title: Early and effective treatment of KCNQ2 encephalopathy.
abstract: OBJECTIVE
  To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life.
  
  
  METHODS
  We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data.
  
  
  RESULTS
  Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment.
  
  
  CONCLUSIONS
  Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.
authors.affiliation: Neurology Unit and Laboratories, A. Meyer Children's Hospital, Florence, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pisano
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, California, U.S.A.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Numis
authors.affiliation: Departments of Medicine and Paediatrics, Florey Institute, Austin Health and Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Sinéad B
authors.initials: SB
authors.lastname: Heavin
authors.affiliation: Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weckhuysen
authors.affiliation: Central Hospital of Bolzano, Bolzano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Angriman
authors.affiliation: Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Arvid
authors.initials: A
authors.lastname: Suls
authors.affiliation: Child Neurology and Psychiatry Unit, S. Croce and S. Carlo Hospital, Cuneo, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Podesta
authors.affiliation: Pediatric Epilepsy Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Thibert
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, California, U.S.A.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Shapiro
authors.affiliation: Neurology Unit and Laboratories, A. Meyer Children's Hospital, Florence, Italy.|University of Florence, Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Departments of Medicine and Paediatrics, Florey Institute, Austin Health and Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.affiliation: Neurology Unit and Laboratories, A. Meyer Children's Hospital, Florence, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Marini
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, California, U.S.A.|Department of Pediatrics, University of California San Francisco, San Francisco, California, U.S.A.
authors.forename: Maria Roberta
authors.initials: MR
authors.lastname: Cilio
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D008297:Male; D009069:Movement Disorders / Q000209:etiology; D009154:Mutation / Q000235:genetics*; D059906:Neuroimaging; D010597:Pharmacogenetics; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants; D051658:KCNQ2 Potassium Channel
keywords: Antiepileptic drug treatment; Epilepsy; KCNQ2 encephalopathy