title: Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy.
abstract: OBJECTIVE
  Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder.
  
  
  METHODS
  Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months.
  
  
  RESULTS
  The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions.
  
  
  CONCLUSIONS
  Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation.
authors.affiliation: Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.affiliation: Department of Neuropediatrics, Christian-Albrechts-Univerisity of Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany; Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, USA.
authors.forename: I
authors.initials: I
authors.lastname: Helbig
authors.affiliation: Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Jansen
authors.affiliation: Epilepsieklinik für Kinder und Jugendliche, Epilepsiezentrum Kork, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Bast
authors.affiliation: Child Neurology Unit, A. Meyer Children's Hospital, University of Florence, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Department of Neuropediatrics, Christian-Albrechts-Univerisity of Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Jähn
authors.affiliation: Department of Neuropediatrics, Christian-Albrechts-Univerisity of Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Muhle
authors.affiliation: Service de Neurologie Pédiatrique et des Maladies Métaboliques, Hôpital Robert Debré, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Auvin
authors.affiliation: Neuropädiatrie, Zentrum für Kinder- und Jugendmedizin, Klinikum Oldenburg, Germany.
authors.forename: G C
authors.initials: GC
authors.lastname: Korenke
authors.affiliation: Children's Hospital Birmingham, England, UK.
authors.forename: S
authors.initials: S
authors.lastname: Philip
authors.affiliation: Neuropädiatrie, Stauferklinikum Mutlangen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Keimer
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Institute Gaslini, University of Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Striano
authors.affiliation: Child Neurology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: N I
authors.initials: NI
authors.lastname: Wolf
authors.affiliation: Neuropädiatrie, Kath. Kinderkrankenhaus Wilhelmstift, Hamburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Püst
authors.affiliation: Neuropädiatrie, Klinik für Kinder- und Jugendmedizin, Klinik der Ruhr-Universität, Bochum, Germany.
authors.forename: Ch
authors.initials: Ch
authors.lastname: Thiels
authors.affiliation: Neurology Department, Bethesda Children's Hospital, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Fogarasi
authors.affiliation: Neuropädiatrie, Kinderklinik Amsterdamer Straße, Kliniken der Stadt Köln, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Waltz
authors.affiliation: Kinderklinik Münster, Neuropädiatrie, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kurlemann
authors.affiliation: Epilepsiezentrum Radeberg-Kleinwachau, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kovacevic-Preradovic
authors.affiliation: Department of Neurology-Child Neurology, University Hospital and University of Antwerp, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Ceulemans
authors.affiliation: University Children's Hospital Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Schmitt
authors.affiliation: Sozialpädiatrisches Zentrum Frankfurt Mitte, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Philippi
authors.affiliation: Rare Diseases Clinical Research Network, Boston Children's Hospital, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tarquinio
authors.affiliation: BC Children's Hospital, Department of Pediatrics, Vancouver, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Buerki
authors.affiliation: Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany; Paracelsus Medical University, Salzburg, Austria.
authors.forename: C
authors.initials: C
authors.lastname: von Stülpnagel
authors.affiliation: Clinic for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany; Paracelsus Medical University, Salzburg, Austria. Electronic address: gkluger@schoen-kliniken.de.
authors.forename: G
authors.initials: G
authors.lastname: Kluger
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D055423:Diet, Ketogenic; D004827:Epilepsy / Q000178:diet therapy* / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012189:Retrospective Studies; D012640:Seizures / Q000517:prevention & control; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human
keywords: AED; CDKL5; Ketogenic diet; Long-term efficacy