Neuropediatrics 2013; 44 - FV14_03
DOI: 10.1055/s-0033-1337733

Effectiveness of antiepileptic therapy in catastrophic infantile epilepsy: Comparison of patients with SCN1A and PCDH19 mutations

J Lotte 1, T Bast 2, P Borusiak 3, I Sánchez Fernández 4, A Fogarasi 5, R Guerrini 6, H Hjalgrim 7, S Leiz 8, M Linder-Lucht 9, T Loddenkemper 4, S Pellacani 6, S Philip 10, S Ruf 11, K Schlachter 12, P Striano 13, J Vermeulen 14, G Kluger 15
  • 1Kinderzentrum Maulbronn, Maulbronn, Germany
  • 2Epilepsieklinik für Kinder und Jugendliche, Epilepsiezentrum Kork, Kehl, Germany
  • 3Department of Pediatrics, HELIOS Hospital Wuppertal, Wuppertal, Germany
  • 4Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Boston, United States
  • 5Neurology Department, Bethesda Children's Hospital, Budapest, Hungary
  • 6Child Neurology Unit, A. Meyer Children's Hospital, Firenze, Italy
  • 7Epilepsihospitalet Filadelfia, Danish Epilepsie Center, Dianalund, Denmark
  • 8Neuropädiatrie, Kinderklinik Dritter Orden, München, Germany
  • 9Servicio de Pediatría y Unidad de Epilepsia, Hospital del Mar, Barcelona, Spain
  • 10Children's Hospital, Birmingham, United Kingdom
  • 11Neuropädiatrie, Universitätskinderklinik Tübingen, Tübingen, Germany
  • 12Department of Pediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria
  • 13Pediatric Neurology, Institute Gaslini, Genoa, Italy
  • 14Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
  • 15Neuropädiatrie, Schön Kliniken Vogtareuth, Vogtareuth, Germany

Aims: Mechanism of epileptogenesis in PCDH19 mutations is not yet clear, but it is thought to be different from SCN1A mutations. Both mutations can cause Dravet syndrome. In both cases, epilepsy is highly pharmaco-resistant. We compared effectiveness of antiepileptic therapy in both groups.

Methods: Retrospective analysis of the effectiveness of antiepileptic drugs used assessed after 3 months in 40 patients (24 male, 16 female) with SCN1A mutations aged 2 to 25 years (mean age: 12.1 years) and 32 patients (all female) with PCDH19 mutations aged 1 to 11 years (mean age: 5.9 years). All patients showed variable seizure types; all of the SCN1A patients and nearly all (84%) of the PCDH19 patients had generalized tonic-clonic seizures.

Results: The administered drugs and their effectiveness are presented in Table 1. In patients with SCN1A mutations, best seizure reduction was achieved with CBR (86%), CLB (84%), and VPA (70%), while aggravation was observed in 31 patients (78%) with OXC (83%), CBZ (82%), ZNS (78%), PHT (70%), LTG (59%), TPM (23%), FBM (17%), LEV (13%), RFN (25%), STP (11%), PB (4%), VGB (⅓), AZA (½), GBP (1/1), and LCM (2/2). In patients with PCDH19 mutations, best seizure reduction was achieved with CLB (94%), PB (50%), and STP (50%), while aggravation was observed in four patients (13%) with OXC (8%), LTG (6%), CBZ (5%), and LCM (½).

Conclusion: The most effective drug in patients with SCN1A mutations was CBR, whereas in PCDH19 patients, CLB was most effective. Both are working on the GABA receptor such as the following ones: being PB, STP, and VPA. Although sodium channel blockers such as CBZ, OXC, LTG, PHT, or ZNS frequently cause aggravation in SCN1A patients (78%), there is a surprisingly low rate of aggravation in PCDH19 patients (13%).

The mechanism of epileptogenesis is still unclear in PCDH19 mutations. Based on the observation of differences in response to various anticonvulsant drugs, it can be speculated that decreased inhibition via altered sodium channels in interneurons causes a susceptibility for aggravation in contrast to a disturbance in brain development based on a deficient structural protein.