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

J Clin Neurosci. 2020 Feb;72:31-38. doi: 10.1016/j.jocn.2020.01.041. Epub 2020 Jan 17.


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 Combined with seven unpublished records of ATP1A3 patients, a sample size of 21 patients was reached.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.

Keywords: AED; ATP1A3; Case report; Epilepsy; Review; Treatment.

MeSH terms

  • Adult
  • Anticonvulsants / therapeutic use
  • Cerebellar Ataxia / genetics
  • Child
  • Dystonic Disorders
  • Epilepsy / diet therapy
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Female
  • Hearing Loss, Sensorineural
  • Hemiplegia / diet therapy
  • Hemiplegia / drug therapy
  • Hemiplegia / genetics*
  • Humans
  • Levetiracetam
  • Male
  • Mutation
  • Optic Atrophy / genetics
  • Reflex, Abnormal
  • Retrospective Studies
  • Seizures / genetics
  • Sodium-Potassium-Exchanging ATPase*
  • Topiramate
  • Valproic Acid / therapeutic use


  • ATP1A3 protein, human
  • Anticonvulsants
  • Topiramate
  • Levetiracetam
  • Valproic Acid
  • Sodium-Potassium-Exchanging ATPase

Supplementary concepts

  • Alternating hemiplegia of childhood
  • Dystonia 12