title: Efficacy of antiepileptic drugs for the treatment of Dravet syndrome with different genotypes.
abstract: OBJECTIVE
  Evaluation of the efficacy of antiepileptic drugs (AEDs) used in the treatment of Dravet syndrome (DS) with different genotypes.
  
  
  METHODS
  Patients with DS were recruited from different tertiary hospitals. Using a direct sequencing method and Multiplex Ligation-Dependent Probe Amplification (MLPA), genetic abnormalities were assessed within the exons and flanking introns of SCN1A gene, which encodes the α1 subunit of neuronal sodium channels. Patients were divided into SCN1A-positive and SCN1A-negative groups according to the results of genetic tests. Medical records, including detailed treatment information, were surveyed to compare the effect of different AEDs on clonic or tonic-clonic seizures (GTCS). Efficacy variable was responder rate with regard to seizure reduction.
  
  
  RESULTS
  One hundred and sixty of 276 (57.97%) patients had mutation in SCN1A gene (only 128 of them had provided detailed medical records). Among the 116 patients without SCN1A mutations, 87 had provided detailed medical records. Both older AEDs (valproate, phenobarbital, bromide, carbamazepine, clonazepam, and clobazam) and newer AEDs such as zonisamide were used in these patients. Valproate was the most frequently used AED (86.72% in the SCN1A-positive group, 78.16% in the SCN1A-negative group), with 52.25% and 41.18% responder rates in SCN1A-positive and SCN1A-negative patients, respectively (P=0.15). Bromide was used in 40.63% of the SCN1A-positive patients and 20.69% of the SCN1A-negative patients, and its responder rates were 71.15% and 94.44% in SCN1A-positive and SCN1A-negative patients, respectively (P=0.05). Efficacy rates of clonazepam, clobazam, phenobarbital, and zonisamide ranged from 30% to 50%, and these rates were not correlated with different genotypes (P>0.05). Carbamazepine had either no effect or aggravated seizures in all SCN1A-positive patients.
  
  
  CONCLUSIONS
  Bromide is most effective and is a well-tolerated drug among DS patients, especially among SCN1A-negative patients. Carbamazepine should be avoided in patients with SCN1A mutations.
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan; Department of Pediatrics, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiu-Yu
authors.initials: XY
authors.lastname: Shi
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tomonoh
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan; Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Wen-Ze
authors.initials: WZ
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan; Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Higurashi
authors.affiliation: Department of Pediatric Neurology, Central Hospital of Aichi Welfare Center for Persons with Developmental Disabilities, Kasugai, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Hirosaki University, Hirosaki, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan. Electronic address: hirose@fukuoka-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001965:Bromides / Q000009:adverse effects / Q000627:therapeutic use; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004831:Epilepsies, Myoclonic / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D012189:Retrospective Studies; D012640:Seizures / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D001965:Bromides; D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D002220:Carbamazepine
keywords: Antiepileptic drug therapy; Dravet syndrome; Efficacy; Genetic tests