for at least one year. However, assessing the effectiveness of the drugs is difficult because a possible age-dependent spontaneous seizure remission must be considered.
PURPOSE:PCDH19 mutations cause epilepsy and mental retardation limited to females (EFMR) or Dravet-like syndromes. Especially in the first years of life, epilepsy is known to be highly pharmacoresistant. The aim of our study was to evaluate the effectiveness of antiepileptic therapy in patients with PCDH19 mutations. METHODS: We report a retrospective multicenter study of antiepileptic therapy in 58 female patients with PCDH19 mutations and epilepsy aged 2-27 years (mean age 10.6 years). RESULTS: The most effective drugs after 3 months were clobazam and bromide, with a responder rate of 68% and 67%, respectively, where response was defined as seizure reduction of at least 50%. Defining long-term response as the proportion of responders after 12 months of treatment with a given drug in relation to the number of patients treated for at least 3 months, the most effective drugs after 12 months were again bromide and clobazam, with a long-term response of 50% and 43%, respectively. Seventy-four percent of the patients became seizure-free for at least 3 months, 47% for at least one year. SIGNIFICANCE: The most effective drugs in patients with PCDH19 mutations were bromide and clobazam. Although epilepsy in PCDH19 mutations is often pharmacoresistant, three quarters of the patients became seizure-free for at least for 3 months and half of them for at least one year. However, assessing the effectiveness of the drugs is difficult because a possible age-dependent spontaneous seizure remission must be considered.
Authors: Miriam H Meisler; Guy Helman; Michael F Hammer; Brandy E Fureman; William D Gaillard; Alan L Goldin; Shinichi Hirose; Atsushi Ishii; Barbara L Kroner; Christoph Lossin; Heather C Mefford; Jack M Parent; Manoj Patel; John Schreiber; Randall Stewart; Vicky Whittemore; Karen Wilcox; Jacy L Wagnon; Phillip L Pearl; Adeline Vanderver; Ingrid E Scheffer Journal: Epilepsia Date: 2016-06-08 Impact factor: 5.864
Authors: Joseph D Symonds; Sameer M Zuberi; Kirsty Stewart; Ailsa McLellan; Mary O'Regan; Stewart MacLeod; Alice Jollands; Shelagh Joss; Martin Kirkpatrick; Andreas Brunklaus; Daniela T Pilz; Jay Shetty; Liam Dorris; Ishaq Abu-Arafeh; Jamie Andrew; Philip Brink; Mary Callaghan; Jamie Cruden; Louise A Diver; Christine Findlay; Sarah Gardiner; Rosemary Grattan; Bethan Lang; Jane MacDonnell; Jean McKnight; Calum A Morrison; Lesley Nairn; Meghan M Slean; Elma Stephen; Alan Webb; Angela Vincent; Margaret Wilson Journal: Brain Date: 2019-08-01 Impact factor: 13.501