ATP1A3-related epilepsy: Report of seven cases and literature-based analysis of treatment response.

Authors

Gasser M1, Boonsimma P2, Netbaramee W3, Wechapinan T4, Srichomthomg C2, Ittiwut C2, Krenn M5, Zimprich F6, Milenkovic I6, Abicht A7, Biskup S8, Roser T1, Shotelersuk V2, Tacke M9, Kuersten M1, Wagner M10, Borggraefe I9, Suphapeetiporn K11, von Stülpnagel C12
    1. Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, Dr. von Haunersches Childrens Hospital, Ludwig-Maximilian-University of Munich, Germany.
    2. Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok 10330, Thailand.
    3. Division of Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
    4. Division of Neurology, Department of Pediatrics, Faculty of Medicine, Queen Sirikit National Institute of Child Health, Bangkok 10400, Thailand.
    5. Institute of Human Genetics, Technical University of Munich, Munich, Germany; Department of Neurology, Medical University of Vienna, Vienna, Austria.
    6. Department of Neurology, Medical University of Vienna, Vienna, Austria.
    7. Medical Genetic Center Munich, Munich, Germany; Department of Neurology, Friedrich-Baur-Institute, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
    8. Praxis für Humangenetik und CeGaT GmbH, Paul-Ehrlich-Str. 23, Tuebingen, Germany.
    9. Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, Dr. von Haunersches Childrens Hospital, Ludwig-Maximilian-University of Munich, Germany; Comprehensive Epilepsy Center, Ludwig-Maximilian- University of Munich, Germany.
    10. Institute of Human Genetics, Technical University of Munich, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany; Institute for Neurogenomics, Helmholtz Zentrum München, Neuherberg, Germany.
    11. Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok 10330, Thailand. Electronic address: kanya.su@chula.ac.th.
    12. Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, Dr. von Haunersches Childrens Hospital, Ludwig-Maximilian-University of Munich, Germany; Comprehensive Epilepsy Center, Ludwig-Maximilian- University of Munich, Germany; Paracelsus Medical University Salzburg, Salzburg, Austria. Electronic address: cvstuelpnagel@steinbeis.co.

Abstract

ATP1A3 related disease is a clinically heterogeneous condition currently classified as alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Recently, it has become apparent that a remarkably large subgroup is suffering from often difficult-to-treat epilepsy. The aim of the present study was to assess the prevalence and efficacy of commonly used anti-epileptic-drugs (AEDs) in patients with ATP1A3 related seizures. Therefore, we performed a retrospective study of patients in combination with a systematic literature-based review. Inclusion criteria were: verified ATP1A3 mutation, seizures and information about AED treatment. The literature review yielded records for 188 epileptic ATP1A3 patients. For 14/188 cases, information about anti-epileptic treatment was available. Combined with seven unpublished records of ATP1A3 patients, a sample size of 21 patients was reached. Most used AED were levetiracetam (n = 9), phenobarbital (n = 8), valproic acid (n = 7), and topiramate (n = 5). Seizure reduction was reported for 57% of patients (n = 12). No individual AEDs used (either alone or combined) had a success rate over 50%. There was no significant difference in the response rate between various AEDs. Ketogenic diet was effective in 2/4 patients. 43% of patients (n = 9) did not show any seizure relief. Even though Epilepsy is a significant clinical issue in ATP1A3 patients, only a minority of publications provide any information about patients’ anti-epileptic treatment. The findings of treatment effectiveness in only 57% (or lower) of patients, and the non-existence of a clear first-line AED in ATP1A3 related epilepsy stresses the need for further research.