Neuropediatrics 2013; 44 - PS12_1186
DOI: 10.1055/s-0033-1337774

Retrospective evaluation of antiepileptic drugs in patients with CDKL5 mutations

A Müller 1, T Bast 2, R Guerrini 3, J Albers 4, S Auvin 5, S Philip 6, C Korenke 7, R Keimer 8, N Wolf 9, G Kurlemann 10, T Kovacevic-Preradovic 11, B Püst 12, C Thiels 13, B Ceulemans 14, G Kluger 1
  • 1Neuropädiatrie, Schön Klinik Vogtareuth, Vogtareuth, Germany
  • 2Epilepsiezentrum Kork, Epilepsieklinik für Kinder und Jugendliche, Kehl-Kork, Germany
  • 3Child Neurology Unit, A. Meyer Children's Hospital,, Florence, Italy
  • 4Klinik für Neuropädiatrie, UKSH, Campus Kiel, Kiel, Germany
  • 5Service de Neurologie Pédiatrique, INSERM U676 Hôpital Robert Debré, Paris cedex 19, France
  • 6Children's Hospital, Birmingham, Birmingham, United Kingdom
  • 7Neuropädiatrie, Zentrum für Kinder-und Jugendmedizin, Klinikum Oldenburg, Oldenburg, Germany
  • 8Neuropädiatrie, Pädiatrie 1, Klinikum Stuttgart, Stuttgart, Germany
  • 9Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
  • 10Klinik für Neuropädiatrie, Kinderklinik Münster, Münster, Germany
  • 11Epilepsiezentrum Radeberg-Kleinwachau, Radeberg, Germany
  • 12Neuropädiatrie, Kath. Kinderkrankenhaus Wilhelmstift, Hamburg, Germany
  • 13Neuropädiatrie, Klinik für Kinder- und Jugendmedizin, Klinik der Ruhr-Universität Bochum, Bochum, Germany
  • 14University Hospital and University of Antwerp, Edegem, Belgium

Aims: Mutations in the X-linked cyclin-dependent kinase-like 5 gene (CDKL5) cause an epileptic encephalopathy with early-onset severe neurological impairment and intractable seizures. Currently, there is no concept how to treat these rare patients.

Methods: In this retrospective study, we evaluated the efficacy of antiepileptic drugs in 34 patients with CDKL5 mutations (29 female; mean age 7.1 years) after 3 and 6 months after the introduction of each drug. Drug response was defined as a 50% seizure reduction.

Results: The patients were treated with 4 to 21 (mean: 9) different AED. A total of 31 patients (91%) showed initial response to at least one AED for several weeks. In most of them, loss of efficacy occurred in the following weeks. One patient became seizure free with CBZ for 9 years. In the other patients, seizures recurred after weeks to months. The responder rate to at least one AED after 3 months was 68% (23/34) and 32% (11/34) after 6 months. The highest rate of seizure reduction after 3 months was reported during treatment with FBM (⅔), CLB (4/17), steroids (5/24), VPA (8/31), and LEV (7/33). In total, 12 patients (35%) experienced a seizure aggravation to at least one AED. LEV (5/33), CBZ (4/14), and LTG (3/19) were described most frequently as aggravating, which led to discontinuation. One patient (1/1) responded to intravenous immunoglobulin and 2/11 to ketogenic diet.

Conclusion: Most patients showed some but only initial response to various AEDs with different modes of actions. Seizure aggravation was frequently reported. Because of age-related and spontaneous fluctuation in seizure frequency and types, overall benefit of different antiepileptic drugs remains unclear. Collaborated clinical long-term observations might help clinicians to define treatment strategies in patients with this rare and refractory epileptic encephalopathy.