title: Effectiveness of antiepileptic therapy in patients with PCDH19 mutations.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Neuropädiatrie, Schön Klinik Vogtareuth, Germany. Electronic address: jan.lotte@web.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Lotte
authors.affiliation: Epilepsy Center Kork, Kehl-Korg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bast
authors.affiliation: Department of Pediatrics, HELIOS Hospital Wuppertal, Witten/Herdecke University, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Borusiak
authors.affiliation: Department of Clinical & Experimental Epilepsy, Great Ormond Street Hospital, University College London, England.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Department of Clinical & Experimental Epilepsy, Great Ormond Street Hospital, University College London, England.
authors.forename: J Helen
authors.initials: JH
authors.lastname: Cross
authors.affiliation: Epilepsy Center, St. Ivan Rilski University Hospital, Sofia, Bulgaria.
authors.forename: Petia
authors.initials: P
authors.lastname: Dimova
authors.affiliation: Neurology Department, Bethesda Children's Hospital, Budapest, Hungary.
authors.forename: Andras
authors.initials: A
authors.lastname: Fogarasi
authors.affiliation: Neuropädiatrie, Waldklinikum Gera, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Graneß
authors.affiliation: Child Neurology Unit, A. Meyer Children's Hospital, University of Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Epilepsihospitalet Filadelfia, Danish Epilepsie Center, Dianalund, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Hjalgrim
authors.affiliation: Kinderklinik, Stauferklinik, Schwäbisch Gmünd, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Keimer
authors.affiliation: Pediatric Neurology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Korff
authors.affiliation: Neuropädiatrie, Universitätskinderklinik Münster, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kurlemann
authors.affiliation: Neuropädiatrie, Kinderklinik Dritter Orden, München, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Leiz
authors.affiliation: Servicio de Pediatría y Unidad de Epilepsia, Hospital del Mar, Barcelona, Spain.
authors.forename: Michaela
authors.initials: M
authors.lastname: Linder-Lucht
authors.affiliation: Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Boston, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Loddenkemper
authors.affiliation: Kinderklinik der Technischen Universität München, Klinikum Schwabing, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Makowski
authors.affiliation: Neuropädiatrische Schwerpunktpraxis, München, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mühe
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Nicolai
authors.affiliation: Epilepsihospitalet Filadelfia, Danish Epilepsie Center, Dianalund, Denmark.
authors.forename: Marina
authors.initials: M
authors.lastname: Nikanorova
authors.affiliation: Child Neurology Unit, A. Meyer Children's Hospital, University of Florence, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pellacani
authors.affiliation: Children's Hospital Birmingham, England.
authors.forename: Sunny
authors.initials: S
authors.lastname: Philip
authors.affiliation: Neuropädiatrie, Universitätskinderklinik Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ruf
authors.affiliation: Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Boston, USA.
authors.forename: Iván
authors.initials: I
authors.lastname: Sánchez Fernández
authors.affiliation: Department of Pediatrics, Landeskrankenhaus Bregenz, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Schlachter
authors.affiliation: Pediatric Neurology, Institute Gaslini, University of Genova, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: "Arabkir" Medical Complex, Pediatric Neurology, Yerevan, Armenia.
authors.forename: Biayna
authors.initials: B
authors.lastname: Sukhudyan
authors.affiliation: Neuropädiatrie, Wedau Kliniken, Duisburg, Germany.
authors.forename: Deyana
authors.initials: D
authors.lastname: Valcheva
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Vermeulen
authors.affiliation: Kinderklinik, Stauferklinik, Schwäbisch Gmünd, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Weisbrod
authors.affiliation: Department of Pediatric Neurology, Kassel Hospital, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wilken
authors.affiliation: Department of Neuropediatrics, DRK-Children's Hospital, Siegen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolf
authors.affiliation: Neuropädiatrie, Schön Klinik Vogtareuth, Germany; Paracelsus Medical University, Salzburg, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kluger
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000627:therapeutic use*; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010597:Pharmacogenetics; D000091363:Protocadherins; D012011:Red Cross; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins
keywords: Antiepileptic drugs; Epilepsy; Long-term effectiveness; PCDH19 mutation; Treatment