Neuropediatrics 2015; 46 - PS02-20
DOI: 10.1055/s-0035-1550732

Therapy and Clinical Course in 52 Patients with PCDH19 Mutations

J. Lotte 1, T. Bast 2, P. Borusiak 3, A. Coppola 4, H. Cross 4, P. Dimova 5, A. Fogarasi 6, I. Graness 7, R. Guerrini 8, H. Hjalgrim 9, G. Kurlemann 10, S. Leiz 11, M. Linder-Lucht 12, T. Loddenkemper 13, C. Makowski 14, C. Mühe 15, A. Müller 16, J. Nicolai 17, S. Pellacani 8, S. Philip 18, S. Ruf 19, I. Fernández Sánchez 13, K. Schlachter 20, P. Striano 21, B. Sukhudyan 22, J. Vermeulen 17, B. Wilken 23, P. Wolf 24, G. Kluger 16, T. Weisbrod 25, R. Keimer 25
  • 1Neuropädiatrie, Salzburger Landeskliniken, Salzburg, Austria
  • 2Epilepsy Center Kork, Kehl, Germany
  • 3Department of Pediatrics, HELIOS Hospital Wuppertal, Wuppertal, Germany
  • 4Department of Clinical and Experimental Epilepsy, Great Ormond Street Hospital, London, United Kingdom
  • 5Clinic of Child Neurology, St. Naum University Hospital of Neurology and Psychiatry, Sofia, Bulgaria
  • 6Neurology Department, Bethesda Children's Hospital, Budapest, Hungary
  • 7Neuropädiatrie, Waldklinikum Gera, Gera, Germany
  • 8Child Neurology Unit, A. Meyer Children's Hospital, Firenze, Italy
  • 9Epilepsihospitalet Filadelfia, Danish Epilepsie Center, Dianalund, Denmark
  • 10Neuropädiatrie, Universitätskinderklinik Münster, Münster, Germany
  • 11Neuropädiatrie, Kinderklinik Dritter Orden, München, Germany
  • 12Servicio de Pediatría y Unidad de Epilepsia, Hospital del Mar, Barcelona, Spain
  • 13Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Boston, United States
  • 14Kinderklinik der Technischen Universität München, Klinikum Schwabing, München, Germany
  • 15Neuropädiatrische Schwerpunktpraxis, München, Germany
  • 16Neuropädiatrie, Schön-Kliniken Vogtareuth, Vogtareuth, Germany
  • 17Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands
  • 18Children's Hospital, Birmingham, United Kingdom
  • 19Neuropädiatrie, Universitätskinderklinik Tübingen, Tübingen, Germany
  • 20Department of Pediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria
  • 21Pediatric Neurology, Institute Gaslini, Genoa, Italy
  • 22“Arabkir” Medical Complex, Yerevan, Armenia
  • 23Sozialpädiatrisches Zentrum, Neuropädiatrie, Kassel, Germany
  • 24Department of Neuropediatrics, DRK-Children's Hospital, Siegen, Germany
  • 25Kinderklinik, Stauferklinikum, Schwäbisch Gmünd, Germany

Aims: Epilepsy in patients with PCDH19 mutations is often pharmacoresistant, there is less data on drug therapy strategies. As PCDH19 mutations are increasingly diagnosed, the spectrum of the known appearance expanded. We therefore investigated the clinical course and the effectiveness of antiepileptic drugs in these patients.

Methods: Retrospective analysis of the clinical course and effectiveness of the drugs used assessed after 3 and 12 months in 52 patients (all females) with epilepsy associated with PCDH19 mutations aged 2 to 27 years (mean, 10.8 years). Patients were defined as responders, if a seizure reduction by at least 50% was achieved.

Results: Seizure onset was at a mean age of 11.3 months (range, 3–78 months), most patients showed variable seizure types (range, 2–6; mean, 2). Nearly, all showed clusters of seizures (96%). Status epilepticus was documented in 50% of the patients. Trigger factors for seizures were fever, afebrile infections, emotional stress, vaccination, and bathing. Most patients were cognitively impaired (85%), had motor impairments (45%), or behavioral problems (63%).

After 3 months, especially CLB, BR, and VPA were effective in 92, 60, and 58% responders. After 12 months, CLB (100%), TPM (100%), and VPA (90%) were most effective. Overall, 78% were seizure-free for 3 months, 47% for 1 year, and 4% for 10 years. A decrease in seizure frequency was often observed with age regardless of the drugs used.

Conclusion: Our patients usually had previously reported typical courses with multiple seizure types and clusters. Cognitive and behavioral disorders were frequently seen, but there were also patients with a normal developmental profile. GABAergic drugs seem to be particularly effective, but the estimating effectiveness is difficult due to fluctuations in the natural history of the disease.

Keywords: PCDH19, epilepsy therapy drugs.